Use of triglyceride and phospholipid compositions

Abstract

Compositions comprising triglycerides and phospholipids, and methods for using them in various medical applications, for example, as imaging agents, coupling agents (e.g., for invasive ultrasound imaging), contrast agents, light dispersants, delivery agents, and / or lubricants, are provided herein. The compositions and methods disclosed herein may be used to diagnose and / or treat various diseases, such as cancer. In one embodiment, the disclosure provides a composition comprising (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) a wetting agent. In one embodiment, the disclosure provides a composition comprising (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) pH buffer, and (e) a wetting agent.

Description

Background Art

[0001] Cross - reference to related applications This application claims the benefit of priority of U.S. Application No. 63 / 514,974, filed Jul. 21, 2023, which is hereby incorporated by reference in its entirety for all purposes.

[0002] In the art, there is a desire for safe and stable compositions that can be used in various in vivo medical applications, such as imaging agents, coupling agents, contrast agents, light - dispersing agents, delivery agents, and / or lubricants. Such compositions can be used in methods for imaging and / or treating various diseases such as cancer.

[0003] For example, ultrasound imaging is widely used in medical examinations for visualizing tissues in real - time and is used in various clinical fields. To ensure proper contact between the transducer / ultrasound probe and the skin / tissue of the examination subject, an ultrasound coupling agent, which is usually a gel or liquid, is used. The ultrasound coupling agent is used to avoid air pockets between the transducer / probe and the tissue and to facilitate good acoustic coupling at the interface between the ultrasound transducer and the tissue being imaged. Ultrasound imaging is often used during invasive procedures, such as during surgery or invasive diagnostic procedures. For example, ultrasound imaging can be used for imaging tumors in brain surgery. In this case, ultrasound imaging can be used to identify the location of the tumor and anatomical structures and to identify residual tumors during surgery. It can also be used to ensure that damaged tissue, such as a tumor, is completely removed and that unnecessary excision of healthy tissue is avoided. However, the in vivo application of invasive ultrasound imaging remains difficult due to the lack of appropriate compositions for reducing artifacts.

[0004] Ideally, high image quality should be maintained throughout a medical procedure (e.g., tumor resection surgery) to monitor its progress. However, surgery can introduce image noise, potentially leading to inaccurate representation of relevant anatomical structures in ultrasound images.

[0005] The term "artifact" is used in medical imaging to describe any part of an image that does not accurately represent the anatomical structure of the object being examined. Ultrasound imaging is well known to be prone to several different types of artifacts that can have adverse consequences for the subject. For example, when using ultrasound in brain tumor surgery, the presence of artifacts can hinder the surgeon's interpretation of the images.

[0006] When using ultrasound for invasive imaging of the body, one common artifact is the enhanced (abnormally bright) signal that occurs beneath fluid-filled cavities. Enhanced brightness of tissues located beneath fluid-filled spaces has been observed in ultrasound imaging of cysts, blood vessels, or other fluid-filled spaces. Due to this apparent enhancement of reflected echoes, this frequently occurring imaging artifact is often called a brightness artifact (sometimes also referred to as an "enhanced artifact" or "bright-rim effect"). This type of artifact is a result of the difference in attenuation of acoustic waves due to the fluid within the cavity and the surrounding biological tissue.

[0007] For example, during brain tumor surgery, the resection cavity is usually filled with saline solution as an ultrasound coupling agent before ultrasound imaging to allow sound propagation and prevent air-induced artifacts. The difference in attenuation between the brain and isotonic saline solution can generate artifacts that degrade ultrasound images and affect the precision of the surgery (e.g., degree of resection and safety). Acoustic waves are transmitted through a saline-filled cavity before reaching biological tissue. The attenuation of acoustic waves in saline solution is very small compared to the attenuation of acoustic waves in biological tissue. The attenuation coefficient (α) of water is 0.0022 dB / (MHz·cm), while in the case of the brain, for example, it has been reported in measurements by various groups to be in the range of approximately 0.4 to 1.0 (Duck FA, In Physical properties of tissue, Academic Press, LTD).

[0008] The main component of sound attenuation in tissues is absorption, which is the conversion of some acoustic energy into heat. Scattering also contributes to the attenuation of acoustic waves. These combined effects result in acoustic waves propagating through saline solution having a larger amplitude than acoustic waves propagating through the same distance in biological tissue. Total attenuation can be estimated by the following equation.

[0009] Attenuation [dB] = α [dB / (MHz*cm)] * l [cm] * f [MHz] In the formula, α is the damping coefficient of the medium. l is the length of the medium (or propagation distance), f is the frequency of the transmitted ultrasound.

[0010] For example, if we select a frequency of 8 MHz and a propagation distance of 10 cm, and assume that the attenuation coefficient of brain tissue is 0.8, then the attenuation of ultrasound propagating through water will be 0.18 dB, and the attenuation of ultrasound propagating through brain tissue will be 64 dB.

[0011] This difference in attenuation can introduce noise into ultrasound images, for example, when ultrasound is used during brain tumor surgery. Ultrasound transmitted through a resection cavity filled with water will have a large amplitude when it reaches the cavity wall because the attenuation of water is small. Therefore, the sound waves reflected from the cavity wall will also have a relatively large amplitude. Furthermore, the sound waves that propagate further within the tissue will also have a relatively large amplitude. Compared to sound waves that have fully propagated through brain tissue, which has a relatively high attenuation coefficient, these transmitted and reflected waves transmitted through saline solution have less attenuation, and thus their amplitude is significantly larger. The intensity fluctuations observed in ultrasound images make image interpretation very difficult. A bright rim observed at the cavity wall may mask the presence of residual tumor, or high-intensity areas extending from the cavity wall may be interpreted as a hyperechoic tumor when they are actually normal brain tissue.

[0012] Several papers on the use of ultrasound in brain tumor surgery describe the presence of a hyperechoic rim in ultrasound imaging of the resection cavity. In ultrasound imaging, this enhanced signal appearing beneath a fluid-filled cavity is considered one of the major imaging artifacts seen in ultrasound imaging during surgery.

[0013] In this field, there is a need for new compositions that are safe, stable, and do not cause image artifacts.

[0014] Better compositions are desired for many in vivo medical applications beyond ultrasound. For example, photodynamic therapy (PDT), a promising cancer therapy, is limited to treating cancer because light can only penetrate tissue to a depth of 0.7–1 cm. Transmission is limited due to the interaction of light and tissue, including absorption, scattering, refraction, and reflection. Compositions that improve light transmission in PDT are desired.

[0015] Furthermore, in this technological field, there is a demand for new contrast agents and solutions for suspending contrast agents. Contrast agents allow physicians to differentiate and identify abnormalities within tissues. Without contrast agents, diagnostic images may be blurry and indistinguishable, hindering effective treatment.

[0016] This disclosure provides such compositions, methods for using such compositions in various medical applications, and the like. [Overview of the project]

[0017] In one embodiment, the Disclosure provides a composition comprising (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) a pH buffer, and (e) a wetting agent. In one embodiment, the Disclosure provides a composition comprising (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) a pH buffer, and (e) a wetting agent. In embodiments, the composition comprises substances other than (a) to (e) in amounts of 5 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.5 w / v% or less, 0.2 w / v% or less, or 0.1 w / v% or less. In embodiments, the composition comprises essentially all of (a) to (e). In embodiments, the composition comprises all of (a) to (e).

[0018] In one embodiment, the Disclosure provides a composition comprising (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, (e) a wetting agent, and (f) a diagnostic agent, a therapeutic agent, or any combination thereof. In one embodiment, the Disclosure provides a composition comprising (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) pH buffer, (e) a wetting agent, and (f) a diagnostic agent, a therapeutic agent, or any combination thereof. In embodiments, the composition comprises substances other than (a) to (f) in amounts of 5 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.5 w / v% or less, 0.2 w / v% or less, or 0.1 w / v% or less. In embodiments, the composition comprises essentially all of (a) to (f). In embodiments, the composition comprises all of (a) to (f).

[0019] In one embodiment, the concentration of at least one triglyceride is approximately 5 w / v% to approximately 9 w / v%. In another embodiment, the concentration of at least one triglyceride is approximately 6 w / v% to approximately 8 w / v%. In yet another embodiment, the concentration of at least one triglyceride is approximately 7 w / v%.

[0020] In one embodiment, the concentration of at least one triglyceride is approximately 0.05 w / v% to approximately 1 w / v%, or approximately 0.1 w / v% to approximately 0.5 w / v%. In another embodiment, the concentration of at least one triglyceride is approximately 0.1 w / v%, approximately 0.2 w / v%, or approximately 0.5 w / v%.

[0021] In the embodiment, at least one triglyceride is olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil, corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, linseed oil, walnut oil, avocado oil, rice bran oil, grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, etc. It is derived from one or more of the following: oat oil, black seed oil, apricot oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, perilla oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuru oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil. In embodiments, at least one triglyceride is derived from soybean oil. In the connection, at least one triglyceride is selected from the group consisting of tristearin, triolein, tripalmitine, triacetin, trilinolein, tricaprine, trilaurine, trialakidine, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimyristine, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, trinonanoin, and any combination thereof. In the embodiment, at least one triglyceride is selected from the group consisting of linolenic acid-oleic acid-linolenic acid, linoleic acid-linoleic acid-linoleic acid, oleic acid-linoleic acid-oleic acid, linoleic acid-oleic acid-linoleic acid, linoleic acid-linoleic acid-linoleic acid, palmitic acid-oleic acid-linoleic acid, palmitic acid-linoleic acid-palmitic acid, stearic acid-oleic acid-linoleic acid, linoleic acid-linolenic acid-linoleic acid, linoleic acid-oleic acid-oleic acid, and any combination thereof. In the embodiment, at least one triglyceride is essentially composed of medium-chain fatty acid triglycerides, including medium-chain fatty acid triglycerides, or composed of medium-chain fatty acid triglycerides.

[0022] In the embodiments, the concentration of at least one phospholipid is approximately 1.2 w / v% at most. In the embodiments, the concentration of at least one phospholipid is approximately 0.1 w / v% to approximately 1.2 w / v%. In the embodiments, the concentration of at least one phospholipid is approximately 0.2 w / v% to approximately 1.2 w / v%. In the embodiments, the concentration of at least one phospholipid is approximately 0.4 w / v% to approximately 1.2 w / v%. In the embodiments, the concentration of at least one phospholipid is approximately 0.42 w / v% to approximately 0.84 w / v%. In the embodiments, the concentration of at least one phospholipid is approximately 3.2 g / L to approximately 5.2 g / L. In the embodiments, the concentration of at least one phospholipid is approximately 0.42 w / v% (approximately 4.2 g / L). In the embodiments, the concentration of at least one phospholipid is approximately 7.4 g / L to approximately 9.4 g / L. In this embodiment, the concentration of at least one phospholipid is approximately 0.84 w / v% (approximately 8.4 g / L).

[0023] In embodiments, the composition comprises lecithin containing at least one phospholipid. In embodiments, the lecithin contains at least one phospholipid in about 20% to about 90% by weight. In embodiments, the lecithin contains at least one phospholipid in about 60% to about 70% by weight. In embodiments, lecithin is derived from one or more of the following: soybeans, sunflower seeds, rapeseed, egg yolks, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseed, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, Brazil nuts, chia seeds, hemp seeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chicken liver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg whites. In embodiments, lecithin is egg yolk lecithin.

[0024] In embodiments, the composition contains up to about 1.2 w / v% lecithin. In embodiments, the composition contains from about 0.1 w / v% to about 1.2 w / v% lecithin. In embodiments, the composition contains from about 0.4 w / v% to about 1.2 w / v% lecithin. In embodiments, the composition contains about 0.42 w / v% or about 0.84 w / v% lecithin.

[0025] In embodiments, the lecithin contains phosphatidylcholine. In embodiments, the lecithin contains from about 10 wt% to about 75 wt% phosphatidylcholine. In embodiments, the lecithin contains from about 20 wt% to about 70 wt% phosphatidylcholine. In embodiments, the lecithin contains from about 60 wt% to about 75 wt% phosphatidylcholine.

[0026] In embodiments, at least one phospholipid contains phosphatidylcholine. In embodiments, at least one phospholipid contains from about 10 wt% to about 70 wt% phosphatidylcholine. In embodiments, at least one phospholipid contains from about 20 wt% to about 70 wt% phosphatidylcholine. In embodiments, at least one phospholipid contains from about 60 wt% to about 75 wt% phosphatidylcholine.

[0027] In embodiments, the concentration of at least one triglyceride is from about 60.0 g / L to about 80.0 g / L, and / or the concentration of at least one phospholipid is from about 3.2 g / L to about 5.2 g / L. In embodiments, the concentration of at least one triglyceride is from about 60.0 g / L to about 80.0 g / L, and / or the concentration of at least one phospholipid is from about 7.4 g / L to about 9.4 g / L.

[0028] In embodiments, the wetting agent is glycerol. In embodiments, the concentration of the wetting agent is from about 10 g / L to about 35 g / L. In embodiments, the concentration of the wetting agent is from about 14 g / L to about 26 g / L. In embodiments, the concentration of the wetting agent is about 16 g / L. In embodiments, the concentration of the wetting agent is from about 21 g / L to about 26 g / L. In embodiments, the concentration of the wetting agent is about 23.7 g / L.

[0029] In an embodiment, the concentration of at least one phospholipid or lecithin and the concentration of glycerol are selected from one of the formulations in Table 3.

[0030] In an embodiment, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is from about 6.5:1 to about 30:1. In an embodiment, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is from about 20:1 to about 30:1. In an embodiment, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is from about 13:1 to about 20:1. In an embodiment, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 16.7:1. In an embodiment, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is from about 6.5:1 to about 10:1. In an embodiment, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 8.3:1.

[0031] In the embodiment, the concentration of at least one triglyceride is about 0.05 w / v% to about 1 w / v%, or about 0.1 w / v% to about 0.5 w / v%, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 6.5:1 to about 20:1, and the pH of the composition is about 6.5 to about 8.5. In the embodiment, the pH of the composition is about 7.0. In the embodiment, the composition has an osmotic pressure of less than 100 mOsm / kg, less than 90 mOsm / kg, less than 80 mOsm / kg, less than 70 mOsm / kg, less than 60 mOsm / kg, less than 50 mOsm / kg, less than 40 mOsm / kg, less than 30 mOsm / kg, less than 20 mOsm / kg, or less than 10 mOsm / kg, but greater than 0 mOsm / kg. In the embodiment, the composition has an osmotic pressure of less than 10 mOsm / kg, less than 9 mOsm / kg, less than 8 mOsm / kg, less than 7 mOsm / kg, less than 6 mOsm / kg, less than 5 mOsm / kg, less than 4 mOsm / kg, less than 3 mOsm / kg, less than 2 mOsm / kg, or less than 1 mOsm / kg, but greater than 0 mOsm / kg.

[0032] In the embodiment, the concentration of at least one triglyceride is about 0.05 w / v% to about 1 w / v%, or about 0.1 w / v% to about 0.5 w / v%, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 6.5:1 to about 20:1, and the concentration of glycerol is about 25% to about 30%. In the embodiment, the composition has an osmotic pressure of about 270 mOsm / kg to about 330 mOsm / kg, about 284 mOsm / kg to about 296 mOsm / kg, about 290 mOsm / kg to about 311 mOsm / kg, or about 290 mOsm / kg to about 305 mOsm / kg. In the embodiment, the pH of the composition is about 7.0.

[0033] In embodiments, the composition contains less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of sodium chloride. In embodiments, the composition does not contain sodium chloride. In embodiments, the composition contains less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of salt. In embodiments, the composition does not contain any salt.

[0034] In the embodiments, the composition contains less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of polysorbate. In the embodiments, the composition does not contain polysorbate 80 (PS80). In the embodiments, the composition does not contain any polysorbate.

[0035] In the embodiments, the composition contains a stabilizer in an amount of less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v%. In the embodiments, the composition does not contain a stabilizer.

[0036] In the embodiments, the pH of the composition is 9-12 or 10-11. In the embodiments, the composition is not sterilized by gamma irradiation.

[0037] In the embodiments, the pH of the composition is approximately 6.5 to approximately 8.5. In the embodiments, the pH of the composition is approximately 6.9 to approximately 7.6. In the embodiments, the pH of the composition is approximately 6.9 to approximately 7.5. In the embodiments, the pH of the composition is approximately 7.3. In the embodiments, the pH of the composition is approximately 7.5. In the embodiments, the pH of the composition is approximately 6.9.

[0038] In this embodiment, the pH buffer contains NaOH.

[0039] In the embodiment, the pH of the composition is measured after sterilization by gamma irradiation and storage for at least 5 days.

[0040] In this embodiment, the composition is sterilized by gamma irradiation.

[0041] In the embodiment, the composition is an ultrasonic coupling agent. In the embodiment, the composition is a contrast agent. In the embodiment, the composition is an aqueous composition. In the embodiment, the composition is a lubricant.

[0042] In the embodiment, the composition has an attenuation coefficient of approximately 0.002 dB / (MHz*cm) to approximately 1.0 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of approximately 0.05 dB / (MHz*cm) to approximately 15 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of approximately 3 dB / (MHz*cm) to approximately 15 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of approximately 0.05 dB / (MHz*cm) to approximately 1.8 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of approximately 0.5 dB / (MHz*cm) to approximately 1.5 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of approximately 0.1 dB / (MHz*cm) to approximately 1.5 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of approximately 0.1 dB / (MHz*cm) to approximately 0.5 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm).

[0043] In embodiments, the composition has a decay coefficient substantially equivalent to that of a tissue or organ selected from bone, brain, lung, liver, kidney, heart, cerebrospinal fluid, soft tissue, bladder, and colon. In embodiments, the tissue or organ is of human origin.

[0044] In the embodiment, the composition has an osmotic pressure of approximately 270 mOsm / kg to approximately 330 mOsm / kg. In the embodiment, the composition has an osmotic pressure of approximately 284 mOsm / kg to approximately 296 mOsm / kg. In the embodiment, the composition has an osmotic pressure of approximately 290 mOsm / kg to approximately 311 mOsm / kg. In the embodiment, the composition has an osmotic pressure of approximately 290 mOsm / kg to approximately 305 mOsm / kg.

[0045] In the embodiments, the composition has a weighted volume-average droplet diameter of approximately 0.2 μm to approximately 0.55 μm. In the embodiments, the composition has a weighted volume-average droplet diameter of approximately 0.26 μm to approximately 0.50 μm. In the embodiments, the composition has a weighted volume-average droplet diameter of approximately 228 nm to approximately 342 nm. In the embodiments, the composition has a weighted volume-average droplet diameter of approximately 258 nm.

[0046] In the embodiment, the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 0.84 μm. In the embodiment, the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 0.96 μm. In the embodiment, the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 1.91 μm. In the embodiment, the composition forms oil droplets, and substantially none of the oil droplets have a diameter exceeding 5000 nm.

[0047] In the embodiments, the composition forms oil droplets having an average diameter of 200 nm to about 750 nm. In the embodiments, the composition forms oil droplets having an average diameter of 250 nm to about 500 nm. In the embodiments, the composition has an average droplet diameter of about 285 nm ± 20%. In the embodiments, the average droplet diameter is measured by dynamic light scattering.

[0048] In the embodiment, the diagnostic agent contained in the composition is a contrast agent. In the embodiment, the contrast agent is a near-infrared (IR) fluorophore. In the embodiment, the near-IR fluorophore is indocyanine green.

[0049] In this embodiment, the therapeutic agent in the composition includes an antibiotic.

[0050] In one embodiment, the shelf life of the composition is at least about 10 hours, at least about 16 hours, at least about 24 hours, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 7 days, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 2 months, at least about 3 months, at least about 4 months, at least about 6 months, at least about 9 months, at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, or at least about 6 years. In another embodiment, the shelf life of the composition is at least 6 months to about 5 years, about 1 year to about 5 years, about 2 years to about 5 years, about 3 years to about 5 years, about 6 months to about 4 years, about 6 months to about 3 years, about 6 months to about 2 years, about 6 months to about 1 year, about 1 year to about 4 years, about 1 year to about 3 years, or about 2 years to about 4 years.

[0051] In one embodiment, the Disclosure provides a method for preparing a composition of the Disclosure, comprising mixing components (a) to (e) or (a) to (f).

[0052] In one embodiment, the Disclosure provides an imaging method comprising administering a composition of the Disclosure to a subject requiring administration and performing imaging. In the embodiment, the composition is administered to a wound, organ, tumor, blood vessel, blood circulation area, or cavity within the body of the subject.

[0053] In one embodiment, the Disclosure provides a method for acquiring an image of a wound, organ, tumor, blood vessel, or cavity, the method comprising i) bringing the wound, organ, tumor, blood vessel, or cavity into contact with a composition of the Disclosure, and ii) acquiring an image with an instrument.

[0054] In the embodiments, imaging is invasive ultrasound imaging. In the embodiments, imaging is Doppler blood flow imaging. In the embodiments, imaging is laser speckle imaging. In the embodiments, imaging is optical coherence tomography, photoacoustic imaging (PAI), computed tomography (CT), magnetic resonance imaging (MRI), or echocardiography. In the embodiments, imaging is fluorescence imaging, radioimaging, positron emission tomography (PET), or magnetic particle imaging (MPI).

[0055] In one embodiment, the Disclosure provides a method for performing surgery on an object requiring surgery, the method comprising administering a composition of the Disclosure into a wound, organ, tumor, blood vessel, area of ​​blood circulation, or cavity of the object to acquire an image, and performing surgery based on the image.

[0056] In one embodiment, the present disclosure provides a method for resecting a tumor, the method comprising administering a composition of the present disclosure to proximal tissue of a tumor, obtaining ultrasound images of the tumor and proximal tissue, identifying the tumor, and resecting the tumor.

[0057] In the embodiment, the tumor is located in or near the bladder, uterus, cervix, colon, or spine.

[0058] In this embodiment, the composition is contained within a balloon catheter.

[0059] In one embodiment, the Disclosure provides a method for performing surgery on an object requiring surgery, the method comprising bringing an instrument to be used in the surgery into contact with a composition of the Disclosure, and inserting the instrument into a wound, organ, tumor, blood vessel, or cavity within the body of the object.

[0060] In one embodiment, the Disclosure provides a method for performing surgery on an object requiring surgery, the method comprising administering a composition of the Disclosure into a wound, organ, tumor, blood vessel, or cavity within the object's body, and inserting surgical instruments into the wound, organ, tumor, blood vessel, or cavity.

[0061] In this embodiment, the surgery is a brain surgery or a neurosurgery.

[0062] In one embodiment, the Disclosure provides a method for placing an instrument inside the body of an object requiring the placement of the instrument, the method comprising sequentially or simultaneously bringing a portion of the object into contact with a composition of the Disclosure and inserting the instrument into the body of the object.

[0063] In this embodiment, the device is for preventing or treating a disease.

[0064] In the embodiment, the device is a catheter. In the embodiment, the catheter is a subdural pressure catheter, a drainage catheter, a cerebral blood flow catheter, a microdialysis catheter, or a cerebral tissue oxygen catheter.

[0065] In the embodiment, the device is an intracranial pressure sensor. In the embodiment, the device is an implantable brain-computer interface (BCI).

[0066] In this embodiment, the composition acts as a lubricant for the instrument.

[0067] In one embodiment, the Disclosure provides a method for delivering a diagnostic or therapeutic agent to an object requiring delivery, the method comprising administering a composition of the Disclosure, the composition comprising a diagnostic or therapeutic agent. In another embodiment, the method is for treating a disease, and the agent comprises a therapeutic agent.

[0068] In one embodiment, the Disclosure provides a method for delivering a diagnostic or therapeutic agent to a subject requiring delivery, the method comprising administering the compositions and agents of the Disclosure. In the embodiments, the compositions and agents are administered sequentially.

[0069] In the embodiment, the therapeutic agent includes a photosensitive agent. In the embodiment, the method includes exposing the photosensitive agent to light.

[0070] In one embodiment, the Disclosure provides a method for treating a disease in a subject requiring treatment using focused ultrasound therapy, the method comprising administering the composition of the Disclosure to the subject and performing focused ultrasound therapy.

[0071] In one embodiment, the Disclosure provides a method for treating a disease in a subject requiring treatment, the method comprising administering the composition of the Disclosure to the subject.

[0072] In this embodiment, the composition includes a therapeutic agent.

[0073] In the embodiment, the method includes administering a composition and then treating the subject using photodynamic therapy.

[0074] In the embodiment, the method includes diluting the composition with water and glycerol to obtain a low triglyceride composition containing about 0.005 w / v% to about 0.5 w / v% triglycerides. In the embodiment, the low triglyceride composition has an osmotic pressure of about 270 mOsm / kg to about 330 mOsm / kg, about 284 mOsm / kg to about 296 mOsm / kg, about 290 mOsm / kg to about 311 mOsm / kg, or about 290 mOsm / kg to about 305 mOsm / kg.

[0075] In this embodiment, the composition is a light dispersant.

[0076] In the embodiment, the therapeutic agent includes a photosensitizer.

[0077] In one embodiment, the present disclosure provides a method for treating a disease, the method comprising: i) contacting a wound, organ, tumor, blood vessel, blood circulation area or cavity, including diseased tissue, with a composition of the present disclosure; ii) obtaining an image of the wound, organ, tumor, blood vessel, blood circulation area or cavity; and iii) treating the disease or removing diseased tissue based on the image. In embodiments, the image is an ultrasound image.

[0078] In embodiments, the composition includes a contrast agent that enables the acquisition of an image. In embodiments, the contrast agent is a near-infrared (IR) fluorophore. In embodiments, the near-IR fluorophore is indocyanine green.

[0079] In the embodiment, the composition comprises a fluorophore.

[0080] In the embodiment, the image is for identifying target tissue or diseased tissue within the body. In the embodiment, the diseased tissue is a residual tumor.

[0081] In embodiments, the method further includes removing and / or treating abnormal or diseased tissue. In embodiments, the method includes removing abnormal or diseased tissue via surgery. In embodiments, the method includes treating abnormal or diseased tissue via chemotherapy, targeted therapy, photodynamic therapy, or radiotherapy.

[0082] In the embodiment, the disease is cancer. In the embodiment, the affected tissue includes tumor tissue.

[0083] In the embodiment, the tumor is a brain tumor. In the embodiment, the tumor is a glioma, glioblastoma, or neuroblastoma.

[0084] In embodiments, the method includes administering one or more methods of cancer treatment. In embodiments, one or more methods are selected from the group consisting of chemotherapy, immunotherapy, alternating electric tumor treating field, laser interstitial hyperthermia (LITT), magnetic hyperthermia (MHT), focused ultrasound, radiofrequency microwaves, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence-guided resection, surgical resection, and magnetic resonance imaging. In embodiments, treating the disease includes exposing cancer cells to light.

[0085] In embodiments, the method includes performing an invasive procedure before administering the composition to allow the composition and / or instrument to access a wound, organ, blood vessel, or lumen.

[0086] In the embodiment, the cavity is selected from any one of the following: oral cavity, nasal cavity, orbit, thoracic cavity, pericardial cavity, pleural cavity, abdominal cavity, pelvic cavity, cranial cavity, spinal cavity, joint cavity, synovial cavity, buccal oral cavity, cranial fossa, mandibular fossa, maxillary sinus, frontal sinus, ethmoid sinus, sphenoid sinus, mastoid air cells, ear canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, venous sinus, fallopian tube infundibulum, alveolar sac, bronchioles, laryngeal cavity, tracheal cavity, gastric pit, intestinal crypt, gallbladder pit, renal sinus, ureteral orifice, bladder trigone, follicle, testicular lobule, vaginal fornix, anal canal, vertebral foramen, intervertebral foramen, foramen magnum, and jugular foramen.

[0087] In embodiments, the organ is selected from any one of the following: brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, breasts, esophagus, diaphragm, adrenal glands, thyroid gland, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries, testes, uterus, prostate, penis, vagina, cervix, urethra, rectum, anus, skeletal muscle, smooth muscle, cardiac muscle, bone marrow, bone, blood vessels, lymph nodes, lymphatic vessels, tonsils, appendix, adipose tissue, nerves, and connective tissue. In embodiments, the organ is the brain, kidneys, liver, pancreas, ovaries, breasts, bladder, uterus, cervix, or colon. In embodiments, the organ is the brain.

[0088] In the embodiment, the organ or cavity includes a tumor.

[0089] In this embodiment, the method includes excising the tumor.

[0090] In the embodiments, the method reduces ultrasound imaging artifacts compared to a control method in which the composition is not administered. In the embodiments, the artifacts are or include brightness elevation artifacts. In the embodiments, the control method uses saline solution as the ultrasound coupling agent instead of the composition.

[0091] In the embodiment, the composition is contained within a balloon catheter. In the embodiment, the lumen is created by the balloon catheter.

[0092] In this embodiment, the subject is a human being.

[0093] In embodiments, a container containing the composition of the present disclosure is provided herein.

[0094] In embodiments, kits comprising the compositions and containers of the present disclosure are provided herein. In embodiments, the container comprises the composition. In embodiments, the kit comprises a bag spike. In embodiments, the kit comprises a syringe. In embodiments, the kit comprises a filter.

[0095] In the embodiment, the container is a syringe. In the embodiment, the container is glass. In the embodiment, the container is stainless steel. In the embodiment, the container is a bag. In the embodiment, the container does not contain one or more of the following: dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl) phthalate (DEHP).

[0096] In the embodiment, the kit further includes a bag spike. In the embodiment, the kit further includes a filter. In the embodiment, the filter has a pore size of about 1.2 μm.

[0097] A composition comprising a) at least one triglyceride in about 60.0 to about 80.0 g / L, b) at least one phospholipid in about 3.2 to about 5.2 g / L, c) water, d) pH buffer, and e) glycerol, wherein the composition has an attenuation constant of about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or about 0.002 to about 1.0 dB / (MHz*cm), is provided herein.

[0098] A composition is provided herein, comprising a) at least one triglyceride, b) at least one phospholipid, c) water, d) pH buffer, and e) glycerol, wherein the composition has an attenuation constant of about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or about 0.002 to about 1.0 dB / (MHz*cm), and the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1.

[0099] A composition comprising a) at least one triglyceride present in about 7 w / v%, b) at least one phospholipid present in about 0.4 w / v%, c) water present in about 92 w / v%, d) pH buffer, and e) glycerol is provided herein.

[0100] A composition is provided herein that comprises a) at least one triglyceride in an amount of about 60.0 g / L to about 80.0 g / L, and b) at least one phospholipid in an amount of about 3.2 g / L to about 5.2 g / L, wherein the composition is free of stabilizers and sodium chloride, and the composition has an attenuation constant of about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or about 0.002 to about 1.0 dB / (MHz*cm).

[0101] A composition comprising a) at least one triglyceride and b) at least one phospholipid is provided herein, wherein the composition is free of stabilizers and sodium chloride, has an attenuation constant of about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or about 0.002 to about 1.0 dB / (MHz*cm), and the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1.

[0102] A composition comprising a) at least one triglyceride present at approximately 7 w / v%, and b) at least one phospholipid present at approximately 0.4 w / v%, wherein the composition is free of stabilizers and sodium chloride, and the composition has an attenuation constant of approximately 0.15 dB / (MHz*cm) to approximately 0.60 dB / (MHz*cm), or approximately 0.002 to approximately 1.0 dB / (MHz*cm).

[0103] In embodiments, the compositions provided herein contain at least one triglyceride in an amount of about 70 g / L.

[0104] In embodiments, at least one triglyceride in the composition provided herein is selected from one or more of soybean oil, olive oil, or fish oil. In embodiments, at least one triglyceride in the composition provided herein is soybean oil.

[0105] In the embodiments, the compositions provided herein include at least one wetting agent. In the embodiments, the at least one wetting agent is glycerol.

[0106] In the embodiments, the compositions provided herein do not contain PS80.

[0107] In some embodiments, the compositions provided herein have a pH of about 6.5 to about 8.5. In some embodiments, the compositions provided herein have a pH of about 7.3.

[0108] In the embodiments provided herein, the compositions have an osmotic pressure of 270 to 330 mOsm / L.

[0109] In the embodiments, the compositions provided herein have an average droplet diameter of about 285 nm ± 20%, the average droplet diameter being measured by dynamic light scattering.

[0110] In embodiments, the compositions provided herein have an effective period of at least about 10 hours.

[0111] In this embodiment, the weight ratio of at least one triglyceride in the composition to at least one phospholipid is approximately 16.7:1.

[0112] In embodiments, a method for obtaining an ultrasound image of an organ is provided herein, comprising i) bringing a composition provided herein into contact with the organ, and ii) obtaining an ultrasound image of the organ, wherein the composition has an attenuation constant of about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm), or about 0.002 to about 1.0 dB / (MHz*cm).

[0113] In the embodiment, the organ is the brain, breast, colon, or heart. In the embodiment, the organ is the brain.

[0114] In embodiments, compositions comprising (a) at least one triglyceride in a concentration of about 60.0 g / L to about 80.0 g / L, (b) at least one phospholipid in a concentration of about 3.2 g / L to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol are provided herein, wherein the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1. In embodiments, compositions comprising (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) at least one phospholipid in a concentration of about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) at least one phospholipid present in an amount of about 0.42 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglyceride, (b) about 4.2 g / L of phospholipid, (c) about 23.7 g / L of glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in a concentration of about 60.0 g / L to about 80.0 g / L, (b) at least one phospholipid in a concentration of about 3.2 g / L to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol, which are stabilizers-free and sodium chloride-free, are provided herein.In embodiments, compositions comprising (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol are provided herein, wherein the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1, and the compositions are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) at least one phospholipid in about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein, wherein the compositions are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) at least one phospholipid present in an amount of about 0.42 w / v%, (c) water, (d) pH buffer, and (e) glycerol, which are free of stabilizers and sodium chloride, are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol, which are free of stabilizers and sodium chloride, are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglyceride, (b) about 4.2 g / L of phospholipid, (c) about 23.7 g / L of glycerol, (d) water, and (e) pH buffer, which are free of stabilizers and sodium chloride, are provided herein. In embodiments, compositions comprising essentially (a) at least one triglyceride in a concentration of about 60.0 g / L to about 80.0 g / L, (b) at least one phospholipid in a concentration of about 3.2 g / L to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising essentially (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol are provided herein, wherein the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1.In embodiments, compositions comprising essentially (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) at least one phospholipid in about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising essentially (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) at least one phospholipid present in about 0.42 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising essentially (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising essentially (a) about 7 w / v% triglycerides, (b) about 4.2 g / L phospholipids, (c) about 23.7 g / L glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglycerides, (b) about 4.2 g / L of at least one phospholipid, (c) about 23.7 g / L glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, the stabilizer is polysorbate 80 (PS80).

[0115] In embodiments, compositions comprising (a) at least one triglyceride in a concentration of about 60.0 g / L to about 80.0 g / L, (b) at least one lecithin in a concentration of about 3.2 g / L to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein, wherein the weight ratio of the at least one triglyceride to lecithin is about 13:1 to about 20:1. In embodiments, compositions comprising (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) lecithin in a concentration of about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) lecithin present in an amount of about 0.42 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglyceride, (b) about 4.2 g / L of lecithin, (c) about 23.7 g / L of glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in a concentration of about 60.0 g / L to about 80.0 g / L, (b) lecithin in a concentration of about 3.2 g / L to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein, where the weight ratio of the at least one triglyceride to lecithin is about 13:1 to about 20:1, and which are free of stabilizers and sodium chloride.In embodiments, compositions comprising (a) at least one triglyceride in amounts of 5 w / v% to 9 w / v%, (b) lecithin in amounts of about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol, which are free of stabilizers and sodium chloride, are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in amounts of 5 w / v% to 9 w / v%, (b) lecithin present in amounts of about 0.42 w / v%, (c) water, (d) pH buffer, and (e) glycerol, which are free of stabilizers and sodium chloride, are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in amounts of 5 w / v% to 9 w / v%, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol, which are free of stabilizers and sodium chloride, are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglycerides, (b) about 4.2 g / L lecithin, (c) about 23.7 g / L glycerol, (d) water, and (e) pH buffer are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising essentially (a) at least one triglyceride in an amount of about 60.0 g / L to about 80.0 g / L, (b) about 3.2 g / L to about 5.2 g / L lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising essentially (a) at least one triglyceride, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein, where the weight ratio of the at least one triglyceride to lecithin is about 13:1 to about 20:1. In embodiments, compositions comprising essentially (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) lecithin in about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising essentially (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) lecithin present in about 0.42 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein.In embodiments, compositions comprising essentially (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising essentially (a) about 7 w / v% triglyceride, (b) about 4.2 g / L lecithin, (c) about 23.7 g / L glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglyceride, (b) about 4.2 g / L lecithin, (c) about 23.7 g / L glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, the stabilizer is polysorbate 80 (PS80). In the embodiment, the composition has an attenuation coefficient of approximately 0.15 dB / (MHz*cm) to approximately 0.60 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of approximately 0.002 dB / (MHz*cm) to approximately 1.0 dB / (MHz*cm). In the embodiment, the composition has an attenuation coefficient of approximately 0.05 dB / (MHz*cm) to approximately 15 dB / (MHz*cm).

[0116] In embodiments, a method for acquiring an ultrasound image of an organ or cavity is provided herein, the method comprising i) contacting the organ or cavity with a composition described herein, and ii) acquiring an ultrasound image of the organ or cavity.

[0117] In embodiments, a method for performing neurosurgical surgery is provided herein, the method comprising bringing an instrument to be used in the surgery into contact with a composition described herein, and inserting the instrument into the brain. [Brief explanation of the drawing]

[0118] [Figure 1A] Figures 1A-1G show ultrasound images of brain tissue mimic phantoms filled with physiological saline (Figure 1A), formulation 2 (Figure 1B), formulation 3 (Figure 1C), formulation 4 (Figure 1D), formulation 5 (Figure 1E), formulation 6 (Figure 1F), and formulation 7 (Figure 1G). Each component of formulations 1-7 is provided in Example 2. [Figure 1B]Figures 1A-1G show ultrasound images of brain tissue mimic phantoms filled with physiological saline (Figure 1A), formulation 2 (Figure 1B), formulation 3 (Figure 1C), formulation 4 (Figure 1D), formulation 5 (Figure 1E), formulation 6 (Figure 1F), and formulation 7 (Figure 1G). Each component of formulations 1-7 is provided in Example 2. [Figure 1C] Figures 1A-1G show ultrasound images of brain tissue mimic phantoms filled with physiological saline (Figure 1A), formulation 2 (Figure 1B), formulation 3 (Figure 1C), formulation 4 (Figure 1D), formulation 5 (Figure 1E), formulation 6 (Figure 1F), and formulation 7 (Figure 1G). Each component of formulations 1-7 is provided in Example 2. [Figure 1D] Figures 1A-1G show ultrasound images of brain tissue mimic phantoms filled with physiological saline (Figure 1A), formulation 2 (Figure 1B), formulation 3 (Figure 1C), formulation 4 (Figure 1D), formulation 5 (Figure 1E), formulation 6 (Figure 1F), and formulation 7 (Figure 1G). Each component of formulations 1-7 is provided in Example 2. [Figure 1E] Figures 1A-1G show ultrasound images of brain tissue mimic phantoms filled with physiological saline (Figure 1A), formulation 2 (Figure 1B), formulation 3 (Figure 1C), formulation 4 (Figure 1D), formulation 5 (Figure 1E), formulation 6 (Figure 1F), and formulation 7 (Figure 1G). Each component of formulations 1-7 is provided in Example 2. [Figure 1F] Figures 1A-1G show ultrasound images of brain tissue mimic phantoms filled with physiological saline (Figure 1A), formulation 2 (Figure 1B), formulation 3 (Figure 1C), formulation 4 (Figure 1D), formulation 5 (Figure 1E), formulation 6 (Figure 1F), and formulation 7 (Figure 1G). Each component of formulations 1-7 is provided in Example 2. [Figure 1G] Figures 1A-1G show ultrasound images of brain tissue mimic phantoms filled with physiological saline (Figure 1A), formulation 2 (Figure 1B), formulation 3 (Figure 1C), formulation 4 (Figure 1D), formulation 5 (Figure 1E), formulation 6 (Figure 1F), and formulation 7 (Figure 1G). Each component of formulations 1-7 is provided in Example 2.

[0119] [Figure 2A]Figures 2A and 2B show ultrasound images of a filled cavity containing a tumor. The cavity is filled with physiological saline (Figure 2A) or formulation 7 (Figure 2B). The components of formulation 7 are provided in Example 2. [Figure 2B] Figures 2A and 2B show ultrasound images of a filled cavity containing a tumor. The cavity is filled with physiological saline (Figure 2A) or formulation 7 (Figure 2B). The components of formulation 7 are provided in Example 2.

[0120] [Figure 3] Figure 3 shows an exemplary kit of the present disclosure, including a syringe, a bag spike, and the composition. [Modes for carrying out the invention]

[0121] A.Definition As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless otherwise explicitly indicated.

[0122] Where used herein, unless otherwise suggested, the term "and / or" in this disclosure shall be used either "and" or "or".

[0123] As used herein, the term “ultrasonic coupling agent” refers to a medium used to exclude air between an ultrasound probe and the tissue being imaged. Therefore, the primary purpose of an ultrasonic coupling agent is to provide acoustic coupling between an ultrasound transducer / probe and the tissue being investigated. In embodiments, the ultrasonic coupling agents described herein are in liquid or gel form under standard temperature and pressure conditions, as well as / or physiological temperature and ambient pressure. Typically, ultrasonic coupling agents are in emulsion form.

[0124] As used herein, the term “aqueous” means a solution or mixture containing water as a solvent or continuous phase. This includes cases where the aqueous phase can freely diffuse within the area of ​​a self-contained three-dimensional structure, such as a hydrogel or a hydrogel (e.g., emulgel) in an emulsion system. The term does not exclude the presence of solvents other than water in the solution / mixture, but water is usually present as the primary solvent (e.g., accounting for at least 50% by weight of the solvent present in the solution / mixture). In one preferred embodiment, the term “aqueous” means a solution or mixture containing water as a solvent or continuous phase, wherein water accounts for at least 90% by weight of the solvent (or continuous phase) present in the solution / mixture. In one embodiment, water is the only solvent present in the solution / mixture (or continuous phase). The aqueous solution or aqueous mixture may contain salts, such as sodium salts and / or potassium salts, and may be isotonic, for example. The aqueous solution or aqueous mixture may be sterile as needed.

[0125] As used herein, the term “invasive ultrasound imaging” refers to any method of imaging the body, particularly the human body, that involves the detection of ultrasound and the introduction of a device (e.g., the tip of an ultrasound probe / transducer) into the body, either through an opening in the body or through an opening in the body other than an opening in the body, such as a tear or injury in the skin. The term “opening in the body” means any natural opening in the body, as well as the outer surface of the eyeball, or a permanent artificial opening, such as a stoma. Thus, invasive ultrasound imaging includes both imaging the body by introducing a device through a natural opening in the body and imaging the body by introducing a device through an artificial opening, such as an incision made during surgery or as part of an invasive diagnostic procedure.

[0126] As used herein, the term “ultrasound” refers to sound waves having frequencies higher than the upper limit of human hearing. Typically, this is about 20 kHz, and therefore generally, ultrasound has frequencies above 20 kHz. However, for the applications described herein, frequencies in the range of about 5 to about 20 MHz are assumed. Therefore, preferably, as used herein, the term “ultrasonic imaging” refers to any method for imaging involving the detection of sound waves having frequencies in the range of 5 to 20 MHz.

[0127] "Image creation" may involve the display of still images and / or moving images on paper or a display screen, or, regardless of whether such images are actually generated, the generation and / or processing of data that can be represented as a visual image by a computer or artificial intelligence device.

[0128] As used herein, amounts indicated as “about,” “approximately,” etc., may be the exact value stated, or may vary by ±10%, preferably ±5%, or ±1%. The same applies to both ends of the range. Formulations that “contain” a particular component may also “essentially consist of” such component, or consist solely of such component. Similarly, compositions that “essentially consist of” the listed components may consist solely of such component, or may contain other materials in amounts less than 10%, preferably 5%, or 1%. Unless otherwise indicated, all percentages are by weight percentages where permitted by context.

[0129] The terms "range" in this document should be understood to encompass both ends. A content range of 1 w / v% to 5 w / v% for a given component includes, for example, content of 1.0 w / v% and 5.0 w / v%. Since each section of this document refers to various possible values, the listing of these values ​​will also include all ranges and sub-ranges between them. This should also be interpreted as disclosing the total range of values ​​listed in the text, as well as any sub-ranges from any one number to another listed in the relevant text. For example, an enumeration of 1%, 2%, 3%, 4%, 5%, or 6% content of a particular component, including all "ranges and sub-ranges" between them, will also include the value range of 1% to 6%, and / or sub-ranges such as 3% to 4%.

[0130] Where a range of values ​​is provided, it is understood that, unless the context explicitly indicates otherwise, each intermediate value is included in this disclosure, up to one-tenth of the lower limit, between the upper and lower limits of that range and any other stated or intermediate value within that stated range. The upper and lower limits of these smaller ranges may independently be included in smaller ranges and are included in this disclosure subject to any specifically excluded limits within the stated range. If a stated range includes one or both of the limit values, the range excluding one or both of those limit values ​​is also included in this disclosure.

[0131] As used herein, the terms “treatment,” “treating,” or “recovering” refer to either therapeutic treatment or preventive / preventive treatment. Treatment is therapeutic if it improves at least one symptom of the disease in the individual being treated, or if it slows the progression of a progressive disease in the individual or prevents the onset of further related diseases.

[0132] As used herein, the term “substantially” refers to a qualitative condition indicating the range or degree of the sum or approximate sum of the features or characteristics of interest. Those skilled in the biological art will understand that biological and chemical phenomena rarely, if any, proceed toward completion and / or completeness, or achieve or avoid absolute results. Therefore, the term “substantially” is used herein to capture the possibility of a lack of completeness inherent in many biological and chemical phenomena.

[0133] B. Composition Compositions and methods for using them in various medical applications are provided herein.

[0134] In embodiments, the composition of the present disclosure comprises (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) a wetting agent. In embodiments, the composition of the present disclosure comprises (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) pH buffer, and (e) a wetting agent. In embodiments, the composition comprises substances other than components (a) to (e) in amounts of 5 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.5 w / v% or less, 0.2 w / v% or less, or 0.1 w / v% or less. In embodiments, the composition essentially consists of components (a) to (e). In embodiments, the composition consists of components (a) to (e). In embodiments, the composition further comprises a diagnostic agent and / or a therapeutic agent. In embodiments, the composition further comprises a diagnostic agent. In embodiments, the composition further comprises a therapeutic agent.

[0135] In embodiments, the compositions of the present disclosure comprise (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, (e) a wetting agent, and (f) a diagnostic agent, a therapeutic agent, or any combination thereof. In embodiments, the compositions of the present disclosure comprise (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) pH buffer, (e) a wetting agent, and (f) a diagnostic agent, a therapeutic agent, or any combination thereof. In embodiments, the compositions comprise substances other than components (a) to (f) in amounts of 5 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.5 w / v% or less, 0.2 w / v% or less, or 0.1 w / v% or less. In embodiments, the compositions comprise essentially components (a) to (f). In embodiments, the compositions comprise components (a) to (f).

[0136] In the embodiment, the composition is a contrast agent. In the embodiment, the composition is an ultrasonic coupling agent. In the embodiment, the composition is a lubricant. In the embodiment, the composition is an aqueous composition.

[0137] In embodiments, the compositions and methods are for ultrasound imaging of a subject. In embodiments, the ultrasound imaging is invasive ultrasound imaging. When used in invasive ultrasound imaging of body tissue, particularly human tissue, the compositions described herein are unexpectedly effective and safe compared to saline in reducing the occurrence of artifacts, such as brightness-up artifacts. In embodiments, advantageously, the compositions do not contain sodium chloride and also do not contain stabilizers such as polysorbate 80 (also known as PS80 or tween® 80). Prior to this disclosure, it was believed that sodium chloride and polysorbate 80 were necessary to produce stable and effective compositions. Sodium chloride was chosen to maintain the osmotic pressure of the solution. However, since sodium chloride destroys fats, an emulsifier (PS80) is needed to stabilize the solution by preventing fat separation. Thus, previous formulations contained triglycerides, phospholipids, NaCl, and PS80, while providing a suitable attenuation constant for providing ultrasound images with minimal artifacts. However, the applicant found that the previous formulations were not safe for ultrasound imaging of the brain. Advantageously, the applicant found that effective compositions could be prepared without using polysorbate 80 and sodium chloride. The compositions described herein, free of PS80 and sodium chloride, were superior to, or substantially equivalent to, formulations containing PS80 and sodium chloride in brain ultrasound imaging. (Example 2)

[0138] In embodiments, compositions comprising (a) at least one triglyceride in a concentration of about 60.0 g / L to about 80.0 g / L, (b) at least one phospholipid in a concentration of about 3.2 g / L to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol are provided herein, wherein the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1. In embodiments, compositions comprising (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) at least one phospholipid in a concentration of about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) at least one phospholipid present in an amount of about 0.42 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) at least one phospholipid in an amount of about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol in an amount of about 21 g / L to about 26 g / L are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglycerides, (b) about 4.2 g / L phospholipids, (c) about 23.7 g / L glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, the pH buffer is NaOH.

[0139] In embodiments, compositions comprising (a) at least one triglyceride in about 60.0 to about 80.0 g / L, (b) lecithin in about 3.2 to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein, wherein the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1. In embodiments, compositions comprising (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) lecithin in about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) about 0.42 w / v% lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) about 0.2 w / v% to about 1.2 w / v% lecithin, (c) water, (d) pH buffer, and (e) about 21 g / L to about 26 g / L glycerol are provided herein. In embodiments, compositions comprising (a) 7 w / v% triglycerides, (b) about 4.2 g / L lecithin, (c) about 23.7 g / L glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, the pH buffer is NaOH.

[0140] In embodiments, compositions are provided herein that comprise (a) at least one triglyceride in about 60.0 to about 80.0 g / L, (b) at least one phospholipid in about 3.2 to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol, and that are free of stabilizers and sodium chloride. In embodiments, compositions are provided herein that comprise (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol, where the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1, and that are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) at least one phospholipid in about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) at least one phospholipid present in about 0.42 w / v%, (c) water, (d) pH buffer, and (e) glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in 5 w / v% to 9 w / v%, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in an amount of 5 w / v% to 9 w / v%, (b) at least one phospholipid in an amount of about 0.2 w / v% to about 1.2 w / v%, (c) water, (d) pH buffer, and (e) glycerol in an amount of about 21 g / L to about 26 g / L, which are free of stabilizers and sodium chloride, are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglyceride, (b) about 4.2 g / L phospholipid, (c) about 23.7 g / L glycerol, (d) water, and (e) pH buffer, which are free of stabilizers and sodium chloride, are provided herein.In this embodiment, the pH buffer is NaOH. In this embodiment, the stabilizer is PS80.

[0141] In embodiments, compositions comprising (a) at least one triglyceride in about 60.0 to about 80.0 g / L, (b) lecithin in about 3.2 to about 5.2 g / L, (c) water, (d) pH buffer, and (e) glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein, where the weight ratio of at least one triglyceride to at least one phospholipid is about 13:1 to about 20:1, and which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in amounts of 5 w / v% to 9 w / v%, (b) about 0.2 w / v% to about 1.2 w / v% of lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in amounts of 5 w / v% to 9 w / v%, (b) about 0.42 w / v% of lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) at least one triglyceride in amounts of 5 w / v% to 9 w / v%, (b) lecithin, (c) water, (d) pH buffer, and (e) glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) 5 w / v% to 9 w / v% triglycerides, (b) about 0.2 w / v% to about 1.2 w / v% of at least one lecithin, (c) water, (d) pH buffer, and (e) about 21 g / L to about 26 g / L of glycerol are provided herein, which are free of stabilizers and sodium chloride. In embodiments, compositions comprising (a) about 7 w / v% triglycerides, (b) about 4.2 g / L of lecithin, (c) about 23.7 g / L of glycerol, (d) water, and (e) pH buffer are provided herein, which are free of stabilizers and sodium chloride. In embodiments, the pH buffer is NaOH. In embodiments, the stabilizer is PS80.

[0142] In embodiments, compositions comprising (a) about 7 w / v% triglycerides, (b) about 4.2 g / L of at least one phospholipid, (c) about 23.7 g / L of glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, compositions comprising (a) about 7 w / v% triglycerides, (b) about 4.2 g / L of lecithin, (c) about 23.7 g / L of glycerol, (d) water, and (e) pH buffer are provided herein. In embodiments, the pH buffer is NaOH.

[0143] In embodiments, the compositions of the present disclosure contain sodium chloride in amounts less than 0.5% w / v, less than 0.4% w / v, less than 0.3% w / v, less than 0.2% w / v, less than 0.1% w / v, less than 0.05% w / v, less than 0.02% w / v, or less than 0.01% w / v. In embodiments, the compositions do not contain sodium chloride.

[0144] In embodiments, the compositions of the present disclosure include salts with concentrations of less than 0.5% w / v, less than 0.4% w / v, less than 0.3% w / v, less than 0.2% w / v, less than 0.1% w / v, less than 0.05% w / v, less than 0.02% w / v, or less than 0.01% w / v. In embodiments, the compositions do not include any salts. As used herein, the term “salt” refers to any compound that can be formed from the reaction of an acid with a base, in which all or some of the hydrogen atoms of the acid are replaced by metals or other cations.

[0145] In embodiments, the compositions of the present disclosure include less than 0.5 w / v%, less than 0.4 w / v%, less than 0.3 w / v%, less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of polysorbate 80 (PS80). In embodiments, the compositions do not include polysorbate 80 (PS80).

[0146] In embodiments, the compositions of the Disclosure include less than 0.5 w / v%, less than 0.4 w / v%, less than 0.3 w / v%, less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of polysorbate. In embodiments, the compositions do not include any polysorbate. In embodiments, the compositions of the Disclosure include less than 0.5 w / v%, less than 0.4 w / v%, less than 0.3 w / v%, less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of stabilizers. In embodiments, the compositions do not include any stabilizers.

[0147] In embodiments, the compositions described in the preceding paragraphs are diluted with water and / or glycerol to prepare low-triglyceride compositions (for example, as photodispersants in photodynamic therapy). In the embodiment, the composition is diluted by approximately 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 200, 250, 300, 400, 500, 600, 700, 800, 900, 100, 200, 250, 300, 400, 500, 600, 700, 800, 900, or 1000 times. In embodiments, the composition is diluted by approximately 2 to 5 times, approximately 5 to 10 times, approximately 10 to 15 times, approximately 15 to 20 times, approximately 20 to 30 times, approximately 30 to 40 times, approximately 40 to 60 times, approximately 60 to 80 times, approximately 80 to 100 times, approximately 100 to 150 times, approximately 150 to 200 times, approximately 200 to 300 times, approximately 300 to 400 times, approximately 400 to 600 times, approximately 600 to 800 times, or approximately 800 to 1000 times, encompassing all ranges in between and lower ranges. In embodiments, the triglyceride:phospholipid or lecithin ratio remains the same after dilution. In embodiments, glycerol is added to the diluted composition to compensate for the decrease in osmotic pressure due to dilution.

[0148] Triglycerides In embodiments, the composition contains at least one triglyceride in an amount of 20.0 to 90.0 g / L. As used herein, the term “triglyceride” (sometimes also referred to as “triacylglycerol” or “triacylglyceride”) refers to a neutral triester derived from glycerol and three fatty acids. Thus, the triglycerides described herein comprise a “head group” derived from polar glycerol and “tail groups” derived from three nonpolar fatty acids. The three nonpolar tail groups may have the same or different numbers of carbon atoms and may be independently saturated or unsaturated. However, it is preferable that at least one of the three nonpolar tail groups is unsaturated.

[0149] Suitable examples of nonpolar groups include C6-C32 alkyl and alkenyl groups, which typically exist as esters of long-chain carboxylic acids. These are often described based on the number of carbon atoms and unsaturated atoms in the carbon chain. Thus, CX:Z indicates a hydrocarbon chain with X carbon atoms and Z unsaturated atoms. Specific examples include the lauroyl (C12:0), myristoyl (C14:0), palmitoyl (C16:0), phytanoyl (C16:0), palmitreoyl (C16:1), stearoyl (C18:0), oleoyl (C18:1), elidoyl (C18:1), linoleoyl (C18:2), linolenoyl (C18:3), arachidonoyl (C20:4), behenoyl (C22:0), and lignoceroyl (C24:9) groups. Therefore, typical nonpolar chains are based on fatty acids of natural ester lipids, such as caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, phytanic acid, palmitoleic acid, stearic acid, oleic acid, elaidic acid, linoleic acid, linolenic acid, arachidonic acid, behenic acid, or lignoceric acid, or their corresponding alcohols. Preferred nonpolar chains are palmitic acid, stearic acid, oleic acid, and linoleic acid, particularly linoleic acid. In a preferred embodiment, component a) comprises at least one triglyceride having one or more C16-C18 alkyl groups, in particular, where such groups are zero, one, or two unsaturated. Specifically, component a) may comprise at least 50% of triglycerides having such alkyl groups.

[0150] At least one triglyceride used as part of component a) may be synthetic or derived from a refined and / or chemically modified natural source. In one particularly preferred embodiment, at least one triglyceride is derived from a natural source. For example, the triglyceride used may be selected from vegetable oils or animal fats. Vegetable oils may preferably be selected from the group consisting of soybean oil, olive oil, palm oil, and copra oil. Examples of animal fats that can be used include milk fat, fish oil, and fish liver oil. The use of soybean oil (typically a mixture of neutral triglycerides) is particularly preferred.

[0151] In the embodiments, triglycerides are present in the composition in amounts of 20.0 to 90.0 g / L (e.g., 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 g / L). In the embodiments, triglycerides are present in amounts of 40.0 to 90.0 g / L, 50.0 to 90.0 g / L, 55.0 to 85.0 g / L, or 60.0 to 80.0 g / L. When a mixture of triglycerides is used, the amount of triglycerides (g / L) refers to the sum of the amounts of each triglyceride in the composition as a whole.

[0152] When using triglycerides obtained from commercial sources, such as certain natural products like soybean oil, a certain proportion of “impurity” lipids with other chain lengths are usually present. In embodiments, the compositions and methods described herein include such “impurities,” and the presence of such “impurities” is not excluded by using “~consisting of” or “essentially consisting of.” In embodiments, the triglyceride may be any pharmaceutically acceptable grade of triglyceride (i.e., commercial purity triglyceride), including the associated impurities. These impurities may be separated and removed by purification, but this is rarely necessary if the grade is consistent. However, if necessary, the triglyceride may be essentially chemically pure triglyceride, for example, triglyceride of at least 80% purity, at least 85% purity, at least 90% purity (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher).

[0153] Given that the composition is intended for use in the human body, those skilled in the art will readily understand that typically at least one triglyceride must satisfy certain additional requirements. Specifically, at least one triglyceride and the fatty acids comprising it must generally be non-toxic, sterile, and biocompatible. Thus, in one preferred embodiment, at least one triglyceride is at least one pharmaceutical-grade triglyceride.

[0154] In the embodiment, at least one triglyceride is olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil, corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, linseed oil, walnut oil, avocado oil, rice bran oil, grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, etc. It is derived from one or more of the following: oat oil, black seed oil, apricot oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, perilla oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuru oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil. In embodiments, at least one triglyceride is derived from soybean oil.

[0155] In the connection, one or more triglycerides are selected from any one of the following: tristearin, triolein, tripalmitin, triacetin, trilinolein, tricaprin, trilaurin, trialakidine, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimyristine, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, and trinonanoin.

[0156] In this embodiment, one or more triglycerides have the structure of formula I shown below.

[0157] [ka] (I) In the formula, R1, R2, and R3 are each independently a saturated or unsaturated alkyl group from C6 to C32. In the embodiment, R1C(O), R2C(O), and R3C(O) of formula I each independently contain a fatty acid residue. In the embodiment, at least one triglyceride of the composition contains a linoleic acid residue (44-62% by weight), an oleic acid residue (19-30% by weight), a palmitic acid residue (7-14% by weight), an α-linolenic acid residue (4-11% by weight), and a stearic acid residue (1.4-5.5% by weight). In embodiments, the composition described herein comprises one or more triglycerides selected from any one of the following: linolenic acid-oleic acid-linolenic acid, linoleic acid-linoleic acid-linoleic acid, oleic acid-linoleic acid-oleic acid, linoleic acid-oleic acid-linoleic acid, linolenic acid-linoleic acid-linoleic acid, palmitic acid-oleic acid-linoleic acid, palmitic acid-linoleic acid-palmitic acid, stearic acid-oleic acid-linoleic acid, linoleic acid-linolenic acid-linoleic acid, and linoleic acid-oleic acid-oleic acid.

[0158] In the embodiment, at least one triglyceride is a medium-chain fatty acid triglyceride. The medium-chain fatty acid triglyceride comprises a glycerol backbone and three fatty acid chains having a length of 6 to 12 carbon atoms.

[0159] In the embodiment, one or more triglycerides include linoleic acid, oleic acid, palmitic acid, alpha-linolenic acid, and stearic acid.

[0160] In the embodiment, at least one triglyceride is present in the composition at a concentration of about 1 w / v% to 15 w / v%. In the embodiment, at least one triglyceride is present at concentrations of about 1 w / v%, about 1.5 w / v%, about 2 w / v%, about 2.5 w / v%, about 3 w / v%, about 3.5 w / v%, about 4 w / v%, about 4.5 w / v%, about 5 w / v%, about 5.5 w / v%, about 6.0 w / v%, about 6.5 w / v%, about 7.0 w / v%, about 7.5 w / v%, about 8.0 w / v%, and about 8 It is present in the composition at concentrations of 0.5 w / v%, approximately 9 w / v%, approximately 9.5 w / v%, approximately 10 w / v%, approximately 10.5 w / v%, approximately 11 w / v%, approximately 11.5 w / v%, approximately 12 w / v%, approximately 12.5 w / v%, approximately 13 w / v%, approximately 13.5 w / v%, approximately 14 w / v%, approximately 14.5 w / v%, approximately 15 w / v%, or any value or range in between.

[0161] In one embodiment, at least one triglyceride is present in the composition at a concentration of 5 w / v% to 9 w / v%. In another embodiment, at least one triglyceride is present at concentrations of 5.1 w / v%, 5.2 w / v%, 5.3 w / v%, 5.4 w / v%, 5.5 w / v%, 5.6 w / v%, 5.7 w / v%, 5.8 w / v%, 5.9 w / v%, 6.0 w / v%, 6.1 w / v%, 6.2 w / v%, 6.3 w / v%, 6.4 w / v%, 6.5 w / v%, 6.6 w / v%, 6.7 w / v%, 6.8 w / v%, 6.9 w / v%, and 7.0 w / v%. The triglycerides are present in the composition at concentrations of 7.1 w / v%, 7.2 w / v%, 7.3 w / v%, 7.4 w / v%, 7.5 w / v%, 7.6 w / v%, 7.7 w / v%, 7.8 w / v%, 7.9 w / v%, 8.0 w / v%, 8.1 w / v%, 8.2 w / v%, 8.3 w / v%, 8.4 w / v%, 8.5 w / v%, 8.6 w / v%, 8.7 w / v%, 8.8 w / v%, 8.9 w / v%, or any value or range in between. In one embodiment, at least one triglyceride is present in the composition at a concentration of about 7 w / v%.

[0162] In the embodiment, at least one triglyceride is present in the composition at a concentration of 50 g / L to 90 g / L. In the embodiment, at least one triglyceride is present at approximately 50 g / L, approximately 51 g / L, approximately 52 g / L, approximately 53 g / L, approximately 54 g / L, approximately 55 g / L, approximately 56 g / L, approximately 57 g / L, approximately 58 g / L, approximately 59 g / L, approximately 60 g / L, approximately 61 g / L, approximately 62 g / L, approximately 63 g / L, approximately 64 g / L, approximately 65 g / L, approximately 66 g / L, approximately 67 g / L, approximately 68 g / L, approximately 69 g / L, approximately 70 g / L, The triglycerides are present in the composition at concentrations of approximately 71 g / L, 72 g / L, 73 g / L, 74 g / L, 75 g / L, 76 g / L, 77 g / L, 78 g / L, 79 g / L, 80 g / L, 81 g / L, 82 g / L, 83 g / L, 84 g / L, 85 g / L, 86 g / L, 87 g / L, 88 g / L, 89 g / L, 90 g / L, or any concentration or range in between. In one embodiment, at least one triglyceride is present in the composition at a concentration of approximately 70 g / L.

[0163] In the embodiments, the composition is diluted to prepare a low-triglyceride composition (for example, as a photodispersant in photodynamic therapy). In the embodiments, the composition is diluted with water. In the embodiments, the composition is diluted with water containing glycerol. In the embodiments, the composition is diluted with Ringer's lactate solution (containing 6 g / L sodium chloride, 3.1 g / L sodium lactate, 0.3 g / L potassium chloride, and 0.2 g / L calcium chloride dihydrate - see www.accessdata.fda.gov / drugsatfda_docs / label / 2019 / 016682s117lbl.pdf). In the embodiments, the composition is diluted with 0.9% physiological saline (0.9 g NaCl per 100 ml of solution). Therefore, in the embodiment, the low triglyceride composition contains salt at a concentration corresponding to the dilution ratio, for example, a diluted triglyceride composition (a mixture of 1 part of the composition and 9 parts of 0.9% physiological saline) with a composition:0.9% physiological saline ratio of 1:9 has about 0.81 w / v% NaCl.

[0164] In the configuration, the low triglyceride composition contains approximately 6 w / v%, approximately 5 w / v%, approximately 4 w / v%, approximately 3 w / v%, approximately 2.5 w / v%, approximately 2.2 w / v%, approximately 2 w / v%, approximately 1.8 w / v%, approximately 1.6 w / v%, approximately 1.4 w / v%, approximately 1.2 w / v%, approximately 1 w / v%, approximately 0.9 w / v%, approximately 0.8 w / v%, approximately 0.7 w / v%, approximately 0.6 w / v%, approximately 0.5 w / v%, approximately 0.4 w / v%, and approximately 0.3 w / v%. Contains triglycerides at concentrations of approximately 0.2 w / v%, 0.1 w / v%, 0.09 w / v%, 0.08 w / v%, 0.07 w / v%, 0.06 w / v%, 0.05 w / v%, 0.04 w / v%, 0.03 w / v%, 0.02 w / v%, 0.01 w / v%, 0.009 w / v%, 0.008 w / v%, 0.007 w / v%, 0.006 w / v%, or 0.005 w / v%. In this embodiment, the low triglyceride composition is approximately 6 w / v% to approximately 4 w / v%, approximately 4 w / v% to approximately 2 w / v%, approximately 2 w / v% to approximately 1 w / v%, approximately 1 w / v% to approximately 0.8 w / v%, approximately 0.8 w / v% to approximately 0.6 w / v%, approximately 0.6 w / v% to approximately 0.4 w / v%, approximately 0.4 w / v% to approximately 0.3 w / v%, approximately 0.3 w / v% to approximately 0.2 w / v%, approximately 0.2 w / v% to approximately 0.1 w / v%, and approximately 0.1 w Contains triglycerides at concentrations of approximately 0.08 w / v%, 0.08 w / v%, 0.05 w / v%, 0.06 w / v%, 0.04 w / v%, 0.04 w / v%, 0.03 w / v%, 0.03 w / v%, 0.02 w / v%, 0.02 w / v%, 0.01 w / v%, 0.01 w / v%, 0.008 w / v%, or 0.008 w / v% to 0.005 w / v%.

[0165] In this embodiment, the low triglyceride composition contains approximately 1 w / v%, approximately 0.9 w / v%, approximately 0.8 w / v%, approximately 0.7 w / v%, approximately 0.6 w / v%, approximately 0.5 w / v%, approximately 0.4 w / v%, approximately 0.3 w / v%, approximately 0.2 w / v%, approximately 0.1 w / v%, approximately 0.09 w / v%, approximately 0.08 w / v%, and approximately 0.07 w / Contains triglycerides at concentrations of v%, approximately 0.06 w / v%, approximately 0.05 w / v%, approximately 0.04 w / v%, approximately 0.03 w / v%, approximately 0.02 w / v%, approximately 0.01 w / v%, approximately 0.009 w / v%, approximately 0.008 w / v%, approximately 0.007 w / v%, approximately 0.006 w / v%, or approximately 0.005 w / v%. In this embodiment, the low triglyceride composition is approximately 1 w / v% to approximately 0.8 w / v%, approximately 0.8 w / v% to approximately 0.6 w / v%, approximately 0.6 w / v% to approximately 0.4 w / v%, approximately 0.4 w / v% to approximately 0.3 w / v%, approximately 0.3 w / v% to approximately 0.2 w / v%, approximately 0.2 w / v% to approximately 0.1 w / v%, approximately 0.1 w / v% to approximately 0.08 w / v%, and approximately 0.08 w / v%. The composition contains triglycerides at concentrations ranging from approximately 0.05 w / v%, 0.06 w / v% to 0.04 w / v%, 0.04 w / v% to 0.03 w / v%, 0.03 w / v% to 0.02 w / v%, 0.02 w / v% to 0.01 w / v%, 0.01 w / v% to 0.008 w / v%, or 0.008 w / v% to 0.005 w / v%. In one embodiment, the low triglyceride composition contains triglycerides at concentrations ranging from approximately 0.1 w / v% to 0.5 w / v%. In another embodiment, the composition contains triglycerides at a concentration of approximately 0.1 w / v%. In yet another embodiment, the composition contains triglycerides at a concentration of approximately 0.2 w / v%. In the embodiment, the composition contains triglycerides at a concentration of about 0.5 w / v%.

[0166] In embodiments, the composition forms small-diameter oil droplets. In embodiments, such compositions have an excellent light-diffusing effect. In embodiments, the small-diameter oil droplets have an average diameter of about 100 nm to about 500 nm, about 200 nm to about 400 nm, about 250 nm to about 350 nm, or about 285 nm. In embodiments, the small-diameter oil droplets have an average diameter in the range of about 250 nm to about 350 nm. In embodiments, the small-diameter oil droplets are produced under high pressure. In embodiments, essentially all oil droplets in the composition have a diameter of less than 500 nm. In embodiments, the composition is a low-triglyceride composition described herein.

[0167] In the embodiments, the low-triglyceride composition contains the triglyceride-to-phospholipid (or lecithin) ratio described herein (for example, the weight ratio of triglycerides to phospholipids in the composition is in the range of 6.5:1 to 30:1, or the weight ratio of triglycerides to lecithin in the composition is in the range of 6.5:1 to 30:1). In the embodiments, the low-triglyceride composition has an osmotic pressure of less than 100 mOsm / kg, less than 90 mOsm / kg, less than 80 mOsm / kg, less than 70 mOsm / kg, less than 60 mOsm / kg, less than 50 mOsm / kg, less than 40 mOsm / kg, less than 30 mOsm / kg, less than 20 mOsm / kg, or less than 10 mOsm / kg, but has an osmotic pressure greater than 0 mOsm / kg. In the embodiment, the low triglyceride composition has an osmotic pressure of less than 10 mOsm / kg, less than 9 mOsm / kg, less than 8 mOsm / kg, less than 7 mOsm / kg, less than 6 mOsm / kg, less than 5 mOsm / kg, less than 4 mOsm / kg, less than 3 mOsm / kg, less than 2 mOsm / kg, or less than 1 mOsm / kg, but has an osmotic pressure greater than 0 mOsm / kg.

[0168] In the embodiments, the low-triglyceride composition contains the triglyceride-to-phospholipid (or lecithin) ratio described herein and further contains glycerol in a concentration that adjusts the osmotic pressure of the composition to an appropriate level (e.g., about 270 mOsm / kg to about 330 mOsm / kg, about 290 mOsm / kg to about 311 mOsm / kg, or about 290 mOsm / kg to about 305 mOsm / kg). In the embodiments, the osmotic pressure of the composition is about 290 + / - 6 mOsm / kg. In the embodiments, the osmotic pressure of the composition is 290 + / - 6 mOsm / kg. In the embodiments, the composition contains relatively high concentrations of triglycerides and phospholipids, as well as a relatively low concentration of glycerol to maintain the osmotic pressure of the composition at an appropriate level. In the embodiments, the composition is formulated so that the composition is biocompatible (e.g., the osmotic pressure corresponds to physiological osmotic pressure). In the embodiments, the composition is formulated such that its osmotic pressure is at a suitable level that matches the physiological osmotic pressure at the application site. Non-limiting examples of lipid and glycerol concentrations are provided in Table 3.

[0169] Phospholipids or lecithin Phospholipids contain a polar head group and at least one nonpolar tail group. The main difference between triglycerides and phospholipids lies in the polar group. The nonpolar portion may originate from the fatty acid or corresponding alcohol mentioned above for triglycerides. Specifically, C16-C18 acyl groups with zero, one, or two unsaturation are suitable groups for forming the nonpolar group of a phospholipid. Typically, a phospholipid may contain two nonpolar groups, but one or more components of this compound may have only one nonpolar group. If two or more nonpolar groups are present, they may be identical or different.

[0170] At least one phospholipid contains a negatively charged phosphate group. Therefore, phospholipids are ionic species. Preferred polar "head" groups of phospholipids include phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI). PC and PE are preferred lipids, either individually or in mixtures. In one embodiment, component b) may contain at least 70% PC, PE, or a mixture thereof. In this embodiment, the phospholipid is phosphatidylcholine (PC). Therefore, in a preferred embodiment, component b) contains at least 50% PC, preferably at least 70% PC, and most preferably at least 80% PC.

[0171] Phospholipids may be synthetic or derived from natural sources. In one embodiment, the phospholipids are derived from natural sources. Suitable natural sources for phospholipids include eggs, hearts (e.g., cows), brains, livers (e.g., cows), and plant sources including soybeans. Such sources may contain any mixture of phospholipids. In one embodiment, the phospholipids are lecithin, preferably egg yolk lecithin, soybean lecithin, or a mixture thereof. Egg yolk lecithin is preferred.

[0172] When using phospholipids derived from natural sources, a certain proportion of “impurities” lipids and other components, such as triglycerides, tocopherols, sterols, phosphatides, metals, pigments, and protein fragments, are generally present. In embodiments, the compositions and methods described herein include such “impurities,” and the presence of such “impurities” is not excluded by using “~consisting of” or “essentially consisting of.” In embodiments, the phospholipid may be any pharmaceutically acceptable grade of phospholipid (i.e., commercially pure triglycerides), including the associated impurities. These impurities may be separated and removed by purification, but this is rarely necessary if the grade is consistent. However, if necessary, triglycerides can be essentially chemically pure triglycerides, for example, triglycerides with a purity of at least 80%, at least 85%, at least 90%, or at least 95% (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher).

[0173] In the embodiment, at least one phospholipid is non-toxic, biocompatible, and sterile. In the embodiment, at least one phospholipid is any pharmaceutically acceptable phospholipid.

[0174] In embodiments, the compositions described herein contain about 1 g / L to about 12 g / L of phospholipids. In embodiments, the compositions described herein contain about 4.2 g / L to about 12 g / L of phospholipids. In embodiments, the compositions described herein contain up to about 12 g / L of phospholipids. In embodiments, the compositions described herein contain about 1 g / L, about 1.2 g / L, about 1.4 g / L, about 1.6 g / L, about 1.8 g / L, about 2 g / L, about 2.2 g / L, about 2.5 g / L, about 3 g / L, about 3.5 g / L, about 4 g / L, about 4.5 g / L, about 5 g / L, about 6 g / L, about 7 g / L, about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, or about 12 g / L of phospholipids, or any concentration or lower range between them. In embodiments, the compositions described herein are about 3 g / L, about 3.1 g / L, about 3.2 g / L, about 3.3 g / L, about 3.4 g / L, about 3.5 g / L, about 3.6 g / L , about 3.7g / L, about 3.8g / L, about 3.9g / L, about 4g / L, about 4.1g / L, about 4.2g / L, about 4.3g / L, about 4.4g / L, about 4.5g / L, about 4 .6g / L, approx. 4.7g / L, approx. 4.8g / L, approx. 4.9g / L, approx. 5g / L, approx. 5.1g / L, approx. 5.2g / L, approx. 5.3g / L, approx. 5.4g / L, approx. 5.5g / L, approx. 5.6g / L, approx. 5.7g / L, approx. 5.8g / L, approx. 5.9g / L, approx. 6g / L, approx. 6.1g / L, approx. 6.2g / L, approx. 6.3g / L, approx. 6.4g / L, Approximately 6.5g / L, approximately 6.6g / L, approximately 6.7g / L, approximately 6.8g / L, approximately 6.9g / L, approximately 7g / L, approximately 7.1g / L, approximately 7.2g / L, approximately 7.3g / L, approximately 7. 4g / L, approx. 7.5g / L, approx. 7.6g / L, approx. 7.7g / L, approx. 7.8g / L, approx. 7.9g / L, approx. 8g / L, approx. 8.1g / L, approx. 8.2g / L, approx. 8.3g / L L, approximately 8.4g / L, approximately 8.5g / L, approximately 8.6g / L, approximately 8.7g / L, approximately 8.8g / L, approximately 8.9g / L, approximately 9g / L, approximately 9.1g / L, approximately 9.2g / L, approximately 9.3 g / L, about 9.4 g / L, about 9.5 g / L, about 9.6 g / L, about 9.7 g / L, about 9.8 g / L, about 9.9 g / L, or about 10 g / L phospholipids.

[0175] In the embodiments, phospholipids are present in the composition in an amount of 2.5 to 5.2 g / L, for example, 3.0 to 5.0 g / L. In the embodiments, the compositions described herein contain about 3.2 g / L to about 5.2 g / L of phospholipids. In the embodiments, phospholipids are present in the composition in an amount of 3.5 to 4.8 g / L, or 3.8 to 4.5 g / L. In the embodiments, the composition contains about 4.2 g / L of phospholipids.

[0176] In the embodiments, phospholipids are present in the composition in an amount of 5.0 to 10.4 g / L, for example, 6.0 to 10.0 g / L. In the embodiments, the compositions described herein contain about 6.4 g / L to about 10.4 g / L of phospholipids. In the embodiments, phospholipids are present in the composition in an amount of 7.0 to 9.6 g / L, or 7.6 to 9.0 g / L. In the embodiments, the composition contains about 8.4 g / L of phospholipids.

[0177] If the composition contains a mixture of phospholipids, the amount of phospholipids refers to the sum of the amounts of each individual phospholipid in the entire composition. The composition may contain low levels of impurities (i.e., lipids other than phospholipids) or may be substantially pure as needed.

[0178] In the embodiment, the weight ratio of triglycerides to phospholipids in the composition is in the range of about 4:1 to 30:1. In the embodiment, the weight ratio of triglycerides to phospholipids in the composition is in the range of about 4:1 to about 6:1, about 6:1 to about 8:1, about 8:1 to about 10:1, about 10:1 to about 12:1, about 12:1 to about 15:1, about 15:1 to about 18:1, about 18:1 to about 21:1, about 21:1 to about 25:1, or about 25:1 to about 30:1. In the embodiments, the weight ratio of triglycerides to phospholipids in the composition is approximately 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1, 9:1, 9.5:1, 10:1, 10.5:1, 11:1, 11.5:1, 12:1, 12.5:1, 13:1, 13.5:1, 14:1, 14.5:1, and 15. The ratios are approximately 1:1, 15.5:1, 16:1, 16.5:1, 17:1, 17.5:1, 18:1, 18.5:1, 19:1, 19.5:1, 20:1, 20.5:1, 21:1, 21.5:1, 22:1, 22.5:1, 23:1, 23.5:1, 24:1, 24.5:1, 25:1, 26:1, 27:1, 28:1, 29:1, or 30:1.

[0179] In the embodiment, the weight ratio of triglycerides to lecithin in the composition is in the range of 4:1 to 30:1. In the embodiment, the weight ratio of triglycerides to lecithin in the composition is in the range of about 4:1 to about 6:1, about 6:1 to about 8:1, about 8:1 to about 10:1, about 10:1 to about 12:1, about 12:1 to about 15:1, about 15:1 to about 18:1, about 18:1 to about 21:1, about 21:1 to about 25:1, or about 25:1 to about 30:1. In the embodiments, the weight ratio of triglycerides in the composition to lecithin is approximately 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1, 9:1, 9.5:1, 10:1, 10.5:1, 11:1, 11.5:1, 12:1, 12.5:1, 13:1, 13.5:1, 14:1, 14.5:1, and 15. The ratios are approximately 1:1, 15.5:1, 16:1, 16.5:1, 17:1, 17.5:1, 18:1, 18.5:1, 19:1, 19.5:1, 20:1, 20.5:1, 21:1, 21.5:1, 22:1, 22.5:1, 23:1, 23.5:1, 24:1, 24.5:1, 25:1, 26:1, 27:1, 28:1, 29:1, or 30:1.

[0180] In the embodiments, the weight ratio of triglycerides to phospholipids in the composition is in the range of 20:1 to 30:1, preferably 21:1 to 29:1, more preferably 22:1 to 28:1, and most preferably 23:1 to 27:1. In the embodiments, the weight ratio of triglycerides to phospholipids is in the range of about 24:1 to about 26:1. In the embodiments, the weight ratio of triglycerides to phospholipids is about 25:1.

[0181] In the embodiments, the weight ratio of triglycerides to lecithin in the composition is in the range of 20:1 to 30:1, preferably 21:1 to 29:1, more preferably 22:1 to 28:1, and most preferably 23:1 to 27:1. In the embodiments, the weight ratio of triglycerides to lecithin is in the range of about 24:1 to about 26:1. In the embodiments, the weight ratio of triglycerides to lecithin is about 25:1.

[0182] In the embodiments, the weight ratio of triglycerides to phospholipids in the composition is in the range of 8:1 to 25:1, preferably 10:1 to 22:1, more preferably 12:1 to 20:1, and most preferably 14:1 to 18:1. In the embodiments, the weight ratio of triglycerides to phospholipids is in the range of about 13:1 to about 20:1. In the embodiments, the weight ratio of triglycerides to phospholipids is about 16.7:1.

[0183] In the embodiments, the weight ratio of triglycerides to lecithin in the composition is in the range of 8:1 to 25:1, preferably 10:1 to 22:1, more preferably 12:1 to 20:1, and most preferably 14:1 to 18:1. In the embodiments, the weight ratio of triglycerides to lecithin is in the range of about 13:1 to about 20:1. In the embodiments, the weight ratio of triglycerides to lecithin is about 16.7:1.

[0184] In the embodiments, the weight ratio of triglycerides to phospholipids in the composition is in the range of 4:1 to 12.5:1, preferably 5:1 to 11:1, more preferably 6:1 to 10:1, and most preferably 7:1 to 9:1. In the embodiments, the weight ratio of triglycerides to phospholipids is in the range of about 6.5:1 to about 10:1. In the embodiments, the weight ratio of triglycerides to phospholipids is about 8.3:1.

[0185] In the embodiments, the weight ratio of triglycerides to lecithin in the composition is in the range of 4:1 to 12.5:1, preferably 5:1 to 11:1, more preferably 6:1 to 10:1, and most preferably 7:1 to 9:1. In the embodiments, the weight ratio of triglycerides to lecithin is in the range of about 6.5:1 to about 10:1. In the embodiments, the weight ratio of triglycerides to lecithin is about 8.3:1.

[0186] In one embodiment, the composition comprises at least one phospholipid in combination with at least one triglyceride. In another embodiment, the composition comprises at least one lecithin in combination with at least one triglyceride.

[0187] In embodiments, the compositions provided herein include lecithin comprising at least one phospholipid (e.g., phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol). In embodiments, the lecithin further comprises glycerol, choline, glycolipids, and triglycerides. In embodiments, the lecithin comprises about 20% to about 70% by weight of phospholipids. In embodiments, the lecithin comprises about 60% to about 70% by weight of phospholipids. In the embodiment, lecithin is approximately 20% by weight, approximately 20% by weight, approximately 21% by weight, approximately 22% by weight, approximately 23% by weight, approximately 24% by weight, approximately 25% by weight, approximately 26% by weight, approximately 27% by weight, approximately 28% by weight, approximately 29% by weight, approximately 30% by weight, approximately 31% by weight, approximately 32% by weight, approximately 33% by weight, approximately 34% by weight, approximately 35% by weight, approximately 36% by weight, approximately 37% by weight, approximately 38% by weight, approximately 39% by weight, approximately 40% by weight, approximately 41% by weight, approximately 42% by weight, approximately 43% by weight, approximately 44% by weight, and approximately 45% by weight. Contains phospholipids in amounts of approximately 46% by weight, approximately 47% by weight, approximately 48% by weight, approximately 49% by weight, approximately 50% by weight, approximately 51% by weight, approximately 52% by weight, approximately 53% by weight, approximately 54% by weight, approximately 55% by weight, approximately 56% by weight, approximately 57% by weight, approximately 58% by weight, approximately 59% by weight, approximately 60% by weight, approximately 61% by weight, approximately 62% by weight, approximately 63% by weight, approximately 64% by weight, approximately 65% ​​by weight, approximately 66% by weight, approximately 67% by weight, approximately 68% by weight, approximately 69% by weight, or approximately 70% by weight, including all ranges and values ​​in between.

[0188] In embodiments, lecithin is derived from one or more of the following: soybeans, sunflower seeds, rapeseed, egg yolk, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseed, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, Brazil nuts, chia seeds, hemp seeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chicken liver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg white. In embodiments, lecithin is derived from egg yolk.

[0189] In the embodiment, lecithin comprises phosphatidylcholine and / or phosphatidylethanolamine and / or lysophosphatidylcholine.

[0190] In the embodiment, lecithin contains phosphatidylcholine. In the embodiment, lecithin contains about 10% to about 100% by weight of phosphatidylcholine. In the embodiment, lecithin contains about 10% to about 90% by weight of phosphatidylcholine. In the embodiment, lecithin contains about 10% to about 80% by weight of phosphatidylcholine. In the embodiment, lecithin contains about 10% to about 70% by weight of phosphatidylcholine. In the embodiment, lecithin contains about 20% to about 70% by weight of phosphatidylcholine. In the embodiment, lecithin contains about 60% to about 70% by weight of phosphatidylcholine. Entity, lecithin, approximately 10% by weight, approximately 11% by weight, approximately 12% by weight, approximately 13% by weight, approximately 14% by weight, approximately 15% by weight, approximately 16% by weight, approximately 17% by weight, approximately 18% by weight, approximately 19% by weight, approximately 20% by weight, approximately 21% by weight, approximately 22% by weight, approximately 23% by weight, approximately 24% by weight, approximately 25% by weight, approximately 26% by weight, approximately 27% by weight, approximately 28% by weight, approximately 29% by weight, approximately 30% by weight, approximately 31% by weight, Approximately 32% by weight, approximately 33% by weight, approximately 34% by weight, approximately 35% by weight, approximately 36% by weight, approximately 37% by weight, approximately 38% by weight, approximately 39% by weight, approximately 40% by weight, approximately 41% by weight, approximately 42% by weight, approximately 43% by weight, approximately 4 4% by weight, approximately 45% by weight, approximately 46% by weight, approximately 47% by weight, approximately 48% by weight, approximately 49% by weight, approximately 50% by weight, approximately 51% by weight, approximately 52% by weight, approximately 53% by weight, approximately 54% by weight, approximately 55% by weight, approximately 56% by weight %, about 57% by weight, about 58% by weight, about 59% by weight, about 60% by weight, about 61% by weight, about 62% by weight, about 63% by weight, about 64% by weight, about 65% by weight, about 66% by weight, about 67% by weight, about 68% by weight, Approximately 69% by weight, approximately 70% by weight, approximately 71% by weight, approximately 72% by weight, approximately 73% by weight, approximately 74% by weight, approximately 75% by weight, approximately 76% by weight, approximately 77% by weight, approximately 78% by weight, approximately 79% by weight, approximately 80% by weight, approximately 8 Contains 1% by weight, approximately 82% by weight, approximately 83% by weight, approximately 84% by weight, approximately 85% by weight, approximately 86% by weight, approximately 87% by weight, approximately 88% by weight, approximately 89% by weight, approximately 90% by weight, approximately 91% by weight, approximately 92% by weight, approximately 93% by weight, approximately 94% by weight, approximately 95% by weight, approximately 96% by weight, approximately 97% by weight, approximately 98% by weight, approximately 99% by weight, or approximately 100% by weight of phosphatidylcholine, including all ranges and values ​​in between.

[0191] In embodiments, lecithin contains phosphatidylethanolamine. In embodiments, lecithin contains about 5% to about 30% by weight of phosphatidylethanolamine. In embodiments, lecithin contains about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, and about 30% by weight of phosphatidylethanolamine, encompassing all ranges and values ​​in between. In the embodiments, the lecithin contains about 7% to about 10% phosphatidylethanolamine. In the embodiments, the lecithin contains about 10% to about 18% phosphatidylethanolamine. In the embodiments, the lecithin contains 0% to about 2% phosphatidylethanolamine. In the embodiments, the lecithin contains about 12% to about 18% phosphatidylethanolamine. In the embodiments, the lecithin contains about 14.6% phosphatidylethanolamine. In the embodiments, the lecithin contains at least about 5% phosphatidylethanolamine.

[0192] In embodiments, lecithin contains lysophosphatidylcholine. In embodiments, lecithin contains about 0% to about 10% by weight of lysophosphatidylcholine. In embodiments, lecithin contains about 5% by weight, about 6% by weight, about 7% by weight, about 8% by weight, about 9% by weight, about 10% by weight, about 11% by weight, about 12% by weight, about 13% by weight, about 14% by weight, about 15% by weight, about 16% by weight, about 17% by weight, about 18% by weight, about 19% by weight, about 20% by weight, about 20% by weight, about 21% by weight, about 22% by weight, about 23% by weight, about 24% by weight, about 25% by weight, about 26% by weight, about 27% by weight, about 28% by weight, about 29% by weight, and about 30% by weight of phosphatidylethanolamine, encompassing all ranges and values ​​in between. In the embodiment, the lecithin contains up to about 3% by weight of lysophosphatidylcholine. In the embodiment, the lecithin contains up to about 4% by weight of lysophosphatidylcholine. In the embodiment, the lecithin contains up to about 1.5% by weight of lysophosphatidylcholine.

[0193] In one embodiment, the lecithin contains about 70% by weight of phosphatidylcholine, 7 to about 10% by weight of phosphatidylethanolamine, and up to 3% by weight of lysophosphatidylcholine. In another embodiment, the lecithin contains at least 45% by weight of phosphatidylcholine, 10 to about 18% by weight of phosphatidylethanolamine, and up to 4% by weight of lysophosphatidylcholine. In yet another embodiment, the lecithin contains about 92% by weight of phosphatidylcholine, 0 to about 2% by weight of phosphatidylethanolamine, and up to 3% by weight of lysophosphatidylcholine. In yet another embodiment, the lecithin contains about 70% by weight of phosphatidylcholine, about 12% to about 18% by weight of phosphatidylethanolamine, and up to 3% by weight of lysophosphatidylcholine. In one embodiment, the lecithin comprises about 69.8% by weight of phosphatidylcholine, about 14.6% by weight of phosphatidylethanolamine, and about 1.5% by weight of lysophosphatidylcholine. In another embodiment, the lecithin comprises at least 50% by weight of phosphatidylcholine and at least 5% by weight of phosphatidylethanolamine. In yet another embodiment, the lecithin comprises at least 20% by weight of phosphatidylcholine and at least 20% by weight of lysophosphatidylcholine.

[0194] In embodiments, the compositions described herein contain about 1 g / L to about 12 g / L of lecithin. In embodiments, the compositions described herein contain about 4.2 g / L to about 12 g / L of lecithin. In embodiments, the compositions described herein contain about 3.2 g / L to about 5.2 g / L of lecithin. In embodiments, the compositions described herein contain about 6.4 g / L to about 10.4 g / L of lecithin. In embodiments, the compositions described herein contain up to about 12 g / L of lecithin. In embodiments, the compositions described herein include lecithin in concentrations of about 1 g / L, about 1.2 g / L, about 1.4 g / L, about 1.6 g / L, about 1.8 g / L, about 2 g / L, about 2.2 g / L, about 2.5 g / L, about 3 g / L, about 3.5 g / L, about 4 g / L, about 4.5 g / L, about 5 g / L, about 6 g / L, about 7 g / L, about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, or about 12 g / L, or any concentration or lower range between these. In embodiments, the compositions described herein are about 3 g / L, about 3.1 g / L, about 3.2 g / L, about 3.3 g / L, about 3.4 g / L, about 3.5 g / L, about 3.6 g / L , about 3.7g / L, about 3.8g / L, about 3.9g / L, about 4g / L, about 4.1g / L, about 4.2g / L, about 4.3g / L, about 4.4g / L, about 4.5g / L, about 4 .6g / L, approx. 4.7g / L, approx. 4.8g / L, approx. 4.9g / L, approx. 5g / L, approx. 5.1g / L, approx. 5.2g / L, approx. 5.3g / L, approx. 5.4g / L, approx. 5.5g / L, approx. 5.6g / L, approx. 5.7g / L, approx. 5.8g / L, approx. 5.9g / L, approx. 6g / L, approx. 6.1g / L, approx. 6.2g / L, approx. 6.3g / L, approx. 6.4g / L, Approximately 6.5g / L, approximately 6.6g / L, approximately 6.7g / L, approximately 6.8g / L, approximately 6.9g / L, approximately 7g / L, approximately 7.1g / L, approximately 7.2g / L, approximately 7.3g / L, approximately 7. 4g / L, approx. 7.5g / L, approx. 7.6g / L, approx. 7.7g / L, approx. 7.8g / L, approx. 7.9g / L, approx. 8g / L, approx. 8.1g / L, approx. 8.2g / L, approx. 8.3g / L Contains L, approximately 8.4g / L, approximately 8.5g / L, approximately 8.6g / L, approximately 8.7g / L, approximately 8.8g / L, approximately 8.9g / L, approximately 9g / L, approximately 9.1g / L, approximately 9.2g / L, approximately 9.3g / L, approximately 9.4g / L, approximately 9.5g / L, approximately 9.6g / L, approximately 9.7g / L, approximately 9.8g / L, approximately 9.9g / L, or approximately 10g / L of lecithin.In the embodiment, the composition contains about 4.2 g / L of lecithin. In the embodiment, the composition contains about 8.4 g / L of lecithin.

[0195] In embodiments, the compositions described herein contain about 0.1 w / v% to about 1.2 w / v% of lecithin. In embodiments, the compositions described herein contain about 0.4 w / v% to about 1.2 w / v% of lecithin. In embodiments, the compositions described herein contain about 0.3 w / v% to about 0.6 w / v% of lecithin. In embodiments, the compositions described herein contain about 0.6 w / v% to about 1.2 w / v% of lecithin. In embodiments, the compositions described herein contain up to about 1.2 w / v% of lecithin. In embodiments, the compositions contain about 0.42 w / v% of lecithin. In embodiments, the compositions contain about 0.84 w / v% of lecithin.

[0196] In embodiments, the compositions described herein contain about 1 g / L to about 12 g / L of phospholipids. In embodiments, the compositions described herein contain about 4.2 g / L to about 12 g / L of phospholipids. In embodiments, the compositions described herein contain about 3.2 g / L to about 5.2 g / L of phospholipids. In embodiments, the compositions described herein contain about 6.4 g / L to about 10.4 g / L of phospholipids. In embodiments, the compositions described herein contain up to about 12 g / L of phospholipids. In embodiments, the compositions described herein contain about 1 g / L, about 2 g / L, about 3 g / L, about 4 g / L, about 5 g / L, about 6 g / L, about 7 g / L, about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, about 12 g / L of phospholipids, or any of these concentrations or lower ranges. In embodiments, the compositions contain about 4.2 g / L of phospholipids. In the embodiment, the composition contains about 8.4 g / L of phospholipid.

[0197] In embodiments, the compositions described herein contain about 0.1 w / v% to about 1.2 w / v% of phospholipids. In embodiments, the compositions described herein contain about 0.4 w / v% to about 1.2 w / v% of phospholipids. In embodiments, the compositions described herein contain up to about 1.2 w / v% of phospholipids. In embodiments, the compositions described herein contain about 0.3 w / v% to about 0.6 w / v% of phospholipids. In embodiments, the compositions contain about 0.42 w / v% of phospholipids. In embodiments, the compositions described herein contain about 0.6 w / v% to about 1.2 w / v% of phospholipids. In embodiments, the compositions contain about 0.84 w / v% of phospholipids.

[0198] In the embodiment, the composition is a) At least one triglyceride in a concentration of 60.0-80.0 g / L, b) Contains at least one phospholipid in a concentration of 3.8 to 4.5 g / L.

[0199] In the embodiment, the composition is a) At least one triglyceride in a concentration of 60.0-80.0 g / L, b) comprising at least one phospholipid in a concentration of 7.6 to 9.0 g / L.

[0200] In the embodiment, the composition is a) Soybean oil at 20.0-90.0 g / L, b) Contains 1.2 to 5.4 g / L of lecithin.

[0201] In the embodiment, the composition is a) Soybean oil at 20.0-90.0 g / L, b) Contains 2.4 to 10.8 g / L of lecithin.

[0202] In the embodiment, the composition is a) Soybean oil with 60.0-80.0 g / L, b) Contains 3.8-4.5 g / L of lecithin.

[0203] In the embodiment, the composition is a) Soybean oil with 60.0-80.0 g / L, b) Contains 7.6-9.0 g / L of lecithin.

[0204] In one preferred embodiment, the lecithin is egg yolk lecithin, soy lecithin, or a mixture thereof.

[0205] In the embodiment, the composition contains triglycerides and phospholipids at concentrations corresponding to one of the formulations listed in Table 1 below. [Table 1-1] [Table 1-2] [Table 1-3]

[0206] In the embodiment, the composition contains triglycerides and lecithin at concentrations corresponding to one of the formulations listed in Table 2 below. [Table 2-1] [Table 2-2]

[0207] In the embodiments, the composition comprises a diluted triglyceride (for example, at a concentration of less than about 1 w / v%). In the embodiments, the triglyceride:phospholipid or lecithin ratio remains the same in the low-triglyceride composition as in the undiluted composition.

[0208] Humectants (e.g., glycerol) In embodiments, the composition comprises at least one wetting agent. As used herein, the term “wetting agent” refers to a hygroscopic substance that can control the water content within a material. Therefore, wetting agents typically comprise molecules having one or more hydrophilic groups, such as hydroxyl groups. In one embodiment, the wetting agent is a polyol.

[0209] In one embodiment, the composition comprises at least one wetting agent. In one embodiment, the wetting agent is biocompatible, sterile, and nontoxic. Any pharmaceutically acceptable wetting agent may be used. In a preferred embodiment, at least one wetting agent is selected from the group consisting of polyols, lactic acid, and mixtures thereof, particularly polyols. Examples of polyols include glycerol (also known as glycerin / glycerine), propylene glycol, and sorbitol. The use of glycerol is particularly preferred.

[0210] In the embodiments, the wetting agent is typically present in the composition in amounts of 2.2–9.5 g / L, 4.5–9.2 g / L, 5.5–9.0 g / L, or 6.5–8.5 g / L. When a mixture of wetting agents is used, the amount of wetting agent refers to the sum of the amounts of each wetting agent present in the composition. In the embodiments, the wetting agent is biocompatible, sterile, and nontoxic.

[0211] As described herein, wetting agents may help control the osmotic pressure of a composition.

[0212] In the embodiment, the composition is a) At least one triglyceride in a concentration of 60.0-80.0 g / L, b) At least one phospholipid in a concentration of 3.8-4.5 g / L, c) comprising at least one humectant in a concentration of 6.5 to 8.5 g / L.

[0213] In the embodiment, the composition is a) At least one triglyceride in a concentration of 60.0-80.0 g / L, b) At least one phospholipid in a concentration of 3.8-4.5 g / L, c) Contains 6.5-8.5 g / L of glycerol.

[0214] In the embodiment, the composition is a) Soybean oil at 20.0-90.0 g / L, b) 1.2-5.4 g / L of lecithin, c) Contains 2.2 to 9.5 g / L of glycerol.

[0215] In the embodiment, the composition is a) Soybean oil with 60.0-80.0 g / L, b) 3.8-4.5 g / L of lecithin, c) Contains 6.5-8.5 g / L of glycerol.

[0216] In the embodiment, the composition is a) Soybean oil with 60.0-80.0 g / L, b) 3.8-4.5 g / L of lecithin, c) Contains 22-25 g / L of glycerol.

[0217] In the embodiment, the composition is a) At least one triglyceride in a concentration of 60.0-80.0 g / L, b) At least one phospholipid in a concentration of 7.6-9.0 g / L, c) comprising at least one humectant in a concentration of 6.5 to 8.5 g / L.

[0218] In the embodiment, the composition is a) At least one triglyceride in a concentration of 60.0-80.0 g / L, b) At least one phospholipid in a concentration of 7.6-9.0 g / L, c) Contains 6.5-8.5 g / L of glycerol.

[0219] In the embodiment, the composition is a) Soybean oil at 20.0-90.0 g / L, b) 2.4-10.8 g / L of lecithin, c) Contains 2.2 to 9.5 g / L of glycerol.

[0220] In the embodiment, the composition is a) Soybean oil with 60.0-80.0 g / L, b) 7.6-9.0 g / L of lecithin, c) Contains 6.5-8.5 g / L of glycerol.

[0221] In the embodiment, the composition is a) Soybean oil with 60.0-80.0 g / L, b) 7.6-9.0 g / L of lecithin, c) Contains 22-25 g / L of glycerol.

[0222] In embodiments, the compositions described herein contain about 8 g / L to about 26 g / L of glycerol. In embodiments, the compositions described herein contain about 14 g / L to about 26 g / L of glycerol. In embodiments, the compositions described herein contain about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, about 12 g / L, about 13 g / L, about 14 g / L, about 15 g / L, about 16 g / L, about 17 g / L, about 18 g / L, about 19 g / L, about 20 g / L, about 21 g / L, about 22 g / L, about 23 g / L, about 24 g / L, about 25 g / L, about 26 g / L of glycerol, or any value or range in between. In embodiments, the compositions described herein contain about 16 g / L of glycerol. In embodiments, the compositions described herein contain about 23.7 g / L of glycerol.

[0223] In embodiments, the compositions described herein contain about 8 g / L to about 30 g / L of glycerol. In embodiments, the compositions described herein contain about 14 g / L to about 30 g / L of glycerol. In embodiments, the compositions described herein contain about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, about 12 g / L, about 13 g / L, about 14 g / L, about 15 g / L, about 16 g / L, about 17 g / L, about 18 g / L, about 19 g / L, about 20 g / L, about 21 g / L, about 22 g / L, about 23 g / L, about 24 g / L, about 25 g / L, about 26 g / L of glycerol, about 27 g / L of glycerol, about 28 g / L of glycerol, about 29 g / L of glycerol, about 30 g / L of glycerol, or any value or range in between.

[0224] In embodiments, the composition of the present disclosure comprising (a) triglycerides and (b) phospholipids or lecithin also comprises glycerol in a concentration that adjusts the osmotic pressure of the composition to be the same as that of a target organ or tissue. In embodiments, the composition comprises glycerol in a concentration that adjusts the osmotic pressure of the composition to about 270 mOsm / kg to about 330 mOsm / kg, preferably about 290 mOsm / kg to about 311 mOsm / kg, more preferably about 290 mOsm / kg to about 305 mOsm / kg. In the embodiment, the composition has an osmotic pressure of approximately 270 mOsm / kg, approximately 275 mOsm / kg, approximately 280 mOsm / kg, approximately 285 mOsm / kg, approximately 290 mOsm / kg, approximately 295 mOsm / kg, approximately 300 mOsm / kg, approximately 305 mOsm / kg, approximately 310 mOsm / kg, approximately 320 mOsm / kg, approximately 325 mOsm / kg, or approximately 330 mOsm / kg, encompassing all values ​​and ranges in between. In the embodiment, the composition has an osmotic pressure of approximately 290 mOsm / kg. In the embodiment, the composition has an osmotic pressure of approximately 284 mOsm / kg to approximately 296 mOsm / kg. In the embodiment, the composition is formulated so that the composition is biocompatible (e.g., the osmotic pressure corresponds to physiological osmotic pressure). In the embodiments, the composition is formulated such that its osmotic pressure is at a suitable level that matches the physiological osmotic pressure at the application site. In the embodiments, the glycerol of the composition is at a concentration level according to one of the formulations listed in Table 3 below. Table 3-1 Table 3-2 Table 3-3

[0225] In the embodiments, the composition contains diluted triglycerides (for example, at a concentration of less than about 1 w / v%). In the embodiments, the triglyceride:phospholipid or lecithin ratio remains the same in the diluted composition as in the undiluted composition, but the composition contains more glycerol to compensate for the decrease in osmotic pressure due to the decrease in triglycerides and phospholipid or lecithin. In the embodiments, the low-triglyceride composition contains about 24 g / L to about 40 g / L of glycerol. In the embodiments, the composition contains about 26 g / L to about 30 g / L of glycerol. In the embodiments, the composition contains about 27 g / L of glycerol. In the embodiments, the composition includes glycerol at approximately 24 g / L, 25 g / L, 26 g / L, 27 g / L, 28 g / L, 29 g / L, 30 g / L, 31 g / L, 32 g / L, 33 g / L, 34 g / L, 35 g / L, 36 g / L, 37 g / L, 38 g / L, 39 g / L, 40 g / L, or any value or range in between. In the embodiments, the low triglyceride composition has an osmotic pressure of approximately 270 mOsm / kg to approximately 330 mOsm / kg. In one embodiment, the low-triglyceride composition has an osmotic pressure of approximately 290 mOsm / kg. In another embodiment, the low-triglyceride composition has an osmotic pressure of approximately 284 mOsm / kg to approximately 296 mOsm / kg. In yet another embodiment, the low-triglyceride composition has an osmotic pressure of approximately 290 mOsm / kg to approximately 311 mOsm / kg. In yet another embodiment, the low-triglyceride composition has an osmotic pressure of approximately 290 mOsm / kg to approximately 305 mOsm / kg. In yet another embodiment, the low-triglyceride composition has an osmotic pressure substantially the same as that of the target organ or tissue. In yet another embodiment, the low-triglyceride composition is formulated so that the composition is biocompatible (e.g., its osmotic pressure corresponds to physiological osmotic pressure). In yet another embodiment, the low-triglyceride composition is formulated so that its osmotic pressure is at an appropriate level that can match the physiological osmotic pressure at the application site.

[0226] Additional ingredients In embodiments, the composition includes at least one pH-adjusting additive to adjust the pH of the composition to a level suitable for the intended clinical use. In one embodiment, the pH-adjusting additive (also called "pH buffer") is a metal hydroxide, preferably a Group 1 metal hydroxide, such as sodium hydroxide, potassium hydroxide, or a mixture thereof. In a preferred embodiment, the pH-adjusting additive is sodium hydroxide. Alternatively, a base, such as a tertiary amine (e.g., trimethylamine), can be added to the composition to adjust its pH. Optionally, a buffer can be added to the composition (e.g., a fluid), but the use of a buffer is not mandatory.

[0227] In this embodiment, the solvent used to prepare the composition is water.

[0228] In one embodiment, the composition may be sterilized by gamma irradiation and adjusted to a pH of 9-12, preferably 10-11, before gamma irradiation. This is thought to compensate for any observed decrease in pH when the formulation is irradiated and / or stored. In another embodiment, the composition may have a pH of 6.0-9.0, preferably 6.5-8.0, after sterilization by gamma irradiation and storage for at least 5 days. Most bacteria are neutrophils, which grow best at a nearly neutral pH, i.e., around 7. If the pH of the formulation is above 9.0 after manufacturing but before irradiation, this minimizes the risk of bacterial growth occurring between mixing and sterilization. By lowering the pH after sterilization (e.g., to 6.5-8.0), the formulation becomes usable without further adjustment.

[0229] Therefore, in the embodiment, the composition has a pH of about 9 to about 12. In the embodiment, the composition has a pH of about 9 to about 10, about 10 to about 11, or about 11 to about 12. In the embodiment, the composition has a pH of about 10 to about 11. In the embodiment, such composition is not sterilized by gamma irradiation. In the embodiment, such composition is sterilized by gamma irradiation.

[0230] In embodiments, the composition may be a fluid or a gel, where technically feasible. Accordingly, the composition may further contain any suitable gelling agent. Examples of gelling agents are well known in the art and include protein-based gelling agents, e.g., gelatin, and polysaccharide-based gelling agents, e.g., pectin, agar, and alginates. Mixtures of gelling agents may be used.

[0231] In the embodiments, the composition is preferably biocompatible, sterile, and nontoxic.

[0232] In embodiments, the composition of the present disclosure comprises a diagnostic agent (e.g., a contrast agent). In embodiments, the composition of the present disclosure is used to suspend the contrast agent. In embodiments, the contrast agent is a near-infrared (IR) fluorophore. Near-IR fluorophores absorb light having wavelengths of 700–2000 nm. Non-limiting examples of near-IR fluorophores include indocyanine green, methylene blue, the cyanine derivative Cy5.5, and the cyanine derivative Cy7. The following publication describes additional near-IR fluorophores, which are incorporated by reference in their entirety for all purposes: Zhang et al. Expert Opin Med Diagn. 2011 May 1;5(3):241–251. In embodiments, the near-IR fluorophore binds to a targeting molecule. The targeting molecule allows this complex to reach a region of interest (e.g., a tumor). In embodiments, the targeting agent is chlorotoxin, a 36-amino acid peptide isolated from the venom of the scorpion Leiurus quinquestriatus. In embodiments, the near-IR fluorophore is indocyanine green, and the targeting agent is chlorotoxin. This complex is referred to as BLZ-100 and is described in the following reference, which is incorporated herein by reference in whole for all purposes: Butte et al. Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve near-complete resection of brain tumors. Neurosurg Focus 36(2):E1, 2014. In embodiments, BLZ-100 is suspended in a composition containing 5% to about 20% by weight of triglycerides. In embodiments, BLZ-100 is suspended in a composition containing 20% ​​by weight of triglycerides. In embodiments, BLZ-100 is suspended in a composition containing 5% by weight of triglycerides. In the embodiment, BLZ-100 is suspended in a composition containing 7% by weight of triglycerides. In the embodiment, the triglycerides are soybean oil.

[0233] In this embodiment, the near-infrared contrast agent is used in laparoscopy, hepatology, coronary artery surgery, vascular surgery, and surgical oncology.

[0234] In the embodiment, the composition is used to suspend the fluorophore.

[0235] In embodiments, the composition comprises a photosensitizer. In embodiments, the composition comprising the photosensitizer is for photodynamic therapy. In embodiments, the photosensitizer is riboflavin, verteporfin, methoxsalen, porfimer sodium, carprofen, aminolevulinic acid, tiaprofenic acid, benzophenone, protoporphyrin, trioxysalen, acetophenone, motexafin lutetium, motexafingadolinium, hexaaminolevulinic acid, rostaporfin, siamemazine, titanium dioxide, temoporfin, talaporfin, bergapten, methyl aminolevulinate, dihematoporphyrin ether Efaproxial, paderiporfin, indapamide, leuprolide, lovastatin, polythiazide, hydroflumethiazide, pitrisant, lamotrigine, chloroquine, trimethoprim, sulfamethoxazole, minocycline, levofloxacin, diclofenac, promethazine, amiodarone, furosemide, ketoconazole, dronedarone, prochlorperazine, enalapril, bupropion, diltiazem, triamterene, simvastatin, methotrexate, misoprostol, hydrochlorothiazide Nadolol, Gemfibrozil, Hydroxychloroquine, Lisinopril, Losartan, Oxcarbazepine, Gabapentin, Cyclobenzaprine, Escitalopram, Enalaprilat, Stiripentol, Simeprevir, Cobimetinib, Enoximon, Febuxostat, Nilotinib, Thiotixene, Pipothiazine, Metotrimeprazine, Isocarboxazide, Dasatinib, Estazolam, Captopril, Zopiclone, Itraconazole, Sertraline, Flucytosine, Diphenhydramine, Thalidomide, Ketop Lofen, cromoglycic acid, doxorubicin, oxaprozin, lomefloxacin, tipranavir, quinidine, chlorothiazide, flupentixol, tacrolimus, diflunisal, perphenazine, trifluoperazine, acetazolamide, mefenamic acid, tetracycline, etodolac, carbinoxamine, hexachlorophene, esomeprazole, paroxetine, fluviprofen, metazolamide, moexipril, pentosan polysulfate, thioridazine, fluphenazine, demeclocycline, ethionamide,Sulindac, Piroxicam, Benazepril, Fluorouracil, Haloperidol, Fosinopril, Nabilon, Chlorpromazine, Nabumetone, Ketrolac, Acitretin, Cyproheptadine, Roxapine, Eszopiclone, Nisoldipine, Clozapine, Pyrazinamide, Chlorthalidone, Valproic acid, Metoprolol, Sulfisoxazole, Doxycycline, Meticlothiazide, Azithromycin, Ramipril, Pravastatin, Interferon One of the following is selected: Fa-2b, clofazimine, methylene blue, trovafloxacin, dapsone, naproxen, nalidixic acid, vemurafenib, voriconazole, ciprofloxacin, celecoxib, bumetanide, isotretinoin, glybride, etretinate, dabrafenib, imatinib, vandetanib, hemoporfin, fosdenopterin, rezafungin, amotosalen, and 5-aminolevulinic acid. The following references describe photodynamic therapy, and are incorporated herein by reference in their entirety: International Publication No. 2022 / 258727, Dupont et al. Future Oncol. A novel device for intraoperative photodynamic therapy dedicated to glioblastoma treatment. 2017, Dupont et al. Intraoperative photodynamic therapy for glioblastomas: Study Protocol for a Phase I Clinical Trial, Neurosurgery, 2018, Vermandel et al. Standardized Intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial. Journal of Neuro-Oncology (2021) 152:501-514.and Mahmoudi et al. 5-Aminolevulinic Acid Photodynamic Therapy for the Treatment of High-Grade Gliomas, J Neurooncol. 2019 141(3):595-607. In embodiments, the photosensitizer is one or more of 5-aminolevulinic acid, hematoporphyrin derivatives (HpD), temoporfin, verteporfin, and porfimer sodium. In embodiments, the photosensitizer is porphyrin, chlorin, pheophorbid, bacteriopheophorbid, metalloporphyrin, purpurin, or phthalocyanine. Mahmoudi et al. (Mahmoudi et al. 5-Aminolevulinic Acid Photodynamic Therapy for the Treatment of High-Grade Gliomas, J Neurooncol. 2019 141(3):595-607) describes several photosensitizers, which are incorporated herein by reference.

[0236] In embodiments, the compositions of the present disclosure include therapeutic agents.

[0237] In the embodiment, the therapeutic agent is an antibiotic. In the embodiment, the antibiotic is selected from the group consisting of aminoglycosides, ansamycin, carbasephalosporins, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monbactam, nitrofuran, oxazolidonone, penicillin, polypeptides, quinolones, sulfonamides, and tetracyclines. In the embodiment, the antibiotic is selected from vancomycin, rifamycin, rifampicin, teicoplanin, sulfacetamide, amoxicillin, novobiocin, tetracycline compounds, tetracycline, oxytetracycline, metacycline, minocycline, chlorotetracycline, doxycycline, lolitetracycline, demeclocycline, sulfanilamide, sulfamethoxazole, norfloxacin, gatifloxacin, gemifloxacin, trimethoprim, pyrimethamine, cefadroxyl, antituberculosis compounds, isoniazid, rifampicin, streptomycin, ciprofloxacin, moxifloxacin, and aminosalicylic acid.

[0238] In the embodiment, the therapeutic agent is a chemotherapeutic agent. In the embodiment, the chemotherapeutic agent is selected from the group consisting of protein synthesis inhibitors, DNA damage chemotherapeutic agents, akylating agents, topoisomerase inhibitors, RNA synthesis inhibitors, DNA complex binders, thiolate alkylating agents, guanine alkylating agents, tubulin binders, DNA polymerase inhibitors, anticancer enzymes, RAC1 inhibitors, thymidylate synthase inhibitors, oxazophosphorine compounds, integrin inhibitors, antifolates, folate antimetabolites, and combinations thereof. In this embodiment, the chemotherapeutic agent is selected from the group consisting of carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, phloxuridine, capecitabine, gemcitabine, mytomycin, cyclophosphamide, decarbazine, abraxane, ifosfamide, topotecan, irinotecan, docetaxel, temozolomide, paclitaxel, etoposide, pemetrexed, and combinations thereof.

[0239] In the embodiment, the composition is used in cancer surgery. In the embodiment, the composition is used as a drug delivery vehicle.

[0240] C. Properties of the composition In embodiments, the compositions of the present disclosure have properties (e.g., attenuation coefficient) that match the target tissue (e.g., blood) to enhance the signal of the target tissue. In embodiments, the compositions of the present disclosure enhance the measurement of the flow or flow rate of a moving fluid in a subject. In embodiments, the moving fluid is arterial blood. In embodiments, the moving fluid is venous blood. In embodiments, the moving fluid is cerebrospinal fluid (CSF). In embodiments, the compositions of the present disclosure have properties (e.g., attenuation coefficient) that match the surrounding tissue / inclusion tissue to enhance the signal of the surrounding tissue (e.g., in the bladder, uterus, cervix, colon, or spine).

[0241] Damping coefficient In embodiments, the compositions described herein include a decay coefficient substantially equivalent to (i.e., within 20%, 15%, 10%, or 5%) that is the decay coefficient of the tissue, organ, or cavity being imaged. In embodiments, the compositions described herein include a decay coefficient that is identical to that of the tissue, organ, or cavity being imaged. In embodiments, by using a composition that is substantially equivalent to or identical to the decay coefficient of the tissue, organ, or cavity being imaged, ultrasonic artifacts are reduced as a result.

[0242] In embodiments, the use of the compositions of the present disclosure reduces artifacts by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or at least 99% compared to the use of a control. In embodiments, the control is physiological saline (e.g., 0.9% physiological saline with 0.9 grams of NaCl per 100 ml of solution). In embodiments, the artifact is a brightness-enhancing artifact.

[0243] In embodiments, the compositions described herein include attenuation coefficients that are within 5%, 10%, 15%, 20%, 25%, or 30% of the attenuation coefficient of the tissue, organ, or cavity being imaged. For example, if the attenuation coefficient of a tissue, organ, or cavity is 1.5 dB / (MHz*cm), a composition having an attenuation coefficient within 20% of that of the tissue, organ, or cavity will have an attenuation coefficient of approximately 1.2 to 1.8 dB / (MHz*cm). In embodiments, the compositions will have attenuation coefficients substantially equivalent to those of bone, brain, lung, liver, kidney, heart, cerebrospinal fluid, soft tissue, bladder, or colon. Attenuation coefficients for various tissues and organs are shown in the table below. [Table 4-1] [Table 4-2]

[0244] In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.05 dB / (MHz*cm) to approximately 15 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 3 dB / (MHz*cm) to approximately 15 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.002 dB / (MHz*cm) to approximately 1.0 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.05 dB / (MHz*cm) to approximately 1.8 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.1 dB / (MHz*cm) to approximately 1.5 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.5 dB / (MHz*cm) to approximately 1.5 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.1 dB / (MHz*cm) to approximately 0.5 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.1 dB / (MHz*cm) to approximately 0.7 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.1 dB / (MHz*cm) to approximately 1.0 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.3 dB / (MHz*cm) to approximately 0.7 dB / (MHz*cm). In the embodiments, the attenuation coefficient of the composition described herein is approximately 0.5 dB / (MHz*cm) to approximately 0.7 dB / (MHz*cm).

[0245] In the embodiments, the attenuation coefficients of the compositions described herein are approximately 0.001 dB / (MHz*cm), approximately 0.005 dB / (MHz*cm), approximately 0.01 dB / (MHz*cm), approximately 0.02 dB / (MHz*cm), approximately 0.03 dB / (MHz*cm), approximately 0.04 dB / (MHz*cm), approximately 0.05 dB / (MHz*cm), approximately 0.06 dB / (MHz*cm), approximately 0.07 dB / (MHz*cm), approximately 0.08 dB / (MHz*cm), approximately 0.09 dB / (MHz*cm), approximately 0.1 dB / (MHz*cm), approximately 0.15 dB / (MHz*cm), Approx. 0.2dB / (MHz*cm), Approx. 0.25dB / (MHz*cm), Approx. 0.3dB / (MHz*cm), Approx. 0.35dB / (MHz*cm), Approx. 0.4dB / (MHz*cm), Approx. 0.45dB / (MHz*cm), Approx. 0.5dB / (MHz*cm), Approx. 0.55dB / (MHz*cm), approximately 0.6dB / (MHz*cm), approximately 0.65dB / (MHz*cm), approximately 0.7dB / (MHz*cm), approximately 0.75dB / (MHz*cm), approximately 0.8dB / (MHz*cm), approximately 0.85dB / (MHz*cm), approximately 0.9dB / (MHz*cm), Approx. 0.95dB / (MHz*cm), Approx. 1dB / (MHz*cm), Approx. 1.05dB / (MHz*cm), Approx. 1.1dB / (MHz*cm), Approx. 1.15dB / (MHz*cm), Approx. 1.2dB / (MHz*cm), Approx. 1.25dB / (MHz*cm), Approx. 1.3dB / (M Hz*cm), approximately 1.35dB / (MHz*cm), approximately 1.4dB / (MHz*cm), approximately 1.45dB / (MHz*cm), approximately 1.5dB / (MHz*cm), approximately 1.55dB / (MHz*cm), approximately 1.6dB / (MHz*cm), approximately 1.65dB / (MHz*cm), approximately 1.7dB / (MHz*cm), approx. 1.75dB / (MHz*cm), approx. 1.8dB / (MHz*cm), approx. 1.85dB / (MHz*cm), approx. 1.9dB / (MHz*cm), approx. 1.95dB / (MHz*cm), approx. 2dB / (MHz*cm), approx. 2.05dB / (MH z*cm), approx. 2.1dB / (MHz*cm), approx. 2.15dB / (MHz*cm), approx. 2.2dB / (MHz*cm), approx. 2.25dB / (MHz*cm), approx. 2.3dB / (MHz*cm), approx. 2.35dB / (MHz*cm), approx. 2.4dB / (MHz*cm), approx.45dB / (MHz*cm), approximately 2.5dB / (MHz*cm), approximately 2.55dB / (MHz*cm), approximately 2.6dB / (MHz*cm), approximately 2.65dB / (MHz*cm), approximately 2.7dB / (MHz*cm), approximately 2.75dB / (MHz*cm), approximately 2.8dB / (MHz*cm), approximately 2.85dB / (MHz*cm), approximately 2.9dB / (MHz*cm), approximately 2.95dB / (MHz*cm), approximately 3dB / (MHz*cm), approximately 3.05dB / (MHz*cm), approximately 3.1dB / (MHz*cm), approximately 3.15dB / (MHz*cm), approximately 3.2dB / (MHz*cm), approximately 3.25dB / (MHz*cm), approximately 3.3dB / (MHz*cm), approximately 3.35dB / (MHz*cm), approximately 3.4dB / (MHz*cm), approximately 3.45dB / (MHz*cm), approximately 3.5dB / (MHz*cm), approximately 3.55dB / (MHz*cm), approximately 3.6dB / (MHz*cm), approximately 3.65dB / (MHz*cm), approximately 3.7dB / (MHz*cm), approximately 3.75dB / (MHz*cm), approximately 3.8dB / (MHz*cm), approximately 3.85dB / (MHz*cm), approximately 3.9dB / (MHz*cm), approximately 3.95dB / (M (Hz*cm), approximately 4dB / (MHz*cm), approximately 4.05dB / (MHz*cm), approximately 4.1dB / (MHz*cm), approximately 4.15dB / (MHz*cm), approximately 4.2dB / (MHz*cm), approximately 4.25dB / (MHz*cm), approximately 4.3dB / (MHz*cm), approximately 4.35dB / (MHz*cm), approximately 4.4dB / (MHz*cm), approximately 4.45dB / (MHz*cm), approximately 4.5dB / (MHz*cm), approximately 4.55dB / (MHz*cm), approximately 4.6dB / (MHz*cm), approximately 4.65dB / (MHz*cm), approximately 4.7dB / (MHz*cm) Approximately 4.75 dB / (MHz*cm), approximately 4.8 dB / (MHz*cm), approximately 4.85 dB / (MHz*cm), approximately 4.9 dB / (MHz*cm), approximately 4.95 dB / (MHz*cm), approximately 5 dB / (MHz*cm), approximately 5.05 dB / (MHz*cm), approximately 5.1 dB / (MHz*cm), approximately 5.15 dB / (MHz*cm), approximately 5.2 dB / (MHz*cm), approximately 5.25 dB / (MHz*cm), approximately 5.3 dB / (MHz*cm), approximately 5.35 dB / (MHz*cm), approximately 5.4 dB / (MHz*cm), approximately 5.45 dB / (MHz*cm), approximately 5.5dB / (MHz*cm), approximately 5.55dB / (MHz*cm), approximately 5.6dB / (MHz*cm), approximately 5.65dB / (MHz*cm), approximately 5.7dB / (MHz*cm), approximately 5.75dB / (MHz*cm), approximately 5.8dB / (MHz*cm), approximately 5.85dB / (MHz*cm), approximately 5.9dB / (MHz*cm), approximately 5.95dB / (MHz*cm), approximately 6dB / (MHz*cm), approximately 6.05dB / (MHz*cm), approximately 6.1dB / (MHz*cm), approximately 6.15dB / (MHz*cm), approximately 6.2dB / (MHz*cm), approximately 6.25dB / (MHz*cm), approximately 6.3dB / (MHz*cm), approximately 6.35dB / (MHz*cm), approximately 6.4dB / (MHz*cm), approximately 6.45dB / (MHz*cm), approximately 6.5dB / (MHz*cm), approximately 6.55dB / (MHz*cm), approximately 6.6dB / (MHz*cm), approximately 6.65dB / (MHz*cm), approximately 6.7dB / (MHz*cm), approximately 6.75dB / (MHz*cm), approximately 6.8dB / (MHz*cm), approximately 6.85dB / (MHz*cm), approximately 6.9dB / (MHz*cm), approximately 6.95dB / (MHz*cm), approximately 7dB / (MHz*cm) (cm), approximately 7.05dB / (MHz*cm), approximately 7.1dB / (MHz*cm), approximately 7.15dB / (MHz*cm), approximately 7.2dB / (MHz*cm), approximately 7.25dB / (MHz*cm), approximately 7.3dB / (MHz*cm), approximately 7.35dB / (MHz*cm), approximately 7.4dB / (MHz*cm), approximately 7.45dB / (MHz*cm), approximately 7.5dB / (MHz*cm), approximately 7.55dB / (MHz*cm), approximately 7.6dB / (MHz*cm), approximately 7.65dB / (MHz*cm), approximately 7.7dB / (MHz*cm), approximately 7.75dB / (MHz*cm) Approximately 7.8 dB / (MHz*cm), approximately 7.85 dB / (MHz*cm), approximately 7.9 dB / (MHz*cm), approximately 7.95 dB / (MHz*cm), approximately 8 dB / (MHz*cm), approximately 8.05 dB / (MHz*cm), approximately 8.1 dB / (MHz*cm), approximately 8.15 dB / (MHz*cm), approximately 8.2 dB / (MHz*cm), approximately 8.25 dB / (MHz*cm), approximately 8.3 dB / (MHz*cm), approximately 8.35 dB / (MHz*cm), approximately 8.4 dB / (MHz*cm), approximately 8.45 dB / (MHz*cm), approximately 8.5 dB / (MHz*cm), approximately 8.55dB / (MHz*cm), approximately 8.6dB / (MHz*cm), approximately 8.65dB / (MHz*cm), approximately 8.7dB / (MHz*cm), approximately 8.75dB / (MHz*cm), approximately 8.8dB / (MHz*cm), approximately 8.85dB / (MHz*cm), approximately 8.9dB / (MHz*cm), approximately 8.95dB / (MHz*cm), approximately 9dB / (MHz*cm), approximately 9.05dB / (MHz*cm), approximately 9.1dB / (MHz*cm), approximately 9.15dB / (MHz*cm), approximately 9.2dB / (MHz*cm), approximately 9.25dB / (MHz*cm), approximately 9.3dB / (MHz*cm), approximately 9.35dB / (MHz*cm), approximately 9.4dB / (MHz*cm), approximately 9.45dB / (MHz*cm), approximately 9.5dB / (MHz*cm), approximately 9.55dB / (MHz*cm), approximately 9.6dB / (MHz*cm), approximately 9.65dB / (MHz*cm), approximately 9.7dB / (MHz*cm), approximately 9.75dB / (MHz*cm), approximately 9.8dB / (MHz*cm), approximately 9.85dB / (MHz*cm), approximately 9.9dB / (MHz*cm), approximately 9.95dB / (MHz*cm), approximately 10dB / (MHz*cm), approximately 10.05dB / ( (MHz*cm), approximately 10.1dB / (MHz*cm), approximately 10.15dB / (MHz*cm), approximately 10.2dB / (MHz*cm), approximately 10.25dB / (MHz*cm), approximately 10.3dB / (MHz*cm), approximately 10.35dB / (MHz*cm), approximately 10.4dB / (MHz*cm), approximately 10.45dB / (MHz*cm), approximately 10.5dB / (MHz*cm), approximately 10.55dB / (MHz*cm), approximately 10.6dB / (MHz*cm), approximately 10.65dB / (MHz*cm), approximately 10.7dB / (MHz*cm), approximately 10.75dB / (MHz*cm). m), approximately 10.8 dB / (MHz*cm), approximately 10.85 dB / (MHz*cm), approximately 10.9 dB / (MHz*cm), approximately 10.95 dB / (MHz*cm), approximately 11 dB / (MHz*cm), approximately 11.05 dB / (MHz*cm), approximately 11.1 dB / (MHz*cm), approximately 11.15 dB / (MHz*cm), approximately 11.2 dB / (MHz*cm), approximately 11.25 dB / (MHz*cm), approximately 11.3 dB / (MHz*cm), approximately 11.35 dB / (MHz*cm), approximately 11.4 dB / (MHz*cm), approximately 11.45 dB / (MHz*cm), approximately 11.5dB / (MHz*cm), approximately 11.55dB / (MHz*cm), approximately 11.6dB / (MHz*cm), approximately 11.65dB / (MHz*cm), approximately 11.7dB / (MHz*cm), approximately 11.75dB / (MHz*cm), approximately 11.8dB / (MHz*cm), approximately 11.85dB / (MHz*cm), approximately 11.9dB / (MHz*cm), approximately 11.95dB / (MHz*cm), approximately 12dB / (MHz*cm), approximately 12.05dB / (MHz*cm), approximately 12.1dB / (MHz*cm), approximately 12.15dB / (MHz*cm), approximately 12.2dB / (MHz*cm), approximately 12.25dB / (MHz*cm), approximately 12.3dB / (MHz*cm), approximately 12.35dB / (MHz*cm), approximately 12.4dB / (MHz*cm), approximately 12.45dB / (MHz*cm), approximately 12.5dB / (MHz*cm), approximately 12.55dB / (MHz*cm), approximately 12.6dB / (MHz*cm), approximately 12.65dB / (MHz*cm), approximately 12.7dB / (MHz*cm), approximately 12.75dB / (MHz*cm), approximately 12.8dB / (MHz*cm), approximately 12.85dB / (MHz*cm), approximately 12.9dB / (MHz*cm) (z*cm), approximately 12.95dB / (MHz*cm), approximately 13dB / (MHz*cm), approximately 13.05dB / (MHz*cm), approximately 13.1dB / (MHz*cm), approximately 13.15dB / (MHz*cm), approximately 13.2dB / (MHz*cm), approximately 13.25dB / (MHz*cm), approximately 13.3dB / (MHz*cm), approximately 13.35dB / (MHz*cm), approximately 13.4dB / (MHz*cm), approximately 13.45dB / (MHz*cm), approximately 13.5dB / (MHz*cm), approximately 13.55dB / (MHz*cm), approximately 13.6dB / (MHz*cm) Approximately 13.65 dB / (MHz*cm), approximately 13.7 dB / (MHz*cm), approximately 13.75 dB / (MHz*cm), approximately 13.8 dB / (MHz*cm), approximately 13.85 dB / (MHz*cm), approximately 13.9 dB / (MHz*cm), approximately 13.95 dB / (MHz*cm), approximately 14 dB / (MHz*cm), approximately 14.05 dB / (MHz*cm), approximately 14.1 dB / (MHz*cm), approximately 14.15 dB / (MHz*cm), approximately 14.2 dB / (MHz*cm), approximately 14.25 dB / (MHz*cm), approximately 14.3 dB / (MHz*cm), approximately 14.35dB / (MHz*cm), approx. 14.4dB / (MHz*cm), approx. 14.45dB / (MHz*cm), approx. 14.5dB / (MHz*cm), approx. 14.5 5dB / (MHz*cm), approx. 14.6dB / (MHz*cm), approx. 14.65dB / (MHz*cm), approx. 14.7dB / (MHz*cm), approx. 14.7. The attenuation coefficient is 5 dB / (MHz*cm), approximately 14.8 dB / (MHz*cm), approximately 14.85 dB / (MHz*cm), approximately 14.9 dB / (MHz*cm), approximately 14.95 dB / (MHz*cm), approximately 15 dB / (MHz*cm), or any value in between or in a lower range. In embodiments, the attenuation coefficient of the composition described herein is approximately 0.5886 dB / (MHz*cm).

[0246] In embodiments, the objective of the compositions described herein is not only to avoid air pockets between the ultrasonic transducer / probe and the tissue to be imaged and to promote good acoustic coupling between the probe and the tissue, but also to minimize artifact generation by matching the attenuation of the composition with the attenuation of the tissue to be imaged. However, since the attenuation of a particular tissue / composition depends in part on the frequency (and propagation distance) of the ultrasound used for imaging, the parameter more frequently used to determine how suitable a composition is for use with a particular type of tissue is the attenuation coefficient (α). This has units dB / (MHz·cm) and is a property of the substance itself, i.e., independent of both frequency and propagation distance. The attenuation coefficient is measured by measuring the amplitude of the signal obtained using pulsed echo measurements applied to the composition and comparing this to the amplitude obtained using pulsed echo measurements applied to a particular reference substance (e.g., water).

[0247] In embodiments, the composition has an attenuation coefficient (α) that is at least 30 times greater than that of water (i.e., α > 0.066 dB / (MHz·cm)). In one embodiment, the attenuation coefficient is about 0.10 to about 1.10, about 0.15 to about 1.00 dB / (MHz·cm), or about 0.20 to about 0.90 dB / (MHz·cm). In embodiments, the attenuation coefficient is about 0.30 to about 0.80 dB / (MHz*cm). In embodiments, the attenuation coefficient is about 0.15 to about 0.60 dB / (MHz*cm). In embodiments, the composition has a target attenuation coefficient of about 0.60 dB / (MHz cm) (±0.10 dB / MHz*cm), which is comparable to the attenuation coefficient of an adult human brain.

[0248] In embodiments, the composition has an attenuation coefficient between the attenuation coefficient of water (i.e., 0.002 dB / (MHz*cm)) and the attenuation coefficient of the target tissue (i.e., the tissue to be imaged). For example, if the composition is intended for use in invasive ultrasound imaging of the brain, the attenuation constant of the composition is about 0.002 to about 1 dB / (MHz*cm), about 0.10 to about 0.60 dB / (MHz*cm), about 0.002 to about 0.8 dB / (MHz*cm), or about 0.15 to about 0.60 dB / (MHz*cm).

[0249] Validity period The “shelf life” of a composition as described herein refers to the period during which the oil droplets (e.g., phospholipids and / or triglycerides) in the composition remain homogeneous with the water in the composition (i.e., the oil droplets and water have not undergone phase separation). In embodiments, the shelf life of the composition is observed visually. The shelf life of the composition must be sufficient so that surgery or ultrasound imaging can be performed without phase separation of the composition. In embodiments, the shelf life is measured at room temperature. In embodiments, room temperature is 20°C to 25°C. In embodiments, room temperature is approximately 25°C.

[0250] In embodiments, the compositions described herein have an effective period of about 6 months to about 10 years, about 6 months to about 5 years, about 1 year to about 5 years, about 2 years to about 5 years, about 3 years to about 5 years, about 6 months to about 4 years, about 6 months to about 3 years, about 6 months to about 2 years, about 6 months to about 1 year, about 1 year to about 4 years, about 1 year to about 3 years, about 1 year to about 2 years, or about 2 years to about 4 years.

[0251] In one embodiment, the validity period is at least about 6 months, at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, at least about 6 years, at least about 7 years, at least about 8 years, at least about 9 years, at least about 10 years, or longer.

[0252] Osmotic pressure The amount of solute (including any dissolved ions) in a composition can be expressed as the osmotic concentration (also called osmotic pressure) of the composition. In embodiments, compositions have osmotic concentrations of about 200 to about 500 mOsm / kg, about 225 to about 400 mOsm / kg, about 250 to about 350 mOsm / kg, about 275 to about 325 mOsm / kg, about 270 to about 330 mOsm / kg, or about 280 to about 300 mOsm / kg. In the embodiment, the composition is approximately 200 mOsm / kg, approximately 201 mOsm / kg, approximately 202 mOsm / kg, approximately 203 mOsm / kg, approximately 204 mOsm / kg, approximately 205 mOsm / kg, approximately 206 mOsm / kg, approximately 207 mOsm / kg, approximately 208 mOsm / kg, approximately 209 mOsm / kg, approximately 210 mOsm / kg, approximately 211 mOsm / kg, approximately 212 mOsm / kg, approximately 213 mOsm / kg, approximately 214 mOsm / kg, approximately 215 mOsm / kg, Approx. 216mOsm / kg, approx. 217mOsm / kg, approx. 218mOsm / kg, approx. 219mOsm / kg, approx. 220mOsm / kg, approx. 221mOsm / kg, approx. 222mOsm / kg, approx. 223mOsm / kg, approx. 224mO sm / kg, approximately 225mOsm / kg, approximately 226mOsm / kg, approximately 227mOsm / kg, approximately 228mOsm / kg, approximately 229mOsm / kg, approximately 230mOsm / kg, approximately 231mOsm / kg, approximately 232mOsm / kg, Approx. 233mOsm / kg, approx. 234mOsm / kg, approx. 235mOsm / kg, approx. 236mOsm / kg, approx. 237mOsm / kg, approx. 238mOsm / kg, approx. 239mOsm / kg, approx. 240mOsm / kg, approx. 241mO sm / kg, approximately 242mOsm / kg, approximately 243mOsm / kg, approximately 244mOsm / kg, approximately 245mOsm / kg, approximately 246mOsm / kg, approximately 247mOsm / kg, approximately 248mOsm / kg, approximately 249mOsm / kg, Approx. 250mOsm / kg, approx. 251mOsm / kg, approx. 252mOsm / kg, approx. 253mOsm / kg, approx. 254mOsm / kg, approx. 255mOsm / kg, approx. 256mOsm / kg, approx. 257mOsm / kg, approx. 258mO sm / kg, approximately 259mOsm / kg, approximately 260mOsm / kg, approximately 261mOsm / kg, approximately 262mOsm / kg, approximately 263mOsm / kg, approximately 264mOsm / kg, approximately 265mOsm / kg, approximately 266mOsm / kg,Approximately 267 mOsm / kg, approximately 268 mOsm / kg, approximately 269 mOsm / kg, approximately 270 mOsm / kg, approximately 271 mOsm / kg, approximately 272 mOsm / kg, approximately 273 mOsm / kg, approximately 274 mOsm / kg, approximately 275 mOsm / kg, approximately 276 mOsm / kg, approximately 277 mOsm / kg, approximately 278 mOsm / kg, approximately 279 mOsm / kg, approximately 280 mOsm / kg, approximately 281 mOsm / kg, approximately 282 mOsm / kg, approximately 283 mOsm / kg, approximately 284 mOsm / kg, approximately 285 mOsm / kg, approximately 286 mOsm / kg, approximately 287 mOsm / kg kg, approximately 288 mOsm / kg, approximately 289 mOsm / kg, approximately 290 mOsm / kg, approximately 291 mOsm / kg, approximately 292 mOsm / kg, approximately 293 mOsm / kg, approximately 294 mOsm / kg, approximately 295 mOsm / kg, approximately 296 mOsm / kg, approximately 297 mOsm / kg, approximately 298 mOsm / kg, approximately 299 mOsm / kg, approximately 300 mOsm / kg, approximately 301 mOsm / kg, approximately 302 mOsm / kg, approximately 303 mOsm / kg, approximately 304 mOsm / kg, approximately 305 mOsm / kg, approximately 306 mOsm / kg, approximately 307 mOsm / kg, approximately 308 mOsm / kg sm / kg, approximately 309mOsm / kg, approximately 310mOsm / kg, approximately 311mOsm / kg, approximately 312mOsm / kg, approximately 313mOsm / kg, approximately 314mOsm / kg, approximately 315mOsm / kg, approximately 316mOsm / kg, approximately 317mOsm / kg, approximately 318mOsm / kg, approximately 319mOsm / kg, approximately 320mOsm / kg, approximately 321mOsm / kg, approximately 322mOsm / kg, approximately 323mOsm / kg, approximately 324mOsm / kg, approximately 325mOsm / kg, approximately 326mOsm / kg, approximately 327mOsm / kg, approximately 328mOsm / kg, approximately 32 9 mOsm / kg, approximately 330 mOsm / kg, approximately 331 mOsm / kg, approximately 332 mOsm / kg, approximately 333 mOsm / kg, approximately 334 mOsm / kg, approximately 335 mOsm / kg, approximately 336 mOsm / kg, approximately 337 mOsm / kg, approximately 338 mOsm / kg, approximately 339 mOsm / kg, approximately 340 mOsm / kg, approximately 341 mOsm / kg, approximately 342 mOsm / kg, approximately 343 mOsm / kg, approximately 344 mOsm / kg, approximately 345 mOsm / kg, approximately 346 mOsm / kg, approximately 347 mOsm / kg, approximately 348 mOsm / kg, approximately 349 mOsm / kg,Approximately 350 mOsm / kg, approximately 351 mOsm / kg, approximately 352 mOsm / kg, approximately 353 mOsm / kg, approximately 354 mOsm / kg, approximately 355 mOsm / kg, approximately 356 mOsm / kg, approximately 357 mOsm / kg, approximately 358 mOsm / kg, approximately 359 mOsm / kg, approximately 360 mOsm / kg, approximately 361 mOsm / kg, approximately 362 mOsm / kg, approximately 363 mOsm / kg, approximately 364 mOsm / kg, approximately 365 mOsm / kg, approximately 366 mOsm / kg, approximately 367 mOsm / kg, approximately 368 mOsm / kg, approximately 369 mOsm / kg, approximately 370 mOsm / kg kg, approximately 371 mOsm / kg, approximately 372 mOsm / kg, approximately 373 mOsm / kg, approximately 374 mOsm / kg, approximately 375 mOsm / kg, approximately 376 mOsm / kg, approximately 377 mOsm / kg, approximately 378 mOsm / kg, approximately 379 mOsm / kg, approximately 380 mOsm / kg, approximately 381 mOsm / kg, approximately 382 mOsm / kg, approximately 383 mOsm / kg, approximately 384 mOsm / kg, approximately 385 mOsm / kg, approximately 386 mOsm / kg, approximately 387 mOsm / kg, approximately 388 mOsm / kg, approximately 389 mOsm / kg, approximately 390 mOsm / kg, approximately 391 mOsm / kg sm / kg, approximately 392mOsm / kg, approximately 393mOsm / kg, approximately 394mOsm / kg, approximately 395mOsm / kg, approximately 396mOsm / kg, approximately 397mOsm / kg, approximately 398mOsm / kg, approximately 399mOsm / kg, approximately 400mOsm / kg, approximately 401mOsm / kg, approximately 402mOsm / kg, approximately 403mOsm / kg, approximately 404mOsm / kg, approximately 405mOsm / kg, approximately 406mOsm / kg, approximately 407mOsm / kg, approximately 408mOsm / kg, approximately 409mOsm / kg, approximately 410mOsm / kg, approximately 411mOsm / kg, approximately 41 2 mOsm / kg, approximately 413 mOsm / kg, approximately 414 mOsm / kg, approximately 415 mOsm / kg, approximately 416 mOsm / kg, approximately 417 mOsm / kg, approximately 418 mOsm / kg, approximately 419 mOsm / kg, approximately 420 mOsm / kg, approximately 421 mOsm / kg, approximately 422 mOsm / kg, approximately 423 mOsm / kg, approximately 424 mOsm / kg, approximately 425 mOsm / kg, approximately 426 mOsm / kg, approximately 427 mOsm / kg, approximately 428 mOsm / kg, approximately 429 mOsm / kg, approximately 430 mOsm / kg, approximately 431 mOsm / kg, approximately 432 mOsm / kg,Approx. 433mOsm / kg, approx. 434mOsm / kg, approx. 435mOsm / kg, approx. 436mOsm / kg, approx. 437mOsm / kg, approx. 438mOsm / kg, approx. 439mOsm / kg, approx. 440mOsm / kg, approx. 441mOsm / kg, approximately 442mOsm / kg, approximately 443mOsm / kg, approximately 444mOsm / kg, approximately 445mOsm / kg, approximately 446mOsm / kg, approximately 447mOsm / kg, approximately 448mOsm / kg, approximately 449mOsm / kg, approximately 450mOs m / kg, approximately 451mOsm / kg, approximately 452mOsm / kg, approximately 453mOsm / kg, approximately 454mOsm / kg, approximately 455mOsm / kg, approximately 456mOsm / kg, approximately 457mOsm / kg, approximately 458mOsm / kg, approximately 459 mOsm / kg, approximately 460mOsm / kg, approximately 461mOsm / kg, approximately 462mOsm / kg, approximately 463mOsm / kg, approximately 464mOsm / kg, approximately 465mOsm / kg, approximately 466mOsm / kg, approximately 467mOsm / kg, approximately 4 68mOsm / kg, approximately 469mOsm / kg, approximately 470mOsm / kg, approximately 471mOsm / kg, approximately 472mOsm / kg, approximately 473mOsm / kg, approximately 474mOsm / kg, approximately 475mOsm / kg, approximately 476mOsm / kg , about 477mOsm / kg, about 478mOsm / kg, about 479mOsm / kg, about 480mOsm / kg, about 481mOsm / kg, about 482mOsm / kg, about 483mOsm / kg, about 484mOsm / kg, about 485mOsm / Having osmotic concentrations of approximately 486 mOsm / kg, 487 mOsm / kg, 488 mOsm / kg, 489 mOsm / kg, 490 mOsm / kg, 491 mOsm / kg, 492 mOsm / kg, 493 mOsm / kg, 494 mOsm / kg, 495 mOsm / kg, 496 mOsm / kg, 497 mOsm / kg, 498 mOsm / kg, 499 mOsm / kg, or 500 mOsm / kg, encompassing all values ​​and ranges within that range.

[0253] In embodiments, the composition has an osmotic pressure of from about 270 mOsm / kg to about 330 mOsm / kg. In embodiments, the composition has an osmotic pressure of about 290 mOsm / kg. In embodiments, the composition has an osmotic pressure of from about 284 mOsm / kg to about 296 mOsm / kg. In embodiments, the composition has an osmotic pressure of from about 290 mOsm / kg to about 311 mOsm / kg. In embodiments, the composition has an osmotic pressure of from about 290 mOsm / kg to about 305 mOsm / kg. In embodiments, the composition has an osmotic pressure of about 270 mOsm / kg, about 275 mOsm / kg, about 280 mOsm / kg, about 285 mOsm / kg, about 290 mOsm / kg, about 295 mOsm / kg, about 300 mOsm / kg, about 305 mOsm / kg, about 310 mOsm / kg, about 320 mOsm / kg, about 325 mOsm / kg, or about 330 mOsm / kg, including all values and ranges therebetween. In embodiments, the composition is formulated such that the composition is biocompatible (e.g., the osmotic pressure corresponds to physiological osmotic pressure). In embodiments, the composition is formulated such that its osmotic pressure is at a suitable level that can match the physiological osmotic pressure at the site of application. Unless otherwise indicated, the osmotic pressure of the compositions described herein is measured with an osmometer that is OSMOMAT 030-D-D3P, serial number 08 02 22 from GonoTec (registered trademark).

[0254] In embodiments, the composition is isotonic with the fluid, tissue, or organ to be imaged. In embodiments, the composition is isotonic with cerebrospinal fluid (about 290 - 292 mOsm / kg).

[0255] pH In embodiments, the composition needs to have a pH that matches or is substantially equivalent to the pH of the tissue it is intended to contact. In embodiments, the composition has a pH of from about 6.0 to about 9.0, from about 6.5 to about 8.5, or from about 6.5 to about 8.0. In embodiments, the pH is about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, about 8.0, about 8.1, about 8.2, about 8.3, about 8.4, about 8.5, or any pH or range therebetween. In embodiments, the compositions described herein have a pH of from about 6.5 to about 8.5, from about 6.5 to about 8, from about 6.9 to about 7.5, or from about 6.9 to about 7.5. In embodiments, the pH of the composition is about 6.9. In embodiments, the pH of the composition is about 7.3. In embodiments, the pH of the composition is about 7.5. In embodiments, the pH of the composition is substantially equivalent to the pH of cerebrospinal fluid (about pH 7.3).

[0256] One of ordinary skill in the art understands that the pH of the composition may change gradually over time depending on storage conditions and the like. For example, generally, the pH of the composition immediately after manufacture is higher than the pH of the composition after long-term storage. Thus, to avoid doubt, the pH of the composition means the pH of the composition immediately prior to its intended application (i.e., about 1 hour), as this pH is important in determining the suitability of the composition for use with a particular tissue type.

[0257] In embodiments, the pH buffer is citrate, phosphate (e.g., monobasic phosphate, dibasic phosphate), acetate, histidine, glycine, bicarbonate, HEPES, Tris, HCl, NaOH, or any combination thereof, or includes them. In embodiments, the pH buffer includes NaOH.

[0258] Droplet diameter In embodiments, triglycerides and phospholipids typically form emulsions when added to a suitable solvent. In embodiments, the triglycerides and phospholipids of the composition form an oil-in-water (o / w) emulsion, i.e., in which oil droplets (containing at least component a) are dispersed in a continuous aqueous phase. The amphiphilic phospholipid component b) helps to stabilize the interface formed between the dispersed triglyceride / oil phase and the continuous aqueous phase.

[0259] In embodiments, the droplet size of the emulsion can be adjusted by varying the properties and / or relative amounts of the triglyceride and phospholipid components (and any optional co-emulsifiers that may be present). Additionally or alternatively, the droplet size can be adjusted by controlling the shear force applied during emulsification.

[0260] In embodiments, the number-average (mean) droplet diameter is approximately 100 nm to approximately 1000 nm, approximately 200 nm to approximately 700 nm, or approximately 230 nm to approximately 340 nm, encompassing all values ​​and ranges in between. In embodiments, the number-average droplet diameter is approximately 250 nm to approximately 320 nm, for example, approximately 285 nm ± 35 nm, preferably 285 nm ± 5 nm. In embodiments, the number-average droplet diameter is 285 nm ± 20%. The average droplet diameter is measured by dynamic light scattering using a Malvern Zetasizer. In the embodiment, the number-average droplet diameters are approximately 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260 nm, 270 nm, 280 nm, 290 nm, 300 nm, and 3. 10nm, about 320nm, about 330nm, about 340nm, about 350nm, about 360nm, about 370nm, about 380nm, about 390nm, about 400nm, about 410nm, about 420nm, Approximately 430nm, approximately 440nm, approximately 450nm, approximately 460nm, approximately 470nm, approximately 480nm, approximately 490nm, approximately 500nm, approximately 510nm, approximately 520nm, approximately 530nm, approximately 540nm , about 550nm, about 560nm, about 570nm, about 580nm, about 590nm, about 600nm, about 610nm, about 620nm, about 630nm, about 640nm, about 650nm, about 660 nm, approximately 670nm, approximately 680nm, approximately 690nm, approximately 700nm, approximately 710nm, approximately 720nm, approximately 730nm, approximately 740nm, approximately 750nm, approximately 760nm, approximately 770nm, approximately 78 These are 0nm, approximately 790nm, approximately 800nm, approximately 810nm, approximately 820nm, approximately 830nm, approximately 840nm, approximately 850nm, approximately 860nm, approximately 870nm, approximately 880nm, approximately 890nm, approximately 900nm, approximately 910nm, approximately 920nm, approximately 930nm, approximately 940nm, approximately 950nm, approximately 960nm, approximately 970nm, approximately 980nm, approximately 990nm, or approximately 1000nm.

[0261] In the embodiment, the composition has a weighted volume-average droplet diameter (i.e., diameter) of approximately 0.2 μm to 5 μm, approximately 0.2 μm to 4.5 μm, approximately 0.2 μm to approximately 4 μm, approximately 0.2 μm to approximately 3.5 μm, approximately 0.2 μm to approximately 3 μm, approximately 0.2 μm to approximately 2.5 μm, approximately 0.2 μm to approximately 2 μm, approximately 0.2 μm to approximately 1.5 μm, approximately 0.2 μm to approximately 1 μm, approximately 0.2 μm to approximately 0.9 μm, approximately 0.2 μm to approximately 0.8 μm, approximately 0.2 μm to approximately 0.7 μm, or approximately 0.2 μm to approximately 0.6 μm. In the embodiment, the composition has a weighted volume-average droplet diameter of approximately 0.2 μm to approximately 0.55 μm. In the embodiments, the composition has a weighted volume-average droplet diameter of approximately 0.26 μm to approximately 0.50 μm. In the embodiments, the composition has a weighted volume-average droplet diameter of approximately 228 nm to approximately 342 nm. In the embodiments, the composition has a weighted volume-average droplet diameter of approximately 258 nm. In the embodiments, the weighted volume-average droplet diameter is measured by laser diffraction.

[0262] In the embodiment, the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 5 μm, less than 4.5 μm, less than 4 μm, less than 3.5 μm, less than 3 μm, less than 2.5 μm, less than 2 μm, less than 1.5 μm, less than 1 μm, less than 0.9 μm, less than 0.8 μm, less than 0.7 μm, less than 0.6 μm, or less than 0.5 μm. In the embodiment, 100% of the oil droplets have a diameter of less than 0.84 μm. In the embodiment, 100% of the oil droplets have a diameter of less than 0.96 μm. In the embodiment, 100% of the oil droplets have a diameter of less than 1.91 μm. In the embodiment, none of the oil droplets have a diameter exceeding 5000 nm.

[0263] In the embodiments, the composition forms oil droplets with an average diameter of approximately 200 nm to approximately 750 nm, or approximately 250 nm to approximately 500 nm. In the embodiments, the composition forms oil droplets having an average diameter of approximately 285 nm ± 20%. In the embodiments, the composition forms oil droplets having an average diameter of approximately 369 nm. In the embodiments, the diameter is measured by dynamic light scattering. In the embodiments, the diameter is measured by laser diffraction.

[0264] In embodiments, the droplets in the emulsion are monodisperse or substantially monodisperse. As used herein, the term “monodisperse” means that at least 90% (D90) of the droplets have a diameter less than or equal to a certain diameter. In embodiments, D90 is in the range of 200–400 nm. In embodiments, the D90 of the emulsion is in the range of 220–350 nm. In embodiments, the D90 of the emulsion is in the range of 230–340 nm. In this embodiment, D90 is approximately 0.2 μm to 5 μm, approximately 0.2 μm to 4.5 μm, approximately 0.2 μm to approximately 4 μm, approximately 0.2 μm to approximately 3.5 μm, approximately 0.2 μm to approximately 3 μm, approximately 0.2 μm to approximately 2.5 μm, approximately 0.2 μm to approximately 2 μm, approximately 0.2 μm to approximately 1.5 μm, approximately 0.2 μm to approximately 1 μm, approximately 0.2 μm to approximately 0.9 μm, approximately 0.2 μm to approximately 0.8 μm, approximately 0.2 μm to approximately 0.7 μm, approximately 0.2 μm to approximately 0.6 μm, approximately 0.2 μm to approximately 1 μm, or approximately 0.4 μm to approximately 1.4 μm. In this embodiment, D90 is approximately 200nm, approximately 210nm, approximately 220nm, approximately 230nm, approximately 240nm, approximately 250nm, approximately 260nm, approximately 270nm, approximately 280nm, approximately 290nm, approximately 300nm, approximately 310nm, approximately 320nm, approximately 330nm, approximately 340nm, approximately 350nm, approximately 360nm, approximately 369nm, approximately 370nm, approximately 380nm, about 390nm, about 400nm, about 410nm, about 420nm, about 430nm, about 440nm, about 450nm, about 460nm, about 470nm, about 480 nm, approximately 490nm, approximately 500nm, approximately 510nm, approximately 520nm, approximately 530nm, approximately 540nm, approximately 550nm, approximately 560nm, approximately 570nm, approximately 580nm, approximately 590nm, about 600nm, about 610nm, about 620nm, about 630nm, about 640nm, about 650nm, about 660nm, about 670nm, about 680nm, about 690 nm, approximately 700nm, approximately 710nm, approximately 720nm, approximately 730nm, approximately 740nm, approximately 750nm, approximately 760nm, approximately 770nm, approximately 780nm, approximately 790nm, approximately 800nm, about 810nm, about 820nm, about 830nm, about 840nm, about 850nm, about 860nm, about 870nm, about 880nm, about 890nm, about 900 nm, approximately 910nm, approximately 920nm, approximately 930nm, approximately 940nm, approximately 950nm, approximately 960nm, approximately 970nm, approximately 980nm, approximately 990nm, approximately 1000nm,Approximately 1010nm, approximately 1020nm, approximately 1030nm, approximately 1040nm, approximately 1050nm, approximately 1060nm, approximately 1070nm, approximately 1080nm, approximately 1090nm, approximately 1100nm, approximately 1110nm, approximately 1120nm, approximately 1130nm, approximately 1140nm, approximately 1150nm, approximately 1160nm, approximately 1170nm, approximately 1180nm, approximately 1190nm, approximately 1200nm, approximately 1210nm, approximately 1220nm, approximately 1230nm, approximately 1240nm, approximately 1250nm, approximately 1260nm, approximately 1270nm, approximately 1280nm, approximately 1290nm, approximately 1300nm, approximately 1310nm, approximately 1 320nm, approximately 1330nm, approximately 1340nm, approximately 1350nm, approximately 1360nm, approximately 1370nm, approximately 1380nm, approximately 1390nm, approximately 1400nm, approximately 1410nm, approximately 1420nm, approximately 1430nm, approximately 1440nm, approximately 1450nm, approximately 1460nm, approximately 1470nm, approximately 1480nm, approximately 1490nm, approximately 1500nm, approximately 1510nm, approximately 1520nm, approximately 1530nm, approximately 1540nm, approximately 1550nm, approximately 1560nm, approximately 1570nm, approximately 1580nm, approximately 1590nm, approximately 1600nm, approximately 1610nm, approximately 1620nm, approximately 163 0nm, approximately 1640nm, approximately 1650nm, approximately 1660nm, approximately 1670nm, approximately 1680nm, approximately 1690nm, approximately 1700nm, approximately 1710nm, approximately 1720nm, approximately 1730nm, approximately 1740nm, approximately 1750nm, approximately 1760nm, approximately 1770nm, approximately 1780nm, approximately 1790nm, approximately 1800nm, approximately 1810nm, approximately 1820nm, approximately 1830nm, approximately 1840nm, approximately 1850nm, approximately 1860nm, approximately 1870nm, approximately 1880nm, approximately 1890nm, approximately 1900nm, approximately 1910nm, approximately 1920nm, approximately 1930nm, approximately 1940nm m, approximately 1950nm, approximately 1960nm, approximately 1970nm, approximately 1980nm, approximately 1990nm, approximately 2000nm, approximately 2010nm, approximately 2020nm, approximately 2030nm, approximately 2040nm, approximately 2050nm, approximately 2060nm, approximately 2070nm, approximately 2080nm, approximately 2090nm, approximately 2100nm, approximately 2110nm, approximately 2120nm, approximately 2130nm, approximately 2140nm, approximately 2150nm, approximately 2160nm, approximately 2170nm, approximately 2180nm, approximately 2190nm, approximately 2200nm, approximately 2210nm, approximately 2220nm, approximately 2230nm, approximately 2240nm, approximately 2250nmApprox. 2260nm, approx. 2270nm, approx. 2280nm, approx. 2290nm, approx. 2300nm, approx. 2310nm, approx. 2320nm, approx. 2330nm, approx. 2340nm, approx. 2350 nm, approximately 2360nm, approximately 2370nm, approximately 2380nm, approximately 2390nm, approximately 2400nm, approximately 2410nm, approximately 2420nm, approximately 2430nm, approximately 2440nm, approximately 24 50nm, approximately 2460nm, approximately 2470nm, approximately 2480nm, approximately 2490nm, approximately 2500nm, approximately 2510nm, approximately 2520nm, approximately 2530nm, approximately 2540nm, approximately 2550nm, about 2560nm, about 2570nm, about 2580nm, about 2590nm, about 2600nm, about 2610nm, about 2620nm, about 2630nm, about 2640nm , about 2650nm, about 2660nm, about 2670nm, about 2680nm, about 2690nm, about 2700nm, about 2710nm, about 2720nm, about 2730nm, about 2740 nm, approximately 2750nm, approximately 2760nm, approximately 2770nm, approximately 2780nm, approximately 2790nm, approximately 2800nm, approximately 2810nm, approximately 2820nm, approximately 2830nm, approximately 28 This includes 40nm, approximately 2850nm, 2860nm, 2870nm, 2880nm, 2890nm, 2900nm, 2910nm, 2920nm, 2930nm, 2940nm, 2950nm, 2960nm, 2970nm, 2980nm, 2990nm, or approximately 3000nm, encompassing all values ​​and ranges in between.

[0265] D. Containers and kits containing the composition In the embodiment, the composition is contained within a balloon. In the embodiment, the balloon is a balloon catheter. In the embodiment, the composition is delivered to a target lumen via the balloon. In the embodiment, the lumen is created by the balloon.

[0266] In embodiments, pre-filled syringes containing the compositions described herein are provided herein. Suitable syringes may have capacities of, for example, 10 to 250 ml, or 25 to 100 ml. In one embodiment, the composition is sterilized by gamma irradiation of the pre-filled syringe containing the composition. The pre-filled syringe may optionally be provided with a filter to reduce the possibility that any larger droplets and particles in the composition may enter the lumen during use. Typically, the filter will have a pore size of about 0.1 to 5 μm, preferably 0.8 to 1.5 μm.

[0267] Advantageously, the kit is suitable for carrying out the preparation or formulation methods of the compositions described herein.

[0268] In another embodiment, a kit is provided herein comprising a mixture containing at least one triglyceride, at least one phospholipid, and optionally at least one wetting agent, and water. The mixture and aqueous solution are preferably as described in any embodiment described herein.

[0269] In embodiments, kits comprising compositions and containers are provided herein. In embodiments, the container is a syringe. In embodiments, the container is glass. In embodiments, the container is stainless steel. In embodiments, the container is a bag. In embodiments, the container does not contain one or more of the following: dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl) phthalate (DEHP). In embodiments, the container contains polypropylene, polyethylene, polycarbonate, cyclic olefin copolymer, cyclic olefin polymer, polymethyl methacrylate, or glass. In embodiments, the container contains cyclin olefin copolymer and cyclic olefin polymer.

[0270] In embodiments, a kit comprising a composition, a container, and a filter is provided herein. In embodiments, the pore size of the filter is small enough to inhibit the growth of microorganisms and large enough to allow oil droplets from the composition to pass through the filter. In embodiments, the filter comprises pores greater than 0.5 μm and smaller than 5 μm. In embodiments, the filter comprises pores of approximately 0.6 μm, approximately 0.7 μm, approximately 0.8 μm, approximately 0.9 μm, approximately 1 μm, approximately 1.1 μm, approximately 1.2 μm, approximately 1.3 μm, approximately 1.4 μm, approximately 1.5 μm, approximately 1.6 μm, approximately 1.7 μm, approximately 1.8 μm, approximately 1.9 μm, approximately 2 μm, approximately 2.1 μm, approximately 2.2 μm, approximately 2.3 μm, approximately 2.4 μm, approximately 2.5 μm, approximately 2.6 μm, approximately 2.7 μm, approximately 2.8 μm, approximately 2 The pore diameters are approximately 0.9 μm, 3 μm, 3.1 μm, 3.2 μm, 3.3 μm, 3.4 μm, 3.5 μm, 3.6 μm, 3.7 μm, 3.8 μm, 3.9 μm, 4 μm, 4.1 μm, 34.2 μm, 4.3 μm, 4.4 μm, 4.5 μm, 4.6 μm, 4.7 μm, 4.8 μm, 4.9 μm, or 5 μm, encompassing all values ​​and ranges in between. In one embodiment, the filter has a pore diameter of approximately 2 μm. In another embodiment, the filter has a pore diameter of approximately 1.2 μm.

[0271] In an embodiment, the kit includes a bag spike and a bag containing the composition. The bag spike is used to puncture the bag containing the composition. In an embodiment, the kit further comprises an inline vent filter. The inline filter is placed directly in the bag. In an embodiment, the filter is provided with vents to allow air to be expelled from the flow path, preventing air bubbles from entering the bloodstream and causing embolism.

[0272] In the embodiment, the kit includes the composition, a syringe, a bag spike, and a filter. In the embodiment, the filter is a 1.2 μm filter.

[0273] In embodiments, containers containing the compositions described herein are provided herein. In embodiments, the container is a syringe. In embodiments, the container is glass. In embodiments, the container is stainless steel. In embodiments, the container is a bag. In embodiments, the container does not contain one or more of the following: dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl) phthalate (DEHP). In embodiments, the container contains polypropylene, polyethylene, polycarbonate, cyclic olefin copolymer, cyclic olefin polymer, polymethyl methacrylate, or glass. In embodiments, the container contains cyclin olefin copolymer and cyclic olefin polymer.

[0274] In the embodiment, the container is a syringe. In the embodiment, the syringe is a 50 mL syringe. In the embodiment, the syringe contains one or more of the following: polypropylene, polyethylene, polycarbonate, cyclic olefin copolymer, cyclic olefin polymer, polymethyl methacrylate, or glass. In the embodiment, the syringe comprises a plunger. In the embodiment, the plunger contains one or more of the following: rubber (e.g., natural or synthetic), thermoplastic elastomer, silicone rubber, polyisoprene, ethylene propylene diene monomer, chlorobutyl rubber, or bromobutyl rubber.

[0275] In the embodiment, the container is a bag. In the embodiment, the composition is present in a sterile in-line bag spike and injection kit. In the embodiment, the bag is a pressure bag.

[0276] E. Method of use of the composition The present disclosure provides methods of using a composition. In embodiments, the composition is used for imaging (e.g., via ultrasound or other imaging methods). In embodiments, the composition is used to provide guidance for surgery. In embodiments, the composition is used as a delivery vehicle (e.g., to deliver a diagnostic or therapeutic agent). In embodiments, the composition is used to diagnose or treat a disease. In embodiments, the composition is used as a lubricant (e.g., to assist in the insertion of an instrument into a body part). The composition can be used in a particular method of the present disclosure or a combination of methods for a subject (e.g., both as a composition for imaging and as a lubricant for a subsequent surgical instrument).

[0277] In embodiments, the present disclosure provides an imaging method of using the composition of the present disclosure. In embodiments, the method includes administering the composition of the present disclosure to a subject that requires administration and then performing imaging. In embodiments, the composition is administered into a wound, an organ, a tumor, a blood vessel, or a cavity within the body of the subject. In embodiments, the composition is administered into the area of the blood vessels or blood circulation of the subject. In embodiments, the method includes obtaining an image of an area of a wound, an organ, a tumor, a blood vessel, or blood circulation, or a cavity, and i) contacting the wound, organ, tumor, blood vessel, or cavity with the composition of the present disclosure and ii) obtaining an image using an instrument (imaging).

[0278] In embodiments, the image is an ultrasonic image. In embodiments, the imaging method is an invasive ultrasonic imaging method.

[0279] In the embodiments, the imaging method is Doppler blood flow imaging. In the embodiments, the method is optical coherence tomography. In the embodiments, the method is laser speckle imaging. In the embodiments, the oil droplets contained in the composition are strong backscatterers that enhance the backscatter signal. In the embodiments, the compositions of the disclosure enhance Doppler detection and reduce imaging delay. In the embodiments, the compositions of the disclosure function as contrast agents. Additional information on the methods can be found, for example, in Liu et al., CS Appl. Nano Mater. 2023, 6, 19, 17691-17697, the contents of which are incorporated in their entirety by reference.

[0280] In embodiments, the compositions and suspensions described herein are used in a laser speckle contrast imaging method. In embodiments, the compositions described herein are diluted with water and / or glycerol and used in a laser speckle contrast imaging method. Laser speckle contrast imaging is described in the following article, which is incorporated herein in its entirety by reference: Wang et al. Assessment of Optical Clearing Induced Improvement of Laser Speckle Contrast Imaging, Vol.3, No.3, 2010, pp.159-167. In embodiments, the suspensions and compositions are used to visualize blood vessels. In embodiments, the suspensions and compositions are used to visualize blood flow.

[0281] In embodiments, the method is photoacoustic imaging (PAI). In PAI, laser irradiation is generally used to induce rapid thermoelastic expansion of a tissue volume that generates an ultrasonic signal, the amplitude of which is proportional to the absorbed optical intensity. In embodiments, an image mapping the accumulation of the original light energy within the target is formed by detecting and processing the ultrasonic signal. In embodiments, the composition of the present disclosure functions as a contrast agent. Additional information on PAI can be found, for example, in Zhang et al., Biomed Opt Express. 2019 Nov 1;10(11):5744-5754, the contents of which are incorporated in their entirety by reference.

[0282] In the embodiments, the method is computed tomography (CT). In the embodiments, the composition of the present disclosure functions as a contrast agent. Additional information on CT can be found, for example, in Hildell et al., AJR Am J Roentgenol. 1981 Oct;137(4):777-80, the contents of which are incorporated in their entirety by reference.

[0283] In the embodiments, the method is echocardiography. In the embodiments, the method is myocardial contrast two-dimensional echocardiography. Additional information on echocardiography can be found, for example, in Myocardial Contrast Two-dimensional Echocardiography (Developments in Cardiovascular Medicine Book 99) by Meerbaum and Richard S. Meltzer (2012), the entire contents of which are incorporated by reference.

[0284] In the embodiments, the method is a magnetic field imaging method. In the embodiments, the method is magnetic resonance imaging (MRI). In the embodiments, the method is magnetic particle imaging (MPI). In the embodiments, the composition comprises a magnetic material (e.g., superparamagnetic nanoparticles) for a magnetic field imaging method.

[0285] In the embodiment, the method is a fluorescence imaging method. In the embodiment, the composition comprises a fluorescent substance for the fluorescence imaging method (e.g., as a diagnostic agent).

[0286] In the embodiments, the method is a radioimaging method. In the embodiments, the method is positron emission tomography (PET). In the embodiments, the composition comprises a radioactive material (e.g., as a diagnostic agent) for such imaging method.

[0287] In embodiments, the compositions of the present disclosure are used as contrast agents. In embodiments, the compositions are used to image blood vessels. In embodiments, the compositions are used to image blood flow.

[0288] In embodiments, the composition is administered into the bloodstream of a target. In embodiments, the composition supplies backscattering material into the bloodstream, which enables improved imaging of a region of blood vessels or blood circulation. In embodiments, the composition functions as a contrast agent. In embodiments, the method includes (i) injecting the composition into the bloodstream of a target; (ii) imaging a region of blood vessels or blood circulation by an imaging method; and optionally (iii) calculating the blood flow velocity of the vessels. In embodiments, the imaging method is optical Doppler tomography (ODT). In embodiments, the imaging method is laser speckle contrast imaging (LSCI). Further descriptions of blood flow imaging can be found, for example, in International Publication No. 2014012042, the contents of which are incorporated in whole by reference.

[0289] In the embodiment, the blood vessels are capillaries. In the embodiment, the area of ​​blood circulation is the microvascular system (e.g., tumor microvascular system).

[0290] Further descriptions of various imaging methods can be found, for example, in Theek et al., Radiologe. 2020 Nov;60(Suppl 1):41-53, the entire content of which is incorporated by reference.

[0291] In embodiments, the methods of the present disclosure are for measuring one or more of the following: neurovascular hemodynamics, pharmacological effects on the brain, imaging of tumor vascular structure, surgical confirmation of suppression of tumor vascular supply during brain surgery, evaluation of wound healing (e.g., non-invasive imaging of angiogenesis), and OCT imaging of vascular abnormalities in the retina.

[0292] In embodiments, the imaging method is linked to surgery. In embodiments, once an image is acquired (for example, of a blood vessel / circulation, wound, organ, tumor, or cavity of interest), the surgeon can perform surgery based on the information provided by the image. In embodiments, the Disclosure provides a method for performing surgery on an object requiring surgery, the method comprising administering a composition of the Disclosure to an area of ​​a wound, organ, tumor, or cavity, or blood vessel or circulation of the object, acquiring an image, and performing surgery based on the image. In embodiments, the surgery is the excision of a tumor.

[0293] In embodiments, the compositions of the present disclosure are used to assist in the insertion of instruments into subjects requiring instrument insertion. In embodiments, the compositions of the present disclosure function as lubricants. In embodiments, the compositions can help deliver instruments to a target site without the instruments and tissues snagging on each other. Advantageously, as discussed herein, the compositions can be formulated such that the compositions are biocompatible (e.g., their osmotic pressure corresponds to physiological osmotic pressure). In embodiments, the present disclosure provides a method for performing surgery on subjects requiring surgery, the method comprising contacting instruments to be used in surgery with the compositions of the present disclosure and inserting the instruments into wounds, organs, tumors, blood vessels, or cavities within the body of the subject. In embodiments, the compositions come into contact with the instruments before they are inserted into the subject. In embodiments, the compositions are first administered into the target area before the instruments are inserted into the target area.

[0294] In embodiments, the Disclosure provides a method for performing surgery on an object requiring surgery, the method comprising administering the composition of the Disclosure into a wound, organ, tumor, blood vessel, or cavity within the object's body, and inserting a surgical instrument into the wound, organ, tumor, blood vessel, or cavity. In embodiments, the Disclosure provides a method for placing an instrument within the body of an object requiring instrument placement, the method comprising sequentially or simultaneously bringing a site of the object into contact with the composition of the Disclosure and inserting the instrument into the object. In embodiments, the site is brought into contact with the composition before instrument placement. In embodiments, the site is brought into contact with the composition simultaneously with instrument placement. In embodiments, the site is brought into contact with the composition after instrument placement.

[0295] In one embodiment, the device is for treating a disease. In another embodiment, the device is for preventing a disease.

[0296] In the embodiment, the device is a catheter. In the embodiment, the catheter is a subdural pressure catheter, a drainage catheter, a cerebral blood flow catheter, a microdialysis catheter, or a cerebral tissue oxygen catheter.

[0297] In this embodiment, the device is an intracranial pressure sensor.

[0298] In embodiments, the device is an implantable brain-computer interface (BCI). Further descriptions of BCIs can be found, for example, in Shih et al., Mayo Clin Proc. 2012 Mar;87(3):268-279, the entire content of which is incorporated by reference.

[0299] In embodiments, the surgery may be angioplasty, stent placement, embolization, injection of thrombolytic agents, catheter placement, gastrostomy tube placement, IVC filter placement, removal of foreign bodies (e.g., bullet fragments), cyst drainage, or needle biopsy. In embodiments, the surgery may be endovascular or endoscopic. Additional descriptions of the surgery may be found, for example, in Mashoufi and Mashoufi, Cureus. 2023 Nov;15(11):e48603, the contents of which are incorporated in their entirety by reference.

[0300] In the embodiment, the surgery is a brain surgery or neurosurgery. In the embodiment, the instrument is inserted into the brain of the subject.

[0301] In one embodiment, the surgery is for the purpose of excising a tumor (for example, removing residual tumor embedded in tissue). In the embodiment, the method includes administering the composition of the present disclosure to tissue proximal to the tumor, obtaining an image of the proximal tissue suspected to contain the tumor, identifying the tumor, and excising the tumor. In the embodiment, the tumor is located in or proximal to the bladder, uterus, cervix, colon, or spine.

[0302] In embodiments, the compositions of the present disclosure have properties (e.g., attenuation coefficient) that match the target tissue (e.g., blood) to enhance the signal of the target tissue. In embodiments, the compositions of the present disclosure enhance the measurement of the flow or flow rate of a moving fluid in a subject. In embodiments, the moving fluid is arterial blood. In embodiments, the moving fluid is venous blood. In embodiments, the moving fluid is cerebrospinal fluid (CSF). In embodiments, the compositions of the present disclosure have properties (e.g., attenuation coefficient) that match the surrounding tissue / inclusion tissue to enhance the signal of the surrounding tissue (e.g., in the bladder, uterus, cervix, colon, or spine).

[0303] In the embodiment, the subject is a patient. In the embodiment, the subject is a mammal. In the embodiment, the subject is a primate. In the embodiment, the subject is a human.

[0304] In the embodiment, delivery of the composition is achieved using a balloon containing the composition. In the embodiment, the balloon is a balloon catheter. In the embodiment, the composition is delivered to a target lumen via the balloon. In the embodiment, the lumen is created by the balloon.

[0305] In some embodiments, the composition is intended for use in invasive ultrasound imaging of the subject. Examples of such use include invasive ultrasound imaging during surgery, as well as non-surgical uses, such as invasive diagnostic methods (e.g., colorectal examination).

[0306] In this embodiment, the composition is intended for use as an ultrasound coupling agent in focused ultrasound therapy. Focused ultrasound therapy concentrates ultrasound energy on a target on the body (e.g., cancer cells). By focusing on the target, focused ultrasound does not harm healthy tissue.

[0307] Various tissues / materials can be imaged using the compositions described herein. In embodiments, the compositions are for use, for example, in invasive ultrasound imaging of the brain during brain surgery. In embodiments, the brain includes a tumor. In embodiments, the compositions described herein are used to image the tumor via ultrasound. In embodiments, the tumor is excised. In embodiments, the use of the compositions allows a neurosurgeon to ensure that tumor tissue is removed without removing healthy tissue.

[0308] In embodiments, the composition is intended for use in invasive ultrasound imaging of other tissues, such as cardiac or breast tissue. In embodiments, the composition described herein is particularly suitable for cardiac imaging, i.e., the composition (e.g., fluid) has an attenuation coefficient that generates fewer artifacts in invasive ultrasound imaging of the heart.

[0309] In embodiments, a method for ultrasound imaging of a subject is provided herein, comprising administering a composition described herein to a subject through an orifice of the subject's body, applying ultrasound to the composition, and detecting ultrasound reflected from the composition. In embodiments, the method is a method for ultrasound imaging of a subject during surgery, for example, brain surgery, breast cancer surgery, or open-heart surgery. In embodiments, the method is a method for ultrasound imaging of a subject during an invasive diagnostic procedure, for example, a colorectal examination.

[0310] The embodiment is a composition, a) At least one triglyceride in a concentration of 20.0 to 90.0 g / L, b) At least one phospholipid in a concentration of 1.2 to 5.4 g / L, c) Optionally, a composition comprising at least one wetting agent, for use in invasive cardiac ultrasound imaging such as during open-heart surgery, wherein the attenuation coefficient (α) of the composition is in the range of 0.1 to 1.0 dB / (MHz·cm), preferably 0.1 to 0.8 dB / (MHz·cm). Unexpectedly, when a composition having an attenuation coefficient within this range is used in invasive cardiac ultrasound imaging, the intensity and frequency of image artifacts, such as luminance artifacts, are reduced.

[0311] The embodiment is a composition, a) At least one triglyceride in a concentration of 20.0 to 90.0 g / L, b) At least one phospholipid in a concentration of 5.5 to 10.8 g / L, c) Optionally, a composition comprising at least one wetting agent, for use in invasive cardiac ultrasound imaging such as during open-heart surgery, wherein the attenuation coefficient (α) of the composition is in the range of 0.1 to 1.0 dB / (MHz·cm), preferably 0.1 to 0.8 dB / (MHz·cm). Unexpectedly, when a composition having an attenuation coefficient within this range is used in invasive cardiac ultrasound imaging, the intensity and frequency of image artifacts, such as luminance artifacts, are reduced.

[0312] The embodiment is a composition, a) At least one triglyceride in a concentration of 20.0 to 90.0 g / L, b) At least one phospholipid in a concentration of 1.2 to 5.4 g / L, c) optionally, including at least one wetting agent, A composition for use in invasive ultrasound imaging of the breast, such as during breast cancer surgery, is provided herein, wherein the attenuation coefficient (α) of the composition is in the range of 0.1 to 1.2 dB / (MHz·cm), preferably 0.1 to 0.8 dB(MHz·cm). Unexpectedly, when a composition having an attenuation coefficient within this range is used in invasive ultrasound imaging of the breast, the intensity and frequency of image artifacts, such as luminance artifacts, are reduced. The properties and amounts of each of the components a) to d) in this embodiment of the composition may be as enumerated for any other embodiment of the composition described herein.

[0313] The embodiment is a composition, a) At least one triglyceride in a concentration of 20.0 to 90.0 g / L, b) At least one phospholipid in a concentration of 5.5 to 10.8 g / L, c) optionally, including at least one wetting agent,

[0314] A composition for use in invasive ultrasound imaging of the breast, such as during breast cancer surgery, is provided herein, wherein the attenuation coefficient (α) of the composition is in the range of 0.1 to 1.2 dB / (MHz·cm), preferably 0.1 to 0.8 dB(MHz·cm). Unexpectedly, when a composition having an attenuation coefficient within this range is used in invasive ultrasound imaging of the breast, the intensity and frequency of image artifacts, such as luminance artifacts, are reduced. The properties and amounts of each of the components a) to d) in this embodiment of the composition may be as enumerated for any other embodiment of the composition described herein.

[0315] In this embodiment, the composition is for brain ultrasound imaging, a) At least one triglyceride in a concentration of approximately 60 g / L to approximately 80.0 g / L, b) At least one phospholipid in a concentration of approximately 1.2 g / L to 12 g / L, c) A composition for ultrasound imaging of the brain is provided herein, comprising approximately 21 g / L to approximately 26 g / L of glycerol.

[0316] In embodiments, compositions as defined above are provided herein for use in invasive ultrasound imaging of the colon in colorectal cancer staging using the balloon standoff method, wherein the attenuation coefficient (α) of the composition is in the range of 0.1 to 0.6 dB / (MHz·cm). Unexpectedly, compositions having an attenuation coefficient within this range, when used in colorectal cancer staging using the balloon standoff method, reduce the intensity and frequency of image artifacts, such as brightness artifacts.

[0317] The balloon standoff method may include an outer "balloon" sheath surrounding at least a portion of an ultrasonic transducer, and an ultrasonic coupling material, which is a liquid or gel, between the ultrasonic transducer and the sheath. In one embodiment, positioning can be facilitated and the balloon shape can be adapted to the biological structure under examination by varying the amount of ultrasonic coupling material between the ultrasonic transducer and the sheath. The ultrasonic coupling material in this embodiment may be any preferred embodiment or composition described herein. The sheath material may be any preferred material, such as an elastomer polymer material. In one embodiment, the sheath material may be latex-free.

[0318] In one embodiment, the composition is intended for use in invasive ultrasound imaging of the brain, heart, breast, blood vessels, or colon.

[0319] In embodiments, a method is provided herein that includes (i) bringing an organ or cavity into contact with a composition described herein, and (ii) obtaining an ultrasound image of the organ or cavity. In embodiments, the organ or cavity includes a tumor. In embodiments, the method further includes excising the tumor.

[0320] In embodiments, the method of the present disclosure includes performing an invasive procedure before administering the composition. In embodiments, the invasive procedure allows access to the composition and / or instrument in a wound, organ, blood vessel, or lumen.

[0321] In the embodiment, the cavity is selected from any one of the following: oral cavity, nasal cavity, orbit, thoracic cavity, pericardial cavity, pleural cavity, abdominal cavity, pelvic cavity, cranial cavity, spinal cavity, joint cavity, synovial cavity, buccal oral cavity, cranial fossa, mandibular fossa, maxillary sinus, frontal sinus, ethmoid sinus, sphenoid sinus, mastoid air cells, ear canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, venous sinus, fallopian tube infundibulum, alveolar sac, bronchioles, laryngeal cavity, tracheal cavity, gastric pit, intestinal crypt, gallbladder pit, renal sinus, ureteral orifice, bladder trigone, follicle, testicular lobule, vaginal fornix, anal canal, vertebral foramen, intervertebral foramen, foramen magnum, and jugular foramen. In the embodiment, the cavity includes a tumor. In the embodiment, the method includes excising the tumor.

[0322] In the embodiment, the composition is delivered to one or more cavities of the body selected from the group consisting of the cranial cavity, spinal canal, thoracic cavity, abdominal cavity, pelvic cavity, apocelvic cavity, ventral body cavity, dorsal body cavity, and pericardial cavity.

[0323] In embodiments, the organ is selected from any one of the following: brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, breasts, esophagus, diaphragm, adrenal glands, thyroid gland, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries, testes, uterus, prostate, penis, vagina, cervix, urethra, rectum, anus, skeletal muscle, smooth muscle, cardiac muscle, bone marrow, bone, blood vessels, lymph nodes, lymphatic vessels, tonsils, appendix, adipose tissue, nerves, and connective tissue. In embodiments, the organ is the brain, kidneys, liver, pancreas, ovaries, breasts, bladder, uterus, cervix, or colon. In embodiments, the organ is the brain. In embodiments, the organ includes a tumor. In embodiments, the method includes excising the tumor.

[0324] In the embodiment, the composition is used in cancer surgery. In the embodiment, the composition is used as a drug delivery vehicle.

[0325] In embodiments, the Disclosure provides a method for delivering a diagnostic or therapeutic agent to a subject requiring delivery, the method comprising administering a composition of the Disclosure, the composition comprising a diagnostic or therapeutic agent. In embodiments, the Disclosure provides a method for delivering a diagnostic or therapeutic agent to a subject requiring delivery, the method comprising administering both a composition of the Disclosure and a diagnostic or therapeutic agent. In embodiments, the composition and the agent are administered sequentially. In embodiments, the composition and the agent are administered simultaneously. In embodiments, the composition and the agent are administered to the same site.

[0326] In the embodiment, the method delivers a diagnostic agent. In the embodiment, the diagnostic agent is a contrast agent. In the embodiment, the diagnostic agent is a near-infrared (IR) fluorophore. In the embodiment, the near-IR fluorophore is indocyanine green. In the embodiment, the diagnostic agent is a fluorophore.

[0327] In embodiments, the method is for identifying target tissue or diseased tissue within the body of a subject. In embodiments, the diseased tissue is a residual tumor. In embodiments, the method further includes removing and / or treating the abnormal area or diseased tissue. In embodiments, the method includes removing the abnormal area or diseased tissue via surgery. In embodiments, the method includes treating the abnormal area via therapy (e.g., photodynamic therapy, radiotherapy, or chemotherapy). In embodiments, the composition includes a therapeutic agent for the therapy (e.g., a photosensitizer, a radioagent, or a chemotherapeutic agent).

[0328] In embodiments, the method is for treating a disease, and the agent is a therapeutic agent. In embodiments, the therapeutic agent comprises a photosensitizer. In embodiments, the method comprises exposing the photosensitizer to light. In embodiments, the method comprises photodynamic therapy. In embodiments, the compositions described herein are diluted with water and / or glycerol and used in a method of photodynamic therapy. Photodynamic therapy is described, for example, in Hu et al., Proc SPIE Int Soc Opt Eng. 2013 Jul 13;7380:73801W, the contents of which are incorporated in their entirety by reference.

[0329] In embodiments, the composition is used as a photodispersant for photodynamic therapy. The term “photodispersant” refers to a solution that diffuses light. Photodynamic therapy involves administering a photosensitizer to cancer cells and exposing the photosensitizer to light. When the photosensitizer is exposed to light, it kills the cancer cells. In embodiments, the photosensitizer is delivered to cancer cells via a balloon. In embodiments, the balloon is also filled with the composition described herein which acts as a photodispersant. In embodiments, the photosensitizer and / or composition described herein is applied directly to a cavity in the human body. In embodiments, the photodispersant and / or photosensitizer is applied directly to a tumor. In embodiments, the photosensitizers and / or compositions described herein are delivered to cancer cells via a system described in any one of the following: International Publication No. 2022258727, Dupont et al. Neurosurgery 84(6):p E414-E419, June 2019, and Vermandel et al. Journal of Neuro-Oncology (2021) 152:501-514, or Dupont et al. Future Oncol. 2017 Nov;13(27):2441-2454, the contents of which are incorporated herein by reference in their entirety.

[0330] In one embodiment, the method comprises diluting the composition with water and / or glycerol. In another embodiment, the method comprises diluting the composition with water and glycerol. In yet another embodiment, the method comprises diluting the composition about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, about 10 times, about 11 times, about 12 times, about 13 times, about 14 times, about 15 times, about 16 times, about 17 times, about 18 times, about 19 times, about 20 times, about 22 times, about 25 times, about 30 times, about 35 times, about 40 times, about 45 times, about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times. In one embodiment, the method comprises diluting the composition by about 2 to 5 times, about 5 to 10 times, about 10 to 15 times, about 15 to 20 times, about 20 to 30 times, about 30 to 40 times, about 40 to 60 times, about 60 to 80 times, or about 80 to 100 times. In another embodiment, the method comprises diluting the composition by about 6 w / v%, about 5 w / v%, about 4 w / v%, about 3 w / v%, about 2.5 w / v%, about 2.2 w / v%, about 2 w / v%, about 1.8 w / v%, about 1.6 w / v%, about 1.4 w / v%, about 1.2 w / v%, about 1 w / v%, about 0.9 w / v%, about 0.8 w / v%, about 0.7 w / This involves diluting to a final concentration of triglycerides that is v%, approximately 0.6 w / v%, approximately 0.5 w / v%, approximately 0.4 w / v%, approximately 0.3 w / v%, approximately 0.2 w / v%, approximately 0.1 w / v%, approximately 0.09 w / v%, approximately 0.08 w / v%, approximately 0.07 w / v%, approximately 0.06 w / v%, or approximately 0.05 w / v%. In one embodiment, the method includes diluting the composition to a final triglyceride concentration of about 6 w / v% to about 4 w / v%, about 4 w / v% to about 2 w / v%, about 2 w / v% to about 1 w / v%, about 1 w / v% to about 0.8 w / v%, about 0.8 w / v% to about 0.6 w / v%, about 0.6 w / v% to about 0.4 w / v%, about 0.4 w / v% to about 0.3 w / v%, about 0.3 w / v% to about 0.2 w / v%, about 0.2 w / v% to about 0.1 w / v%, about 0.1 w / v% to about 0.08 w / v%, or about 0.08 w / v% to about 0.05 w / v%. In another embodiment, the method includes diluting the composition to a final triglyceride concentration of about 0.1 w / v% to about 0.5% w / v%. In the embodiment, the method includes diluting the composition to a final triglyceride concentration of about 0.1 w / v%.In the embodiments, the method includes diluting the composition to a final triglyceride concentration of about 0.2 w / v%. In the embodiments, the method includes diluting the composition to a final triglyceride concentration of about 0.5 w / v%. In the embodiments, the triglyceride:phospholipid or lecithin ratio remains the same.

[0331] In the embodiment, the low-triglyceride composition has an osmotic pressure of about 270 mOsm / kg to about 330 mOsm / kg. In the embodiment, the diluted composition has an osmotic pressure of about 290 mOsm / kg. In the embodiment, the diluted composition has an osmotic pressure of about 284 mOsm / kg to about 296 mOsm / kg. In the embodiment, the diluted composition has an osmotic pressure of about 290 mOsm / kg to about 311 mOsm / kg. In the embodiment, the diluted composition has an osmotic pressure of about 290 mOsm / kg to about 305 mOsm / kg. In the embodiment, the low-triglyceride composition has an osmotic pressure substantially the same as the osmotic pressure of the target organ or tissue. In the embodiment, the low-triglyceride composition is formulated so that the composition is biocompatible (e.g., the osmotic pressure corresponds to physiological osmotic pressure). In the embodiment, the low-triglyceride composition is formulated such that its osmotic pressure is at an appropriate level that matches the physiological osmotic pressure at the application site. In the embodiment, glycerol is added during the dilution of the composition with water to increase the osmotic pressure to the target level.

[0332] In embodiments, the Disclosure provides a method for treating a disease in a subject requiring treatment, the method comprising administering a composition of the Disclosure. In embodiments, the composition comprises a therapeutic agent. In embodiments, the method comprises performing a treatment (e.g., photodynamic therapy or focused ultrasound therapy).

[0333] In embodiments, the present disclosure provides a method for treating a disease using focused ultrasound therapy in a subject requiring treatment, the method comprising administering the composition of the present disclosure to the subject and performing focused ultrasound therapy.

[0334] In embodiments, the Disclosure provides a method for treating a disease in an object requiring treatment, the method comprising: i) bringing a wound, organ, tumor, or cavity containing diseased tissue into contact with a composition of the Disclosure; ii) obtaining an image of the wound, organ, tumor, or cavity; and iii) treating the disease or removing diseased tissue based on the image.

[0335] In embodiments, the Disclosure provides a method for treating a disease related to blood flow or blood circulation in an object requiring treatment, the method comprising: i) bringing a region of blood vessels or blood circulation into contact with a composition of the Disclosure; ii) obtaining an image of the region of blood vessels or blood circulation; and iii) treating the disease or removing diseased tissue based on the image.

[0336] In embodiments, diseases related to blood flow or blood circulation are selected from atherosclerosis, myocardial infarction, angina pectoris, arrhythmia, irregular rhythm, myocardial ischemia, stroke, vascular disease, peripheral artery disease, coronary artery disease, Buerger's disease, mitral valve prolapse, mitral valve regurgitation, or mitral valve stenosis. In embodiments, treatment methods include angioplasty, stent placement, embolization, injection of thrombolytic agents, catheter placement, and / or IVC filter placement.

[0337] The route of administration will naturally vary depending on the location and nature of the disease being treated, or the condition being diagnosed, for example, the auricle, buccal, conjunctiva, skin, teeth, cervix, paranasal sinuses, trachea, intestines, epidural, interstitial, intra-articular, intra-arterial, intraperitoneal, auricle, bile duct, bronchi, sac, corpus cavernosum, cerebrum, cisterna magna, cornea, intracornal, coronary artery, intracranial, intradermal, intervertebral disc, duct, duodenum, duodenal, intradural, epicardial, epidermal, esophagus, stomach, gingiva, liver, ileum, lesion, tongue, cavity, lymphatic vessel, breast, intramedullary, meninges, muscle, nasal cavity, nodule, eye, reticular, ovary, abdominal cavity, pericardium, pleura This may include administration in the following locations: intra-articular, intraprostate, intrapulmonary, intrarum, intrarum, intrasinus, intrathecal cavity, intrasynovial bursa, intratendinous, intratesticular, intratracheal, subarachnoid, intrathoracic, intratubular, intratumoral, intratympanic, intrauterine, intraperitoneal, intravascular, intraventricular, intrabladder, intravesical, intravenous, intravitreous, larangeal, nasal, transnasogastrocnemius, oral, ocular, oropharynx, parenteral, percutaneous, periarticular, epidural, perineurial, periodontal, respiratory tract, retrotubular, rectum, spine, subarachnoid, subconjunctival, subcutaneous, subdermal, subgingival, sublingual, submucosal, subretinal, local, percutaneous, transendocardial, transmucosal, transplacental, transtracheal, transtympanic membrane, ureter, urethra, vaginal irrigation, lavage, direct injection, oral administration, or any combination thereof.

[0338] Cancer or tumor-related applications In embodiments, the methods of the present disclosure relate to the identification and / or treatment of a tumor. In embodiments, the tumor is a residual tumor. In embodiments, the methods include identifying the tumor using an imaging method of the present disclosure. In embodiments, the methods further include removing or treating the tumor identified by the imaging method. In embodiments, the methods of the present disclosure include removing the tumor by surgery. In embodiments, the methods of the present disclosure include treating the tumor with a composition of the present disclosure (e.g., a composition containing a therapeutic agent). In embodiments, the methods of the present disclosure include treating the tumor with the assistance of a composition of the present disclosure (e.g., a composition functioning as a photodispersant for photodynamic therapy).

[0339] In embodiments, the tumor is located in or near the bladder, uterus, cervix, colon, or spine. In embodiments, the tumor is a brain tumor. In embodiments, the tumor is a glioma, glioblastoma, or neuroblastoma.

[0340] In embodiments, the methods described herein may be combined with one or more alternative methods for treating cancer. Non-limiting examples of alternative methods for treating cancer include chemotherapy, immunotherapy, alternating electric tumor treating field, laser interstitial hyperthermia (LITT), magnetic hyperthermia (MHT), focused ultrasound, radiofrequency microwave, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence-guided resection, surgical resection, and magnetic resonance imaging. In embodiments, the method includes administering one or more methods for treating cancer. In embodiments, one or more methods are selected from the group consisting of chemotherapy, immunotherapy, alternating electric tumor treating field, laser interstitial hyperthermia (LITT), magnetic hyperthermia (MHT), focused ultrasound, radiofrequency microwave, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence-guided resection, surgical resection, and magnetic resonance imaging. In some embodiments, treating cancer involves exposing cancer cells to light (for example, via photodynamic therapy).

[0341] F. Method for preparing the composition In one embodiment, a method for preparing the compositions of the present disclosure is provided herein. In an embodiment, the method comprises mixing (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) a wetting agent. In an embodiment, the method comprises mixing (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) pH buffer, and (e) a wetting agent. In an embodiment, the method comprises mixing (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, (e) a wetting agent, and (f) a diagnostic agent and / or a therapeutic agent. In an embodiment, the method comprises mixing (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) pH buffer, (e) a wetting agent, and (f) a diagnostic agent and / or a therapeutic agent.

[0342] In this embodiment, the method is i) To provide a mixture comprising at least one triglyceride, at least one phospholipid, and optionally at least one wetting agent, ii) Diluting the mixture with water, etc.

[0343] The mixture provided in step i) is preferably an aqueous solution of at least one triglyceride, at least one phospholipid, and optionally at least one wetting agent. Optionally, other components, such as pH-adjusting additives, may also be included in the mixture. The properties of the triglyceride, phospholipid, and optionally wetting agent components may be any of the options described in the embodiments above. A mixture containing soybean oil, lecithin, and optionally glycerol is particularly preferred.

[0344] The amount of water used to dilute the aforementioned mixture can be adjusted to obtain the desired concentrations of triglycerides, phospholipids, and any other components in the composition.

[0345] In one embodiment, any of the methods described herein includes sterilization of the composition (of any embodiment disclosed herein), which is achieved by heat, gamma irradiation, etc. In the embodiment, the sterilization includes gamma irradiation, with a radiation dose of 10 to 100 kGy. In the embodiment, the method includes filling a syringe with the composition and sterilizing the composition by gamma irradiation of the pre-filled syringe containing the composition.

[0346] In embodiments, a method for formulating the compositions described herein is provided herein, and the method is i) To provide a mixture comprising at least one triglyceride, at least one phospholipid, and optionally at least one wetting agent, ii) Determining the damping coefficient (α) of the mixture, iii) Calculate the difference (d) between the damping coefficient of the mixture determined in step ii) and the reference damping coefficient (αr), iv) Diluting the mixture provided in step i) with an amount of water determined by a function f(d) of the difference (d) calculated in step iii) to form a diluted mixture, v) optionally repeating steps ii) to iv) with the diluted mixture obtained in step iv).

[0347] Starting from a concentrated mixture of at least one triglyceride, at least one phospholipid, and optionally other components, it is possible to obtain a composition (usually a fluid) having a desired attenuation coefficient, i.e., a baseline attenuation coefficient, simply by varying the amount of water or aqueous solution added to the mixture. Preferably, the baseline attenuation coefficient (αr) corresponds to the attenuation coefficient of the target tissue being imaged, such as brain tissue, cardiac tissue, or breast tissue. The values ​​of these baseline attenuation coefficients for any particular tissue can be found in published reference tables. The properties of the mixture / aqueous solution may be the same as those in the method of preparing the composition according to the embodiments described above. Preferably, the mixture contains soybean oil, lecithin, and glycerol.

[0348] The function f(d) used to determine the amount of water / aqueous solution to add to the mixture to form a diluted mixture can be determined experimentally, for example, using a calibration curve. In one embodiment, the function is a linear function, i.e., represented by the following equation. f(d) = kd + c

[0349] In the formula, k and c are constants. The values ​​of the constants k and c can be determined experimentally. [Examples]

[0350] Example 1 - Preparation of Exemplary Composition Concentrates of the compositions described herein were formulated as emulsions. The concentrates contained at least one triglyceride, at least one phospholipid, water, and glycerol. The concentrates were then diluted with water to a suitable concentration. The concentrates were free of stabilizers (e.g., polysorbate 80 was absent) or physiological saline (i.e., sodium chloride was absent). The pH was adjusted with NaOH to about 6.5 to about 8.5. The following table provides exemplary concentrate formulations. [Table A-1] [Table A-2]

[0351] The droplet size, osmotic pressure, and pH of the emulsion were measured as described below.

[0352] The samples were stored at room temperature, away from direct sunlight. Visual analysis was performed by observing the syringe without stirring the sample, which could cause redispersion or transient mixing, before extraction for further analysis. At each measurement point, 5 ml of emulsion was squeezed out of the respective syringe after visual analysis. These 5 ml aliquots were then used for all analyses at specific time points. The autoclave (CertoClav® CVEL 12L) temperature was manually controlled by a pressure gauge, and the time for each cycle was controlled by a timer. The conditions used were 121°C for 20 minutes.

[0353] As part of routine operations, pH measurements were collected using a Mettler Toledo SevenEasy pH meter calibrated with AVS TITRINORM buffer solution pH 4 and AVS TITRINORM buffer solution pH 7, and controlled with AVS TITRINORM buffer solution pH 5.

[0354] Dynamic light scattering measurements were collected using a Malvern zetasizing Nano-series Nano-ZS. Here, samples were diluted 100-fold in DI water immediately before analysis. For size control and calibration, a Nanosphere size standard of 203 ± 5 nm was used. This was freshly prepared and performed each day the measurements were taken. The average droplet diameter reported from the zetasizing measurements is the Z-average diameter.

[0355] The microscope used was an Olympus BX43 equipped with an Olympus XM10 camera with pre-calibrated measurements (embedded in the image). Osmotic pressure measurements were performed using a Gonotec OSMOMAT 030-D-D3P, serial number 08 02 22. Here, 50 microliters of sample were pipetted into the measuring container, taking care to avoid the generation of air bubbles. Before sample analysis, the instrument was calibrated with a Gonotec calibration standard using NaCl / H2O with an expected value of 300 mOsmol / kg (tolerance range 298-302 mOsmol / kg). The calibration standard was performed three times each.

[0356] Example 2 - Evaluation of an exemplary composition for ultrasound-guided imaging of the brain The composition is crucial for ultrasound-guided resection of brain tumors. Without a composition (e.g., saline alone), ultrasound images become difficult to interpret due to the presence of enhancement artifacts, making it challenging to determine the presence of residual tumor in the cavity. Developing compositions for the brain is difficult because they must possess acoustic properties substantially similar to cerebrospinal fluid and be safe. An ideal composition for the brain would allow neurosurgeons to accurately identify and remove tumor cells. One composition used for this purpose is Formulation 7 in Table B below. Compared to saline, the use of Formulation 7 as a composition results in the elimination of enhancement artifacts and improved tumor visualization (comparing Figure 2A (use of saline) to Figure 2B (use of Formulation 7 as a composition)). While Formulation 7 possesses ideal acoustic properties for imaging and thus allows neurosurgeons to accurately identify and remove tumor cells, safety concerns have been identified with this formulation due to the presence of polysorbate 80 (PS80) in the formulation. PS80 is a surfactant used to stabilize lipid emulsions and may unsafely alter the lipid content in the brain.

[0357] Developing an alternative formulation that does not contain PS80 while exhibiting acoustic properties equivalent to or better than formulation 7 is difficult. Since PS80 was used as a stabilizer to stabilize droplets in the emulsion and produce a homogeneous solution, it was anticipated that the removal of PS80 would cause separation of triglycerides and phospholipids from the solution in the composition (phase separation), which could render the composition ineffective for imaging tumors.

[0358] Previous versions of the ultrasound coupling agent were modified using sodium chloride to make the coupling agent's osmotic pressure isotonic with cerebrospinal fluid. However, if PS80 is removed to address safety concerns, the sodium chloride will destabilize the emulsion, causing phase separation of triglycerides and phospholipids. The resulting composition would be unsuitable for use as an ultrasound coupling agent. Furthermore, removing sodium chloride from the formulation alters the osmotic pressure of the coupling agent, making it no longer isotonic with cerebrospinal fluid. Contrast agents must be isotonic with their environment to prevent affecting surrounding cells. For example, if a contrast agent is hypertonic with respect to its environment, water will be drawn out of cells, causing them to disintegrate. This would pose a significant safety risk.

[0359] The inventors of this specification unexpectedly discovered that formulations free of both PS80 and sodium chloride can function effectively as compositions and can be used to accurately visualize brain tissue mimic phantoms (Cirs' Multipurpose Phantom). The advantage of these formulations is that, because they do not contain PS80, there are no safety concerns.

[0360] The formulations in Table B were evaluated in terms of imaging of tissue-mimicking phantoms. [Table B]

[0361] This phantom had an attenuation coefficient of 0.5 dB / cm-MHz ± 0.07, a sound velocity of 1540 m / s ± 10 m / s, and a scattering or relative contrast of -15 dB to +15 dB. The phantom had a tubular structure that was both highly echogenic and hypoechoic, measuring 3 cm to 4 cm in length. The phantom also contained a cubic cavity within the prefabricated tubular structure, approximately 2 cm long, 1 cm wide, and 2 cm deep.

[0362] One of the formulations listed in Table B was filled into the cubic cavity of the phantom and imaged using an ultrasound device (BK5000 with automatic or fixed gain). A neurosurgeon evaluated (1) enhancement artifacts, (2) visual CNR, (3) overall image quality, and (4) similarity between formulations 1-6 and formulation 7 on a scale of 1-5, with higher scores indicating the most desirable formulation for imaging. Table C shows the scores for each formulation using the BK5000 ultrasound device. [Table C]

[0363] Formulations containing 7 w / v% triglycerides (Formulation 3 (Figure 1C), Formulation 5 (Figure 1E), and Formulation 6 (Figure 1F)) were superior compositions to those containing 5 w / v% triglycerides (Formulation 2, Figure 1B) or 9 w / v% triglycerides (Formulation 4, Figure 1D). Surprisingly, formulations without salts and stabilizers were substantially equivalent to or improved upon Formulation 7, which contained salts (i.e., NaCl) and stabilizers (i.e., PS80). Also surprisingly, Formulations 3, 5, and 6 contained 207% more glycerol than Formulation 7, yet were still preferred compositions.

[0364] Example 3 - Ultrasonic fluid properties of exemplary compositions The particle size of the composition must be less than 5 μm to ensure safe administration of the composition via intravenous injection. The osmotic pressure of the composition must be 270–330 mOsm / L to ensure that the composition is isotonic with cerebrospinal fluid. The pH of the composition should be approximately 6.5–8.5. Multiple compositions were evaluated to determine whether they exhibited ideal particle size, osmotic pressure, and pH.

[0365] The initial formulations were produced by adding glycerol to three different lipid emulsion stocks. Each lipid emulsion stock contains a different triglyceride source. For example, the triglyceride source for lipid emulsion 1 is soybean oil. The triglyceride sources for emulsion 2 are medium-chain triglycerides, olive oil, and fish oil, and the triglyceride source for emulsion 3 is high-purity fish oil. Each lipid emulsion stock also contains a different phospholipid source. The formulations for each lipid emulsion stock are shown in Table D. [Table D]

[0366] The formulations in Table D were prepared by diluting triglycerides to 5%, 7%, or 9%, and adding varying amounts of glycerol to each formulation. Table E shows the pH and osmotic pressure of each formulation containing varying amounts of glycerol. [Table E-1] [Table E-2]

[0367] Next, formulations with osmotic pressures of approximately 290 mOsm / kg to 311 mOsm / kg were prepared, and the oil droplet size was characterized. Table F shows the 100% ≤ x μm value and D[4,3] value for each formulation in the mastersizer. The 100% ≤ x μm value in the mastersizer ("mastersizer") describes the oil droplet size, and in the formula, it indicates that 100% of the oil droplets are smaller than this value. D[4,3] is the weighted volume-average droplet diameter. [Table F]

[0368] Each of the above formulations possessed both optimal osmotic pressure and oil droplet size distribution for imaging brain tumors.

[0369] Example 4 - Use of the composition in photodynamic therapy Selected compositions disclosed herein (e.g., compositions containing 70 g / l soybean oil, 4.2 g / l egg yolk phospholipid, and 23.7 g / l glycerol) are diluted with diluents to a range of final triglyceride concentrations ranging from 0.005 w / v% to 5 w / v%, e.g., 0.005 w / v%, 0.01 w / v%, 0.05 w / v%, 0.1 w / v%, 0.2 w / v%, 0.5 w / v%, 1 w / v%, 2 w / v%, and 5 w / v%. Essentially, all oil droplets in the low-triglyceride compositions have a diameter of less than 500 nm, with an average diameter of approximately 250 nm to approximately 350 nm (e.g., approximately 285 nm ± 20%). Before administering the low-triglyceride compositions, the patient ingests a photosensitizer that is preferentially absorbed by target cells. Next, a low-triglyceride composition is injected into and / or into a suitable container such as a balloon, which may be a cavity created by the removal of a tumor in the patient's body. Then, a laser light is activated at a specific wavelength to activate the photosensitizer, in which case the low-triglyceride composition acts to evenly diffuse the laser light around the cavity to achieve improved activation of the photosensitizer absorbed at the target site.

[0370] Example 5 - Use of the composition as a lubricant Selected compositions disclosed herein (e.g., compositions containing 70 g / l soybean oil, 4.2 g / l egg yolk phospholipid, and 23.7 g / l glycerol) can be used to provide an external and / or internal lubricating coating on medical devices placed in containers such as stents or valves, or between tissues, such as positioning a pressure transducer / monitor within the ventricles of the brain, allowing the device to move freely between tissues without any snagging or irritation. In some procedures, the composition is applied sterile to the medical device outside the body before entering the body. In some procedures, the composition is applied during the procedure at the target site using a syringe and catheter combination. Using the composition as a lubricant helps to position the device more safely and with more predictable hand and device movements.

[0371] Example 6 - Use of the composition as a contrast agent Selected compositions disclosed herein, containing small oil droplets (e.g., compositions containing 70 g / l soybean oil, 4.2 g / l egg yolk phospholipid, and 23.7 g / l glycerol), are used as contrast agents. Essentially, all oil droplets in the compositions have a diameter of less than 500 nm, with average diameters ranging from about 150 nm to about 250 nm, about 250 nm to about 350 nm (e.g., 285 nm ± 20%), about 350 nm to about 450 nm, or about 450 nm to about 500 nm. Each of the compositions is injected into a blood vessel or lumen under ultrasound guidance to increase the contrast between tissue and blood vessels, thereby improving the image quality and diagnostic accuracy of the imaging.

[0372] In another study, selected compositions disclosed herein (e.g., compositions containing 70 g / l soybean oil, 4.2 g / l egg yolk phospholipid, and 23.7 g / l glycerol) containing small oil droplets were used as contrast agents. Essentially, all oil droplets in the compositions have a diameter of less than 500 nm, with average diameters being approximately 150 nm to approximately 250 nm, approximately 250 nm to approximately 350 nm (e.g., 285 nm ± 20%), approximately 350 nm to approximately 450 nm, or approximately 450 nm to approximately 500 nm. Each of the compositions is injected into a blood vessel or lumen under the condition that Doppler ultrasound is used to improve blood flow measurements. The oil droplets of the compositions, when Doppler ultrasound is used, improve the measurement of blood echobrightness, as well as the structure and movement of the blood vessel / wall, resulting in a better assessment of blood flow.

[0373] Numbered Embodiments of the Present Disclosure Notwithstanding the attached claims, this disclosure illustrates the following numbered embodiments:

[0374] Embodiment 1. A composition comprising (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, and (e) a wetting agent.

[0375] Embodiment 2. A composition comprising (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) pH buffer, and (e) a wetting agent.

[0376] Embodiment 3. The composition according to Embodiment 1 or 2, comprising substances other than (a) to (e) in amounts of 5 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.5 w / v% or less, 0.2 w / v% or less, or 0.1 w / v% or less.

[0377] Embodiment 4. The composition is the composition according to Embodiment 1 or 2, comprising essentially all of (a) to (e).

[0378] Embodiment 5. The composition is the composition according to Embodiment 1 or 2, comprising all of (a) to (e).

[0379] Embodiment 6. A composition comprising (a) at least one triglyceride, (b) at least one phospholipid, (c) water, (d) pH buffer, (e) a wetting agent, and (f) a diagnostic agent, a therapeutic agent, or any combination thereof.

[0380] Embodiment 7. A composition comprising (a) at least one triglyceride, (b) lecithin containing at least one phospholipid, (c) water, (d) pH buffer, (e) a wetting agent, and (f) a diagnostic agent, a therapeutic agent, or any combination thereof.

[0381] Embodiment 8. The composition according to Embodiment 6 or 7, comprising substances other than (a) to (f) in amounts of 5 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.5 w / v% or less, 0.2 w / v% or less, or 0.1 w / v% or less.

[0382] Embodiment 9. The composition is the composition according to Embodiment 6 or 7, which essentially consists of all of (a) to (f).

[0383] Embodiment 10. The composition is the composition according to Embodiment 6 or 7, comprising all of (a) to (f).

[0384] Embodiment 11. The composition according to any one of Embodiments 1 to 10, wherein the concentration of at least one triglyceride is about 5 w / v% to about 9 w / v%.

[0385] Embodiment 12. The composition according to any one of Embodiments 1 to 10, wherein the concentration of at least one triglyceride is about 6 w / v% to about 8 w / v%.

[0386] Embodiment 13. The composition according to any one of Embodiments 1 to 10, wherein the concentration of at least one triglyceride is about 7 w / v%.

[0387] Embodiment 14. The composition according to any one of Embodiments 1 to 10, wherein the concentration of at least one triglyceride is about 0.05 w / v% to about 1% w / v%, or about 0.1 w / v% to about 0.5 w / v%.

[0388] Embodiment 15. The composition according to any one of Embodiments 1 to 10, wherein the concentration of at least one triglyceride is about 0.1 w / v%, about 0.2 w / v%, or about 0.5 w / v%.

[0389] Embodiment 16. At least one triglyceride is present in olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil, corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, linseed oil, walnut oil, avocado oil, rice bran oil, grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, poppy oil, black seed oil, and apricot oil. A composition according to any one of Embodiments 1 to 15, derived from one or more of the following: oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, perilla oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuru oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil.

[0390] Embodiment 17. The composition according to any one of Embodiments 1 to 15, wherein at least one triglyceride is derived from soybean oil.

[0391] Embodiment 18. The composition according to any one of Embodiments 1 to 17, wherein at least one triglyceride is selected from the group consisting of tristearin, triolein, tripalmitin, triacetin, trilinolein, tricaprin, trilaurin, trialakidine, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimiristin, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, trinonanoin, and any combination thereof.

[0392] Embodiment 19. The composition according to any one of Embodiments 1 to 18, wherein at least one triglyceride is selected from the group consisting of linolenic acid-oleic acid-linolenic acid, linoleic acid-linoleic acid-linoleic acid, oleic acid-linoleic acid-oleic acid, linoleic acid-oleic acid-linoleic acid, linoleic acid-linoleic acid-linoleic acid, palmitic acid-oleic acid-linoleic acid, palmitic acid-linoleic acid-palmitic acid, stearic acid-oleic acid-linoleic acid, linoleic acid-linolenic acid-linoleic acid, linoleic acid-oleic acid-oleic acid, and any combination thereof.

[0393] Embodiment 20. A composition according to any one of Embodiments 1 to 19, wherein at least one triglyceride comprises a medium-chain fatty acid triglyceride, is essentially composed of medium-chain fatty acid triglycerides, or is composed of medium-chain fatty acid triglycerides.

[0394] Embodiment 21. A composition of any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is approximately 1.2 w / v% at most.

[0395] Embodiment 22. The composition according to any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is about 0.1 w / v% to about 1.2 w / v%.

[0396] Embodiment 23. The composition according to any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is about 0.2 w / v% to about 1.2 w / v%.

[0397] Embodiment 24. The composition according to any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is approximately 0.4 w / v% to approximately 1.2 w / v%.

[0398] Embodiment 25. The composition according to any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is approximately 0.42 w / v% to approximately 0.84 w / v%.

[0399] Embodiment 26. The composition according to any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is approximately 3.2 g / L to approximately 5.2 g / L.

[0400] Embodiment 27. The composition according to any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is approximately 0.42 w / v% (approximately 4.2 g / L).

[0401] Embodiment 28. The composition according to any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is approximately 7.4 g / L to approximately 9.4 g / L.

[0402] Embodiment 29. The composition according to any one of Embodiments 1 to 20, wherein the concentration of at least one phospholipid is approximately 0.84 w / v% (approximately 8.4 g / L).

[0403] Embodiment 30. The composition is the composition according to any one of Embodiments 1 to 29, comprising lecithin containing at least one phospholipid.

[0404] Embodiment 31. The composition according to any one of embodiments 2 to 5 and 7 to 30, wherein the lecithin comprises at least one phospholipid in an amount of about 20% to about 90% by weight.

[0405] Embodiment 32. The composition according to any one of embodiments 2 to 5 and 7 to 31, wherein the lecithin comprises at least one phospholipid in an amount of about 60% to about 70% by weight.

[0406] Embodiment 33. The composition according to any one of embodiments 2 to 5 and 7 to 32, wherein the lecithin is derived from one or more of the following: soybeans, sunflower seeds, rapeseed, egg yolk, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseed, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, Brazil nuts, chia seeds, hemp seeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chicken liver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg whites.

[0407] Embodiment 34. The composition according to any one of embodiments 2 to 5 and 7 to 33, wherein the lecithin is egg yolk lecithin.

[0408] Embodiment 35. The composition is the composition according to any one of Embodiments 2 to 5 and 7 to 34, comprising a maximum of approximately 1.2 w / v% lecithin.

[0409] Embodiment 36. The composition is the composition according to any one of Embodiments 2 to 5 and 7 to 34, comprising about 0.1 w / v% to about 1.2 w / v% of lecithin.

[0410] Embodiment 37. The composition is the composition according to any one of Embodiments 2 to 5 and 7 to 34, comprising about 0.4 w / v% to about 1.2 w / v% of lecithin.

[0411] Embodiment 37.1. The composition is the composition according to any one of Embodiments 2 to 5 and 7 to 34, comprising lecithin in an amount of about 0.32 w / v to about 0.52 w / v.

[0412] Embodiment 37.2. The composition is the composition according to any one of embodiments 2 to 5 and 7 to 34, comprising lecithin in an amount of about 0.37 w / v to about 0.47 w / v.

[0413] Embodiment 37.3. The composition is the composition according to any one of Embodiments 2 to 5 and 7 to 34, comprising lecithin in an amount of about 0.64 w / v to about 1.04 w / v.

[0414] Embodiment 37.4. The composition is the composition according to any one of Embodiments 2 to 5 and 7 to 34, comprising lecithin in an amount of about 0.74 w / v to about 0.94 w / v.

[0415] Embodiment 38. The composition is the composition according to any one of Embodiments 2 to 5 and 7 to 34, comprising about 0.42 w / v% or about 0.84 w / v% of lecithin.

[0416] Embodiment 39. The composition according to any one of embodiments 2 to 5 and 7 to 38, wherein the lecithin comprises phosphatidylcholine.

[0417] Embodiment 40. The composition according to any one of embodiments 2 to 5 and 7 to 39, wherein the lecithin contains about 10% to about 75% by weight of phosphatidylcholine.

[0418] Embodiment 41. The composition according to any one of embodiments 2 to 5 and 7 to 40, wherein the lecithin contains about 20% to about 70% by weight of phosphatidylcholine.

[0419] Embodiment 42. The composition according to any one of embodiments 2 to 5 and 7 to 41, wherein the lecithin contains about 60% to about 75% by weight of phosphatidylcholine.

[0420] Embodiment 43. A composition comprising at least one phospholipid, phosphatidylcholine, any one of embodiments 1 to 42.

[0421] Embodiment 44. The composition according to any one of Embodiments 1 to 43, wherein at least one phospholipid comprises about 10% to about 70% by weight of phosphatidylcholine.

[0422] Embodiment 45. The composition according to any one of Embodiments 1 to 43, wherein at least one phospholipid comprises about 20% to about 70% by weight of phosphatidylcholine.

[0423] Embodiment 46. The composition according to any one of Embodiments 1 to 43, wherein at least one phospholipid comprises about 60% to about 75% by weight of phosphatidylcholine.

[0424] Embodiment 47. A composition according to any one of Embodiments 1 to 46, wherein the concentration of at least one triglyceride is about 60.0 g / L to about 80.0 g / L, and / or the concentration of at least one phospholipid is about 3.2 g / L to about 5.2 g / L.

[0425] Embodiment 48. A composition according to any one of Embodiments 1 to 46, wherein the concentration of at least one triglyceride is about 60.0 g / L to about 80.0 g / L, and / or the concentration of at least one phospholipid is about 7.4 g / L to about 9.4 g / L.

[0426] Embodiment 49. The composition according to any one of Embodiments 1 to 48, wherein the wetting agent is glycerol.

[0427] Embodiment 50. The composition according to any one of Embodiments 1 to 49, wherein the concentration of the wetting agent is approximately 10 g / L to approximately 35 g / L.

[0428] Embodiment 51. The composition according to any one of Embodiments 1 to 50, wherein the concentration of the wetting agent is approximately 14 g / L to approximately 26 g / L.

[0429] Embodiment 52. The composition according to any one of Embodiments 1 to 51, wherein the concentration of the wetting agent is approximately 16 g / L.

[0430] Embodiment 53. The composition according to any one of Embodiments 1 to 50, wherein the concentration of the wetting agent is approximately 21 g / L to approximately 26 g / L.

[0431] Embodiment 54. The composition according to any one of Embodiments 1 to 50, wherein the concentration of the wetting agent is approximately 23.7 g / L.

[0432] Embodiment 55. The composition according to any one of Embodiments 1 to 54, wherein the concentration of at least one phospholipid or lecithin and the concentration of glycerol are selected from one of the formulations in Table 3.

[0433] Embodiment 56. The composition according to any one of Embodiments 1 to 55, wherein the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 6.5:1 to about 30:1.

[0434] Embodiment 56.1. The composition according to any one of Embodiments 1 to 56, wherein the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 20:1 to about 30:1.

[0435] Embodiment 56.2. The composition according to any one of Embodiments 1 to 56.1, wherein the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 25:1.

[0436] Embodiment 57. The composition according to any one of Embodiments 1 to 56, wherein the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 13:1 to about 20:1.

[0437] Embodiment 58. The composition according to any one of Embodiments 1 to 57, wherein the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 16.7:1.

[0438] Embodiment 59. The composition according to any one of Embodiments 1 to 56, wherein the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 6.5:1 to about 10:1.

[0439] Embodiment 60. The composition according to any one of Embodiments 1 to 56, wherein the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 8.3:1.

[0440] Embodiment 61. A composition according to any one of Embodiments 1 to 60, wherein the concentration of at least one triglyceride is about 0.05 w / v% to about 1 w / v%, or about 0.1 w / v% to about 0.5 w / v%, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 6.5:1 to about 20:1, the pH of the composition is about 6.5 to about 8.5, and optionally the pH of the composition is about 7.

[0441] Embodiment 61.1. The composition according to Embodiment 61, wherein the composition has an osmotic pressure of less than 50 mOsm / kg, less than 40 mOsm / kg, less than 30 mOsm / kg, less than 20 mOsm / kg, less than 10 mOsm / kg, less than 5 mOsm / kg, less than 3 mOsm / kg, less than 2 mOsm / kg, or less than 1 mOsm / kg, but greater than 0 mOsm / kg.

[0442] Embodiment 61.2. The composition according to any one of Embodiments 1 to 60, wherein the concentration of at least one triglyceride is about 0.05 w / v% to about 1 w / v%, or about 0.1 w / v% to about 0.5 w / v%, the weight ratio of at least one triglyceride to at least one phospholipid or lecithin is about 6.5:1 to about 20:1, and the concentration of glycerol is about 25% to about 30%.

[0443] Embodiment 61.3. The composition according to Embodiment 61.2, having an osmotic pressure of approximately 270 mOsm / kg to approximately 330 mOsm / kg, approximately 290 mOsm / kg to approximately 311 mOsm / kg, or approximately 290 mOsm / kg to approximately 305 mOsm / kg.

[0444] Embodiment 61.4. The composition is the composition according to Embodiment 61.2 or 61.3, having an osmotic pressure of about 290 mOsm / kg, or about 284 mOsm / kg to about 296 mOsm / kg.

[0445] Embodiment 62. The composition is one of the compositions according to any one of Embodiments 1 to 61.4, comprising less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of sodium chloride.

[0446] Embodiment 63. The composition is the composition according to any one of Embodiments 1 to 62, which does not contain sodium chloride.

[0447] Embodiment 64. The composition is one of any one of Embodiments 1 to 63, comprising a salt in an amount of less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v%.

[0448] Embodiment 65. The composition is the composition according to any one of Embodiments 1 to 64, which does not contain any salts.

[0449] Embodiment 66. The composition is one of any one of Embodiments 1 to 65, comprising a polysorbate in an amount of less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v%.

[0450] Embodiment 67. The composition is one of the compositions from Embodiments 1 to 66, which does not contain polysorbate 80 (PS80).

[0451] Embodiment 68. The composition is the composition according to any one of Embodiments 1 to 67, which does not contain any polysorbate.

[0452] Embodiment 69. The composition is one of any one of Embodiments 1 to 68, comprising a stabilizer in an amount of less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v%.

[0453] Embodiment 70. The composition is the composition according to any one of Embodiments 1 to 69, which does not contain a stabilizer.

[0454] Embodiment 71. The composition according to any one of Embodiments 1 to 70, wherein the pH of the composition is 9 to 12 or 10 to 11.

[0455] Embodiment 72. The composition is the composition according to any one of embodiments 1 to 71, which has not been sterilized by gamma irradiation.

[0456] Embodiment 73. The composition according to any one of Embodiments 1 to 70, wherein the pH of the composition is approximately 6.5 to approximately 8.5.

[0457] Embodiment 74. The composition according to any one of Embodiments 1 to 70, wherein the pH of the composition is approximately 6.9 to approximately 7.6.

[0458] Embodiment 75. The composition according to any one of Embodiments 1 to 70, wherein the pH of the composition is approximately 6.9 to approximately 7.5.

[0459] Embodiment 76. The composition according to any one of Embodiments 1 to 70, wherein the pH of the composition is approximately 7.3.

[0460] Embodiment 77. The composition according to any one of Embodiments 1 to 70, wherein the pH of the composition is approximately 7.5.

[0461] Embodiment 78. The composition according to any one of Embodiments 1 to 70, wherein the pH of the composition is approximately 6.9.

[0462] Embodiment 79. The pH buffer is NaOH or a composition according to any one of Embodiments 1 to 78, wherein the pH buffer is NaOH or contains NaOH.

[0463] Embodiment 80. The composition according to any one of embodiments 1 to 70 and 73 to 79, wherein the pH of the composition is measured after sterilization by gamma irradiation and storage for at least 5 days.

[0464] Embodiment 81. The composition is sterilized by gamma irradiation, as described in any one of embodiments 1 to 70 and 73 to 80.

[0465] Embodiment 82. The composition is an ultrasonic coupling agent, as described in any one of Embodiments 1 to 81.

[0466] Embodiment 83. The composition is a contrast agent, as described in any one of Embodiments 1 to 82.

[0467] Embodiment 84. The composition is an aqueous composition, as described in any one of Embodiments 1 to 83.

[0468] Embodiment 85. The composition is a lubricant, as described in any one of Embodiments 1 to 84.

[0469] Embodiment 86. The composition is the composition according to any one of Embodiments 1 to 85, having an attenuation coefficient of about 0.002 dB / (MHz*cm) to about 1.0 dB / (MHz*cm).

[0470] Embodiment 87. The composition is the composition according to any one of Embodiments 1 to 86, having an attenuation coefficient of about 0.05 dB / (MHz*cm) to about 15 dB / (MHz*cm).

[0471] Embodiment 88. The composition is the composition according to any one of Embodiments 1 to 87, having an attenuation coefficient of approximately 3 dB / (MHz*cm) to approximately 15 dB / (MHz*cm).

[0472] Embodiment 89. The composition is the composition according to any one of Embodiments 1 to 88, having an attenuation coefficient of about 0.05 dB / (MHz*cm) to about 1.8 dB / (MHz*cm).

[0473] Embodiment 90. The composition is the composition according to any one of Embodiments 1 to 89, having an attenuation coefficient of about 0.5 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).

[0474] Embodiment 91. The composition is the composition according to any one of Embodiments 1 to 89, having an attenuation coefficient of about 0.1 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).

[0475] Embodiment 92. The composition is the composition according to any one of Embodiments 1 to 89, having an attenuation coefficient of about 0.1 dB / (MHz*cm) to about 0.5 dB / (MHz*cm).

[0476] Embodiment 93. The composition is the composition according to any one of Embodiments 1 to 92, having an attenuation coefficient of about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm).

[0477] Embodiment 94. The composition according to any one of Embodiments 1 to 93, wherein the composition has a decay coefficient substantially equivalent to that of a tissue or organ selected from bone, brain, lung, liver, kidney, heart, cerebrospinal fluid, soft tissue, bladder, and colon.

[0478] Embodiment 95. The composition according to Embodiment 94, wherein the tissue or organ is of human origin.

[0479] Embodiment 96. The composition is the composition according to any one of Embodiments 1 to 95, having an osmotic pressure of approximately 270 mOsm / kg to approximately 330 mOsm / kg.

[0480] Embodiment 96.1. The composition is the composition according to any one of Embodiments 1 to 95, having an osmotic pressure of approximately 290 mOsm / kg.

[0481] Embodiment 96.2. The composition is the composition according to any one of Embodiments 1 to 95, having an osmotic pressure of approximately 284 mOsm / kg to approximately 296 mOsm / kg.

[0482] Embodiment 97. The composition is the composition according to any one of Embodiments 1 to 95, having an osmotic pressure of approximately 290 mOsm / kg to approximately 311 mOsm / kg.

[0483] Embodiment 98. The composition is the composition according to any one of Embodiments 1 to 95, having an osmotic pressure of approximately 290 mOsm / kg to approximately 305 mOsm / kg.

[0484] Embodiment 99. The composition is the composition according to any one of Embodiments 1 to 98, having a weighted volume-average droplet diameter of about 0.2 μm to about 0.55 μm.

[0485] Embodiment 100. The composition is the composition according to any one of Embodiments 1 to 99, having a weighted volume-average droplet diameter of about 0.26 μm to about 0.50 μm.

[0486] Embodiment 101. The composition is the composition according to any one of Embodiments 1 to 100, having a weighted volume-average droplet diameter of approximately 228 nm to approximately 342 nm.

[0487] Embodiment 102. The composition is the composition according to any one of Embodiments 1 to 101, having a weighted volume-average droplet diameter of approximately 258 nm.

[0488] Embodiment 103. The composition is one of any one of Embodiments 1 to 102, wherein the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 0.84 μm.

[0489] Embodiment 104. The composition is one of any one of Embodiments 1 to 102, wherein the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 0.96 μm.

[0490] Embodiment 105. The composition is one of any one of Embodiments 1 to 102, wherein the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 1.91 μm.

[0491] Embodiment 106. The composition according to any one of Embodiments 1 to 105, wherein the composition forms oil droplets, and substantially none of the oil droplets have a diameter greater than 5000 nm.

[0492] Embodiment 107. The composition is one of any one of Embodiments 1 to 106, wherein the composition forms oil droplets, and the oil droplets have an average diameter of 200 nm to about 750 nm.

[0493] Embodiment 108. The composition is one of any one of Embodiments 1 to 107, wherein the composition forms oil droplets, and the oil droplets have an average diameter of 250 nm to about 500 nm.

[0494] Embodiment 109. The composition is the composition according to any one of Embodiments 1 to 108, having an average droplet diameter of approximately 285 nm ± 20%.

[0495] Embodiment 110. The composition according to any one of embodiments 99 to 109, wherein the average droplet diameter is measured by dynamic light scattering.

[0496] Embodiment 111. The diagnostic agent is a contrast agent, according to any one of embodiments 6 to 110.

[0497] Embodiment 112. The composition according to Embodiment 111, wherein the contrast agent is a near-infrared (IR) fluorophore.

[0498] Embodiment 113. The composition according to Embodiment 112, wherein the near-IR fluorophore is indocyanine green.

[0499] Embodiment 114. The therapeutic agent is a composition according to any one of embodiments 6 to 113, comprising an antibiotic.

[0500] Embodiment 115. The composition according to any one of the embodiments 1 to 114, wherein the shelf life of the composition is at least about 10 hours, at least about 16 hours, at least about 24 hours, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 7 days, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 2 months, at least about 3 months, at least about 4 months, at least about 6 months, at least about 9 months, at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, or at least about 6 years.

[0501] Embodiment 116. The composition according to any one of the embodiments 1 to 114, wherein the shelf life of the composition is approximately 6 months to approximately 5 years, approximately 1 year to approximately 5 years, approximately 2 years to approximately 5 years, approximately 3 years to approximately 5 years, approximately 6 months to approximately 4 years, approximately 6 months to approximately 3 years, approximately 6 months to approximately 2 years, approximately 6 months to approximately 1 year, approximately 1 year to approximately 4 years, approximately 1 year to approximately 3 years, approximately 1 year to approximately 2 years, or approximately 2 years to approximately 4 years at room temperature.

[0502] Embodiment 117. A method for preparing the composition according to any one of Embodiments 1 to 116, comprising mixing components (a) to (e) or (a) to (f).

[0503] Embodiment 118. An imaging method comprising administering a composition described in any one of Embodiments 1 to 116 to a subject requiring administration, and performing imaging.

[0504] Embodiment 119. The method according to Embodiment 118, wherein the composition is administered to a wound, organ, tumor, blood vessel, area of ​​blood circulation, or cavity within the body of the target.

[0505] Embodiment 120. A method for obtaining an image of a wound, organ, tumor, blood vessel, or cavity, comprising: i) contacting the wound, organ, tumor, blood vessel, or cavity with a composition described in any one of Embodiments 1 to 116; and ii) obtaining an image using an instrument.

[0506] Embodiment 121. The imaging is performed using invasive ultrasound imaging, according to any one of embodiments 118 to 120.

[0507] Embodiment 122. The composition according to any one of embodiments 118 to 120, wherein imaging is Doppler blood flow imaging.

[0508] Embodiment 123. The imaging is laser speckle imaging, according to any one of embodiments 118 to 120 of the composition.

[0509] Embodiment 124. The composition according to any one of embodiments 118 to 120, wherein imaging is optical coherence tomography, photoacoustic imaging (PAI), computed tomography (CT), magnetic resonance imaging (MRI), or echocardiography.

[0510] Embodiment 125. The composition according to any one of embodiments 118 to 120, wherein imaging is performed by fluorescence imaging, radioimaging, positron emission tomography (PET), or magnetic particle imaging (MPI).

[0511] Embodiment 126. A method for performing surgery on a subject requiring surgery, comprising administering a composition according to any one of Embodiments 1 to 116 to a wound, organ, tumor, blood vessel, area of ​​blood circulation, or cavity of the subject, acquiring an image, and performing surgery based on the image.

[0512] Embodiment 127. A method for excising a tumor, comprising: administering a composition according to any one of embodiments 1 to 116 to tissue proximal to the tumor; obtaining ultrasound images of the tumor and proximal tissue; identifying the tumor; and excising the tumor.

[0513] Embodiment 128. The method according to Embodiment 127, wherein the tumor is located in or proximal to the bladder, uterus, cervix, colon, or spine.

[0514] Embodiment 129. The composition is contained within a balloon catheter, according to any one of embodiments 118 to 128.

[0515] Embodiment 130. A method for performing surgery on a subject requiring surgery, comprising bringing an instrument used in the surgery into contact with a composition described in any one of Embodiments 1 to 116, and inserting the instrument into a wound, organ, tumor, blood vessel, or cavity within the subject's body.

[0516] Embodiment 131. A method for performing surgery on a subject requiring surgery, comprising administering a composition described in any one of Embodiments 1 to 116 into a wound, organ, tumor, blood vessel, or cavity within the subject's body, and inserting surgical instruments into the wound, organ, tumor, blood vessel, or cavity.

[0517] Embodiment 132. The method according to embodiment 130 or 131, wherein the surgery is a brain surgery or neurosurgery.

[0518] Embodiment 133. A method for placing an instrument inside the body of an object requiring instrument placement, comprising sequentially or simultaneously bringing a portion on the object into contact with a composition described in any one of embodiments 1 to 116, and inserting the instrument into the object.

[0519] Embodiment 134. The method according to any one of embodiments 130 to 133, wherein the device is for preventing or treating a disease.

[0520] Embodiment 135. The method according to any one of embodiments 130 to 134, wherein the instrument is a catheter.

[0521] Embodiment 136. The method according to Embodiment 135, wherein the catheter is a subdural pressure catheter, a drainage catheter, a cerebral blood flow catheter, a microdialysis catheter, or a cerebral tissue oxygen catheter.

[0522] Embodiment 137. The method according to any one of embodiments 130 to 134, wherein the device is an intracranial pressure sensor.

[0523] Embodiment 138. The device is an implantable brain-computer interface (BCI) according to any one of embodiments 130 to 134.

[0524] Embodiment 139. The composition according to any one of embodiments 130 to 138, which acts as a lubricant for an instrument.

[0525] Embodiment 140. A method for delivering a diagnostic or therapeutic agent to a subject requiring delivery, comprising: i) a composition according to any one of Embodiments 1 to 116, wherein the composition comprises a diagnostic or therapeutic agent; or ii) a composition according to any one of Embodiments 1 to 116; and administering the agent.

[0526] Embodiment 141. The method is for treating a disease, and the drug is a therapeutic agent, according to Embodiment 140.

[0527] Embodiment 142. The composition and drug are administered sequentially according to Embodiment 140 or 141.

[0528] Embodiment 143. The therapeutic agent is the method according to any one of embodiments 140 to 142, comprising a photosensitizer.

[0529] Embodiment 144. The method according to Embodiment 143, comprising exposing a photosensitive agent to light.

[0530] Embodiment 145. A method for treating a disease in a subject requiring treatment using focused ultrasound therapy, comprising administering a composition described in any one of Embodiments 1 to 116 to the subject and performing focused ultrasound therapy.

[0531] Embodiment 146. A method for treating a disease in a subject requiring treatment, comprising administering a composition according to any one of Embodiments 1 to 116 to the subject.

[0532] Embodiment 147. The composition comprises a therapeutic agent, according to any one of embodiments 145 to 146.

[0533] Embodiment 148. The method is according to any one of embodiments 145 to 147, comprising administering a composition and then treating the subject using photodynamic therapy.

[0534] Embodiment 149. The method is according to any one of Embodiments 145 to 148, comprising diluting the composition with water and glycerol to obtain a low triglyceride composition containing about 0.005 w / v% to about 0.5 w / v% triglycerides.

[0535] Embodiment 149.1. The low triglyceride composition is less than 50 mOsm / kg, less than 40 mOsm / kg, less than 30 mOsm / kg, less than 20 mOsm / kg, less than 10 mOsm / kg, less than 5 mOsm / kg, less than 3 mOsm / kg, less than 2 mOsm / kg, or less than 1 mOsm / kg, but has an osmotic pressure greater than 0 mOsm / kg, according to Embodiment 149.

[0536] Embodiment 150. The low triglyceride composition according to Embodiment 149, having an osmotic pressure of approximately 270 mOsm / kg to approximately 330 mOsm / kg, approximately 290 mOsm / kg to approximately 311 mOsm / kg, or approximately 290 mOsm / kg to approximately 305 mOsm / kg.

[0537] Embodiment 150.1. The low triglyceride composition according to Embodiment 149, having an osmotic pressure of about 290 mOsm / kg, or about 284 mOsm / kg to about 296 mOsm / kg.

[0538] Embodiment 151. The composition is a light dispersant, according to any one of Embodiments 146 to 150.1.

[0539] Embodiment 152. The therapeutic agent is the method according to any one of embodiments 146 to 151, comprising a photosensitizer.

[0540] Embodiment 153. A method for treating a disease, comprising: i) contacting a wound, organ, tumor, blood vessel, area of ​​blood circulation, or cavity containing diseased tissue with a composition according to any one of Embodiments 1 to 116; ii) obtaining an image of the wound, organ, tumor, blood vessel, area of ​​blood circulation, or cavity; and iii) treating the disease or removing diseased tissue based on the image.

[0541] Embodiment 154. The image is an ultrasound image, according to the method of embodiment 153.

[0542] Embodiment 155. The composition comprises a contrast agent that enables the acquisition of an image, according to any one of embodiments 153 to 154.

[0543] Embodiment 156. The method according to Embodiment 155, wherein the contrast agent is a near-infrared (IR) fluorophore.

[0544] Embodiment 157. The method according to Embodiment 156, wherein the near-IR fluorophore is indocyanine green.

[0545] Embodiment 158. The composition comprises a fluorophore, according to any one of embodiments 153 to 157.

[0546] Embodiment 159. The method according to any one of embodiments 153 to 158, wherein the image is for identifying target tissue or diseased tissue within the body of the subject.

[0547] Embodiment 160. The diseased tissue is residual tumor, as described in Embodiment 159.

[0548] Embodiment 161. The method is the method according to any one of embodiments 140 to 160, further comprising removing and / or treating abnormal or diseased tissue.

[0549] Embodiment 162. The method according to Embodiment 161, comprising removing abnormal or diseased tissue via surgery.

[0550] Embodiment 163. The method according to Embodiment 161 or 162, comprising treating abnormal or affected tissue via chemotherapy, targeted therapy, photodynamic therapy, or radiotherapy.

[0551] Embodiment 164. The method according to any one of embodiments 141 to 163, wherein the disease is cancer and / or the affected tissue includes tumor tissue.

[0552] Embodiment 165. The method according to any one of embodiments 119 to 132 and 153 to 164, wherein the tumor is a brain tumor.

[0553] Embodiment 166. The method according to any one of embodiments 119 to 132 and 153 to 164, wherein the tumor is a glioma, glioblastoma, or neuroblastoma.

[0554] Embodiment 167. The method according to any one of embodiments 118 to 166, comprising administering one or more methods of cancer treatment.

[0555] Embodiment 168. The method according to Embodiment 167, wherein one or more methods are selected from the group consisting of chemotherapy, immunotherapy, alternating electric tumor treating field, laser interstitial hyperthermia (LITT), magnetic hyperthermia (MHT), focused ultrasound, radiofrequency microwave, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence-guided resection, surgical resection, and magnetic resonance imaging.

[0556] Embodiment 169. The method according to embodiment 167 or 168, wherein treating the disease involves exposing cancer cells to light.

[0557] Embodiment 170. The method is according to any one of embodiments 118 to 169, comprising performing an invasive procedure before administration of the composition to allow access to the composition and / or instrument in a wound, organ, blood vessel, or cavity.

[0558] Embodiment 171. The method according to any one of embodiments 119 to 126, 128 to 132, 134 to 139 and 153 to 170, wherein the cavity is selected from any one of the oral cavity, nasal cavity, orbit, thoracic cavity, pericardial cavity, pleural cavity, abdominal cavity, pelvic cavity, cranial cavity, spinal cavity, joint cavity, synovial cavity, buccal oral cavity, cranial fossa, mandibular fossa, maxillary sinus, frontal sinus, ethmoid sinus, sphenoid sinus, mastoid air cells, ear canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, venous sinus, fallopian tube infundibulum, alveolar sac, bronchioles, laryngeal cavity, tracheal cavity, gastric pit, enteric crypt, gallbladder pit, renal sinus, ureteral orifice, bladder trigone, follicle, testicular lobule, vaginal fornix, anal canal, vertebral foramen, intervertebral foramen, foramen magnum, and jugular foramen.

[0559] Embodiment 172. The method according to any one of embodiments 119 to 126, 128 to 132, 134 to 139 and 153 to 170, wherein the organ is selected from any one of the following: brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, mammary gland, esophagus, diaphragm, adrenal gland, thyroid gland, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries, testes, uterus, prostate gland, penis, vagina, cervix, urethra, rectum, anus, skeletal muscle, smooth muscle, cardiac muscle, bone marrow, bone, blood vessels, lymph nodes, lymphatic vessels, tonsils, appendix, adipose tissue, nerves, and connective tissue.

[0560] Embodiment 173. The method according to any one of embodiments 119 to 126, 128 to 132, 134 to 139 and 153 to 170, wherein the organ is the brain, kidney, liver, pancreas, ovary, breast, bladder, uterus, cervix, or colon.

[0561] Embodiment 174. The organ is the brain, according to the method of embodiment 173.

[0562] Embodiment 175. The method according to any one of embodiments 119 to 126, 128 to 132, 134 to 139 and 153 to 174, wherein the organ or cavity is a tumor.

[0563] Embodiment 176. The method according to Embodiment 175, comprising excising a tumor.

[0564] Embodiment 177. The method is according to any one of embodiments 118 to 176, which reduces artifacts in ultrasound imaging compared to a control method without the application of the composition.

[0565] Embodiment 178. The method according to Embodiment 178, wherein the artifact is a luminance enhancement artifact or includes one.

[0566] Embodiment 179. A control method is the method according to embodiment 177 or 178, in which physiological saline is used as the ultrasonic coupling agent instead of the composition.

[0567] Embodiment 180. The composition is contained within a balloon catheter, according to any one of embodiments 130 to 179.

[0568] Embodiment 181. The method according to embodiment 180, wherein the lumen is created by a balloon catheter.

[0569] Embodiment 182. The method according to any one of embodiments 118 to 181, wherein the subject is a human.

[0570] Embodiment 183. A container comprising the composition described in any one of Embodiments 1 to 116.

[0571] Embodiment 184. The container is a syringe, as described in Embodiment 183.

[0572] Embodiment 185. The container is made of glass, as described in Embodiment 183 or 184.

[0573] Embodiment 185.1. The container is made of stainless steel, as described in embodiment 183 or 184.

[0574] Embodiment 186. The container is a bag, as described in embodiment 183 or 184.

[0575] Embodiment 187. The container is one of any one of embodiments 183 to 186, and does not contain one or more of the following: dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl) phthalate (DEHP).

[0576] Embodiment 188. A kit comprising a composition according to any one of Embodiments 1 to 116 and a container.

[0577] Embodiment 189. The container is a syringe, as described in Embodiment 188 of the kit.

[0578] Embodiment 190. The container is made of glass, as described in Embodiment 188 or 189 of the kit.

[0579] Embodiment 190.1. The container is made of stainless steel, as described in Embodiment 188 or 189 of the kit.

[0580] Embodiment 191. The container is a bag, as described in Embodiment 188 of the kit.

[0581] Embodiment 192. The container is a kit according to any one of Embodiments 188 to 191, which does not contain one or more of the following: dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl) phthalate (DEHP).

[0582] Embodiment 193. A kit according to any one of embodiments 188 to 192, further including a bag spike.

[0583] Embodiment 194. A kit according to any one of embodiments 188 to 193, further including a filter.

[0584] Embodiment 195. The filter is the kit described in Embodiment 194, having a pore size of approximately 1.2 μm.

[0585] Further numbered embodiments Notwithstanding the attached claims, this disclosure illustrates the following further numbered embodiments: 1. a) At least one triglyceride in an amount of approximately 60.0 to 80.0 g / L, b) At least one phospholipid in a concentration of approximately 3.2 to 5.2 g / L, c) water; d) pH buffer, and e) A composition comprising glycerol, The composition has an attenuation constant of approximately 0.15 dB / (MHz*cm) to approximately 0.60 dB / (MHz*cm) or approximately 0.002 to approximately 1.0 dB / (MHz*cm). 2. a) at least one triglyceride, b) At least one phospholipid, c) Water, and d) pH buffer, and e) A composition comprising glycerol, The composition has an attenuation constant of approximately 0.15 dB / (MHz*cm) to approximately 0.60 dB / (MHz*cm) or approximately 0.002 to approximately 1.0 dB / (MHz*cm). A composition in which the weight ratio of at least one triglyceride to at least one phospholipid is approximately 13:1 to approximately 20:1. 3. a) At least one triglyceride present at approximately 7 w / v%, b) At least one phospholipid present at approximately 0.4 w / v%, c) Water, present at approximately 92 w / v%, d) pH buffer, and e) A composition consisting of glycerol. 4. a) At least one triglyceride in a concentration of approximately 60.0 g / L to approximately 80.0 g / L, b) A composition comprising at least one phospholipid in an amount of approximately 3.2 g / L to 5.2 g / L, The composition does not contain stabilizers and does not contain sodium chloride. The composition has an attenuation constant of approximately 0.15 dB / (MHz*cm) to approximately 0.60 dB / (MHz*cm) or approximately 0.002 to approximately 1.0 dB / (MHz*cm). 5. a) at least one triglyceride, and b) A composition comprising at least one phospholipid, The composition does not contain stabilizers and does not contain sodium chloride. The composition has an attenuation constant of approximately 0.15 dB / (MHz*cm) to approximately 0.60 dB / (MHz*cm) or approximately 0.002 to approximately 1.0 dB / (MHz*cm). A composition in which the weight ratio of at least one triglyceride to at least one phospholipid is approximately 13:1 to approximately 20:1. 6. a) At least one triglyceride present at approximately 7 w / v%, and b) A composition containing at least one phospholipid present at approximately 0.4 w / v%, The composition does not contain stabilizers and does not contain sodium chloride. The composition has an attenuation constant of approximately 0.15 dB / (MHz*cm) to approximately 0.60 dB / (MHz*cm) or approximately 0.002 to approximately 1.0 dB / (MHz*cm). 7. The compositions according to Embodiments 1, 2, 4, and 5, comprising at least one triglyceride in an amount of approximately 70 g / L. 8. The composition according to any one of Embodiments 1 to 7, wherein at least one triglyceride is derived from one or more of soybean oil, olive oil, or fish oil. 9. The composition according to any one of Embodiments 1 to 8, wherein at least one triglyceride is derived from soybean oil. 10. A composition according to any one of Embodiments 4 to 9, comprising at least one wetting agent. 11. The composition according to Embodiment 10, wherein at least one wetting agent is glycerol. 12. The composition is the composition according to any one of Embodiments 4 to 11, which does not contain PS80. 13. The composition according to any one of Embodiments 1 to 12, wherein the pH is approximately 6.5 to approximately 8.5. 14. A composition according to any one of Embodiments 1 to 12, wherein the pH is approximately 7.3. 15. A composition according to any one of Embodiments 1 to 14, wherein the osmotic pressure is 270 to 330 mOsm / L. 16. The composition according to any one of Embodiments 1 to 15, wherein the composition has an average droplet diameter of about 285 nm ± 20%, and the average droplet diameter is measured by dynamic light scattering. 17. The composition according to any one of Embodiments 1 to 15, wherein the effective period of the composition is at least about 10 hours. 18. The composition according to any one of Embodiments 1 to 17, wherein the weight ratio of at least one triglyceride to at least one phospholipid is about 16.7:1. 19. A method for obtaining an ultrasound image of an organ, i) Bringing the composition described in any one of Embodiments 1 to 18 into contact with an organ, ii) including obtaining ultrasound images of organs, The composition does not contain stabilizers and does not contain sodium chloride. A method comprising a composition having an attenuation constant of approximately 0.15 dB / (MHz*cm) to approximately 0.60 dB / (MHz*cm) or approximately 0.002 to approximately 1.0 dB / (MHz*cm). 20. The method according to embodiment 19, wherein the organ is the brain. Additional Embodiments 1. Essentially, (a) At least one triglyceride in a concentration of approximately 60.0 g / L to approximately 80.0 g / L (b) At least one phospholipid in a concentration of approximately 3.2 g / L to approximately 5.2 g / L (c) water; (d) pH buffer, and (e) A composition comprising glycerol. 2. Essentially, (a) at least one triglyceride, (b) at least one phospholipid, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, A composition in which the weight ratio of at least one triglyceride to at least one phospholipid is approximately 13:1 to approximately 20:1. 3. Essentially, (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) At least one phospholipid in an amount of approximately 0.2 w / v% to approximately 1.2 w / v%, (c) water; (d) pH buffer, and (e) A composition comprising glycerol. 4. Essentially, (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) At least one phospholipid present at approximately 0.42 w / v%, (c) water; (d) pH buffer, and (e) A composition comprising glycerol. 5. Essentially, (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) at least one phospholipid, (c) water; (d) pH buffer, and (e) A composition comprising glycerol. 6. Essentially, (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) At least one phospholipid in an amount of approximately 0.2 w / v% to approximately 1.2 w / v%, (c) water; (d) pH buffer, and (e) A composition consisting of approximately 21 g / L to approximately 26 g / L of glycerol. 7. Essentially, (a) Approximately 7 w / v% triglycerides, (b) Approximately 4.2 g / L of phospholipids, (c) Approximately 23.7 g / L of glycerol, (d) water, and (e) A composition comprising a pH buffer. 8. Essentially, (a) At least one triglyceride in an amount of approximately 60.0 to 80.0 g / L, (b) Lecithin of approximately 3.2 to 5.2 g / L (c) water; (d) pH buffer, and (e) A composition comprising glycerol. 9. Essentially, (a) at least one triglyceride, (b) Lecithin, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, A composition in which the weight ratio of at least one triglyceride to at least one phospholipid is approximately 13:1 to approximately 20:1. 10. Essentially, (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) Lecithin at approximately 0.2 w / v% to 1.2 w / v%, (c) water; (d) pH buffer, and (e) A composition comprising glycerol. 11. Essentially, (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) Approximately 0.42 w / v% lecithin, (c) water; (d) pH buffer, and (e) A composition comprising glycerol. 12. Essentially, (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) Lecithin, (c) water; (d) pH buffer, and (e) A composition comprising glycerol. 13. Essentially, (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) Lecithin at approximately 0.2 w / v% to 1.2 w / v%, (c) water; (d) pH buffer, and (e) A composition consisting of approximately 21 g / L to approximately 26 g / L of glycerol. 14. Essentially, (a) 7 w / v% triglycerides, (b) Approximately 4.2 g / L of lecithin, (c) Approximately 23.7 g / L of glycerol, (d) water, and (e) A composition comprising a pH buffer. 15. (a) At least one triglyceride in an amount of approximately 60.0 to 80.0 g / L, (b) At least one phospholipid in an amount of approximately 3.2 to 5.2 g / L, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The composition is free of stabilizers and sodium chloride. 16. (a) at least one triglyceride, (b) at least one phospholipid, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The weight ratio of at least one triglyceride to at least one phospholipid is approximately 13:1 to approximately 20:1. The composition is free of stabilizers and sodium chloride. 17. (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) At least one phospholipid in an amount of approximately 0.2 w / v% to approximately 1.2 w / v%, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The composition is free of stabilizers and sodium chloride. 18. (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) At least one phospholipid present at approximately 0.42 w / v%, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The composition is free of stabilizers and sodium chloride. 19. (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) at least one phospholipid, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The composition is free of stabilizers and sodium chloride. 20. (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) At least one phospholipid in an amount of approximately 0.2 w / v% to approximately 1.2 w / v%, (c) water; (d) pH buffer, and (e) A composition containing approximately 21 g / L to approximately 26 g / L of glycerol, The composition is free of stabilizers and sodium chloride. twenty one. (a) Approximately 7 w / v% triglycerides, (b) Approximately 4.2 g / L of phospholipids, (c) Approximately 23.7 g / L of glycerol, (d) water, and (e) A composition comprising a pH buffer, The composition is free of stabilizers and sodium chloride. twenty two. (a) At least one triglyceride in an amount of approximately 60.0 to 80.0 g / L, (b) Lecithin of approximately 3.2 to 5.2 g / L (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The composition is free of stabilizers and sodium chloride. twenty three. (a) at least one triglyceride, (b) Lecithin, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The weight ratio of at least one triglyceride to at least one phospholipid is approximately 13:1 to approximately 20:1. The composition is free of stabilizers and sodium chloride. twenty four. (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) Lecithin at approximately 0.2 w / v% to 1.2 w / v%, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The composition is free of stabilizers and sodium chloride. twenty five. (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) Approximately 0.42 w / v% lecithin, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The composition is free of stabilizers and sodium chloride. 26. (a) at least one triglyceride in a concentration of 5 w / v% to 9 w / v%, (b) Lecithin, (c) water; (d) pH buffer, and (e) A composition comprising glycerol, The composition is free of stabilizers and sodium chloride. 27. (a) Triglycerides of 5 w / v% to 9 w / v%, (b) At least one lecithin in an amount of approximately 0.2 w / v% to approximately 1.2 w / v%, (c) water; (d) pH buffer, and (e) A composition containing approximately 21 g / L to approximately 26 g / L of glycerol, The composition is free of stabilizers and sodium chloride. 28. (a) Approximately 7 w / v% triglycerides, (b) Approximately 4.2 g / L of lecithin, (c) Approximately 23.7 g / L of glycerol, (d) water, and (e) A composition comprising a pH buffer, The composition is free of stabilizers and sodium chloride. 29. (a) Approximately 7 w / v% triglycerides, (b) At least one phospholipid in approximately 4.2 g / L (c) Approximately 23.7 g / L of glycerol, (d) water, and (e) A composition containing a pH buffer. 30. (a) Approximately 7 w / v% triglycerides, (b) Approximately 4.2 g / L of lecithin, (c) Approximately 23.7 g / L of glycerol, (d) water, and (e) A composition containing a pH buffer. 31. The composition according to any one of Embodiments 15 to 28, wherein the stabilizer is polysorbate 80 (PS80). 32. The composition according to any one of Embodiments 1 to 31, having an attenuation coefficient of ...

Claims

1. (a) at least one triglyceride, (b) at least one phospholipid, (c) water; (d) pH buffer, and (e) A composition comprising a wetting agent.

2. (a) at least one triglyceride, (b) Lecithin containing at least one phospholipid, (c) water; (d) pH buffer, and (e) A composition comprising a wetting agent.

3. The composition according to claim 1 or 2, wherein the composition contains substances other than (a) to (e) in amounts of 5 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.5 w / v% or less, 0.2 w / v% or less, or 0.1 w / v% or less.

4. The composition according to claim 1 or 2, wherein the composition essentially comprises all of (a) to (e).

5. The composition according to claim 1 or 2, comprising all of (a) to (e).

6. (a) at least one triglyceride, (b) at least one phospholipid, (c) water; (d) pH buffer; (e) Wetting agents, and (f) A composition comprising a diagnostic agent, a therapeutic agent, or any combination thereof.

7. (a) at least one triglyceride, (b) Lecithin containing at least one phospholipid, (c) water; (d) pH buffer; (e) Wetting agents, and (f) A composition comprising a diagnostic agent, a therapeutic agent, or any combination thereof.

8. The composition according to claim 6 or 7, wherein the composition contains substances other than (a) to (f) in amounts of 5 w / v% or less, 2 w / v% or less, 1 w / v% or less, 0.5 w / v% or less, 0.2 w / v% or less, or 0.1 w / v% or less.

9. The composition according to claim 6 or 7, wherein the composition essentially comprises all of (a) to (f).

10. The composition according to claim 6 or 7, comprising all of (a) to (f).

11. The composition according to any one of claims 1 to 10, wherein the concentration of the at least one triglyceride is about 5 w / v% to about 9 w / v%.

12. The composition according to any one of claims 1 to 10, wherein the concentration of the at least one triglyceride is about 6 w / v% to about 8 w / v%.

13. The composition according to any one of claims 1 to 10, wherein the concentration of the at least one triglyceride is about 7 w / v%.

14. The composition according to any one of claims 1 to 10, wherein the concentration of the at least one triglyceride is about 0.05 w / v% to about 1% w / v%, or about 0.1 w / v% to about 0.5 w / v%.

15. The composition according to any one of claims 1 to 10, wherein the concentration of the at least one triglyceride is about 0.1 w / v%, about 0.2 w / v%, or about 0.5 w / v%.

16. The above at least one triglyceride is olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil, corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, linseed oil, walnut oil, avocado oil, rice bran oil, grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, poppy oil, black seed oil, and A composition according to any one of claims 1 to 15, derived from one or more of the following: lentil oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, perilla oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuru oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil.

17. The composition according to any one of claims 1 to 15, wherein the at least one triglyceride is derived from soybean oil.

18. The composition according to any one of claims 1 to 17, wherein the at least one triglyceride is selected from the group consisting of tristearin, triolein, tripalmitin, triacetin, trilinolein, tricaprin, trilaurin, trialakidine, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimiristin, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, trinonanoin, and any combination thereof.

19. The composition according to any one of claims 1 to 18, wherein the at least one triglyceride is selected from the group consisting of linolenic acid-oleic acid-linolenic acid, linoleic acid-linoleic acid-linoleic acid, oleic acid-linoleic acid-oleic acid, linoleic acid-oleic acid-linoleic acid, linoleic acid-linoleic acid-linoleic acid, palmitic acid-oleic acid-linoleic acid, palmitic acid-linoleic acid-palmitic acid, stearic acid-oleic acid-linoleic acid, linoleic acid-linolenic acid-linoleic acid, linoleic acid-oleic acid-oleic acid, and any combination thereof.

20. The composition according to any one of claims 1 to 19, wherein the at least one triglyceride comprises a medium-chain fatty acid triglyceride, essentially consisting of a medium-chain fatty acid triglyceride, or consisting of a medium-chain fatty acid triglyceride.

21. The composition according to any one of claims 1 to 20, wherein the concentration of at least one phospholipid is at most about 1.2 w / v%.

22. The composition according to any one of claims 1 to 20, wherein the concentration of the at least one phospholipid is about 0.1 w / v% to about 1.2 w / v%.

23. The composition according to any one of claims 1 to 20, wherein the concentration of at least one phospholipid is about 0.2 w / v% to about 1.2 w / v%.

24. The composition according to any one of claims 1 to 20, wherein the concentration of the at least one phospholipid is about 0.4 w / v% to about 1.2 w / v%.

25. The composition according to any one of claims 1 to 20, wherein the concentration of the at least one phospholipid is about 0.42 w / v% to about 0.84 w / v%.

26. The composition according to any one of claims 1 to 20, wherein the concentration of at least one phospholipid is about 3.2 g / L to about 5.2 g / L.

27. The composition according to any one of claims 1 to 20, wherein the concentration of at least one phospholipid is about 0.42 w / v% (about 4.2 g / L).

28. The composition according to any one of claims 1 to 20, wherein the concentration of at least one phospholipid is about 7.4 g / L to about 9.4 g / L.

29. The composition according to any one of claims 1 to 20, wherein the concentration of at least one phospholipid is about 0.84 w / v% (about 8.4 g / L).

30. The composition according to any one of claims 1 to 29, wherein the composition comprises lecithin containing at least one phospholipid.

31. The composition according to any one of claims 2 to 5 and 7 to 30, wherein the lecithin comprises about 20% to about 90% by weight of at least one phospholipid.

32. The composition according to any one of claims 2 to 5 and 7 to 31, wherein the lecithin comprises about 60% to about 70% by weight of at least one phospholipid.

33. The composition according to any one of claims 2 to 5 and 7 to 32, wherein the lecithin is derived from one or more of soybeans, sunflower seeds, rapeseed, egg yolk, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseed, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, Brazil nuts, chia seeds, hemp seeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chicken liver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg whites.

34. The composition according to any one of claims 2 to 5 and 7 to 33, wherein the lecithin is egg yolk lecithin.

35. The composition according to any one of claims 2 to 5 and 7 to 34, comprising a maximum of about 1.2 w / v% of the lecithin.

36. The composition according to any one of claims 2 to 5 and 7 to 34, comprising about 0.1 w / v% to about 1.2 w / v% of the lecithin.

37. The composition according to any one of claims 2 to 5 and 7 to 34, comprising about 0.4 w / v% to about 1.2 w / v% of the lecithin.

38. The composition according to any one of claims 2 to 5 and 7 to 34, comprising about 0.42 w / v% or about 0.84 w / v% of the lecithin.

39. The composition according to any one of claims 2 to 5 and 7 to 38, wherein the lecithin comprises phosphatidylcholine.

40. The composition according to any one of claims 2 to 5 and 7 to 39, wherein the lecithin comprises about 10% to about 75% by weight of phosphatidylcholine.

41. The composition according to any one of claims 2 to 5 and 7 to 40, wherein the lecithin comprises about 20% to about 70% by weight of phosphatidylcholine.

42. The composition according to any one of claims 2 to 5 and 7 to 41, wherein the lecithin comprises about 60% to about 75% by weight of phosphatidylcholine.

43. The composition according to any one of claims 1 to 42, wherein the at least one phospholipid comprises phosphatidylcholine.

44. The composition according to any one of claims 1 to 43, wherein the at least one phospholipid comprises about 10% to about 70% by weight of phosphatidylcholine.

45. The composition according to any one of claims 1 to 43, wherein the at least one phospholipid comprises about 20% to about 70% by weight of phosphatidylcholine.

46. The composition according to any one of claims 1 to 43, wherein the at least one phospholipid comprises about 60% to about 75% by weight of phosphatidylcholine.

47. The composition according to any one of claims 1 to 46, wherein the concentration of the at least one triglyceride is about 60.0 g / L to about 80.0 g / L, and / or the concentration of the at least one phospholipid is about 3.2 g / L to about 5.2 g / L.

48. The composition according to any one of claims 1 to 46, wherein the concentration of the at least one triglyceride is about 60.0 g / L to about 80.0 g / L, and / or the concentration of the at least one phospholipid is about 7.4 g / L to about 9.4 g / L.

49. The composition according to any one of claims 1 to 48, wherein the wetting agent is glycerol.

50. The composition according to any one of claims 1 to 49, wherein the concentration of the wetting agent is about 10 g / L to about 35 g / L.

51. The composition according to any one of claims 1 to 50, wherein the concentration of the wetting agent is about 14 g / L to about 26 g / L.

52. The composition according to any one of claims 1 to 51, wherein the concentration of the wetting agent is about 16 g / L.

53. The composition according to any one of claims 1 to 50, wherein the concentration of the wetting agent is about 21 g / L to about 26 g / L.

54. The composition according to any one of claims 1 to 50, wherein the concentration of the wetting agent is approximately 23.7 g / L.

55. The composition according to any one of claims 1 to 54, wherein the concentration of at least one phospholipid or the lecithin, and the concentration of glycerol are selected from one of the formulations in Table 3.

56. The composition according to any one of claims 1 to 55, wherein the weight ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 6.5:1 to about 30:

1.

57. The composition according to any one of claims 1 to 56, wherein the weight ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 13:1 to about 20:

1.

58. The composition according to any one of claims 1 to 57, wherein the weight ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 16.7:

1.

59. The composition according to any one of claims 1 to 56, wherein the weight ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 6.5:1 to about 10:

1.

60. The composition according to any one of claims 1 to 56, wherein the weight ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 8.3:

1.

61. The composition according to any one of claims 1 to 60, wherein the concentration of the at least one triglyceride is about 0.05 w / v% to about 1 w / v%, or about 0.1 w / v% to about 0.5 w / v%, the weight ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 6.5:1 to about 20:1, and the pH of the composition is about 6.5 to about 8.

5.

62. The composition according to any one of claims 1 to 61, wherein the composition comprises less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of sodium chloride.

63. The composition according to any one of claims 1 to 62, wherein the composition does not contain sodium chloride.

64. The composition according to any one of claims 1 to 63, wherein the composition comprises a salt in an amount of less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v%.

65. The composition according to any one of claims 1 to 64, wherein the composition does not contain any salt.

66. The composition according to any one of claims 1 to 65, wherein the composition comprises less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v% of polysorbate.

67. The composition according to any one of claims 1 to 66, wherein the composition does not contain polysorbate 80 (PS80).

68. The composition according to any one of claims 1 to 67, wherein the composition does not contain any polysorbate.

69. The composition according to any one of claims 1 to 68, wherein the composition comprises a stabilizer in an amount of less than 0.2 w / v%, less than 0.1 w / v%, less than 0.05 w / v%, less than 0.02 w / v%, or less than 0.01 w / v%.

70. The composition according to any one of claims 1 to 69, wherein the composition does not contain a stabilizer.

71. The composition according to any one of claims 1 to 70, wherein the pH of the composition is 9 to 12 or 10 to 11.

72. The composition according to any one of claims 1 to 71, wherein the composition has not been sterilized by gamma irradiation.

73. The composition according to any one of claims 1 to 70, wherein the pH of the composition is about 6.5 to about 8.

5.

74. The composition according to any one of claims 1 to 70, wherein the pH of the composition is about 6.9 to about 7.

6.

75. The composition according to any one of claims 1 to 70, wherein the pH of the composition is about 6.9 to about 7.

5.

76. The composition according to any one of claims 1 to 70, wherein the pH of the composition is about 7.

3.

77. The composition according to any one of claims 1 to 70, wherein the pH of the composition is about 7.

5.

78. The composition according to any one of claims 1 to 70, wherein the pH of the composition is about 6.

9.

79. The composition according to any one of claims 1 to 78, wherein the pH buffer is NaOH or contains NaOH.

80. The composition according to any one of claims 1 to 70 and 73 to 79, wherein the pH of the composition is measured after sterilization by gamma irradiation and storage for at least 5 days.

81. The composition according to any one of claims 1 to 70 and 73 to 80, wherein the composition is sterilized by gamma irradiation.

82. The composition according to any one of claims 1 to 81, wherein the composition is an ultrasonic coupling agent.

83. The composition according to any one of claims 1 to 82, wherein the composition is a contrast agent.

84. The composition according to any one of claims 1 to 83, wherein the composition is an aqueous composition.

85. The composition according to any one of claims 1 to 84, wherein the composition is a lubricant.

86. The composition according to any one of claims 1 to 85, wherein the composition has an attenuation coefficient of about 0.002 dB / (MHz*cm) to about 1.0 dB / (MHz*cm).

87. The composition according to any one of claims 1 to 86, wherein the composition has an attenuation coefficient of about 0.05 dB / (MHz*cm) to about 15 dB / (MHz*cm).

88. The composition according to any one of claims 1 to 87, wherein the composition has an attenuation coefficient of about 3 dB / (MHz*cm) to about 15 dB / (MHz*cm).

89. The composition according to any one of claims 1 to 88, wherein the composition has an attenuation coefficient of about 0.05 dB / (MHz*cm) to about 1.8 dB / (MHz*cm).

90. The composition according to any one of claims 1 to 89, wherein the composition has an attenuation coefficient of about 0.5 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).

91. The composition according to any one of claims 1 to 89, wherein the composition has an attenuation coefficient of about 0.1 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).

92. The composition according to any one of claims 1 to 89, wherein the composition has an attenuation coefficient of about 0.1 dB / (MHz*cm) to about 0.5 dB / (MHz*cm).

93. The composition according to any one of claims 1 to 92, wherein the composition has an attenuation coefficient of about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm).

94. The composition according to any one of claims 1 to 93, wherein the composition has a decay coefficient substantially equivalent to that of a tissue or organ selected from bone, brain, lung, liver, kidney, heart, cerebrospinal fluid, soft tissue, bladder, and colon.

95. The composition according to claim 94, wherein the tissue or organ is of human origin.

96. The composition according to any one of claims 1 to 95, wherein the composition has an osmotic pressure of about 270 mOsm / kg to about 330 mOsm / kg, or about 284 mOsm / kg to about 296 mOsm / kg.

97. The composition according to any one of claims 1 to 95, having an osmotic pressure of about 290 mOsm / kg to about 311 mOsm / kg.

98. The composition according to any one of claims 1 to 95, having an osmotic pressure of about 290 mOsm / kg to about 305 mOsm / kg.

99. The composition according to any one of claims 1 to 98, wherein the composition has a weighted volume average droplet diameter of about 0.2 μm to about 0.55 μm.

100. The composition according to any one of claims 1 to 99, wherein the composition has a weighted volume average droplet diameter of about 0.26 μm to about 0.50 μm.

101. The composition according to any one of claims 1 to 100, wherein the composition has a weighted volume average droplet diameter of about 228 nm to about 342 nm.

102. The composition according to any one of claims 1 to 101, wherein the composition has a weighted volume-average droplet diameter of about 258 nm.

103. The composition according to any one of claims 1 to 102, wherein the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 0.84 μm.

104. The composition according to any one of claims 1 to 102, wherein the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 0.96 μm.

105. The composition according to any one of claims 1 to 102, wherein the composition forms oil droplets, and 100% of the oil droplets have a diameter of less than 1.91 μm.

106. The composition according to any one of claims 1 to 105, wherein the composition forms oil droplets, and substantially none of the oil droplets have a diameter greater than 5,000 nm.

107. The composition according to any one of claims 1 to 106, wherein the composition forms oil droplets, and the oil droplets have an average diameter of 200 nm to about 750 nm.

108. The composition according to any one of claims 1 to 107, wherein the composition forms oil droplets, and the oil droplets have an average diameter of 250 nm to about 500 nm.

109. The composition according to any one of claims 1 to 108, having an average droplet diameter of about 285 nm ± 20%.

110. The composition according to any one of claims 99 to 109, wherein the average droplet diameter is measured by dynamic light scattering.

111. The composition according to any one of claims 6 to 110, wherein the diagnostic agent is a contrast agent.

112. The composition according to claim 111, wherein the contrast agent is a near-infrared (IR) fluorophore.

113. The composition according to claim 112, wherein the near-IR fluorophore is indocyanine green.

114. The therapeutic agent is a composition according to any one of claims 6 to 113, comprising an antibiotic.

115. The composition according to any one of claims 1 to 114, wherein the effective period of the composition is at least about 10 hours, at least about 16 hours, at least about 24 hours, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 7 days, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 2 months, at least about 3 months, at least about 4 months, at least about 6 months, at least about 9 months, at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, or at least about 6 years.

116. The composition according to any one of claims 1 to 114, wherein the effective period of the composition is approximately 6 months to approximately 5 years, approximately 1 year to approximately 5 years, approximately 2 years to approximately 5 years, approximately 3 years to approximately 5 years, approximately 6 months to approximately 4 years, approximately 6 months to approximately 3 years, approximately 6 months to approximately 2 years, approximately 6 months to approximately 1 year, approximately 1 year to approximately 4 years, approximately 1 year to approximately 3 years, approximately 1 year to approximately 2 years, or approximately 2 years to approximately 4 years at room temperature.

117. A method for preparing the composition according to any one of claims 1 to 116, comprising mixing components (a) to (e) or (a) to (f).

118. An imaging method comprising administering a composition according to any one of claims 1 to 116 to a subject requiring administration, and performing imaging.

119. The method according to claim 118, wherein the composition is administered to a wound, organ, tumor, blood vessel, blood circulation area, or cavity within the body of the subject.

120. A method for obtaining images of wounds, organs, tumors, blood vessels, or cavities, i) bringing the wound, organ, tumor, blood vessel, or cavity into contact with the composition according to any one of claims 1 to 116, ii) A method comprising acquiring the image using an apparatus.

121. The composition according to any one of claims 118 to 120, wherein the imaging is performed using invasive ultrasound imaging.

122. The composition according to any one of claims 118 to 120, wherein the imaging is Doppler blood flow imaging.

123. The composition according to any one of claims 118 to 120, wherein the imaging is laser speckle imaging.

124. The composition according to any one of claims 118 to 120, wherein the imaging is optical coherence tomography, photoacoustic imaging (PAI), computed tomography (CT), magnetic resonance imaging (MRI), or echocardiography.

125. The composition according to any one of claims 118 to 120, wherein the imaging is performed by fluorescence imaging, radioimaging, positron emission tomography (PET), or magnetic particle imaging (MPI).

126. A method for performing surgery on a subject requiring surgery, comprising: administering a composition according to any one of claims 1 to 116 to a wound, organ, tumor, blood vessel, blood circulation area, or cavity of the subject, acquiring an image; and performing surgery based on the image.

127. A method for excising a tumor, comprising: administering a composition according to any one of claims 1 to 116 to tissue proximal to the tumor; obtaining ultrasound images of the tumor and the proximal tissue; identifying the tumor; and excising the tumor.

128. The method according to claim 127, wherein the tumor is located in or proximal to the bladder, uterus, cervix, colon, or spine.

129. The method according to any one of claims 118 to 128, wherein the composition is contained in a balloon catheter.

130. A method for performing surgery on a subject requiring surgery, comprising: bringing an instrument used in the surgery into contact with a composition according to any one of claims 1 to 116; and inserting the instrument into a wound, organ, tumor, blood vessel, or cavity inside the subject's body.

131. A method for performing surgery on a subject requiring surgery, comprising: administering a composition according to any one of claims 1 to 116 into a wound, organ, tumor, blood vessel, or cavity within the subject's body; and inserting an instrument used in the surgery into the wound, organ, tumor, blood vessel, or cavity.

132. The method according to claim 130 or 131, wherein the surgery is a brain surgery or a neurosurgery.

133. A method for placing an instrument inside the body of an object requiring the placement of the instrument, comprising sequentially or simultaneously bringing a portion of the object into contact with a composition described in any one of claims 1 to 116, and inserting the instrument into the object.

134. The method according to any one of claims 130 to 133, wherein the device is for preventing or treating a disease.

135. The method according to any one of claims 130 to 134, wherein the instrument is a catheter.

136. The method according to claim 135, wherein the catheter is a subdural pressure catheter, a drainage catheter, a cerebral blood flow catheter, a microdialysis catheter, or a cerebral tissue oxygen catheter.

137. The method according to any one of claims 130 to 134, wherein the device is an intracranial pressure sensor.

138. The method according to any one of claims 130 to 134, wherein the device is an implantable brain-computer interface (BCI).

139. The method according to any one of claims 130 to 138, wherein the composition acts as a lubricant for the instrument.

140. A method for delivering a diagnostic or therapeutic agent to a target requiring delivery, i) A composition according to any one of claims 1 to 116, comprising the diagnostic agent or therapeutic agent, or ii) A method comprising administering the composition and the agent according to any one of claims 1 to 116.

141. The method according to claim 140, wherein the method is for treating a disease, and the agent includes the therapeutic agent.

142. The method according to claim 140 or 141, wherein the composition and the drug are administered sequentially.

143. The therapeutic agent according to any one of claims 140 to 142, comprising a photosensitizer.

144. The method according to claim 143, comprising exposing the photosensitive agent to light.

145. A method for treating a disease in a subject requiring treatment using focused ultrasound therapy, comprising administering a composition according to any one of claims 1 to 116 to the subject, and performing the focused ultrasound therapy.

146. A method for treating a disease in a subject requiring treatment, comprising administering a composition according to any one of claims 1 to 116 to the subject.

147. The method according to any one of claims 145 to 146, wherein the composition comprises a therapeutic agent.

148. The method according to any one of claims 145 to 147, wherein the method comprises administering the composition and then treating the subject with photodynamic therapy.

149. The method according to any one of claims 145 to 148, comprising diluting the composition with water and glycerol to obtain a diluted composition containing about 0.005 w / v% to about 0.5 w / v% of the triglyceride.

150. The method according to claim 149, wherein the diluted composition has an osmotic pressure of about 270 mOsm / kg to about 330 mOsm / kg, about 284 mOsm / kg to about 296 mOsm / kg, about 290 mOsm / kg to about 311 mOsm / kg, or about 290 mOsm / kg to about 305 mOsm / kg.

151. The method according to any one of claims 146 to 150, wherein the composition is a light dispersant.

152. The therapeutic agent according to any one of claims 146 to 151, comprising a photosensitizer.

153. A method of treating a disease, i) Contacting a wound, organ, tumor, blood vessel, area of ​​blood circulation, or cavity containing tissue of the disease with the composition according to any one of claims 1 to 116, ii) To obtain images of the wound, organ, tumor, blood vessel, blood circulation area, or cavity, iii) A method comprising treating the disease or removing diseased tissue based on the image.

154. The method according to claim 153, wherein the image is an ultrasound image.

155. The method according to any one of claims 153 to 154, wherein the composition comprises a contrast agent that enables the acquisition of the image.

156. The method according to claim 155, wherein the contrast agent is a near-infrared (IR) fluorophore.

157. The method according to claim 156, wherein the near-IR fluorophore is indocyanine green.

158. The method according to any one of claims 153 to 157, wherein the composition comprises a fluorophore.

159. The method according to any one of claims 153 to 158, wherein the image is for identifying target tissue or diseased tissue within the body of the subject.

160. The method according to claim 159, wherein the diseased tissue is a residual tumor.

161. The method according to any one of claims 140 to 160, further comprising removing and / or treating abnormal or diseased tissue.

162. The method according to claim 161, wherein the method comprises removing the abnormal or diseased tissue via surgery.

163. The method according to claim 161 or 162, wherein the method comprises treating the abnormal or affected tissue via chemotherapy, targeted therapy, photodynamic therapy, or radiotherapy.

164. The method according to any one of claims 141 to 163, wherein the disease is cancer and / or the affected tissue includes tumor tissue.

165. The method according to any one of claims 119 to 132 and 153 to 164, wherein the tumor is a brain tumor.

166. The method according to any one of claims 119 to 132 and 153 to 164, wherein the tumor is a glioma, glioblastoma, or neuroblastoma.

167. The method according to any one of claims 118 to 166, comprising administering one or more methods of cancer treatment.

168. The method according to claim 167, wherein the one or more methods are selected from the group consisting of chemotherapy, immunotherapy, alternating electric tumor treatment field, laser interstitial hyperthermia (LITT), magnetic hyperthermia (MHT), focused ultrasound, radiofrequency microwave, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence-guided resection, surgical resection, and magnetic resonance imaging.

169. The method according to claim 167 or 168, wherein treating the disease comprises exposing cancer cells to light.

170. The method according to any one of claims 118 to 169, wherein the method includes performing an invasive procedure before administering the composition to enable access to the composition and / or instrument in the wound, the organ, the blood vessel, or the cavity.

171. The method according to any one of claims 119 to 126, 128 to 132, 134 to 139 and 153 to 170, wherein the cavity is selected from one of the oral cavity, nasal cavity, orbit, thoracic cavity, pericardial cavity, pleural cavity, abdominal cavity, pelvic cavity, cranial cavity, vertebral cavity, joint cavity, synovial cavity, buccal oral cavity, cranial fossa, mandibular fossa, maxillary sinus, frontal sinus, ethmoid sinus, sphenoid sinus, mastoid air cells, ear canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, venous sinus, fallopian tube infundibulum, alveolar sac, bronchioles, laryngeal cavity, tracheal cavity, gastric pit, intestinal crypt, gallbladder fossa, renal sinus, ureteral orifice, bladder trigone, follicle, testicular lobule, vaginal fornix, anal canal, vertebral foramen, intervertebral foramen, foramen magnum, and jugular foramen.

172. The method according to any one of claims 119-126, 128-132, 134-139 and 153-170, wherein the organ is selected from any one of the following: brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, mammary gland, esophagus, diaphragm, adrenal gland, thyroid gland, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries, testes, uterus, prostate gland, penis, vagina, cervix, urethra, rectum, anus, skeletal muscle, smooth muscle, cardiac muscle, bone marrow, bone, blood vessels, lymph nodes, lymphatic vessels, tonsils, appendix, adipose tissue, nerves, and connective tissue.

173. The method according to any one of claims 119-126, 128-132, 134-139 and 153-170, wherein the organ is the brain, kidney, liver, pancreas, ovary, breast, bladder, uterus, cervix, or colon.

174. The method according to claim 173, wherein the organ is the brain.

175. The method according to any one of claims 119-126, 128-132, 134-139 and 153-174, wherein the organ or cavity includes a tumor.

176. The method according to claim 175, comprising excising the tumor.

177. The method according to any one of claims 118 to 176, wherein the method reduces artifacts in ultrasound imaging compared to a control method in which the composition is not applied.

178. The method according to claim 178, wherein the artifact is a luminance increase artifact or includes one.

179. The control method is the method according to claim 177 or 178, wherein physiological saline is used as the ultrasonic coupling agent instead of the composition.

180. The method according to any one of claims 130 to 179, wherein the composition is contained within a balloon catheter.

181. The method according to claim 180, wherein the cavity is created by the balloon catheter.

182. The method according to any one of claims 118 to 181, wherein the subject is a human.

183. A container comprising the composition according to any one of claims 1 to 116.

184. The container according to claim 183, wherein the container is a syringe.

185. The container according to claim 183 or 184, wherein the container is made of glass or stainless steel.

186. The container according to claim 183 or 184, wherein the container is a bag.

187. The container according to any one of claims 183 to 186, wherein the container does not contain one or more of the following: dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl) phthalate (DEHP).

188. A kit comprising the composition according to any one of claims 1 to 116, and a container.

189. The kit according to claim 188, wherein the container is a syringe.

190. The kit according to claim 188 or 189, wherein the container is made of glass or stainless steel.

191. The kit according to claim 188, wherein the container is a bag.

192. The kit according to any one of claims 188 to 191, wherein the container does not contain one or more of the following: dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl) phthalate (DEHP).

193. A kit according to any one of claims 188 to 192, further comprising a back spike.

194. A kit according to any one of claims 188 to 193, further comprising a filter.

195. The kit according to claim 194, wherein the filter has a pore size of approximately 1.2 μm.

Images