Method for injecting substance from device and method for operating medical device

Abstract

Methods of injecting a substance from a device and methods of operating a medical device are provided. A method of injecting a substance from a device, comprising: providing a device comprising a first compartment, a second compartment, and a third compartment; the first compartment and the second compartment are in fluid communication with a first opening covered by a first seal, and the second compartment and the third compartment are in fluid communication with a second opening covered by a second seal; the third compartment comprises a needle assembly with a spring and a needle; pressing the movable element to a first predetermined position such that the insertion rod moves the first seal away from the first opening, thereby allowing fluid communication between the first compartment and the second compartment; further pressing the movable element to a second predetermined position such that the insertion rod moves the second seal away from the second opening, thereby allowing fluid communication between the second compartment and the third compartment; and continuing to press the movable element to a third predetermined position such that the needle assembly injects the substance through the needle.

Description

[0001] This application is a divisional application of the patent application with the application number 202180024489.4 and the invention name of "Drug Injection Device, System and Method", the application date of which is February 26, 2021.

[0002] Cross - reference to related applications

[0003] This application claims the priority of the US Provisional Application No. 62 / 981,811 filed on February 26, 2020, which is incorporated herein by reference in its entirety. Technical field

[0004] The present disclosure relates to a device including a needle for administering an active agent to a subject, wherein the active agent is in solid or liquid form in one compartment, separated from a diluent or pharmaceutically acceptable carrier in another compartment, and the device is capable of exposing the active agent to the diluent or pharmaceutically acceptable carrier for mixing or dissolution prior to administration. The present disclosure also relates to systems, methods and devices for storing, transporting, mixing and injecting a drug as a solution, and in some embodiments, the drug injection devices and systems involved are intended to mix a pre - measured amount and dose of a drug with a liquid such as water as needed and inject the drug mixture using an integrated subcutaneous injection needle assembly. Methods of using such devices and systems are also provided. Background art

[0005] For a long time, emergency injections have been utilized in response to any form of extremely time - sensitive and life - threatening events, including overdose, allergic reaction, angioedema or adrenal insufficiency (AI). The urgent need and nature of the active ingredient make accurate and rapid drug delivery essential. In fact, naloxone auto - injectors and auto - injectors containing epinephrine provide dosing systems that are easier to manipulate and administer. However, steroid syringes due to their reliance on reconstitution, although equally important, are still adversely affected by bulky delivery systems and thus provide sub - optimal dosing devices in terms of drug preparation and delivery.

[0006] At this point, the steroid emergency injection, hydrocortisone, remains the drug of choice for adrenal insufficiency, which is manifested by the adrenal glands' inability to produce sufficient amounts of the glucocorticoid cortisol. Cortisol itself is released in response to both stress and hypoglycemia, where this essential steroid is responsible for, among other processes such as glycogenogenesis, electrolyte balance, and gastric acid secretion, the production of glucose and immunosuppression and can affect sleep, mood, and stress levels. Conversely, cortisol reduction (or absence) can lead to weakness, fatigue, weight loss, and depression, while complete absence of cortisol can result in adrenal shock or adrenal crisis, where the body lacks the ability to maintain its homeostatic functions and the patient can exhibit severe lethargy, confusion, psychosis, cramps, diarrhea, vomiting, spasms, hypoglycemia, and other life-threatening sequelae up to death.

[0007] To date, patients with congenital adrenal hyperplasia (CAH), Addison’s disease, and idiopathic adrenal insufficiency have faced challenges in terms of medication. Conventionally, to prepare hydrocortisone for intramuscular (IM) administration, an individual can inject bacteriostatic water or bacteriostatic sodium chloride into a sterile vial containing dry hydrocortisone powder or utilize a system where the diluent in the upper vial is attached to the lower vial containing the active dry hydrocortisone ingredient. Similarly, both require laborious manipulation of different or connected vials to mix, extract, and administer the reconstituted mixture, all of which need to be done in a critically short amount of time. Even for the relatively simpler drug mixing systems, an average of 12 user steps are required for injection, including (1) obtaining the needle and diluent / drug containers, (2) pressing the plastic cap onto the vial containing the diluent (releasing the diluent into the lower vial containing the dry ingredient), (3) mixing the dry powder with the solution, (4) removing the plastic cap, (5) disinfecting the docking needle stopper, (6) inserting the needle through the center of the stopper, (7) extracting the dose, and finally, (8) injecting the appropriate dose intramuscularly. Due to the complexity of the system, the delivery system requires trained medical personnel to ensure proper acquisition and administration of the potentially life-saving drug. The delivery system is not designed for use by laypersons or individuals with adrenal insufficiency. SUMMARY OF THE INVENTION

[0008] The present disclosure relates to systems, methods, and devices for transporting, storing, mixing, and injecting drugs into a patient, such as for administering a single-dose drug that is transported, stored, mixed, and injected by using a drug injection device.

[0009] The steroid emergency injectable, hydrocortisone, remains the drug of choice for adrenal insufficiency, which is manifested as the adrenal glands being unable to produce sufficient amounts of the glucocorticoid cortisol. A decrease or absence of cortisol can lead to a variety of conditions, including weakness, fatigue, weight loss, and depression, and a complete absence of cortisol can lead to adrenal shock or adrenal crisis, which can be life-threatening. It is against this backdrop that the importance of immediate administration of exogenous cortisol (i.e., hydrocortisone) becomes necessary and mandatory. To date, hydrocortisone has been available for inpatients via intravenous injection or intramuscular injection (IM), but is provided to outpatients only specifically for acute short-term illnesses via reconstituted intramuscular injectables prepared from doses that typically range between 100 mg and 500 mg.

[0010] Aiming to address the drawbacks of the prior art devices, the focus of the present disclosure is to create a more patient-friendly and effective drug delivery system. The present disclosure aims to improve the administration of life-saving injectable drugs using a twist-to-mix delivery system and device to benefit millions of patients globally suffering from congenital adrenal hyperplasia (CAH), Addison's disease, and idiopathic adrenal insufficiency. Exemplary embodiments of the disclosed system and device require as few as four injection steps and can be designed for individuals experiencing adrenal crisis and their caregivers.

[0011] The present disclosure is mainly concerned with filling the gaps in the field of emergency injectable steroids. The present disclosure is also concerned with further advancing the efficient and effective administration of other emergency drugs (e.g., adrenaline and naloxone) as well as non-emergency drugs, which include but are not limited to non-emergency steroids, antibiotics, painkillers, disease-specific therapeutic agents (e.g., MS treatment, psoriasis treatment), insulin, glycoproteins, immunomodulators, G-CSF, erythropoietin biologics, antihypertensives, vaccines, hormones (including contraceptives), antihormones, sedatives, antiepileptics, antineoplastics, insecticides (e.g., dobutamine), antipsychotics, antidotes, cosmetics, selective serotonin reuptake inhibitors (SSRI), proton pump inhibitors (PPI), anesthetics, diuretics, antidiuretics, blood thinners (e.g., low molecular weight heparin), streptokinase, etc., either alone or in combination, whether in liquid form, reconstitutable form, or other forms. In some embodiments, the systems and devices of the present disclosure can be used to deliver drugs that have been used in the past drugs delivered by the system, namely methylprednisolone for multiple sclerosis, certain cancers, and autoimmune diseases. In some embodiments, the systems and devices of the present disclosure are used to deliver glucagon for use in hypoglycemic emergencies. In some embodiments, the systems and devices of the present disclosure are used to deliver hydroxythienamycin for treating high-incidence infections. In some embodiments, the systems and devices of the present disclosure are used to deliver chlordiazepoxide for treating alcohol withdrawal. In some embodiments, the systems and devices of the present disclosure are used to deliver desoxycorticosterone trimethylacetate for use in veterinary emergencies. In some embodiments, the systems and devices of the present disclosure are used for in vitro fertilization procedures.

[0012] As described below, embodiments of the present disclosure include drug delivery and storage containers, drug mixing systems, and drug injection assemblies implemented using devices, components, systems, and methods different from those of the prior art.

[0013] This disclosure sets forth one or more best modes contemplated for carrying out the various embodiments disclosed herein so that those skilled in the art can practice the disclosure. However, the preferred embodiments are not intended to be limiting, but rather are included without limitation within the spirit and scope of the disclosure and the appended claims, and may be changed and varied.

[0014] According to one aspect of the present disclosure, there is provided a device for transporting, storing, mixing, and injecting a drug into a patient, wherein the device includes: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly. The transport assembly is adapted to provide a convenient mode for transporting the drug prior to administering the drug to the patient. The storage assembly is adapted to store the drug and to mix the individual components within the transport assembly prior to mixing the drug and the components to create the drug in solution just prior to injecting the mixture into the patient. The mixing assembly is adapted to properly mix the drug and the components to create the drug in solution within the transport assembly just prior to preparing to inject the mixture into the patient. The injection assembly is adapted to properly inject the drug in solution into the patient once the mixture is obtained.

[0015] According to one aspect of the present disclosure, there is provided a method of using a device for transporting, storing, mixing, and injecting a drug into a patient, wherein the device includes: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the method includes: providing the device, engaging the mixing assembly to mix the drug and create the drug in solution just prior to administering the drug to the patient, and engaging the injection assembly to inject the drug in solution into the patient. In some embodiments, the method further includes removing a safety device prior to engaging the injection assembly to inject the drug in solution into the patient.

[0016] According to one aspect of the present disclosure, a method of assembling a device for transporting, storing, mixing, and injecting a drug into a patient is disclosed, wherein the device includes: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the method includes: providing and assembling the transport assembly, providing and assembling the storage assembly, providing and assembling the mixing assembly, and providing and assembling the injection assembly.

[0017] According to one aspect of the present disclosure, a system for assembling a device for transporting, storing, mixing, and injecting a drug into a patient is disclosed, wherein the device includes: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the system includes: means for assembling the transport assembly, means for assembling the storage assembly, means for assembling the mixing assembly, and means for assembling the injection assembly.

[0018] Accordingly, the present disclosure provides an apparatus, the apparatus comprising: (a) a first compartment and a second compartment, each of the first compartment and the second compartment defining a first chamber and a second chamber respectively, the first compartment and the second compartment being in fluid communication with a first opening and being separated from each other at the first opening; (b) a needle assembly; and (c) an insertion rod positioned in the first compartment, the insertion rod being operatively connected to a movable element, wherein the first opening is covered by a seal; in some embodiments, the insertion rod of the disclosed apparatus includes two oppositely directed faces, a first face physically contacting the movable element and a second face being positioned within the first chamber; wherein the second face includes a protrusion and at least one valve positioned away from the protrusion. In some embodiments, the protrusion on the second face of the insertion rod has a beveled surface. In some embodiments, the movable element of the disclosed apparatus is physically adjacent to the insertion rod and wherein the insertion rod is capable of moving in a direction along a longitudinal axis when the movable element is pressed, the longitudinal axis being parallel to and within the first compartment and the second compartment.

[0019] In some embodiments, the second compartment of the disclosed device contains an active agent, and the first compartment contains a pharmaceutically acceptable carrier. In some embodiments, the second compartment contains a pharmaceutically acceptable carrier, and the first compartment contains an active agent. In some embodiments, each of the first and second compartments contains one or more active agents. In some embodiments, each of the first and second compartments contains: one or more active agents or one or more pharmaceutically acceptable carriers. In some embodiments, the second compartment contains an active agent in solid or semi-solid form, and the first compartment contains a pharmaceutically acceptable carrier in liquid form. In some embodiments, the second compartment contains an active agent in liquid form, and the first compartment contains a pharmaceutically acceptable carrier in liquid form. In some embodiments, the active agent of the disclosed device is lyophilized.

[0020] In some embodiments, the disclosed device further includes a third compartment that defines a third chamber, and the third compartment is adjacent to the second compartment and is separated from the second compartment by a second opening covered by a second seal. In some embodiments, the second seal is a movable plug operatively connected to the movable element, and wherein displacement of the movable plug is permitted when the movable element is depressed to effect fluid communication between the second compartment and the third compartment. In some embodiments, displacement of the movable plug and an insertion rod is permitted when the movable element is depressed to effect fluid communication between the second compartment and the third compartment.

[0021] In some embodiments, the third compartment of the disclosed device houses the needle assembly; the needle assembly includes a spring and a needle operatively connected to the spring; wherein the needle includes a first fluid opening located within the third chamber and a second fluid opening located opposite and remote from the first and second chambers. In some embodiments, the first and second fluid openings are covered by a movable seal operatively connected to the movable element such that displacement of the first seal and the second seal is caused when the movable element is depressed to a first predetermined position and a second predetermined position, respectively.

[0022] In some embodiments, the disclosed device is in a first operable condition and includes a first compartment, a second compartment, and a third compartment. The first compartment and the second compartment are in fluid communication with each other through a first opening including a first seal; the second compartment and the third compartment are in fluid communication with each other through a second opening covered by a second seal; wherein the second compartment is positioned between the first compartment and the third compartment on opposite sides of the second compartment; wherein the movable element is in a fully extended position laterally relative to the device, wherein the first compartment contains a pharmaceutically acceptable carrier, the second compartment contains one or more active agents, the third compartment contains a needle assembly, and wherein the first seal and the second seal covering each of the first opening and the second opening are intact, thereby preventing fluid from flowing from one compartment to another. In some embodiments, the disclosed device is in a second operable condition and includes a first compartment, a second compartment, and a third compartment. The first compartment and the second compartment are in fluid communication with each other through a first opening; the second compartment and the third compartment are in fluid communication with each other through a second opening covered by a second seal; wherein the second compartment is positioned between the first compartment and the third compartment on opposite sides of the second compartment; wherein the movable element is in a partially pressed-in position laterally relative to the device, wherein the first compartment and the second compartment contain a pharmaceutically acceptable carrier and one or more active agents; wherein the third compartment contains a needle assembly, and wherein the second seal covering the second opening prevents fluid from flowing from the third compartment to the first compartment or the second compartment. In some embodiments, the disclosed device is in a third operable condition and includes a first compartment, a second compartment, and a third compartment. The first compartment, the second compartment, and the third compartment are in fluid communication with each other; wherein the second compartment is positioned between the first compartment and the third compartment on opposite sides of the second compartment; wherein the movable element is in a partially pressed-in position laterally relative to the device such that the insertion rod has caused the second seal to be punctured, wherein the first compartment, the second compartment, and the third compartment contain a pharmaceutically acceptable carrier and one or more active agents; wherein the third compartment contains the needle assembly, and wherein the second seal has been punctured or displaced relative to its position covering the second opening, and the needle assembly is exposed to the active agent and the pharmaceutically acceptable carrier.In some embodiments, the disclosed device is in a fourth operable condition and includes a first compartment, a second compartment, and a third compartment, the first compartment, the second compartment, and the third compartment being in fluid communication with each other; wherein the second compartment is positioned between the first compartment and the third compartment on opposite sides of the second compartment; wherein the movable element is in a fully depressed position relative to the lateral side of the device, and the needle of the needle assembly is exposed. In embodiments where the disclosed device is in the second, third, or fourth position, the active agent contained in the disclosed device is dissolved in one or more pharmaceutically acceptable carriers.

[0023] In some embodiments, the active agent contained in any of the disclosed devices is any one or a combination of the active agents selected from those in Table 1. In some embodiments, the active agent is any one or a combination of the active agents selected from those in Table 1 and has the dose identified in Table 1. In some embodiments, the active agent is corticosterone or a corticosterone derivative. In some embodiments, the corticosterone derivative is sodium hydrocortisone succinate, wherein the derivative is present as an active agent in a solution of a pharmaceutically acceptable carrier per unit volume at a weight of about 50 mg / mL to 250 mg / mL, or about 25 mg / mL to 150 mg / mL.

[0024] In some embodiments, the first compartment and the second compartment of the disclosed device contain a pharmaceutically acceptable carrier in fluid form having a viscosity of about 1 cP to about 150 cP.

[0025] In some embodiments, the present disclosure provides a method of treating and / or preventing a disease or disorder in a subject in need thereof, comprising administering one or more active agents to the subject via any of the devices described herein. In some embodiments, the present disclosure provides a method of treating a subject in need of administering one or more active agents, comprising administering a pharmaceutically effective amount of the one or more active agents to the subject via any of the devices described herein. In some embodiments, the present disclosure provides a method of treating cortisol depletion in a subject in need thereof, comprising administering corticosterone or a corticosterone derivative thereof to the subject via any of the devices described herein. In some embodiments, the cortisol depletion is caused by: Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenomyeloneuropathy, adrenoleukodystrophy, adrenal tumor, Schmidt syndrome, hyperaldosteronism, pituitary tumor, pituitary cyst, and / or corticosteroid insufficiency associated with critical illness. In some embodiments, the present disclosure provides a method of treating cortisol dysregulation in a subject in need thereof, comprising administering cortisol or a cortisol derivative thereof to the subject using any of the devices described herein. In some embodiments, the administering step in any of the disclosed treatment methods comprises: pressing the movable element of the disclosed device to a first predetermined position, a second predetermined position, and a third predetermined position; wherein the device comprises: a first compartment, a second compartment, and a third compartment, each of the first compartment, the second compartment, and the third compartment defining a first chamber, a second chamber, and a third chamber, respectively; the first compartment and the second compartment are in fluid communication with a first opening and are separated from each other at the first opening; and the second chamber and the third chamber are in fluid communication with a second opening and are separated from each other at the second opening; wherein the first opening is covered by a first seal, and the second opening is covered by a second seal; wherein the third compartment comprises a needle assembly, the needle assembly comprising a spring and a needle operably connected to the spring; wherein pressing the movable element to the first predetermined position causes the insertion rod to cause the first seal to move away from the first opening and expose the first opening between the first compartment and the second compartment, thereby causing fluid communication between the first compartment and the second compartment; and wherein pressing the movable element to the second predetermined position causes the insertion rod to cause the second seal to move away from the second opening and expose the second opening between the second compartment and the third compartment, thereby causing fluid communication between the second compartment and the third compartment; and wherein pressing the movable element to the third predetermined position causes the contents of the third compartment to be injected out through the needle assembly.In some embodiments, the disclosed method further includes the step of unlocking the needle assembly before the movable element is pressed to the third predetermined position.

[0026] In some embodiments, the present disclosure provides a method of treating a subject in need thereof for congenital adrenal hyperplasia or Addison's disease, comprising administering corticosterone or a corticosterone derivative thereof to the subject by any of the devices described herein.

[0027] The present disclosure provides a method of manufacturing any of the devices described herein, comprising placing one or more of the active agents in a sterile or sterilized environment. In some embodiments, the method further includes weighing the one or more active agents. In some embodiments, the method further includes attaching the first compartment and the second compartment. In some embodiments, the method includes attaching the first compartment and the second compartment to each other in a sterile environment by compression or threading into a fastener.

[0028] The present disclosure provides a method of administering an active agent to a subject in need thereof by any of the devices described herein, comprising: (a) pressing the movable element to a first predetermined position; and (b) pressing the movable element to a second predetermined position; wherein the first predetermined position causes sufficient displacement of the insertion rod to pierce the first seal, such that the first compartment and the second compartment are in fluid communication; and wherein the displacement produced by the second predetermined position is sufficient to cause displacement of the movable seal, thereby allowing fluid communication between the second compartment and the third compartment. In some embodiments, the displacement produced by the second predetermined position is sufficient to load the spring in the third compartment with a force of from about 0 Newtons to about 100 Newtons.

[0029] The present disclosure further provides an apparatus, comprising: (a) a first compartment, a second compartment, and a third compartment, each of the first compartment, the second compartment, and the third compartment defining a first chamber, a second chamber, and a third chamber, respectively, and the second compartment being positioned adjacent between the first compartment and the third compartment; (b) a needle protection assembly operably acting in the third chamber and at least partially received in the third chamber, and comprising a needle operably attached to a spring; and (c) an insertion rod positioned in the first compartment, the insertion rod being operably connected to a movable element, the insertion rod and the movable element being capable of moving along the longitudinal axis of the first compartment, the second compartment, and the third compartment; wherein the first compartment and the second compartment are in fluid communication through a first opening, and the second compartment and the third compartment are in fluid communication through a second opening; the first opening is covered by a first seal and the second opening is covered by a second seal. In some embodiments, the first compartment contains one or more active agents and the second compartment contains one or more pharmaceutically acceptable carriers. In some embodiments, the first compartment contains one or more pharmaceutically acceptable carriers and the second compartment contains one or more active agents. In some embodiments, the cylindrical peripheries of the first compartment, the second compartment, and the third compartment are aligned along the longitudinal axis of the three chambers. In some embodiments, the needle protection assembly includes a spring, a needle sheath, and an inner surface, the inner surface comprising one or more guide rail elements operably connected to the needle, the guide rail elements being capable of guiding the needle to move through the needle sheath after the spring moves. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Referring to the drawings showing exemplary embodiments of the present disclosure, the detailed description provided below explains in detail various features, advantages, and aspects of the present disclosure. Accordingly, the features of the present disclosure may be more clearly understood from the following detailed description in conjunction with the drawings, in which like reference numerals denote the same, similar, or comparable elements throughout. The exemplary embodiments shown in the drawings are not necessarily drawn to scale or shape, and are not considered to be a limitation of their scope, as the present disclosure may admit other equally effective embodiments having different combinations of the features shown in the drawings.

[0031] Figure 1A A side cross-sectional view of an embodiment of the apparatus disclosed herein is shown. 100: A three-chamber system that allows for the accommodation and mixing of one or more solid or liquid materials. 102: A first chamber containing a liquid or solid material, the first chamber being separated from the second chamber 104 by a barrier. 104: A second chamber containing a liquid or solid material, the second chamber being separated from the first chamber 102 by a barrier.

[0032] Figure 1B A side cross-sectional view of the device is shown Figure 1A in which the materials contained in each chamber are mixed by the operation of a compression mechanism. 116: A three-chamber system that allows the accommodation and mixing of one or more solid or liquid materials. 112: A first chamber containing a liquid or solid material, which is separated from a second chamber 110 by a barrier. 110: A second chamber containing a liquid, solid, semi-solid, or gaseous material, which is separated from the first chamber 112 by a barrier. 114: A compression system, such as a plunger, spring, screw system, or a combination of two or more such systems, to initiate mixing between chambers 112 and 110.

[0033] Figure 2A A side cross-sectional view of another embodiment of the device disclosed herein is shown, which further includes a movable member, a chamber barrier, a seal, and other components associated with an auto-injector. 200: A three-chamber system including a housing, a plunger, a mechanism for separating the three chambers, and a compression system for initiating the mixing of the materials held in the first two chambers and moving the materials into the third chamber. 202: An activation system for initiating the mixing of the materials held in chambers 214 and 208 and moving the materials into chamber 210. 204: An insertion rod that pierces barrier 206 to allow the transfer of materials between chambers 216 and 208. The insertion rod will be pushed into chamber 208 to help push the liquid from 216 into 208. The insertion rod 204 may be composed of or surrounded by a sealing material to prevent the flow of fluid behind the insertion rod. 206: A barrier between chambers 216 and 208 that prevents the transfer of materials between the two chambers until the barrier is pierced by the insertion rod 204. 208: A second chamber containing a liquid, solid, semi-solid, or gaseous material to be mixed with the material held in chamber 216 after piercing seal 206. 210: The third chamber in the device where the materials from chambers 208 and 216 are mixed after the device is activated. 212: A spring that compresses the materials transferred into chamber 210 after the barrier 206 is pierced and the material mixing occurs. 214: A movable seal assembly that moves through chamber 210 when the materials in chambers 208 and 216 are mixed. 216: The first chamber in the device that may contain a liquid or solid material to be mixed with the material in chamber 208 after the insertion rod pierces the barrier 206. 218: A housing that houses the three chambers 216, 218, and 210, and the activation system 202.

[0034] Figure 2BA side cross-sectional view of another embodiment of the device disclosed herein is shown, where the insertion rod for piercing the seal includes two components (220, 254) instead of one. 220: Another embodiment of a three-chamber system for mixing two materials. 222: An activation system for initiating the mixing of the materials held in chambers 254 and 234 and moving the materials into chamber 210. 224: An insertion rod assembly that pierces barrier 232 to allow the materials in chambers 254 and 234 to mix. 226: A seal component that prevents fluid from moving backward through the device. 228: A fluid outlet that allows fluid transfer between chambers 254 and 234. 230: A fluid path through insertion rod 224 that allows fluid transfer between chambers 254 and 234. 232: A barrier between chambers 254 and 234 that prevents material transfer between the two chambers until the barrier is pierced by insertion rod 224. 234: A second chamber that holds a liquid or solid material to be mixed with the material held in chamber 254 after the seal 232 is pierced. 236: The outer housing of chamber 234, which can be enclosed on its side or end by a material transfer barrier. 238: A sliding seal for the movable assembly 246 that prevents fluid from passing around its edge. 240: A third chamber in the device where the materials from chambers 254 and 234 are mixed after the device is activated. 242: A needle for injecting the combined material. 244: A spring that is compressed when filling chamber 240 and then moves assembly 246 through chamber 240. 246: A seal assembly that acts as a barrier for chamber 234 before the device is activated and, after activation, forms the wall of chamber 240 and is the compression mechanism that pushes the mixed material out of the device.

[0035] 248: A seal that prevents material from entering syringe 242 until the seal is pierced by the movement of assembly 246 during device activation. 250: Sealing material on chamber 236. 252: The entry point of the insertion rod into chamber 234. 254: The first chamber that contains a material to be mixed with the material in chamber 234. 256: The outer housing that holds the mixing chamber, the materials, and all the device components. 258: The outer housing of insertion rod 224 that allows the rod to move inward and may contain a seal. 260: The insertion rod assembly. 262: The needle guide and spring attachment.

[0036] Figure 3A A side cross-sectional view of another embodiment of the device disclosed herein is shown, where the needle assembly has a needle guard 302 attached to the main device 300. 300: A device component for mixing two materials. 302: The needle assembly and needle guard for injecting the two mixed materials. A more detailed view of the needle assembly and needle guard of this embodiment is shown in Figure 3BShown in 304: A needle guard assembly that prevents fluid from leaving the device and blocks accidental injection. In this state, the guard extends over the needle. 306: A needle guard housing that hides the needle 308 and is retractable to allow injection. 308: An injection needle. 310: A safety clip that prevents the needle guard from being activated until it is removed. 312: A compression spring that holds the needle guard 306 in place and pushes the guard 306 backward to cover the needle once injection is complete. 314: A seal that prevents fluid from entering the needle 308. Figure 3C Shows a state where Figure 3A the device is activated and the components are assembled but injection has not yet started. 316: A needle guard assembly that prevents fluid from leaving the device and blocks accidental injection. In this state, the guard housing is retracted to allow injection. 318: An injection needle. 320: A needle guard housing that hides the needle 318 and is retractable to allow injection. 322: A seal that prevents fluid from entering the needle 308. A more detailed view of the needle assembly and needle guard of this embodiment is shown in Figure 3D Shown in 323: A needle guard assembly that prevents fluid from leaving the device and blocks accidental injection. In this state, the guard extends over the needle. 324: A needle guard housing that hides the needle 342 and is retractable to allow injection. 326: A guide rail that allows the needle guard to be slid into place using the guard guide 328. 328: A needle guard guide that mates with the guide rail 326. 330: A needle stabilizer and attachment. 338: A safety clip that prevents the needle guard housing 324 from retracting before intended use. 340: A connection between the needle guard assembly and the injection device. 342: An injection needle. 344: A compression spring that pushes the needle guard into place around the needle. 346: A seal that prevents liquid from entering or leaving the needle before injection. Figure 3E Shows another embodiment of the needle assembly and needle guard. 348: Another embodiment of a needle guard assembly that prevents fluid from leaving the device and blocks accidental injection. In this state, the guard extends over the needle. 350: A needle guard housing that hides the needle and is retractable to allow injection. 352: A device housing that also serves as a needle guard guide. 354: A needle exit that may include a seal for preventing fluid from entering or leaving the injection needle.

[0037] Figure 4A side cross-sectional view of an embodiment having a device body, a needle assembly, and an attached guard is shown. 400: A needle guard assembly that prevents fluid from leaving the device and blocks accidental injection. In this state, the guard extends over the needle. 402: A guide rail that allows the needle guard to be slid into place using a guard guide 446. 404: The attachment point of the needle guard assembly to the main device. 406: A needle stabilizer and attachment. 408: A spring that compresses when the filling chamber 444 is filled and then moves the assembly 410 through the chamber 444. 410: A movable seal assembly. 412: A seal that prevents material from entering the syringe 448. 414: Sealing material on the chamber 438. 416: The beveled entry point for the insertion rod 428. 418: The first chamber in the device. 420: The main device housing. 422: A fluid outlet that allows fluid transfer between the chambers 418 and 436. 424: An embodiment of a three-chamber system for mixing two materials having a needle assembly and a guard. 426: An activation system that initiates the mixing of the materials. 428: An insertion rod. 430: A seal around the insertion rod. 434: A pierceable seal between the chambers 418 and 436. 436: The second chamber in the device. 438: The housing of the second chamber. 440: A sliding seal for the movable component 246. 442: A safety clip that prevents the needle guard from being activated until it is removed. 444: The third chamber in the device. 448: A needle for performing an injection. 450: A seal that prevents fluid from entering the needle 448. 452: An exit point for the needle to extend from the needle guard.

[0038] Figure 5A A side cross-sectional view of a first operable condition of the device disclosed herein is shown. 500: The first operable condition before the device is activated. 502: A needle guard housing that extends around the needle. 504: In this state, the mixing chamber is empty. 506: A movable seal assembly that acts as a barrier between the chambers 508 and 504. 508: The chamber 508 contains material to be mixed with the material in the chamber 510. 510: The chamber 510 contains material to be mixed with the material in the chamber 508. 512: An insertion rod for piercing the barrier 516 and pushing the material from the chamber 510 into the chamber 508. 514: An activation assembly, which can be a plunger, a screw system, or some other type of mechanism, for compressing the device and moving the materials to be mixed into the chamber 504. 516: A barrier between the chambers 510 and 508. 518: A safety clip that prevents the needle guard 502 from retracting.

[0039] Figure 5BA side cross-sectional view showing a second operable condition of the device disclosed herein. 542: Insertion rod, partially inserted into cavity 546. 544: Activation assembly, which can be a plunger, screw system, or some other type of mechanism for compressing the device and moving the materials to be mixed. 546: First cavity in the device. 548: Pierced seal, allowing cavity 550 and 546 to be in fluid contact. 550: Second cavity in the device.

[0040] Figure 5C A side cross-sectional view showing a third operable condition of the device disclosed herein. 520: Third operable condition, where the device has been activated and the materials have been mixed but not yet injected. 522: Mixing cavity containing materials from the first two cavities. 524: Compression assembly, activated to allow the materials in the first two cavities to mix. 526: Insertion rod, fully moved through the first cavity to push all the materials through the second cavity and into cavity 522. 528: Sealing assembly, moved away from the input end of the materials from the first two cavities to create a space for material mixing in cavity 522. 530: Compression spring, loaded at this time and capable of injecting the mixed materials once the needle guard 532 retracts. 532: Needle guard, in the non-retracted position, preventing the mixed materials in cavity 522 from being removed from cavity 522 through the needle. 534: Seal preventing the materials in cavity 522 from being removed through the needle.

[0041] Figure 5D A side cross-sectional view showing a fourth operable condition of the device disclosed herein. 536: Fourth operable condition, where the needle guard has retracted and the mixed materials have been extruded from the mixing cavity. 538: Needle guard, retracted to expose the needle and allow the mixed liquid to be extruded from the device. 540: Sealing assembly, moved back into the device to extrude the mixed liquid through the needle from the device. 542: Compression spring, moved back into the device to extrude the mixed liquid from the device. 544: Injection needle.

[0042] Figure 6 A side cross-sectional view showing three main operable conditions of the device disclosed herein and the final state where the device has been removed from the injection site. 600: Operable condition before the safety pin is removed. The device has been activated and the materials for injection are mixed as shown due to the presence of a movable sealing assembly near the bottom of the third cavity. 602: The safety pin has been removed and the device can now be pressed against a surface, such as the patient's skin, for injection. 604: The device has been pushed onto the patient or other surface, causing the needle guard to retract and the needle to enter the injection volume. The device is held in place until the injection is complete. 606: After all the liquid has been injected, the device is moved upward, causing the needle guard to extend and cover the needle again. In the case where the movable sealing assembly moves to a position away from the bottom of the device, it indicates the completion of the injection.

[0043] Figure 7 A side cross-sectional view shows the internal components of the second chamber 722 of an embodiment of the device disclosed herein and how they are distributed between the other two chambers 714 and 728. 700: The internal components of the second chamber and associated components. 702: A compression spring that holds the seal assembly 724 in place and allows the mixed material from chamber 728 to be extruded from the device during injection. 704: A seal that prevents the transfer of material from chamber 722 to chamber 728 and prevents liquid from entering the needle 726. 706: The housing of chamber 722. 708: The entry point for inserting the rod 714 into chamber 722. 710: A seal around chamber 710 that prevents fluid flow. 712: A barrier that prevents the transfer of material between chambers 714 and 722. 714: The first chamber in the device, which contains material to be mixed with the material in chamber 722. 716: An insertion rod for piercing the barrier 712 and squeezing the material from 714 into 722. 718: A fluid path that allows fluid transfer between chambers 720 and 714. 720: A piercing point that allows the barrier 712 to be pierced. 722: Chamber 722 contains material to be mixed with the material in 714. 724: A seal assembly that acts as a barrier between 728 and 722 and pushes the fluid out of the device during injection. 726: An injection needle. 728: A mixing chamber that holds the mixed material from 714 and 722 waiting to be injected.

[0044] Figure 8 A side cross-sectional view shows an embodiment of the device disclosed herein that uses a screw mechanism to drive a piston downward. 800: Another embodiment of the activation assembly, where the device is twisted and the screw mechanism pushes the piston downward. This is the state of the device before activation. 802: The activation assembly, in the state after activation, where the piston has been pushed downward to cause the mixing of the two materials. Detailed Description

[0045] The present disclosure relates to systems, methods, and devices for storing, transporting, mixing, and injecting drugs in solution. The disclosed systems, methods, and devices can be better understood by reference to the following detailed description of specific embodiments and examples included herein, and by reference to the accompanying drawings and their prior and following descriptions.

[0046] It should be understood that the terms used herein are only for describing specific embodiments and are not intended to limit the scope of the present disclosure, which will be limited only by the appended claims.

[0047] It must be noted that, as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a nucleic acid sequence" includes a plurality of nucleotides that are formed, and reference to "the nucleic acid sequence" refers to one or more nucleic acid sequences and equivalents thereof known to those skilled in the art, and so on.

[0048] Ranges may be expressed herein as from "about" one particular value and / or to "about" another particular value. When expressing such ranges, ranges from one particular value and / or to another particular value are also specifically contemplated and considered to be disclosed, unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent "about", it will be understood that the particular value forms another specifically contemplated embodiment and should be considered to be disclosed, unless the context specifically indicates otherwise. It will be further understood that each of the two endpoints of each range is significant with respect to the other endpoint and independent of the other endpoint, unless the context specifically indicates otherwise. When referring to measurable values such as amounts, durations, etc., the term "about" as used herein is intended to cover variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or ±0.1% because such variations are appropriate for carrying out the disclosed methods.

[0049] "Optional" or "optionally" means that the subsequent described event, circumstance, or material may or may not occur, exist or not exist, and the description includes the case where the described event, circumstance, or material occurs or exists, as well as the case where it does not occur or does not exist.

[0050] As used in the specification and claims herein, the term "and / or" shall be understood to mean "either or both" of the elements so combined, i.e., elements that exist in some cases in a combined form and in other cases in a non-combined form. Except for the elements specifically identified by the "and / or" language, other elements may optionally exist, whether related or unrelated to those specifically identified elements, unless there is a clear contrary indication. Thus, as a non-limiting example, when used in conjunction with open-ended language such as "comprising", in some embodiments, reference to "A and / or B" means having A and not having B (optionally including elements other than B); in another embodiment, reference to "A and / or B" means having B and not having A (optionally including elements other than A); in yet another embodiment, reference to "A and / or B" means having both A and B (optionally including other elements).

[0051] As used in the specification and claims of this application, "or" shall be understood to have the same meaning as "and / or" as defined above. For example, when separating items in a list, "or" or "and / or" shall be interpreted inclusively, that is, including at least one of a plurality of elements or a list of elements, and may also include more than one, and optionally further includes additional unlisted items. Only terms that explicitly indicate the contrary meaning, such as "only one of them" or "exactly one of them", or when used in the claims, "consisting of" shall refer to exactly one of a plurality of elements or a list of elements. Generally, the term "or" as used herein shall be interpreted as referring to an exclusive alternative (i.e., "one or the other, but not both at the same time") only when preceded by an exclusive term such as "any one of", "one of", "only one of", or "exactly one of". When used in the claims, "consisting essentially of" shall have the ordinary meaning used in the field of patent law.

[0052] As used herein, the term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable diluent" is intended to mean an excipient, carrier, or diluent that can be administered to a subject together with the formulations or pharmaceutical compositions disclosed herein, and that excipient, carrier, or diluent is inert or does not abrogate the pharmacological activity of the active agent of the pharmaceutical composition. In some embodiments, the pharmaceutically acceptable carrier does not actually disrupt or abrogate the pharmacological activity of the active agent / vaccine, and the carrier is non-toxic when the dose administered is sufficient to deliver a therapeutic dose of the active agent. As used herein, the term "pharmaceutically acceptable salt" can be an acid salt or a base salt that is generally recognized in the art as suitable for contact with human or animal tissue without undue toxicity, irritation, allergic response, or other problems or complications. Such salts include mineral salts and organic acid salts having basic residues such as amine salts, and base salts or organic salts having acidic residues such as carboxylate salts. Specific pharmaceutical salts include, but are not limited to, salts of acids such as hydrochloric acid, phosphoric acid, hydrobromic acid, malic acid, gluconic acid, fumaric acid, sulfuric acid, amidosulfonic acid, sulfonic acid, formic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, nitric acid, benzoic acid, 2-p-acetylbenzoic acid, citric acid, tartaric acid, lactic acid, stearic acid, salicylic acid, glutamic acid, ascorbic acid, pantothenic acid, succinic acid, fumaric acid, maleic acid, propionic acid, hydroxymaleic acid, hydriodic acid, phenylacetic acid, alkanoic acids such as acetic acid, HOOC-(CH2)n-COOH where n is 0-4, and the like. Similarly, pharmaceutically acceptable cations include, but are not limited to, sodium, potassium, calcium, aluminum, lithium, and ammonium. One of ordinary skill in the art will recognize from this disclosure and common general knowledge in the art that additional pharmaceutically acceptable salts for the viral-specific antigens or polynucleotides for aggregation are provided herein, and such additional pharmaceutically acceptable salts include those listed in the 17th edition of Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, PA, p. 1418 (1985)). Generally, pharmaceutically acceptable acid salts or base salts can be synthesized from the parent compounds containing basic or acidic moieties that can be obtained by conventional chemical methods. Briefly, such salts can be prepared by reacting the free acid or base forms of these compounds with an appropriate basic or acidic component in a suitable solvent in a stoichiometric amount.

[0053] As used herein, the term "prevent" (e.g., "prevent" or "preventing") is intended to mean reducing the likelihood of the occurrence of a disease or disorder in a subject who is not diseased but is at risk of or predisposed to the disease or disorder.

[0054] As used herein, the terms "subject", "individual", "host", and "patient" are used interchangeably herein and refer to a vertebrate individual in need of diagnosis, treatment, or cure, including but not limited to mammals or humans, particularly humans. Mammals include but are not limited to rodents, apes, humans, farm animals, cows, pigs, goats, sheep, horses, dogs, sport animals, and pets. The methods described herein are applicable to human therapy and veterinary applications. In some instances, in the context of the description of the present disclosure, the term "patient" refers to a human patient suffering from a particular disease or disorder. In some embodiments, the subject is an animal, and in other embodiments, the subject is a human.

[0055] As used herein, the term "treat" ("treat", "treated", "treating", "treatment", etc.) refers to reducing or alleviating a disease and / or symptoms associated therewith (such as a viral infection). "Treat" can refer to administering to a subject the DNA vaccine described herein after the onset or suspected onset of a viral infection. "Treatment" encompasses the concept of "alleviation", which refers to reducing the occurrence, recurrence frequency, or severity of any symptoms or other adverse reactions associated with the virus and / or side effects associated with virus treatment. The term "treatment" also encompasses the concept of "management", which refers to reducing the severity of a particular disease or disorder in a patient or delaying its recurrence, for example, prolonging the remission period of a patient already suffering from the disease. It is understood that while not excluded, treating a disease or disorder does not require the complete elimination of the disease, disorder, or symptoms associated therewith.

[0056] For the therapeutic agents described herein, a therapeutically effective amount can be initially determined from preliminary in vitro studies and / or animal models. A therapeutically effective dose can also be determined from human data. The dose administered can be adjusted based on the relative bioavailability and potency of the preparation administered. Adjusting the dose to achieve maximum efficacy based on the foregoing methods and other well-known methods is within the ability of one of ordinary skill in the art. The general principles for determining therapeutic effectiveness, which can be found in Chapter 1 of Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th Edition, McGraw-Hill (New York) (2001) and are incorporated herein by reference, are summarized as follows. Pharmacokinetic principles provide the basis for adjusting dosing regimens to achieve a desired degree of therapeutic effect and minimal unacceptable adverse reactions. In cases where the plasma concentration of a drug can be measured and is related to a therapeutic time window, additional guidance for dose adjustment can be obtained. Pharmaceutical products are considered pharmaceutically equivalent if they contain the same active ingredient and are identical in strength or concentration, dosage form, and route of administration. Two pharmaceutically equivalent products can be considered bioequivalent if the rate and extent of bioavailability of the active ingredient in the two products do not differ significantly under appropriate test conditions.

[0057] As used herein, the term “comprising” (and any form of “comprising,” such as “comprise,” “comprises,” and “comprised”), or “containing” (and any form of “containing,” such as “contains” and “contain”) is inclusive or open-ended and does not exclude additional, unrecited elements or method steps.

[0058] As used herein, the term “about” means that the value is approximate and that small variations will not significantly affect the implementation of the disclosed embodiments. When referring to measurable values such as amounts, durations, etc., the term “about” as used herein is intended to cover variations of ±10%, ±5%, ±1%, or ±0.1% around a particular value, as such variations are suitable for carrying out the disclosed methods. If a numerical limitation is used, unless the context otherwise indicates, “about” means that the numerical value can vary by ±10%, ±5%, ±4%, ±3%, ±2%, or ±1% and still remain within the scope of the disclosed embodiments.

[0059] References in the specification and in the appended claims to the weight portions of specific elements or components in a composition denote the weight relationship between that element or component and any other element or component in the composition or article which is expressed in weight portions. Thus, in a compound containing two weight portions of X and five weight portions of Y, the weight ratio of X to Y is 2:5, and this ratio exists regardless of whether additional components are present in the compound.

[0060] Unless otherwise specifically stated, the weight percentage (wt.%) of a component is based on the total weight of the formulation or composition containing that component.

[0061] As used herein, the terms “administering,” “administered,” and “administration” refer to any method of providing a pharmaceutical preparation to a subject. Such methods are well known to those of skill in the art and include, but are not limited to, oral, transdermal, inhalation, nasal, topical, intravaginal, ophthalmic, otic, intracerebral, rectal, and parenteral administration, including injectables such as intravenous, arterial, intramuscular, and subcutaneous administration. Administration may be continuous or intermittent. In various embodiments, the preparation may be administered therapeutically; that is, administered to treat an existing disease or condition. In various additional embodiments, the preparation may be administered prophylactically; that is, administered to prevent a disease or condition. As used herein, the terms “parenteral administration” and “administered parenterally” refer to modes of administration other than enteral and topical administration, usually by injection, including, but not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, and intrasternal injection.

[0062] As used herein, the term “optional” or “optionally” means that the subsequent described event or circumstance may or may not occur, and that the description includes examples where said event or circumstance occurs and examples where it does not.

[0063] As used herein, the term “diagnosed” means having been examined physically by a person of skill, such as a physician, and found to have a condition that can be diagnosed or treated by the compounds, compositions, or methods disclosed herein.

[0064] The present disclosure relates to systems, methods, and devices for storing, transporting, mixing, and injecting a drug in solution. The disclosed systems, methods, and devices are more readily understood by reference to the following detailed description of specific embodiments and examples included in the specific embodiments, and by reference to the accompanying drawings and their prior and following descriptions.

[0065] As used herein, the term "contact" means bringing one of the disclosed compounds into contact with a cell, target receptor, or other biological entity such that the compound can directly affect the activity of the target (e.g., receptor, cell, etc.), i.e., by interacting with the target itself; or such that the compound can indirectly affect the target, i.e., by interacting with another molecule, cofactor, factor, or protein upon which the activity of the target depends.

[0066] As used herein, the term "compartment" means a space defined by one or more continuous surfaces to form an internal volume separated from the external environment by said one or more surfaces. In some embodiments, the compartment is defined by one or more surfaces and can be a volume of any shape, such as a rectangular prism or a cylindrical space. The present invention generally relates to devices comprising a first compartment, a second compartment, and / or a third compartment, these compartments including cylindrical or substantially cylindrical cavities or spaces having walls aligned in sequence such that at least one end of the cylindrical or substantially cylindrical space is adjacent or close to at least one end of another compartment, such cylindrically aligned compartments defining the interior of the device. In some embodiments, the compartments become part of a closed system once aligned and fixed to each other via a physical connection between one or more exteriors or interiors of one or more of their surfaces.

[0067] As used herein, the term "active agent" means a drug or other substance that treats a subject upon administration. In some embodiments, the active agent or derivative thereof is selected from one or a combination of the following:

[0068]

[0069]

[0070] *Doses are expressed in approximate amounts. Any dose should be interpreted to mean "from about X to about Y". For example, the dose of sodium succinate hydrocortisone should be from about 50 milligrams per milliliter to about 150 milligrams per milliliter.

[0071] The term "movable element" refers to a shaft, plunger, rod, fastener, or other component or element of the device that is capable of moving in any direction relative to the longitudinal axis of the device. In the case where the device is cylindrical, the longitudinal axis defines the center point around the circumference of the device.

[0072] "Derivatives" of the compounds disclosed herein are pharmaceutically acceptable salts, prodrugs, deuterated forms, radiolabeled forms, isomers, solvents, and combinations thereof. The "combinations" referred to in the context mean derivatives that fall within the scope of at least two of the following: pharmaceutically acceptable salts, prodrugs, deuterated forms, radiolabeled forms, isomers, and solvents. Examples of radiolabeled forms include compounds labeled with tritium, phosphorus-32, iodine-129, carbon-11, fluorine-18, etc.

[0073] As used herein, the term "disease" refers to an affliction of a subject that causes a malfunction of the body. In some embodiments, the disease is one or a combination of diseases selected from the diseases in Table 2.

[0074]

[0075]

[0076] As used herein, the term "carrier" refers to a diluent, adjuvant, or excipient by which a compound is administered. A pharmaceutical carrier can be a liquid, such as water and oils, including petroleum, animal, vegetable or synthetically-derived oils, such as peanut oil, soybean oil, mineral oil, sesame oil, etc. The pharmaceutical carrier can also be saline, gum arabic, gelatin, starch paste, talc, keratin, colloidal silica, urea, and the like. In addition, adjuvants, stabilizers, thickeners, lubricants, and coloring agents can be used. A pharmaceutical composition includes a compound carried in a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier refers to a sterile aqueous or non-aqueous solution, dispersion, suspension or emulsion, and sterile powders for the reconstitution of sterile injectable solutions or dispersions prior to use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.), carboxymethyl cellulose and suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters, such as ethyl oleate. Compounds can be formulated using pharmaceutically acceptable carriers or diluents and any other known adjuvants and excipients according to conventional techniques such as those disclosed in Remington: The Science and Practice of Pharmacy (19th Edition, edited by Gennaro, published by Mack Publishing Company, Easton, Pa., 1995). The term "pharmaceutically acceptable carrier" is well recognized in the art and includes pharmaceutically acceptable materials, compositions or vehicles suitable for administering the compounds of the present invention to mammals. The carrier includes liquid or solid fillers, diluents, excipients, solvents or encapsulating materials for transporting a pharmaceutical formulation from one organ or body part to another. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials that serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil, etc.; glycols, such as propylene glycol; polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. Suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by E.W. Martin, the entire text of which is incorporated herein by reference.

[0077] Wetting agents, emulsifying agents and lubricants, such as sodium sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening agents, flavoring agents, filling agents, preservatives and antioxidants may also be present in the composition.

[0078] Examples of pharmaceutically acceptable antioxidants include: water-soluble antioxidants such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, etc.; oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, etc.; and metal chelating agents such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, etc.

[0079] The amount of the active ingredient that can be combined with the carrier material to produce a single dosage form is usually the amount of the compound that can produce a therapeutic effect. Generally, relative to the total amount of 100%, the amount of the active ingredient ranges from about 1% to about 99%, preferably from about 5% to about 70%, more preferably from about 10% to about 30%. The methods for preparing these preparations or compositions include the step of mixing the compounds of the present invention with the carrier and optionally one or more auxiliary components. Generally, the preparation is prepared by uniformly and intimately mixing the compounds of the present invention with a liquid carrier or a subdivided solid carrier or both, and then, if necessary, shaping the product.

[0080] In the solid dosage forms for oral administration (capsules, tablets, pills, dragees, powders, granules, etc.) of the present invention, the active ingredient is mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or calcium phosphate, and / or any one of the following: fillers or bulking agents such as starch, lactose, sucrose, glucose, mannitol and / or silicic acid; binders such as, for example, carboxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose and / or acacia; humectants such as glycerol; disintegrants such as agar, calcium carbonate, potato starch or tapioca starch, alginic acid, certain silicates and sodium carbonate; solution retarders such as paraffin wax; absorption promoters such as quaternary ammonium compounds; wetting agents such as, for example, cetyl alcohol and glyceryl monostearate; adsorbents such as kaolin and bentonite clay; lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof; and coloring agents. For capsules, tablets and pills, the pharmaceutical composition may also include buffering agents. Solid compositions of a similar type may also use excipients such as such adjuvants of lactose or milk sugar, as well as high molecular weight polyethylene glycols, etc. as fillers in soft-filled and hard-filled gelatin capsules.

[0081] Tablets can preferably be made by compression or molding using one or more auxiliaries. Compressed tablets are prepared using binders (e.g., gelatin or hydroxypropyl methylcellulose), lubricants, inert diluents, preservatives, disintegrants (e.g., sodium starch glycolate or croscarmellose sodium), surfactants or dispersants. Molded tablets can be made by molding a mixture of powdered compounds moistened with an inert liquid diluent in a suitable machine.

[0082] Tablets and other solid dosage forms of the pharmaceutical compositions of the present invention, such as dragees, capsules, pills and granules, can optionally be scored or prepared using coatings and shells such as enteric coatings and other coatings known in the art of pharmaceutical formulation. They can also be formulated using, for example, hydroxypropyl methylcellulose in various proportions to facilitate slow or controlled release of the active ingredient to provide the desired release profile, other polymer matrices, liposomes, vesicles and / or microspheres. For example, they can be filtered through bacteria-retaining filters, or sterilized by adding a sterilizing agent to form a sterile solid composition that can be dissolved in sterile water, or sterilized with some other sterile injection medium immediately prior to use. These compositions can also optionally contain opacifying agents and can be compositions that release one or more active ingredients solely or preferentially in a specific part of the gastrointestinal tract, optionally in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. If appropriate, the active ingredient can also be used in microencapsulated form together with one or more of the above excipients.

[0083] Liquid dosage forms for oral administration of the compounds of the present invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms can contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizers and emulsifying agents, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol and fatty acid esters of sorbitol, and mixtures thereof.

[0084] In addition to the inert diluent, the oral compositions can also include adjuvants such as wetting agents, emulsifying agents and suspending agents, sweetening agents, flavoring agents, coloring agents, perfuming agents and preservatives. Suspensions, in addition to the active compound, may contain suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, metahydroxyaluminum, bentonite, agar and tragacanth, and mixtures thereof.

[0085] It should be understood that all individual values and sub-ranges of values included within the explicitly disclosed scope are also specifically contemplated and should be considered to be disclosed herein, unless the context indicates otherwise. The foregoing applies regardless of whether some or all of these embodiments are explicitly disclosed in a particular instance.

[0086] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed methods and compositions pertain. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present methods and compositions, particularly useful methods, devices, and materials are described herein. Publications cited herein and the materials referenced therein are hereby incorporated by specific reference. Nothing in this disclosure shall be construed as an admission that the present disclosure is not entitled to antedate such disclosure by virtue of prior disclosure. No admission is made that any reference cited herein constitutes prior art. The discussion of references states the claims of their authors, and the applicant reserves the right to challenge the accuracy and relevance of the cited literature. It will be clearly understood that, although some publications are cited herein, such references do not constitute an admission that any of these publications forms part of the common general knowledge in the art.

[0087] In the detailed description and claims of this specification, the word “comprising” and variations thereof, such as “comprises” and “comprising,” mean “including but not limited to” and are not intended to exclude, for example, other additives, components, integers, or steps. Specifically, in a method stated to comprise one or more steps or operations, each step is to be considered to comprise the recited elements (unless the step contains limiting terms such as “consisting of”), which means that each step is not intended to exclude, for example, other additives, components, integers, or steps not listed in that step.

[0088] Multiple possible embodiments of the present disclosure are contemplated and described in more detail herein. Minor changes in the physical properties of the components can be made without departing from the meaning of the present disclosure and while remaining within the disclosed purpose and function of the present disclosure to design commercial products for various objectives, including cost control, chemical compatibility, ease of use, manufacturing cost and convenience, various drugs, and target disease indications. For example, the disclosed device can be utilized with various drugs, including but not limited to those for Hydrocortisone, methylprednisolone for multiple sclerosis, chemotherapy for certain cancers, chronic treatment drugs for autoimmune diseases, biotherapy, glucagon for hypoglycemic emergencies, ticarcillin for high-incidence infections, chlordiazepoxide for alcohol withdrawal symptoms, and deoxycorticosterone trimethylacetate for veterinary emergencies, etc.

[0089] During the administration of its drugs, such as during adrenal crisis periods, some embodiments of the present disclosure are beneficial to patients with congenital adrenal hyperplasia (CAH), Addison's disease, and idiopathic adrenal insufficiency. For example, for the 144 million patients globally with CAH, Addison's disease, and idiopathic adrenal insufficiency, some embodiments of the present disclosure are expected to improve the administration efficacy of life-saving injectable drugs. Some exemplary embodiments of the present disclosure require as few as four injection steps and can be designed specifically for patients experiencing adrenal crisis and their caregivers. For example, the exemplary embodiments of the present disclosure can specifically improve the efficacy of the drug, mainly for use in patients with CAH.

[0090] In some embodiments, the present disclosure provides an apparatus comprising: (1) a delivery assembly including a main tube and a handle fixed at a mixing end of the main tube opposite the injection end of the main tube; (2) a storage assembly adapted to fit within the lumen of the main tube and including a first seal, a liquid-impermeable plunger adapted to fit within the first seal, a liquid injection piston adapted to couple the first seal and the liquid-impermeable plunger together, a drug container adapted to contain an unmixed drug, a foil seal attached to the liquid injection side of the drug container, a second seal adapted to couple to an injection side of the drug container opposite the liquid injection side, and an optional air filter adapted to be placed between the second seal and the injection side of the drug container; (3) a mixing assembly adapted to attach to the handle and partially fit within the lumen of the main tube, adapted to engage the storage assembly, and including a twist cap having an internal thread and rotatably engaging the handle, a piston guide engaging the twist cap, and a mixing spring engaging the guide, wherein the guide has a flange located within the internal thread, the guide sequentially passes through a cap hole of the twist cap, a handle hole of the handle, and the lumen of the main tube, and the mixing spring is adapted to fit within the lumen of the main tube and be located between the guide and the first seal of the storage assembly; and (4) an injection assembly adapted to engage the injection end of the main tube and partially fit within the lumen of the main tube, adapted to engage the storage assembly, and including a protective cap, a cap spring, a hollow needle, a needle driver, and an injection spring, wherein the protective cap is adapted to movably cover the injection tip of the needle, the cap spring is adapted to be positioned between the protective cap and the needle driver and be compressed to move the protective cap away to expose the injection tip of the needle, the needle passes through the needle driver and is integrated within the needle driver, the needle passes through a tube closure at the injection end of the lumen of the main tube, and the injection spring is adapted to be positioned between the tube closure and the second seal of the storage assembly, wherein the needle is adapted to pierce the second seal when the protective cap is fully compressed against the needle driver and the needle driver is fully compressed against the injection end of the lumen of the main tube.

[0091] In some embodiments, the devices or apparatuses of the present disclosure are used to facilitate the transportation and proper storage of drugs within the device or apparatus until the drugs are needed by the patient, at which time the device is used to administer the drugs to the patient. To administer the drugs to the patient, the drugs must be mixed with a liquid such as water to prepare a drug mixture in solution. To use the mixing assembly to mix the drugs, the user twists the twist cap relative to the handle such that the flange of the piston guide rotates within the threads, causing the guide to move towards the mixing spring and compress the mixing spring, such that the mixing spring applies pressure to the first seal and pushes the liquid injection piston towards the drug container. As the liquid injection piston moves towards the drug container, the liquid injection piston pierces the foil seal and enters the container bore of the drug container, such that the liquid stored in the main tube between the first seal and the foil seal enters the drug container and mixes with the unmixed drugs to form a drug in solution. The movement of the liquid injection piston towards and against the drug container creates a liquid pressure that pushes the drug in solution through the drug container to the injection end of the main tube, and pushes the second seal towards the tube closure, thereby compressing the injection spring. The displacement of the second seal towards the tube closure forms a chamber between the second seal (near the injection end) and the drug container (near the mixing end), and the drug in solution contained in the chamber is under the pressure of the injection spring against the second seal. The injection assembly optionally further includes a safety device adapted to be attached to the needle driver, the protective cap, and / or the main tube, such as a removable safety clip, to prevent the protective cap and the needle driver from moving such that the cap spring is compressed and the injection tip of the needle is exposed, and to prevent the needle driver from moving towards the main tube such that the second seal is pierced. The safety device can be disengaged, such as by removing the safety clip, to allow the injection assembly to be engaged. After the removable safety clip has been removed, the device is ready for the protective cap to be pressed against the patient, such as against the patient's bare skin. With the removable safety clip removed, pressing the protective cap against the patient causes the protective cap to retract towards the needle driver, causing the needle driver to retract towards the main tube, and causing the needle driver to drive the needle inward into the tube bore of the main tube. In the case where the drugs have been mixed using the mixing assembly, the drug in solution is located in the chamber, waiting to be injected into the patient. Driving the needle inward causes the input tip of the needle to pierce the second seal. The input tip of the needle then enters the chamber, allowing the drug in solution to enter the needle bore of the hollow needle and withdraw the drug in solution from the chamber. The drug in solution enters the input tip of the needle, passes through the needle bore, and exits the needle at the injection tip. The injection spring, which has been compressed by the mixing step using the mixing assembly, applies pressure to the second seal to move the second seal backward towards the drug container, thereby reducing the chamber volume of the chamber and pushing the drug in solution out of the chamber, through the needle, out of the injection tip and into the patient's body.

[0092] Other aspects of the disclosure are set forth herein. Details of the exemplary embodiments of the disclosure are set forth in the accompanying drawings and the specification below. Other features, objects, and advantages of the invention will be apparent from the specification and drawings and from the claims.

[0093] In some embodiments, in the disclosed device: (1) a transmission assembly including a main tube and a spring piston screwed into the main tube at a mixing end opposite the injection end of the main tube; (2) a storage assembly adapted to fit within the lumen of the main tube and including a first seal, a liquid-impermeable plunger adapted to fit within the first seal, a liquid ejection piston adapted to couple the first seal and the liquid-impermeable plunger together, a drug container adapted to contain an unmixed drug, a foil seal attached to the liquid ejection side of the drug container, a second seal adapted to couple to the injection side of the drug container opposite the liquid ejection side, and an optional air filter adapted to be placed between the second seal and the injection side of the drug container; (3) a mixing assembly adapted to attach to the main tube and partially fit within the lumen of the main tube, adapted to engage the storage assembly, and including a push rod having an annular groove and slidably engaging the main tube, wherein the push rod passes through a tube opening of the lumen of the main tube, the push rod is adapted to fit within the lumen of the main tube, and abuts against the piston and the first seal of the storage assembly, and when the push rod is further pushed into the lumen of the main tube and is pushed from an un-pushed position to a pushed position to mix the drug and the liquid, the spring piston of the transmission assembly is adapted to engage the annular groove; and (4) an injection assembly adapted to engage the injection end of the main tube and partially fit within the lumen of the main tube, adapted to engage the storage assembly, and including a hollow needle, a needle driver, a tube plunger, and an injection spring, wherein the needle passes through the needle driver and is integrated within the needle driver, the needle driver is adapted to slide on the injection end of the main tube, the needle passes through the tube plunger, the tube plunger includes a tube closure at the injection end of the lumen of the main tube, and the injection spring is adapted to be positioned between the tube closure and the second seal of the storage assembly, wherein when the needle driver is fully compressed against the injection end of the main tube, the needle is adapted to pierce the second seal. In some embodiments, the second seal may include a chamber piston having an inner cavity with a piston center hole proximate the drug container, a diaphragm placed within the inner cavity and covering the piston center hole, and a spring guide placed within the inner cavity and covering the diaphragm, wherein the spring guide includes a guide center hole and engages the injection spring of the injection assembly.

[0094] In some embodiments, the devices or apparatuses of the present disclosure are used to facilitate the transportation and proper storage of a drug within the device or apparatus until the drug is needed by the patient, at which time the device is used to administer the drug to the patient. In some embodiments, the needle driver is adapted to be transported and stored separately from the remainder of the device until the device is used. The separate needle driver optionally may include tip protectors at the injection tip and at the input tip to protect the tips and to protect the user from accidental needle sticks. When administering the drug to the patient, the drug must be mixed, the needle driver readied for use (e.g., any tip protectors and sterile packaging removed), the needle driver grasped by its sidewall, the injection end of the needle inserted into the patient (preferably with the patient's skin flush with the surface of the needle driver proximate the injection tip), and the needle driver slid onto the injection end of the main tube such that the input tip of the needle pierces the second seal and the drug in the solution is discharged from the chamber. In some embodiments, the needle driver is slid onto the main tube before the injection tip of the needle is inserted into the patient's skin, thereby starting the release of the drug in the solution.

[0095] Before administering the drug to a patient, the drug must be mixed with a liquid such as water to prepare a drug mixture in solution. In a second specific embodiment, in order to use the mixing assembly to mix the drug, the user pushes the push rod relative to the main tube until the annular groove reaches the spring plunger, such that the spring plunger extends into the annular groove and locks the push rod in place. Pushing the push rod causes the liquid injection piston to move forward to apply pressure to the first seal and push the liquid injection piston towards the drug container. As the liquid injection piston moves towards the drug container, the liquid injection piston pierces the foil seal and enters the container bore of the drug container, such that the liquid stored in the main tube between the first seal and the foil seal enters the drug container and mixes with the unmixed drug to produce a drug in solution. The movement of the liquid injection piston towards and against the drug container creates a liquid pressure that pushes the drug in solution through the drug container towards the injection end of the main tube and pushes the second seal towards the tube closure, thereby compressing the injection spring. The displacement of the second seal towards the tube closure creates a cavity between the second seal (near the injection end) and the drug container (near the mixing end), and the drug in solution contained in the cavity is under the pressure of the injection spring against the second seal. The injection assembly optionally further includes a safety device, such as a removable safety cap, adapted to be attached to the main tube to protect the tube closure at the injection end. The safety device can be disengaged, such as by removing the safety cap, to allow the injection assembly to be engaged. After the removable safety device is removed, the device is ready to have the needle driver pressed against a patient, such as flush with the patient's exposed skin, where the needle pierces the patient's skin to a desired depth determined by the length of the needle extending beyond the needle driver, which is equal to the distance from the injection tip to the surface of the needle driver near the injection tip. Pressing the needle driver against the patient can be accompanied by and cause the needle driver to slide onto the main tube, such that the needle driver drives the needle inward into the tube bore of the main tube. Assuming that the mixing assembly has been used to mix the drug, the drug in solution is located in the cavity, waiting to be injected into the patient. At this time, driving the needle inward will cause the input end of the needle to pierce the second seal. The input end of the needle then enters the cavity, thereby allowing the drug in solution to enter the needle bore of the hollow needle and discharge the drug in solution from the cavity. The drug in solution enters the input end of the needle, passes through the needle bore, and exits the needle at the injection tip. The injection spring that has been compressed by the mixing step using the mixing assembly applies pressure to the second seal to move the second seal backward towards the drug container, thereby reducing the cavity volume of the cavity and pushing the drug in solution out of the cavity, through the needle, out of the injection tip and into the patient's body. Alternatively, before the injection tip of the needle is inserted into the patient's skin, the needle driver can be slid onto the main tube, thereby starting to release the drug in solution.

[0096] Other aspects of the disclosure are set forth herein. Details of the exemplary embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.

[0097] Now refer to Figure 1A and Figure 1B . Figure 1A FIG. shows a side cross-sectional view of one embodiment of the device disclosed herein. Assembly 100 includes two chambers, a first chamber 102 and a second chamber 104, separated by a seal in an unactivated state to prevent material transfer between the two chambers. The first chamber 102 houses a material in liquid, solid, semi-solid, or gaseous form, to be mixed with another material housed in the second chamber 104. Upon activation, the material located within the first chamber 102 is pushed through the second chamber 104, whereby the material located within the second chamber 104 is mixed with the material from the first chamber 102. These materials are mixed by the action of a compression mechanism 114, as Figure 1B shown. The compression mechanism 114 moves the material from the first chamber 112 (equivalent to Figure 1A 102 in Figure 1A ) to the second chamber 110 (equivalent to

[0098] Now refer to Figure 2A , Figure 2A which shows a side cross-sectional view of another embodiment of the device disclosed herein. Figure 2A The device in

[0099] also includes a movable member, a chamber barrier, a seal, and other components associated with an auto-injector. Device assembly 200 consists of a housing 218 containing three chambers and associated components. The device includes a compression assembly 202 that interacts with an insertion rod 204. The insertion rod is pushed through the first chamber 216 to pierce the chamber seal 206. The chamber seal 206 is an impermeable membrane that prevents material transfer between the first chamber 216 and the second chamber 208. Upon device activation and subsequent pressing of the compression assembly 202, the insertion rod 204 pierces the barrier 206 and pushes the material from the first chamber 216 through the pierced seal 206 and into the second chamber 208. The material from the first chamber 216 moves into the second chamber 208, where it mixes with the material in the second chamber 208 and together they move into the third chamber 210. As the mixed material moves into the third chamber 210, the combined mixed materials push the seal assembly 214 into the third chamber 210. When the seal assembly 214 is pushed inward into the third chamber 210, the spring 212 is compressed, storing energy that will subsequently be used to drive the material through a needle for injection out of the device.

[0099] Now refer to Figure 2B, which shows a side cross-sectional view of another embodiment of the device disclosed herein, wherein the insertion rod of the piercing seal is two components (220, 254) instead of one. The device assembly 220 includes a housing 256, three chambers (a first chamber 254, a second chamber 234, and a third chamber 240), and an insertion rod assembly 260 composed of multiple components including an internal insertion rod 224, an external housing 258, and a seal 226. The internal insertion rod 224 further includes a fluid path 230 and a fluid discharge port 228 that allow fluid to transfer between the first chamber 254 and the second chamber 234. When the compression mechanism 222 is pressed inward onto the assembly 260, the internal assembly rod is pushed in and pierces the barrier 232. After the barrier 232 is pierced, fluid can enter the fluid discharge port 228 and be transmitted through the fluid path 230 into the second chamber 234, or fluid can move from the second chamber 234 in the opposite direction through the fluid path 230 and out of the fluid discharge port 228. Once the internal insertion rod 224 has pierced the barrier 232 and becomes flush with the external assembly 258 on the rear side, the entire assembly 260 is compressed by the compression mechanism 222 into the second chamber 234. The insertion part of the internal rod will move entirely into the second chamber 234 and the external assembly, and the large head end of the insertion rod will be flush with the outside of the second chamber 234. During the compression, the material from the first chamber 254 moves through the first chamber 254 and mixes with the material in the second chamber 234. An optional seal 250 around the chamber housing 236 prevents the material from flowing out of the chamber. The mixed material is pushed inward into the third chamber 240. When the mixed material is pushed into the third chamber 240, the movable seal assembly 246 moves inward into the third chamber 240, thereby creating a space for accommodating the mixed material. The movable seal assembly 246 includes a seal 238 and a housing 262 that serves as an attachment point for the needle guide and spring 244.

[0100] When the assembly 246 moves into the third chamber 240, the seal 248 is pierced by the non-injection end of the injection needle 242. This allows fluid to enter the injection needle 242 provided that the injection end of the needle 242 is open. When the assembly 246 moves inward into the third chamber 240, the spring 244 is compressed. The compression force of the spring 244 will be used to inject the mixed material.

[0101] Now refer to Figure 3A , which shows a side cross-sectional view of another embodiment of the device disclosed herein, wherein the needle assembly has a needle guard 302 attached to the main device 300. In some embodiments, the needle assembly and the guard are attached to the device by a threaded connection system, but they can also be attached by gluing, welding, snapping, press-fitting, or other known attachment methods in the art.

[0102] A more detailed view of the needle assembly and the guard of this embodiment is shown inFigure 3B is shown. In this state, the device has not been activated and no component mixing has occurred. The needle guard 304 includes a housing 306 that is held in an extended position covering the needle 308 by a spring 312. The injection end of the needle is covered by a seal 314 that prevents fluid from entering or leaving the needle until the guard 304 retracts and the needle 308 penetrates the seal 314 and is exposed. To activate the needle guard 304, the safety pin 310 is removed from the device, which allows the housing 306 to retract on the device housing, thereby exposing the needle 308. When the needle guard 316 retracts, as shown in Figure 3C , when the needle housing 320 retracts and the needle 318 has penetrated the seal 322, the needle 318 is exposed, which will allow the material to be injected. In Figure 3C the state shown, the device has been activated and the components have been mixed, but the injection operation has not yet started.

[0103] Figure 3D shows a further more detailed embodiment of the needle guard 328 and the assembly 322. The guard housing 324 is guided in its movement by aligning with and seating in a guide 328 in a rail 326. The needle 342 is held in place by a needle attachment 330. The needle 342 is sealed at the injection end by a seal 346 that prevents fluid from entering or leaving the device until the needle guard housing 322 retracts to expose the needle 342. To activate the needle guard, the safety pin 338 is removed to allow the assembly 322 to retract and the needle to penetrate the seal 346 and be exposed. After injection, the spring 344 pushes the needle guide back into place to hide the needle.

[0104] Now refer to Figure 3E , which shows another embodiment of the needle assembly and the needle guard, where the needle guard 348 is formed by a housing 350 and is guided in its movement by the body of the device 352. The injection end of the needle is sealed by a seal 354.

[0105] Now refer to Figure 4, shows a side cross-sectional view of another embodiment with a device body, a needle assembly, and a guard attached. The needle assembly and guard 400 are attached to the main device body 424 by attachment points 404. The attachment can be by threads, adhesives, welds, press fits, snap fits, or other well-known means in the art. The device body consists of an activation mechanism 426 and three chambers (a first chamber 418, a second chamber 436, and a third chamber 444), all located within a housing 420. The insertion rod 428 is contained within the first chamber 418 and optionally includes a seal 430. A fluid path 432 and a fluid outlet 422 are contained within the insertion rod 428. The end of the insertion rod 428 is adjacent to a barrier 434 that separates the first chamber 418 and the second chamber 436. The second chamber 436 is contained within a housing 438, which may include a seal 414 or may be a part of the housing itself. The second chamber 436 is kept separated from the third chamber 444 by a movable seal assembly 410 and an optional seal 440. A seal 412 is attached to the movable seal assembly 410 to prevent material from entering the needle 448 before device activation.

[0106] Upon device activation, the compression mechanism 426 pushes the insertion rod 428 through the barrier 434 and into the second chamber 436. The insertion rod 428 enters the second chamber 436 through an opening 416, which allows material transfer and possible seating of the insertion rod 428. Material from the second chamber 436 and the first chamber 418 moves through the second chamber 436, and the movable seal assembly 410 moves into the third chamber 444 to compress a spring 408. The mixed material resides inside the third chamber 444 until the needle guard assembly 400 retracts for injection.

[0107] To allow injection after device activation, a clip is removed, allowing the needle guard 400 to retract and expose the needle 400. Before the needle guard 400 retracts, the injection end of the needle is sealed by a seal 450 that prevents material from entering or leaving the needle 448. After retraction, the needle 448 is exposed through a needle port 452. During retraction, the needle guide 446 follows a needle rail 402 to allow proper movement of the needle guard assembly. The needle 448 is attached by a needle attachment 406.

[0108] The device of the present disclosure can be held under Figures 5A to 5D four different operable conditions shown in Figure 5A, the first operable condition 500 is the state before equipment startup in which no material mixing has occurred. The compression mechanism 514 has not been activated and thus does not press the insertion rod 512. The first chamber 510 contains the first material to be mixed, and the seal 516 has not been pierced. The second chamber 508 contains all the materials to be mixed. The movable seal assembly 506 serves as a barrier between the second chamber 508 and the third chamber 504, and no material enters the third chamber 504. The safety pin 518 is still located on the equipment, and the needle guard has not retracted.

[0109] See Figure 5B , under the second operable condition, the compression assembly 544 has been partially activated. The insertion rod has pierced into the first chamber 546 by piercing the seal 548. The first chamber 546 and the second chamber 550 are in fluid communication, but the materials have not been fully mixed.

[0110] See Figure 5C , under the third operable condition 520, the compression assembly 524 has been fully activated and has pushed the insertion rod 526 into the first chamber 527. The materials have been mixed and moved into the second chamber 522. The movable seal 528 has caused the spring 530 to retract and compress. The safety pin 529 is still in place, the needle guard 532 has not retracted, and the seal 534 has not been pierced by the injection needle.

[0111] See Figure 5D , under the fourth operable condition 536, the safety pin has been removed, and the needle guard 538 has retracted, thus exposing the injection needle 544. The spring 542 has been pushed back into the equipment and the fluid has been driven out from the needle 544. The movable seal 540 has been pushed backward to the middle of the equipment.

[0112] Now see Figure 6 , which shows three main operable conditions, and the final state in which the equipment has been removed from the injection position. Before injection (state 600), the equipment is close to the surface for injection. Once located at or near the injection surface (state 602), the pin is removed, and then the equipment is pushed downward (state 604), thus pushing the needle through the injection surface. After injection is completed (state 606), the equipment is lifted and the needle guard hides the needle again.

[0113] Now see Figure 7, which shows an embodiment of the internal components of the second chamber 722 and how they are distributed between the other two chambers (the first chamber 714 and the third chamber 728). The second chamber 722 is housed within a housing 706, which in turn is housed within an outer casing 700 and is optionally surrounded by a seal 710. The insertion rod 716 is initially held adjacent to the barrier 712. The insertion rod 716 includes a fluid path 718 and a piercing end for piercing the barrier 712. The piercing end 720 may have one or more sharp or blunt protrusions to allow easy piercing of the seal 712. Once the seal 712 is pierced, the insertion rod is pushed through the opening 708 into the second chamber 722, which opening 708 may be beveled or otherwise shaped to facilitate entry of the insertion rod and transfer of material from the first chamber 714 into the second chamber 722. Material from the first chamber 714 is pushed into the second chamber 722 and through the second chamber 722, and the movable seal assembly 724 and the needle seal 704 are moved into the third chamber 728 to allow transfer of material into the third chamber 728. After the above components are moved into the third chamber 728, the spring 702 is compressed and the needle seal 704 is pierced by the non-injecting end of the needle 726, thereby allowing material to enter the needle during injection.

[0114] Now refer to Figure 8 , which shows a side cross-sectional view of an embodiment of the device disclosed herein that uses a screw mechanism to drive a piston downward. Assembly state 800 shows the device in an unactivated state, and when rotated in assembly state 802, the assembly drives the piston into the device to compress the components and activate the device.

[0115] The devices described herein may be implemented as specific articles of various sizes and may use components of various sizes, and are applied to their uses according to various operating parameters for various purposes.

[0116] These dimensional characteristics and use parameters may be the subject of selection for a specific purpose and may include the force applied to the injection site for injecting an active agent, the volume of the drug to be delivered, the size of the internal passage through the needle, the injection depth determined by the length of the needle protruding from the device, the spring force applied to the needle tip to expel the drug, and the time interval required to inject the drug when the device is activated. It is believed that these factors, alone and / or in combination and possibly in other circumstances, act on the effectiveness of the device in delivering the drug into the patient's body and dispersing the drug from the initial injection site into the surrounding body tissue, which may be referred to as the "uptake" of the drug.

[0117] The force applied to the injection site is ultimately determined by the pressure with which the device is pressed against the user's body, as selected by the user, but the minimum level of this force is determined by the design of the device itself and the force required to drive the device. In some embodiments, the driving force for releasing the active agent is between 4 pounds and 8 pounds. In some embodiments, the driving force for releasing the active agent is between 2 pounds and 8 pounds. In some embodiments, the driving force for releasing the active agent is between 4 pounds and 6 pounds. In some embodiments, the driving force for releasing the active agent is between 2 pounds and 6 pounds. In some embodiments, the force actually applied by the user is at least about 2 pounds. In some embodiments, the force actually applied by the user is at least about 3 pounds. In some embodiments, the force actually applied by the user is at least about 4 pounds. In some embodiments, the force actually applied by the user is at least about 5 pounds. In some embodiments, the force actually applied by the user is at least about 6 pounds. In some embodiments, the force actually applied by the user is at least about 7 pounds. In some embodiments, the force actually applied by the user is at least about 8 pounds.

[0118] The force required to inject an active agent into a patient can also vary depending on the viscosity of the fluid mixture obtained from the active agent and a pharmaceutically acceptable carrier. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of from about 1 cP (centipoise) to about 150 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of from about 5 cP (centipoise) to about 125 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of from about 10 cP (centipoise) to about 100 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of from about 15 cP (centipoise) to about 75 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of from about 20 cP (centipoise) to about 60 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of from about 25 cP (centipoise) to about 50 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 1 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 5 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 10 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 25 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 50 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 75 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 100 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 110 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 120 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 130 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 140 cP will be injected by the disclosed device.In some embodiments, a fluid mixture of an active agent having a viscosity of about 150 cP and a pharmaceutically acceptable carrier will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent having a viscosity greater than about 150 cP and a pharmaceutically acceptable carrier will be injected by the disclosed device.

[0119] After injection, the time interval during which the needle is held in place against the injection site is typically determined based on the manufacturer's recommendations printed on the autoinjector label. In some embodiments, a time interval of at least about 2 seconds is recommended for holding in place. In some embodiments, a time interval of at least about 3 seconds is recommended for holding in place. In some embodiments, a time interval of at least about 4 seconds is recommended for holding in place. In some embodiments, a time interval of at least about 5 seconds is recommended for holding in place.

[0120] The volume of the drug to be delivered depends on the internal dimensions of the device, which are selected by the manufacturer to administer the desired volume of the active agent. For example, when administering epinephrine using an autoinjector, an injection volume of about 0.15 mL or about 0.30 mL can be used. Larger volumes of injection can also be administered. In some embodiments, depending on viscosity and other factors, volumes from about 0.50 mL to about 3.0 mL can be rapidly injected using any of the disclosed devices. In these embodiments, the injection volume or dispersion volume of the active agent referred to is the total volume of the liquid injected into the patient and these references are independent of the amount of active ingredient contained in the injection volume. However, in some embodiments, the devices of the present disclosure can be used to deliver a predetermined amount or dose of the active agent into the patient. In some embodiments, when using corticosterone or a corticosterone derivative, a dose of the corticosterone or corticosterone derivative weighing from about 5 mg to about 500 mg is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative weighing from about 10 mg to about 400 mg is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative weighing from about 25 mg to about 300 mg is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative weighing from about 50 mg to about 250 mg is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative weighing from about 60 mg to about 200 mg is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative weighing from about 75 mg to about 150 mg is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative having a weight content of the active agent in the unit volume solution in a pharmaceutically acceptable carrier from about 5 mg / mL to about 300 mg / mL is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative having a weight content of the active agent in the unit volume solution in a pharmaceutically acceptable carrier from about 10 mg / mL to about 250 mg / mL is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative having a weight content of the active agent in the unit volume solution in a pharmaceutically acceptable carrier from about 15 mg / mL to about 200 mg / mL is used with the disclosed devices. In some embodiments, a dose of the corticosterone or corticosterone derivative having a weight content of the active agent in the unit volume solution in a pharmaceutically acceptable carrier from about 20 mg / mL to about 175 mg / mL is used with the disclosed devices.In some embodiments, a corticosterone or corticosterone derivative at a dosage of about 25 mg / mL to about 150 mg / mL by weight of the active agent in a unit volume of solution in a pharmaceutically acceptable carrier is used with the disclosed device. In some embodiments, a corticosterone or corticosterone derivative at a dosage of about 30 mg / mL to about 125 mg / mL by weight of the active agent in a unit volume of solution in a pharmaceutically acceptable carrier is used with the disclosed device.

[0121] It should be understood that the amount of the active agent, such as corticosterone or a corticosterone derivative, in the drug of the injection volume can vary. The amount of the active agent in the injection volume can vary according to the dosage prescribed for the patient. The prescribed dosage of corticosterone or a corticosterone derivative can be, for example, about 1 mg, about 5 mg, about 10 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg. These dosages of the active agent can be formulated with other ingredients, such as a pharmaceutically acceptable carrier, to comprise a volume of the drug from 0.15 mL to about 0.6 mL. The amount of the active agent does not have to be directly related to the volume of the drug to be injected, as the volume can be diluted as needed. For example, 0.30 mL of the injected drug can comprise from about 1 mg to about 25 mg of the active agent.

[0122] The size of the internal passage of the needle is determined by the manufacturer by selecting a suitable gauge of tubing for the needle. Small-diameter stainless steel tubing commonly used for subcutaneous injection needles is available in various standard sizes known as gauges. The gauge determines the nominal outer diameter of the tubing. Then, for each gauge, the tubing is typically available in various wall thicknesses known as regular wall (RW), thin wall (TW), extra-thin wall (ETW), and ultra-thin wall (UTW). The thinner the wall of the tubing for a given gauge, the larger the inner diameter or bore of the tubing will be. And for each standard tubing size, such as, for example, 22-gauge RW tubing, applicable standards specify minimum, nominal, and maximum values for each dimension, such as the inner diameter. For the devices of the present disclosure, the needle can be constructed from RW stainless steel tubing in gauges as large as 18 gauge and as small as 24 gauge. Wall thicknesses other than RW can also be selected. The following table shows the standard minimum inner diameter, nominal inner diameter, and maximum inner diameter of 18-gauge to 24-gauge RW stainless steel tubing. All dimensions are given in inches.

[0123] Specification Type Minimum Inner Diameter Nominal Inner Diameter Maximum Inner Diameter 18 RW 0.0315 0.0330 0.0345 19 RW 0.0255 0.0270 0.0285 20 RW 0.0230 0.0238 0.0245 21 RW 0.0195 0.0203 0.0210 22 RW 0.0155 0.0163 0.0170 23 RW 0.0125 0.0133 0.0140 24 RW 0.0115 0.0123 0.0130

[0124] Accordingly, the minimum of these inner diameters is selected, and the minimum inner diameter of the 24-gauge RW tubing is about 0.0115 inches. In the case of selecting the 23-gauge RW tubing, its inner diameter will be at least about 0.0125 inches. In the case of selecting the 22-gauge RW tubing, its inner diameter will be at least about 0.0155 inches. For all selections shown in the table above, the inner diameter of the needle will not be greater than about 0.0345 inches, and about 0.0345 inches is the maximum inner diameter of the 18-gauge RW tubing.

[0125] The injection depth determined by the needle length protruding from the disclosed device is shown, for example, in Figure 6 The dimensions determined by the sizes of the various internal components are adapted to the particular active agent to be injected. For example, for subcutaneous injection of an active agent, the device can provide an injection in the subcutaneous region, where, in some embodiments, the depth of the injection is from about 0.15 inches to about 0.30 inches. In other embodiments, the depth of the injection into the subject's body is from about 0.2 inches to about 0.25 inches. For intramuscular injection of an active agent, the disclosed device can provide an injection in the muscle region, where, in some embodiments, the depth of the injection is from about 0.4 inches to about 0.7 inches. In other embodiments, the depth of the injection into the subject's body is about 0.6 inches. In some embodiments, the depth of the intramuscular injection that the disclosed device can provide is up to about 1.25 inches into the subject's body.

[0126] The spring force applied to expel the active agent is determined by the manufacturer's selection of the biasing spring and by the design of the various internal components, which will affect how much of the available spring force is actually applied. A given spring will have a certain static force when compressed that holds the spring in the compressed state and is appropriate for the surrounding structure. When the spring is released, some of its potential energy will be lost due to friction and moving the needle and collapsing the needle sheath, such that the force that the spring actually applies to the plunger to expel the active agent, i.e., the dynamic force applied to the plunger, is less than the initial static force output of the spring. For example, when compressed, the spring can have a nominal static force output of about 100 Newtons. Due to manufacturing tolerances, the actual static force output of this spring can range from about 0 Newtons to about 100 Newtons. Then, the dynamic force that the spring actually applies to the plunger to expel the active agent ranges from about 10 Newtons to about 75 Newtons. The dynamic force can be described as at least about 10 Newtons, about 20 Newtons, about 30 Newtons, about 40 Newtons, about 50 Newtons, about 60 Newtons, about 70 Newtons, about 80 Newtons, about 90 Newtons, or about 100 Newtons.

[0127] The device according to the present disclosure can be used to deliver a wide range of active agents into a subject's body. Of particular interest is to provide the active agents in Table 1 at the doses listed herein.

[0128] Table 1. Active agents and corresponding doses applicable to the present disclosure

[0129]

[0130]

[0131] In some embodiments, the disclosed device is used to deliver one or more of the active agents selected from Table 1 into a patient. In some embodiments, the disclosed device is used to deliver one or more of the active agents selected from Table 1 in the doses identified in Table 1 into a patient. In some embodiments, the disclosed device is used to deliver corticosterone into a patient. In some embodiments, the disclosed device is used to deliver a corticosterone derivative into a patient. In some embodiments, the disclosed device is used to deliver sodium hydrocortisone succinate into a patient. In some embodiments, one or more of the active agents are delivered into a patient using the disclosed device in the presence of one or more of pharmaceutically acceptable carriers. In some embodiments, the pharmaceutically acceptable carrier used is water for injection. In some embodiments, the pharmaceutically acceptable carrier used is sterile water for injection. In some embodiments, the pharmaceutically acceptable carrier used is bacteriostatic water for injection. In some embodiments, the pharmaceutically acceptable carrier used is sodium chloride in water. In some embodiments, the pharmaceutically acceptable carrier used is sodium bicarbonate in water. In some embodiments, the pharmaceutically acceptable carrier used is a dimethyl sulfoxide solution in water.

[0132] Method

[0133] The present disclosure provides methods for treating and / or preventing a disease or disorder in a patient, including administering one or more active agents by any of the devices disclosed herein. The present disclosure further provides a method of treating a subject in need of administration of one or more active agents, including administering a pharmaceutically effective amount of one or more of the active agents by any of the disclosed devices. In some embodiments, the subject is diagnosed with or suspected of having a cortisol disorder. As used herein, "cortisol disorder" refers to a disease or disorder in which the cortisol secretory function is dysregulated to an abnormal level. In some embodiments, the cortisol disorder is Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenomyeloneuropathy, adrenoleukodystrophy, adrenal tumor, Schmidt syndrome, hyperaldosteronism, pituitary tumor, pituitary cyst, or corticosteroid insufficiency associated with critical illness. In some embodiments, the subject is diagnosed with or suspected of having cortisol depletion. In some embodiments, the subject's cortisol depletion is caused by: Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenal neuropathy, adrenoleukodystrophy, adrenal tumor, Schmidt syndrome, hyperaldosteronism, pituitary tumor, pituitary cyst, or corticosteroid insufficiency associated with critical illness.

[0134] In addition to corticosterone or corticosterone derivatives, the disclosed devices can also be used to deliver other non-emergency active agents to a subject in need thereof for the desired treatment. Examples of such non-emergency active agents include, but are not limited to, non-emergency steroids, antibiotics, painkillers, disease-specific therapies (e.g., MS therapy, psoriasis therapy), insulin, glycoproteins, immunomodulators, G-CSF, erythropoietin biological agents, antihypertensives, vaccines, hormones (including contraceptives), antihormones, sedatives, antiepileptics, antineoplastics, insecticides (e.g., dobutamine), antipsychotics, antidotes, cosmetics, selective serotonin reuptake inhibitors (SSRI), proton pump inhibitors (PPI), anesthetics, diuretics, antidiuretics, blood thinners (e.g., low molecular weight heparin), streptokinase, etc., used alone or in combination, whether in liquid form, reconstitutable form or other form. In some embodiments, the devices of the present disclosure can be used to deliver agents that have been used previously drugs delivered by the system, namely methylprednisolone for multiple sclerosis, certain cancers, and autoimmune conditions. In some embodiments, the devices of the present disclosure are used to deliver glucagon for hypoglycemic emergencies. In some embodiments, the devices of the present disclosure are used to deliver ticarcillin for treating high-incidence infections. In some embodiments, the devices of the present disclosure are used to deliver chlordiazepoxide for treating alcohol withdrawal symptoms. In some embodiments, the devices of the present disclosure are used to deliver desoxycorticosterone trimethylacetate for veterinary emergencies. In some embodiments, the devices of the present disclosure are used for in vitro fertilization procedures.

[0135] The devices of the present disclosure can be manufactured from any device known to those skilled in the relevant art, particularly in the field of autoinjectors. In some embodiments, the first compartment, the second compartment, and the third compartment are physically attached to the housing by friction fitments, rivets, plugs, or plastic welding such as radio frequency welding or ultrasonic welding. These compartments can also be attached to the housing or to each other via the same techniques or by protrusions such as snap fitments. The components of the device can be plastic, rubber, glass, or metal. Most, if not all, of the sealing materials will be composed of plastic or rubber, while the chambers will be composed of plastic, glass, or metal. The plunger rod will be plastic or metal and will be attached to any seal by an interlocking mechanism based on grooves for attachment, or by helical threads. In embodiments where a movable system is attached to the plunger rod, the movable system will be attached by friction. The seal attached to the chamber will be press-fitted into place using friction, attached by an interlocking groove system, or threaded into place. In some embodiments, these compartments are cylindrical or substantially cylindrical, having protrusions for fastening at both ends. In some embodiments, there is one or more fasteners on each side of the compartment and on each side of the device components.

[0136] Methods according to various aspects of the present disclosure include, for example, methods of using a device for transporting, storing, mixing, and injecting a drug into a patient, wherein the device includes: a delivery assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the method includes: providing the device, engaging the mixing assembly to mix the drug and create the drug in solution when ready to administer the drug to the patient, and engaging the injection assembly to inject the drug in solution into the patient. The method may also include disengaging a safety device prior to engaging the injection assembly to inject the drug in solution into the patient.

[0137] Another method according to various aspects of the present disclosure includes, for example, a method of assembling a device for transporting, storing, mixing, and injecting a drug into a patient, wherein the device includes: a transfer assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the method includes: providing and assembling the transfer assembly, providing and assembling the storage assembly, providing and assembling the mixing assembly, and providing and assembling the injection assembly.

[0138] A system according to various aspects of the present disclosure includes, for example, a system for assembling a device for transporting, storing, mixing, and injecting a drug into a patient, wherein the device includes: a transfer assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the system includes: a device for assembling the transfer assembly, a device for assembling the storage assembly, a device for assembling the mixing assembly, and a device for assembling the injection assembly.

[0139] A method according to various aspects of the present disclosure includes, for example, a method of using a device for transporting, storing, mixing, and injecting a drug into a patient, wherein the device includes: a transfer assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the method includes: providing the device, engaging the mixing assembly to mix the drug and create the drug in solution when preparing to administer the drug to the patient, and engaging the injection assembly to inject the drug in solution into the patient. The method may further include disengaging a safety device prior to engaging the injection assembly to inject the drug in solution into the patient's body.

[0140] Another method according to various aspects of the present disclosure includes, for example, a method of assembling a device for transporting, storing, mixing, and injecting a drug into a patient, wherein the device includes: a transfer assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the method includes: providing and assembling the transfer assembly, providing and assembling the storage assembly, providing and assembling the mixing assembly, and providing and assembling the injection assembly.

[0141] A system according to various aspects of the present disclosure includes, for example, a system for assembling a device for transporting, storing, mixing, and injecting a drug into a patient, wherein the device includes: a transfer assembly, a storage assembly, a mixing assembly, and an injection assembly, and wherein the system includes: a device for assembling the transfer assembly, a device for assembling the storage assembly, a device for assembling the mixing assembly, and a device for assembling the injection assembly.

[0142] Manufacturing method

[0143] The devices described herein include active agents to be injected into the body and must therefore be manufactured using aseptic sterilization techniques. General techniques for manufacturing include sterilization of the device components, filling of the active agent and the carrier agent, assembly of the active agent in contact components, and assembly of non-active agent in contact components. Filling of the active agent and the carrier agent and assembly of some of the active agent in contact components must be done within a sterilization processing manufacturing facility commonly referred to as the sterilization core.

[0144] Component sterilization techniques are known in the art. Filling of the medicament depends on the device characteristics and whether the active medicament is solid or liquid. Liquids can be filled using dispensing techniques by volume measurement or flow measurement. Powders and other solids can be filled by inserting the powder or solid material using a density or weight-based measurement system for determining the total fill amount.

[0145] In one manufacturing method of the device, the cavity is capped at the distal end using a movable seal, and the capped cavity is then inserted into the sterilization core. The active agent is inserted into the cavity by a powder filling method or a liquid filling method. The liquid can be lyophilized or not, depending on the active agent type and device requirements. The filled cavity is then capped at the proximal end and inserted into the main device tube for injection. Then, a second medicament is filled onto the first cavity using a powder or liquid filling method, an insertion rod is added, and the exposed end of the second filled cavity is sealed. A needle is added to the device, and the complete subassembly is removed from the sterilization core. The remaining components are assembled onto the device outside the sterilization core.

[0146] In another manufacturing method, the device components are sterilized outside the sterilization core. The needle assembly, the movable seal, and a chamber are inserted into the main device housing outside the sterilization core, and the assembled subassembly is then transferred into the sterilization core, where the active agent is inserted into the exposed cavity using a liquid or powder filling method. The cavity is capped, and again using a liquid or powder filling method, a second active agent is added on top of the first active agent. An insertion rod and a seal are added above the newly filled cavity, and the assembly is removed from the sterilization core. Any final manufacturing assembly steps are completed, and the device is packaged and labeled for distribution.

[0147] In another manufacturing method, the component is sterilized. The main device tube and the needle are assembled and inserted into a sterilization core. The device cavity is sealed at the distal end with a movable seal and placed into the same sterilization core. The active agent is inserted into the cavity using a powder filling method or a liquid filling method. If desired, the liquid is lyophilized. Once filling is complete, the cavity is sealed at the proximal end. The filled and sealed cavity is inserted into the main device tube. Liquid or powder is then filled on top of the previous cavity. An insertion rod and a seal are added above the newly filled cavity, and the assembly is removed from the sterilization core. Any final manufacturing assembly steps are completed, and the device is packaged and labeled for distribution.

[0148] In some embodiments, the first compartment, the second compartment, and the third compartment are physically attached to the housing by friction fit members, rivets, plugs, or plastic welding such as radio frequency welding or ultrasonic welding. These compartments may also be attached to the housing or to each other via the same techniques or by protrusions such as snap fit members. The components of the device will be plastic, rubber, glass, or metal. In some embodiments, the sealing material will be made of plastic or rubber, while the cavity will be made of plastic, glass, or metal. In some embodiments, the insertion rod will be plastic or metal and attached to any seal by an interlocking mechanism based on grooves for attachment, or by helical threads. In embodiments where a movable system is attached to the insertion rod, the movable system will be operably attached by friction. The seal attached to the cavity will be press fit in place using friction, attached by an interlocking groove system, or threaded in place. In some embodiments, these compartments are cylindrical or substantially cylindrical, having protrusions for fastening at both ends. In some embodiments, there is one or more fasteners on each side of the compartment and on each side of the device component.

[0149] The foregoing description discloses exemplary embodiments of the present disclosure. While the invention disclosed herein has been described by its specific embodiments and their applications, various modifications and variations can be made thereto by those skilled in the art without departing from the scope of the invention as set forth in the claims. Modifications to the devices and methods disclosed above that fall within the scope of the claimed invention will be apparent to those of ordinary skill in the art. Accordingly, other embodiments may also fall within the spirit and scope of the claimed invention, as defined by the following claims.

[0150] The present disclosure relates to a method of administering one or more active agents using a device to treat a subject in need thereof. In some embodiments, the administration method includes compressing a movable element to a first predetermined position such that an insertion rod pierces a seal for separating a first compartment and a second compartment on a first opening. In some embodiments, the method further includes waiting for a period of time to elapse to allow the active agent and the diluent in the first compartment and the second compartment to mix and dissolve and / or activate the active agent. In some embodiments, the method further includes, after a first pressing step, pressing the movable element to a second predetermined position at a second sequential time such that the insertion rod is displaced and pierces a seal for separating the second compartment and a third compartment. In some embodiments, the method further includes allowing a second period of time to elapse such that the active agent contacts the end of the needle with a pharmaceutically acceptable carrier or diluent. In some embodiments, the method further includes pressing the movable element a third time to a fully compressed position such that a spring of the needle assembly is released and a distal end of the needle is deployed into the patient's body. In some embodiments, the method further includes unlocking the needle assembly before fully compressing the movable element. In some embodiments, the first predetermined distance is about 1 cm to about 5 cm during movement toward the needle assembly. In some embodiments, the second predetermined distance is about 1 cm to about 5 cm during movement toward the needle assembly. In some embodiments, the third predetermined distance is about 2 cm to 6 cm.

[0151] In some embodiments, the administration method does not include a third pressing of the movable element, and the final release of the spring of the needle assembly is accomplished by applying pressure only to the end of the device proximal to the needle assembly. In this case, the operation of applying pressure to the device by the patient or operator in the longitudinal axis direction releases the spring and ejects the needle tip with a certain force, thereby injecting the pharmaceutical composition into the subject.

[0152] The therapeutically effective amount or dose of a compound can vary within a wide range. Such doses can be adjusted according to the individual requirements of each particular case, which include administering one or more specific compounds, the route of administration, the condition being treated, and the patient being treated. Generally, in the case of oral administration or parenteral administration, a daily dose for an adult weighing about 70 Kg or more should be about 10 mg to 10,000 mg, preferably about 200 mg to 1000 mg, although the upper limit can also be exceeded. The daily dose can be administered as a single dose once a day or in divided doses multiple times a day, or for parenteral administration, continuous injection administration can be used. A single dose composition can contain such an amount or multiple amounts of the compound or composition to constitute a daily dose. The dose can be adjusted by each individual doctor according to the situation of any contraindications. Over one day or several days, the dose can vary, and it can be administered as a single dose once a day or in divided doses multiple times a day.

[0153] In the foregoing description, numerous specific details have been set forth in order to provide a more thorough understanding of embodiments of the present invention. However, it will be apparent to those of ordinary skill in the art that the present invention may be practiced without incorporating all aspects of the specific details described herein. Not all possible embodiments of the present invention are set forth verbatim herein. Multiple combinations of various aspects of the present invention may be formed to create different embodiments that fall within the scope of the claims set forth below. Additionally, specific details well known to those of ordinary skill in the art are not described in detail so as not to obscure the present invention. The reader should note that although examples of the present invention are set forth herein, the full scope of the claims and any equivalents thereof are the measure and limit used to define the scope of protection of the present invention.

[0154] The foregoing specification discloses exemplary embodiments of the present disclosure. Although the present disclosure has been described by way of specific embodiments and their applications, various modifications and variations thereof will be apparent to those skilled in the art without departing from the scope of the present disclosure set forth in the claims. Modifications to the apparatus and methods disclosed above that fall within the scope of the claimed subject matter will be apparent to those of ordinary skill in the art. Accordingly, other embodiments may also fall within the spirit and scope of the claimed subject matter, as defined by the following claims.

[0155] In the foregoing description, numerous specific details have been set forth in order to provide a more thorough understanding of embodiments of the present disclosure. However, it will be apparent to those of ordinary skill in the art that the present disclosure may be practiced without incorporating all aspects of the specific details described herein. Not all possible embodiments of the present disclosure are set forth verbatim herein. Multiple combinations of various aspects of the present disclosure may be formed to create different embodiments that fall within the scope of the claims set forth below. Additionally, specific details well known to those of ordinary skill in the art are not described in detail so as not to obscure the present disclosure. The reader should note that although examples of the present disclosure are set forth herein, the full scope of the claims and any equivalents thereof are the measure and limit used to define the scope of the claimed protection.

Claims

1. A method of injecting a substance from a device, comprising: Providing a device including a first compartment, a second compartment, and a third compartment, each of the first compartment, the second compartment, and the third compartment defining a first chamber, a second chamber, and a third chamber respectively; the first compartment and the second compartment being in fluid communication with a first opening covered by a first seal and separated from each other at the first opening, and the second compartment and the third compartment being in fluid communication with a second opening covered by a second seal and separated from each other at the second opening; the third compartment including a needle assembly having a spring and a needle; Pressing a movable element to a first predetermined position such that an insertion rod moves the first seal away from the first opening, thereby allowing fluid communication between the first compartment and the second compartment; Further pressing the movable element to a second predetermined position such that the insertion rod moves the second seal away from the second opening, thereby allowing fluid communication between the second compartment and the third compartment; And Continuing to press the movable element to a third predetermined position such that the needle assembly injects the substance through the needle.

2. The method according to claim 1, wherein, The first compartment includes a pharmaceutically acceptable carrier in liquid form, and the second compartment includes an active agent in solid or semi-solid form, and wherein fluid communication between the first compartment and the second compartment reconstitutes the active agent in the pharmaceutically acceptable carrier.

3. The method according to claim 1, wherein, The displacement generated by the second predetermined position is sufficient to load the spring in the third compartment with a force of 0 Newton to 100 Newtons, thereby preparing the needle assembly for injection.

4. The method according to claim 1, further comprising the step of unlocking the needle assembly before pressing the movable element to the third predetermined position, ensuring that the needle is exposed and ready for injecting the substance.

5. The method according to claim 1, further comprising releasing the energy stored in the spring when reaching the third predetermined position, thereby driving the needle to inject the substance.

6. A method of operating a medical device, comprising: Pressing a movable element of the device to a first predetermined position, a second predetermined position, and a third predetermined position; Wherein the device includes: a first compartment, a second compartment, and a third compartment, each of the first compartment, the second compartment, and the third compartment defining a first chamber, a second chamber, and a third chamber respectively; the first compartment and the second compartment being in fluid communication with a first opening and separated from each other at the first opening, and the second compartment and the third compartment being in fluid communication with a second opening and separated from each other at the second opening; Wherein the first opening is covered by a first seal, and the second opening is covered by a second seal; and Wherein the third compartment includes a needle assembly, the needle assembly including a spring and a needle operably connected to the spring; Wherein pressing the movable element to the first predetermined position causes the insertion rod to move the first seal away from the first opening and expose the first opening between the first compartment and the second compartment, thereby resulting in fluid communication between the first compartment and the second compartment; Therein, the movable element is pressed to the second predetermined position such that the insertion rod moves the second seal away from the second opening and exposes the second opening between the second compartment and the third compartment, thereby causing fluid communication between the second compartment and the third compartment; and Therein, the movable element is pressed to the third predetermined position such that the contents of the third compartment are injected out through the needle assembly.

7. The method according to claim 6, further comprising unlocking the needle assembly before pressing the movable element to the third predetermined position.

8. The method according to claim 6, further comprising releasing the energy stored in the spring when the third predetermined position is reached, thereby driving the needle to inject the substance.

9. The method according to claim 6, wherein The spring in the third compartment is pre-loaded with a force sufficient to ensure complete injection of the substance through the needle upon activation.

10. A method of injecting a substance from a device, the device including a first compartment, a second compartment, and a third compartment, each of the first compartment, the second compartment, and the third compartment defining a first chamber, a second chamber, and a third chamber respectively; the first compartment and the second compartment are in fluid communication with and separated from each other at a first opening covered by a first seal, and the second compartment and the third compartment are in fluid communication with and separated from each other at a second opening covered by a second seal; the third compartment includes a needle assembly having a spring and a needle, the method comprising pressing a movable element such that: (i) the movable element moves to a first predetermined position such that an insertion rod moves the first seal away from the first opening, thereby allowing fluid communication between the first compartment and the second compartment; (ii) the movable element moves to a second predetermined position such that the insertion rod moves the second seal away from the second opening, thereby allowing fluid communication between the second compartment and the third compartment; and (iii) the movable element moves to a third predetermined position such that the needle assembly injects the substance through the needle.

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