Method for discharging substance from apparatus and method for operating injection device

Abstract

To provide a method for discharging a substance from an apparatus.SOLUTION: By pressing an actuation assembly 426 of the apparatus down to a first predetermined position, an insertion rod 428 displaces a sealing member 434 from an opening 416, thereby allowing fluid communication between a first chamber 418 and a second chamber 436. By pressing the actuation assembly 426 down to a second predetermined position, the insertion rod 428 displaces a sealing member 412 from a second opening, thereby allowing fluid communication between the second chamber 436 and a third chamber 444. By pressing the actuation assembly 426 down to a third predetermined position, a needle assembly discharges a substance through a needle 448.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 981,811, filed February 26, 2020, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to a needle-based device for administering an active agent to a subject, the active agent being in solid or liquid form in one compartment isolated from a diluent or pharmaceutically acceptable carrier in another compartment, the device being capable of exposing the diluent or pharmaceutically acceptable carrier for mixing or dissolving the active agent prior to administration. The present disclosure also relates to systems, methods, and apparatus for storing, transporting, mixing, and injecting drugs as a solution, and in some embodiments, to an injection device intended for use in mixing a drug with a liquid, such as water, in pre-measured amounts and dosages as needed and injecting the drug mixture using an integrated hypodermic needle assembly. [Background technology]

[0003] Emergency injections have long been utilized in response to many forms of extremely time-sensitive, life-threatening events, such as overdose, anaphylaxis, angioedema, or adrenal insufficiency (AI). The urgent and essential nature of the active ingredients necessitates accurate and rapid drug delivery. Indeed, while naloxone auto-injectors (Evzio®) and epinephrine auto-injectors (Epi-pen® and Auvi-Q®) offer dosing systems that are easier to operate and administer, steroid injectors (Solu-Cortef® and Solu-Medrol®) rely on reconstitution and, while equally essential, continue to suffer from cumbersome delivery systems that provide a suboptimal administration device for drug preparation and delivery.

[0004] In this regard, steroid emergency injections, i.e., hydrocortisone, remain the drug of choice in adrenal insufficiency, a condition characterized by the inability of the adrenal glands to produce sufficient amounts of the glucocorticoid cortisol. Cortisol itself is released in response to stress and hypoglycemia; this essential steroid is responsible for glucose production, immunosuppression, and, among other processes, gluconeogenesis, electrolyte balance, and gastric acid secretion, and can also affect sleep, mood, and stress levels. Conversely, a decrease (or deficiency) in cortisol can lead to weakness, fatigue, weight loss, and depression; complete cortisol deficiency can result in sudden adrenal shock or adrenal crisis, in which the body loses its ability to maintain homeostatic function and the individual can experience severe lethargy, confusion, psychosis, convulsions, diarrhea, vomiting, seizures, hypoglycemia, and other life-threatening sequelae, including fatality.

[0005] Historically, patients with congenital adrenal hyperplasia (CAH), Addison's disease, and idiopathic adrenal insufficiency have had difficulty administering their medications. Traditionally, to prepare hydrocortisone for intramuscular (IM) administration, individuals either inject bacteriostatic water or bacteriostatic sodium chloride into a sterile vial containing dry hydrocortisone powder, or utilize the Act-o-Vial® system, which connects a diluent in an upper vial with a lower vial containing the active dry hydrocortisone ingredient. Both methods similarly require the difficult manipulation of different or multiple vials to mix, withdraw, and administer the reconstituted mixture, all within a very short, life-threatening time frame. Even the relatively simple Act-o-vial® drug mixing system requires an average of 12 injection steps by the user, including (1) removing the needle and diluent / drug container, (2) depressing the plastic cover over the vial containing the diluent (releasing the diluent into the vial containing the dry ingredients below), (3) mixing the dry powder with the solution, (4) removing the plastic cover, (5) sterilizing the needle-receiving stopper, (6) inserting the needle into the center of the stopper, (7) drawing up the dose, and (8) injecting the appropriate amount intramuscularly. Due to the complexity of this system, the Act-o-vial® delivery system requires trained medical personnel to ensure accurate withdrawal and administration of potentially life-saving medication. The Act-o-vial® delivery system is not designed for use by non-professionals or individuals with adrenal insufficiency. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] US Patent Application Publication No. 2008 / 0171971 [Patent Document 2] US Patent Application Publication No. 2005 / 0177100 [Patent Document 3] International Publication No. 2009 / 103251 [Patent Document 4] US Patent Application Publication No. 2018 / 0085531 [Patent Document 5] U.S. Patent No. 4,643,721 Summary of the Invention [Problem to be solved by the invention]

[0007] The present disclosure relates to systems, methods, and devices for transporting, storing, mixing, and injecting drugs into a patient, including administering a single dose of a drug to a patient using a drug injection device.

[0008] Rescue steroid injections, i.e., hydrocortisone, remain the drug of choice in adrenal insufficiency, a condition characterized by the inability of the adrenal glands to produce sufficient amounts of the glucocorticoid cortisol. Reduced or absent cortisol can lead to numerous pathologies, including weakness, fatigue, weight loss, and depression. Complete cortisol deficiency can lead to sudden adrenal shock or adrenal crisis, which can be life-threatening. Against this backdrop, the importance of immediate administration of exogenous cortisol (i.e., hydrocortisone) has become essential and mandatory. To date, hydrocortisone is available for hospitalized patients via intravenous injection, intravenous infusion, or intramuscular (IM) injection, but for outpatients, it is typically available as a reconstituted IM injection, typically prepared from a 100 mg to 500 mg dose, for acute, short-term symptoms. [Means for solving the problem]

[0009] Intended to address the shortcomings of prior art devices, the present disclosure focuses on creating a more patient-friendly and effective drug delivery system. The present disclosure aims to improve the efficacy of administering life-saving injectable medications through twist-to-mix delivery systems and devices for the millions of people worldwide who suffer from congenital adrenal hyperplasia (CAH), Addison's disease, and idiopathic adrenal insufficiency. Exemplary embodiments of the disclosed systems and devices require four steps for injection and can be designed for people experiencing adrenal crisis and their caregivers.

[0010] The present disclosure is primarily intended to remedy deficiencies in the area of ​​emergency injectable steroids. The present disclosure also provides a comprehensive range of other emergency medications (e.g., epinephrine and naloxone), as well as other medications, including, but not limited to, non-emergency steroids, antibiotics, painkillers, disease-specific medications (e.g., medications for multiple sclerosis (MS), medications for psoriasis), insulin, glycoproteins, immunomodulators, granulocyte colony-stimulating factor (G-CSF), erythropoietin (Epogen®, Procrit®), biologics, antihypertensives, vaccines, hormones (including birth control), antihormones, and the like. The present disclosure aims to further advance the efficient and effective administration of non-emergency medications, such as steroids, sedatives, antiepileptics, antineoplastics, insecticides (e.g., Dobutrex), antipsychotics, antidotes, cosmetics, selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors (PPIs), anesthetics, diuretics, antidiuretics, blood thinners (e.g., low molecular weight heparin), streptokinase, and the like, alone or in combination, whether in liquid, reconstitutable, or other dosage forms. In some embodiments, the disclosed systems and devices are used to deliver medications previously used with the Act-o-vial® system, namely, methylprednisolone for multiple sclerosis, certain cancers, and autoimmune diseases. In some embodiments, the disclosed systems and devices are used to deliver glucagon for use in hypoglycemic emergencies. In some embodiments, the disclosed systems and devices are used to deliver ticarcillin for use in treating infectious diseases with high morbidity. In some embodiments, the systems and devices of the present disclosure are used to deliver chlordiazepoxide for use in treating alcohol withdrawal. In some embodiments, the systems and devices of the present disclosure are used to deliver desoxycorticosterone pivalate for use in veterinary emergencies. In some embodiments, the systems and devices of the present disclosure are used for in vitro fertilization treatments.

[0011] As described below, embodiments of the present disclosure include the use of drug transport and storage containers, drug mixing systems, and drug injection assemblies using devices, assemblies, systems, and methods that differ from those of the prior art.

[0012] While this disclosure sets forth the best mode(s) contemplated for carrying out the various embodiments disclosed herein, so as to enable those skilled in the art to practice the disclosure, the preferred embodiments are not intended to be limiting, but rather are included in a non-limiting sense suitable for changes and modifications within the scope and spirit of this disclosure and the appended claims.

[0013] According to one aspect of the present disclosure, an apparatus for transporting, storing, mixing, and injecting a drug into a patient is disclosed. The apparatus comprises a transport assembly, a storage assembly, a mixing assembly, and an injection assembly. The transport assembly is configured to provide a convenient method of transporting a drug prior to administration to a patient. The storage assembly is configured to appropriately store the drug and mixing components within the transport assembly prior to drug mixing and to mix the components to form a drug solution immediately prior to injecting the mixture into the patient. The mixing assembly is configured to appropriately mix the drug and mixing components to form a drug solution within the transport assembly in preparation for injecting the mixture into the patient. The injection assembly is configured to appropriately inject the drug solution into the patient once the mixture has been formed.

[0014] According to one aspect of the present disclosure, a method is disclosed for using the device disclosed herein for transporting, storing, mixing, and injecting a drug into a patient. The device includes a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, and the method comprises providing the device, engaging the mixing assembly to mix the drugs to form a drug solution in preparation for administering the drug to the patient, and engaging the injection assembly to inject the drug solution into the patient. In some embodiments, the method further comprises disengaging a safety device before engaging the injection assembly to inject the drug solution into the patient.

[0015] According to one aspect of the present disclosure, a method is disclosed for assembling an apparatus for transporting, storing, mixing, and injecting a drug into a patient, the apparatus comprising a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, the method comprising the steps of 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.

[0016] According to one aspect of the present disclosure, there is disclosed a system for assembling an apparatus for transporting, storing, mixing, and injecting a drug into a patient, the apparatus comprising a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, the system comprising a means for assembling the transport assembly, a means for assembling the storage assembly, a means for assembling the mixing assembly, and a means for assembling the injection assembly.

[0017] Accordingly, the present disclosure provides devices comprising: (a) a first compartment and a second compartment, each defining a first cavity and separated from each other by a first opening in fluid communication with the first opening; (b) a needle assembly; and (c) an insertion rod disposed within the first compartment and operably connected to a movable element, wherein the first opening is covered by a sealing member. In some embodiments, the insertion rod of the disclosed devices comprises two opposing surfaces, the first surface being in physical contact with the movable element and the second surface being disposed within the first cavity, the second surface comprising a protrusion and at least one valve disposed distally from the protrusion. In some embodiments, the protrusion on the second surface of the insertion rod has a chamfered surface. In some embodiments, the movable element of the disclosed devices is physically disposed adjacent to the insertion rod, and the insertion rod is movable when the movable element is depressed into the first compartment and the second compartment in a direction along a longitudinal axis parallel to the first and second compartments.

[0018] In some embodiments, the second compartment of the disclosed device contains an active agent and the first compartment of the disclosed device 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, both the first and second compartments each contain one or more active agents. In some embodiments, both the first and second compartments each contain one or more active agents and 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 contained in the disclosed device is lyophilized.

[0019] In some embodiments, the disclosed device further comprises a third compartment defining a third cavity, the third cavity adjacent to the second compartment and separated from the second compartment by a second opening covered by a second sealing member. In some embodiments, the second sealing member is a movable stopper operatively connected to the movable element, such that when the movable element is depressed, the movable stopper is displaced, placing the second compartment in fluid communication with the third compartment. In some embodiments, when the movable element is depressed, the movable stopper and insertion rod are displaced, placing the second compartment in fluid communication with the third compartment.

[0020] In some embodiments, the third compartment of the disclosed device comprises a needle assembly, the needle assembly comprising a spring and a needle operably connected to the spring, the needle comprising a first fluid opening within the third cavity and a second fluid opening spaced apart from the first and second cavities and opposite the first fluid opening, In some embodiments, the first and second fluid openings are covered by a movable sealing member operably connected to a movable element, such that depression of the movable element into the first and second predetermined positions displaces the first and second sealing members, respectively.

[0021] In some embodiments, the disclosed device, in a first operable state, comprises first, second, and third compartments, the first and second compartments being fluidly connected to one another through a first opening comprising a first sealing member, the second and third compartments being fluidly connected to one another through a second opening covered by a second sealing member, the second compartment being disposed between the first and third compartments on opposite sides of the second compartment, the movable element being in a fully extended position relative to the lateral direction of the device, the first compartment containing a pharmaceutically acceptable carrier, the second compartment containing one or more active agents, and the third compartment containing a needle assembly, and the first and second sealing members covering the first and second openings, respectively, remaining fully intact to prevent fluid from passing from one compartment to another. In some embodiments, the disclosed device, in a second operable state, comprises first, second, and third compartments, the first and second compartments fluidly communicating with each other through a first opening, the second and third compartments fluidly communicating with each other through a second opening covered by a second sealing member, the second compartment being disposed between the first and third compartments located on opposite sides of the second compartment, the movable element being in a partially depressed position relative to the lateral direction of the device, the first and second compartments containing a pharmaceutically acceptable carrier and one or more active agents, the third compartment containing a needle assembly, and the second sealing member covering the second opening to prevent fluid from flowing from the third compartment into the first or second compartment.In some embodiments, the disclosed device, in a third operable state, comprises first, second, and third compartments, the first, second, and third compartments being fluidly connected to one another, the second compartment being disposed between the first and third compartments on opposite sides of the second compartment, the movable element being in a partially depressed position relative to the lateral direction of the device such that the insertion rod pierces the second sealing member, the first, second, and third compartments containing a pharmaceutically acceptable carrier and one or more active agents, the third compartment containing a needle assembly, the second sealing member being pierced or removed from its position covering the second opening, exposing the needle assembly to the active agent and the pharmaceutically acceptable carrier. In some embodiments, the disclosed device, in a fourth operable state, comprises first, second, and third compartments, the first, second, and third compartments in fluid communication with one another, the second compartment disposed between the first and third compartments on opposite sides of the second compartment, the movable element in a fully depressed position relative to the lateral direction of the device, and the needle of the needle assembly exposed. In some embodiments, when the disclosed device is in the second, third, or fourth position, the active agent contained within the disclosed device is dissolved in one or more pharmaceutically acceptable carriers.

[0022] In some embodiments, the active agent contained in any of the disclosed devices is selected from any one or combination of active agents in Table 1. In some embodiments, the active agent is selected from any one or combination of active agents in Table 1 at the dosages specified in Table 1. In some embodiments, the active agent is cortisone or a cortisone derivative. In some embodiments, the cortisone derivative is hydrocortisone sodium succinate, and the dosage of the derivative is about 50 mg to about 250 mg, or about 25 mg / mL to about 150 mg / mL, by weight based on the volume of solution of the active agent in a pharmaceutically acceptable carrier.

[0023] In some embodiments, the first or second compartment of the disclosed device contains a pharmaceutically acceptable carrier in fluid form having a viscosity of about 1 mPa·s to about 150 mPa·s (about 1 cP to about 150 cP).

[0024] In some embodiments, the present disclosure provides a method of treating and / or preventing a disease or disorder in a subject in need thereof, the method comprising administering one or more active agents to the subject via any of the devices disclosed herein. In some embodiments, the present disclosure provides a method of treating a subject in need thereof, the method comprising administering a pharmaceutically effective amount of one or more active agents via any of the devices disclosed herein. In some embodiments, the present disclosure provides a method of treating cortisol deficiency in a subject in need thereof, the method comprising administering cortisone or a cortisone derivative to the subject via any of the devices disclosed herein. In some embodiments, the cortisol deficiency in the subject is caused by Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenal myeloneuropathy, adrenoleukodystrophy, adrenal tumor, Schmidt's syndrome, hyperaldosteronism, pituitary tumor, pituitary cyst, and / or severely associated corticosteroid deficiency. In some embodiments, the present disclosure provides a method of treating a cortisol disorder in a subject in need thereof, the method comprising administering cortisol or a cortisol derivative to the subject using any of the devices disclosed herein.In some embodiments, the administering step in any of the disclosed methods of treatment comprises depressing a movable element of a disclosed device to a first predetermined position, a second predetermined position, and a third predetermined position, the device comprising a first compartment, a second compartment, and a third compartment, each of the first, second, and third compartments defining a first, second, and third cavity, respectively, the first and second compartments being separated by a first opening and in fluid communication with the first opening, the second and third compartments being separated by a second opening and in fluid communication with the second opening, the first opening being covered by a first sealing member, the second opening being covered by a second sealing member, and the third cavity being covered by a second sealing member, respectively. The compartment comprises a needle assembly comprising a spring and a needle operably connected to the spring, wherein the insertion rod displaces the first sealing member from the first opening by depressing the movable element to a first predetermined position, exposing a first opening between the first and second compartments and establishing fluid communication between the first and second compartments, and the insertion rod displaces the second sealing member from the second opening by depressing the movable element to a second predetermined position, exposing a second opening between the second and third compartments and establishing fluid communication between the second and third compartments, and the movable element is depressed to a third predetermined position, causing the contents of the third compartment to be expelled through the needle assembly. In some embodiments, the disclosed methods further comprise unlocking the needle assembly before depressing the movable element to the third predetermined position.

[0025] In some embodiments, the present disclosure provides a method of treating congenital adrenal hyperplasia or Addison's disease in a subject in need thereof, the method comprising administering cortisone or a cortisone derivative to the subject by any of the devices disclosed herein.

[0026] The present disclosure further provides methods of manufacturing any of the devices disclosed herein, the methods comprising placing an active agent(s) in a sterile or aseptic environment. In some embodiments, the methods further comprise weighing the active agent(s). In some embodiments, the methods further comprise attaching the first compartment and the second compartment. In some embodiments, the methods comprise attaching the first compartment and the second compartment in a sterile environment by compression or threading onto fasteners.

[0027] The present disclosure also provides methods of administering an active agent to a subject in need thereof with any of the devices disclosed herein, the method comprising the steps of: (a) depressing the movable element to a first predetermined position; and (b) depressing the movable element to a second predetermined position, wherein the first predetermined position causes sufficient displacement for the insertion rod to pierce the first sealing member, thereby placing the first compartment in fluid communication with the second compartment, and the second predetermined position causes sufficient displacement to displace the movable sealing member, thereby placing the second compartment in fluid communication with a third compartment. In some embodiments, the second predetermined position causes sufficient displacement to load a spring in the third compartment with a force of about 0 to about 100 Newtons.

[0028] The present disclosure further provides a device comprising: (a) a first compartment, a second compartment, and a third compartment, each of the first, second, and third compartments defining a first, second, and third cavity, respectively, the second compartment disposed adjacent to and between the first and third compartments, (b) a needle guard assembly operably functioning within the third cavity and comprising a needle at least partially contained within the third cavity and operably attached to a spring, and (c) an insertion rod disposed within the first compartment operably connected to a movable element, the insertion rod and movable element being movable along longitudinal axes of the first, second, and third compartments, wherein the first and second compartments are in fluid communication through a first opening and the second and third compartments are in fluid communication through a second opening, the first opening being covered by a first sealing member and the second opening being covered by a second sealing member. 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 first, second, and third compartments are cylindrically arranged along the longitudinal axis of the cavity. In some embodiments, the needle guard assembly of the device comprises a spring, a needle sheath, and an inner surface comprising one or more track elements operably connected to the needle, such track elements being capable of guiding movement of the needle through the needle sheath after movement of the spring.

[0029] Various features, advantages, and aspects of the present disclosure will be explained in detail in the detailed description provided below with reference to the accompanying drawings, which illustrate exemplary embodiments of the present disclosure. Accordingly, the features of the present disclosure will be more clearly understood from the following detailed description considered in conjunction with the following drawings, in which like reference numerals indicate identical, similar, or equivalent elements throughout. The exemplary embodiments illustrated in the drawings are not necessarily to scale or shape and should not be considered limiting in scope, as the present disclosure may permit other equally effective embodiments having different combinations of features, as set forth in the appended claims. [Brief explanation of the drawings]

[0030] [Figure 1A] 1 is a side cross-sectional view of one embodiment of a device disclosed herein. 100: A three-chamber system allowing for the containment and mixing of one or more solid or liquid substances. 102: A first chamber, which is a first compartment defining a first cavity for containing a liquid or solid substance and separated from a second chamber 104 by a barrier. 104: A second chamber, which is a second compartment defining a second cavity for containing a liquid or solid substance. This second chamber 104 is separated from the first chamber 102 by a barrier. [Figure 1B] 1A is a side cross-sectional view of the device of FIG. 1A. In this device, the substances contained in each chamber are combined by the action of a compression mechanism. 116: A three-chamber system that allows for the containment and mixing of one or more solid or liquid substances. 112: A first chamber, which is a first compartment defining a first cavity that contains a liquid or solid substance and is separated from a second chamber 110 by a barrier. 110: A second chamber, which is a second compartment defining a second cavity that contains a liquid, solid, semi-solid, or gaseous substance. This second chamber 110 is separated from the first chamber 112 by a barrier. 114: An actuating assembly (compression system), which is a movable element such as a plunger, spring, screw system, or a combination of two or more of these systems, that actuates the mixing of the first chamber 112 and the second chamber 110. [Figure 2A]This is a side cross-sectional view of another embodiment of the device disclosed herein. The device further comprises movable parts, chamber barriers, sealing members, and other components associated with an automatic injector. 200: A three-chamber system including a housing, a plunger, a mechanism for isolating three chambers, and a compression system, which is actuated to combine substances held in the first two chambers and transfer the substances to the third chamber. 202: An actuation assembly (actuation system) is a movable element that initiates the combination of substances held in the first chamber 216 and the second chamber 208 and transfers the substances to the third chamber 210. 204: An insertion rod that penetrates the barrier (sealing member 206) and enables transfer of substances between the first chamber 216 and the second chamber 208. The insertion rod 204 has a protrusion that is pressed into the second chamber 208, facilitating the transfer of liquid from the first chamber 216 to the second chamber 208. The insertion rod 204 may be comprised of or surrounded by a sealing material to help prevent fluid from flowing behind the insertion rod 204. 206: A sealing member, which is a barrier between the first chamber 216 and the second chamber 208 that prevents material transfer between the two chambers 208, 216 until the insertion rod 204 penetrates the barrier (sealing member 206), and is the first sealing member. 208: A second chamber, which is a second compartment defining a second cavity that contains a liquid, solid, semi-solid, or gaseous substance that combines with the substance held in the first chamber 216 after penetration of the sealing member 206. 210: A third chamber, which is a third compartment defining a third cavity that combines the substances from the second chamber 208 and the first chamber 216 after activation of the device. 212: A spring that compresses upon material transfer into the third chamber 210 after penetration of the sealing member 206, combining the substances. 214: A movable seal member assembly, which is a movable stopper that moves through third chamber 210 upon combination of the substances in second chamber 208 and first chamber 216. As movable seal member assembly 214 moves into third chamber 210, it compresses spring 212. 216: A first chamber, which is a first compartment that defines a first cavity within the device. It can contain a liquid or solid substance that combines with the substance in second chamber 208 after insertion rod 204 penetrates seal member 206.218: Housing containing the three-chamber system 200 of the first chamber 216, the second chamber 208, and the third chamber 210, and the actuation assembly 202. [Figure 2B]2 is a side cross-sectional view of another embodiment of the device disclosed herein, in which the insertion rod that breaches the sealing member is two pieces instead of one. 220: Another embodiment of a three-chamber system for mixing two substances. 222: An actuation assembly (actuation system) that is a movable element that initiates combination of the substances held in the first chamber 254 and the second chamber 234 and moves the substances to the third chamber 240. 224: An insertion rod that penetrates the barrier (sealing member 232) and combines the substances in the first chamber 254 and the second chamber. 226: A sealing member that prevents fluid from moving backward through the device. 228: A fluid vent that is a valve that allows fluid transfer between the first chamber 254 and the second chamber 234. 230: A fluid path that passes through the insertion rod 224 and allows fluid transfer between the first chamber 254 and the second chamber 234. 232: A sealing member, which is a barrier between the first chamber 254 and the second chamber 234 and prevents mass transfer between the two chambers 254, 234 until the barrier (sealing member 232) is penetrated by the insertion rod 224; 234: A second chamber, which is a second compartment defining a second cavity for containing a liquid or solid substance that combines with the substance held in the first chamber 254 after penetration of the sealing member 232; 236: A housing for the second chamber 234. The housing 236 may be surrounded by a mass transfer barrier on both sides or both ends; 238: A slidable sealing member for the movable sealing member assembly 246. This sealing member 238 prevents fluid from passing around its edges; 240: A third chamber, which is a third compartment defining a third cavity that combines substances from the first chamber 254 and the second chamber 234 after device operation. 242: Needle (injection needle) for injecting the compounded substance. 244: Spring that compresses upon filling of third chamber 240 and subsequent movement of movable seal assembly 246 through third chamber 240. 246: Movable seal assembly, which is a movable stopper that acts as a barrier for second chamber 234 before activation of the device. After activation, seal 248 becomes a wall for third chamber 240 and then a compression mechanism for expelling the compounded substance from the device.248: A sealing member, which is a second sealing member that prevents the entry of material into the needle 242 until the sealing member 248 is pierced by movement of the movable sealing member assembly 246 upon actuation of the device. 250: A sealing member attached to the second chamber 234. 252: An entry point for the insertion rod 224 into the second chamber 234. 254: A first chamber, which is a first compartment defining a first cavity for containing a material that combines with the material in the second chamber 234. 256: A housing that contains the mixing chamber, material, and all device assemblies. 258: An outer housing for the insertion rod 224, into which the insertion rod 224 may move and which may contain the sealing member 232. 260: An insertion rod assembly. 262: A housing that is an attachment for the needle guide and spring 244. [Figure 3A] 1 is a side cross-sectional view of another embodiment of a device disclosed herein, the device comprising a needle assembly with a needle guard 302 attached to a main device 300. 300: Main device for mixing two substances. 302: Needle assembly and needle guard for injecting the two combined substances. [Figure 3B] A more detailed view of the needle assembly and needle guard of this embodiment. 304: Needle guard assembly that prevents fluid from exiting the device and discourages accidental injection. In this position, the needle guard extends over the needle. 306: Needle guard housing, a needle sheath that conceals the needle 308 and retracts to allow injection. 308: Needle (injection needle). 310: Safety clip that prevents activation of the needle guard before removal. 312: Compression spring that holds the needle guard housing 306 in place and pushes it back over the needle once the injection is complete. 314: Sealing member that prevents fluid from entering the needle 308. [Figure 3C] This shows the injection device of Figure 3A in a state where the ingredients have been combined but injection has not yet begun. 316: Needle guard assembly that prevents fluid from escaping the injection device and prevents accidental injection. In this state, the needle guard housing 320 is retracted to allow injection. 318: Needle (injection needle). 320: Needle guard housing that conceals the needle 318 and is retracted to allow injection. 322: Sealing member that prevents fluid from entering the needle 318. [Figure 3D]A more detailed view of the needle assembly and needle guard. 323: Needle guard assembly that prevents fluid from exiting the device and discourages accidental injection. In this position, the needle guard extends over the needle. 324: Needle guard housing that conceals the needle 342 and retracts to allow injection. 326: Guide track, a track element that slides the needle guard housing 324 into place using guard guide 328. 328: Guard guide for guide track 326. 330: (Needle stabilizer and) needle attachment. 338: Safety clip that prevents retraction of the needle guard housing 324 prior to intended use. 340: Connection between the needle guard assembly 323 and the injection device. 342: Needle (injection needle). 344: Compression spring that presses the needle guard into place around the needle 342. 346: Sealing member that prevents fluid from entering or exiting the needle 342 prior to injection. [Figure 3E] 3 shows another embodiment of the needle assembly and needle guard. 348: Another embodiment of the needle guard assembly that prevents fluids from leaving the device and discourages accidental injection. In this state, the needle guard extends over the needle. 350: Needle guard housing, which is a needle sheath that hides the needle and retracts to allow injection. 352: Device housing that also acts as a needle guard guide. 354: Needle outlet that can be equipped with a sealing member to prevent fluids from entering or leaving the needle (injection needle). [Figure 4]1 is a side cross-sectional view of an embodiment with the device body, needle assembly, and guard attached. 400: Needle guard assembly that prevents fluid from exiting the device and discourages accidental injection. In this state, the needle guard extends over the needle. 402: Guide track, a track element that slides the needle guard into place using needle guard guide 446. 404: Needle guard attachment point to the main device. 406: (Needle stabilizer and) needle attachment. 408: Spring that compresses upon filling of third chamber 444 and subsequent movement of movable seal assembly 410 through third chamber 444. 410: Movable seal assembly, a movable stopper. 412: Sealing member, a second sealing member and movable sealing member that prevents material from entering needle 448. 414: Sealing member on housing 438. 416: Opening (entry point), a chamfered first opening for insertion rod 428. 418: First chamber, a first compartment defining a first cavity. 420: Housing of main device. 422: Fluid vent, a valve for allowing fluid transfer between first chamber 418 and second chamber 436. 424: An embodiment of a three-chamber system for mixing two substances, including a needle assembly and guard. In this embodiment, the substances are not mixed. 426: Actuation assembly (actuation system), a movable element that initiates the combination of the substances. 428: Insertion rod. 430: Sealing member around insertion rod 428. 432: Fluid passageway. 434: Sealing member, a breakable first sealing member between first chamber 418 and second chamber 436. 436: Second chamber, a second compartment defining a second cavity. 438: Housing of second chamber 436. 440: Slidable sealing member for movable sealing member assembly 410. 442: Safety clip that prevents activation of the needle guard before removal. 444: Third chamber, a third compartment that defines a third cavity. 448: Needle (injection needle). 450: Sealing member that prevents fluid from entering needle 448. 452: Needle port, an exit point for the needle from the needle guard. [Figure 5A]1 is a side cross-sectional view of a device disclosed herein in a first operational state. 500: The first operational state before the device is activated. 502: The needle guard housing is a needle sheath extending around the needle. 504: The third chamber (combination chamber) is empty in this state and is a third compartment defining a third cavity. 506: The movable sealing member assembly is a movable stopper acting as a barrier between the second chamber 508 and the third chamber 504. 508: The second chamber is a second compartment defining a second cavity that contains a substance that combines with the substance in the first chamber 510. 510: The first chamber is a first compartment defining a first cavity that contains a substance that combines with the substance in the second chamber 508. 512: An insertion rod that breaks the sealing member 516 and pushes the substance from the first chamber 510 into the second chamber 508. 514: Actuation assembly, which is a movable element that may be a plunger, screw system, or some other type of method that compresses the device and moves the compounding substance into the third chamber 504. 516: Sealing member, which is a barrier between the first chamber 510 and the second chamber 508 and is a first sealing member. 518: Safety clip, which prevents the needle guard housing 502 from moving back. [Figure 5B] 1 is a side cross-sectional view showing a second operable state of a device disclosed herein. 542: An insertion rod partially inserted into second chamber 550. 544: An actuation assembly which may be a plunger, screw system, or some other type of method for compressing the device and displacing the compounding material. 546: A first chamber, which is a first compartment defining a first cavity. 548: A sealing member, which is a ruptured first sealing member placing second chamber 550 in fluid contact with first chamber 546. 550: A second chamber, which is a second compartment defining a second cavity. [Figure 5C]1 is a side cross-sectional view of a device disclosed herein in a third operational state. 520: The device is activated to combine the substances but not inject them in the third operational state. 522: The third chamber (combination chamber) containing the substances from the first two chambers (first and second chambers). 524: The actuation assembly (compression system) activated to combine the substances in the first two chambers. 526: The insertion rod has traveled completely through the first chamber, forcing all of the substances through the second chamber and into the third chamber 522. 528: The movable seal assembly, which is a movable stopper that moves away from the inlet for the substances from the first two chambers and creates a space for the compound substance in the third chamber 522. 530: The spring (compression spring) that is loaded to inject the combined substance when the needle guard 532 is retracted. 532: The needle guard, which is a needle sheath that, in its unretracted position, prevents the combined substance in the third chamber 522 from being expelled through the needle and out of the third chamber 522. 534: A sealing member that prevents material in the third chamber 522 from being expelled through the needle. [Figure 5D] 1 is a side cross-sectional view of a device disclosed herein in a fourth operational state. 536: The fourth operational state in which the needle guard 538 is retracted, forcing the combined material out of the combination chamber. 538: The needle guard is a needle sheath that is retracted to expose the needle 544 and force the combined liquid out of the device. 540: The movable seal assembly is a movable stopper that moves back into the device, forcing the combined liquid out of the needle 544 and out of the device. 542: The spring (compression spring) that moves back into the device, forcing the combined material out of the device. 544: The needle (injection needle). [Figure 6]6A-6C are side cross-sectional views showing the three main operational states of the device disclosed herein, as well as the final state where the device has been removed from the injection site. 600: The operational state before the safety clip is removed. The device is activated to compound the injectable substance, as indicated by the presence of the movable seal assembly with the bottom of the third chamber. 602: The safety clip is removed, allowing the device to be depressed against a surface such as a patient's skin for injection. 604: The device is pressed against a patient or other surface, the needle guard is retracted, the needle enters the injection site, and the device is held in place until the injection is complete. 606: After all the liquid has been injected, the device is moved upward, and the needle guard is extended to cover the needle again. With the movable seal assembly clear of the bottom of the device, the injection is completed as described above. [Figure 7]7 is a side cross-sectional view of the internal components of the second chamber 722 according to one embodiment of the device disclosed herein, showing how the second chamber 722 is positioned between the other two chambers 714 and 728. 700: Housing assembly (internal assembly) for the second chamber 722 and associated components. 702: Spring (compression spring) that holds the movable seal assembly 724 in place and forces the combined substance out of the third chamber 728 and out of the device during injection. 704: Sealing member, a second sealing member that prevents substance from migrating from the second chamber 722 to the third chamber 728 and prevents fluid from entering the needle 726. 706: Housing for the second chamber 722. 708: Opening (entry point), a first opening for the insertion rod 716 into the second chamber 722. 710: Sealing member surrounding the second chamber 722, preventing fluid flow. 712: A sealing member, which is a barrier preventing substance transfer between the first chamber 714 and the second chamber 722, and is a first sealing member. 714: A first chamber, which is a first compartment defining a first cavity within the device that contains a substance that combines with the substance in the second chamber 722. 716: An insertion rod that penetrates the sealing member 712 and pushes the substance from the first chamber 714 into the second chamber 722. 718: A fluid passageway that allows fluid transfer between the second chamber 722 and the first chamber 714. 720: A perforation end (perforation point) that allows penetration of the sealing member 712. 722: A second chamber, which is a second compartment defining a second cavity that contains a substance that combines with the substance in the first chamber 714. 724: A movable sealing member assembly, which is a movable stopper that acts as a barrier between the third chamber 728 and the second chamber 722 and also forces fluid out of the device when an injection is being performed. 726: Needle (injection needle). 728: Third chamber (combination chamber), which is a third compartment defining a third cavity that awaits injection of the combined substances from the first chamber 714 and the second chamber 722. [Figure 8]800: Another embodiment of the actuation assembly, where the device is twisted and the screw mechanism depresses the plunger. This view shows the device before actuation. 802: The actuation assembly after actuation, where the plunger forces down the two-substance composite. DETAILED DESCRIPTION OF THE INVENTION

[0031] The present disclosure relates to systems, methods, and devices for storing, transporting, mixing, and injecting drugs as solutions. The disclosed systems, methods, and devices may be more readily understood by reference to the following detailed description of certain embodiments, examples included therein, and the figures and description surrounding the figures.

[0032] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present disclosure, which will be limited only by the appended claims.

[0033] It should be noted that, as used in this specification and the appended claims, the singular forms include the plural forms of the referenced term unless the context clearly dictates otherwise. Thus, for example, reference to "a nucleic acid sequence" includes the plurality of nucleotides formed, and reference to "the nucleic acid sequence" is a reference to one or more nucleic acid sequences and equivalents thereof known to those of skill in the art.

[0034] Ranges may be expressed herein as ranging from "about" one particular value and / or to "about" another particular value. When such a range is expressed, the range from the one particular value and / or to the other particular value is considered to be specifically contemplated and disclosed unless the context specifically dictates otherwise. Similarly, when values ​​are expressed as approximations, the use of the antecedent "about" is understood to indicate that the particular value forms another specifically contemplated embodiment that is to be considered disclosed unless the context clearly dictates otherwise. Further, it is understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint, unless the context specifically dictates otherwise. As used herein, the term "about" when referring to a measurable value, such as an amount, duration, or the like, is intended to encompass variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or ±0.1% from the specified value, as such variations are appropriate for carrying out the disclosed methods.

[0035] "Optional" or "optionally" means that the subsequently described event, circumstance, or substance may or may not occur or exist, and that the description includes instances in which the event, circumstance, or substance occurs or exists, as well as instances in which it does not occur or exist.

[0036] The term "and / or," as used in the specification and claims, should be understood to mean "either or both" of the elements so connected, i.e., elements present together in some cases and independently in other cases. Unless expressly indicated to the contrary, other elements may optionally be present other than the elements specifically named by the "and / or" clause, whether related or unrelated to the elements specifically named. Thus, as a non-limiting example, a reference to "A and / or B," when used in conjunction with open-ended language such as "consisting of," can refer in some embodiments to A without B (optionally including elements other than B); in other embodiments to B without A (optionally including elements other than A); in yet other embodiments to both A and B (optionally including other elements); etc.

[0037] As used in this specification and the claims, "or" should 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 as inclusive, i.e., including all elements, or at least one, if not more than one, of the listed elements, and optionally including additional, unlisted items. Conversely, only clearly indicated terms such as "only one of" or "only one of," or, when used in the claims, "consisting only of," refer to the inclusion of all elements or only one of the listed elements. In general, the term "or" as used herein shall only be interpreted as indicating exclusive alternatives (i.e., "one or the other, but not both") when preceded by the exclusive terms "either," "one of," "only one of," or "only one of." When used in the claims, "consisting essentially of" shall have its ordinary meaning as used in the field of patent law.

[0038] As used herein, the term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable diluent" refers to an excipient, carrier, or diluent that can be administered to a subject with a drug or pharmaceutical composition disclosed herein, and which is inert or unable to eliminate the pharmacological activity of the active agent of the pharmaceutical composition. In some embodiments, a pharmaceutically acceptable carrier is one that does not destroy or unable to eliminate the pharmacological activity of the active agent / vaccine and is non-toxic when administered in a dose sufficient to deliver a therapeutic amount of the active agent. As used herein, the term "pharmaceutically acceptable salt" of a nucleic acid can be an acid or base salt that is generally considered in the art to be suitable for use in contact with human or animal tissues without undue toxicity, irritation, allergic response, or other problems or complications. Such salts include mineral and organic acid salts of basic residues, such as amines, and alkali or organic acid salts of acidic residues, such as carboxylic acids. Specific pharmaceutical salts include, but are not limited to, salts of acids such as hydrochloric acid, phosphoric acid, hydrobromic acid, malic acid, glycolic acid, fumaric acid, sulfuric acid, sulfamic acid, sulfanilic acid, formic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanedisulfonic acid, 2-hydroxyethylsulfonic acid, nitric acid, benzoic acid, 2-acetoxybenzoic acid, citric acid, tartaric acid, lactic acid, stearic acid, salicylic acid, glutamic acid, ascorbic acid, pamoic acid, succinic acid, fumaric acid, maleic acid, propionic acid, hydroxymaleic acid, hydroiodic acid, phenylacetic acid, acetic acid, and alkanoic acids such as HOOC-(CH)-COOH, where n is 0 to 4. Similarly, pharmaceutically acceptable cations include, but are not limited to, sodium, potassium, calcium, aluminum, lithium, and ammonium. Those skilled in the art will be aware, from this disclosure and knowledge in the art, of additional pharmaceutically acceptable salts of the deposited virus-specific antigens or polynucleotides provided herein, including those listed in Remington, Pharmaceutical Sciences, 17th Edition, Mack Publishing, Easton, PA, 1985, p. 1418.In general, pharmaceutically acceptable acid or base salts can be synthesized from a parent compound that contains a basic or acidic moiety by any conventional chemical method. Briefly, such salts can be prepared by reacting the free acid or base form of such compound with a stoichiometric amount of the appropriate base or acid in a suitable solvent.

[0039] As used herein, the terms "prevent" or "preventing" and the like refer to reducing the probability of developing a disease or condition in a subject who does not have the disease or condition but is at risk of or susceptible to developing the disease or condition.

[0040] As used herein, the terms "subject," "individual," "host," and "patient" are used interchangeably herein and refer to an individual vertebrate, including a mammal or human, particularly, but not limited to, a human, in need of diagnosis, treatment, or therapy. Mammals include, but are not limited to, murines, apes, humans, livestock, cattle, swine, goats, sheep, horses, dogs, game animals, and pets. The methods described herein are applicable to both human therapy and veterinary applications. In some instances within the description of this disclosure, the term "patient" refers to a human patient suffering from a particular disease or disorder. In some embodiments, the subject is a mammal, and in other embodiments, the subject is a human.

[0041] As used herein, the terms "treat," "treated," "treating," "treatment," and the like refer to alleviating or ameliorating a disorder and / or symptoms associated with the disorder (e.g., a viral infection). "Treating" can refer to administering a DNA vaccine described herein to a subject after a viral infection has occurred or is suspected to have occurred. "Treating" encompasses the concept of "alleviating," which refers to reducing the frequency or severity of any symptoms or other pathological effects associated with a virus and / or side effects associated with viral therapy. The term "treating" also encompasses the concept of "managing," which refers to reducing the severity or delaying the recurrence of a particular disease or disorder in a patient, e.g., increasing the duration of remission in a patient afflicted with a disease. It is understood that treating a disorder or condition does not necessarily mean completely eliminating, nor does it necessarily mean eliminating, the disorder, condition, or symptoms associated therewith.

[0042] For any therapeutic agent described herein, the therapeutically effective amount may be initially determined from preliminary in vitro studies and / or animal models. The therapeutically effective dose may also be determined from human data. The applied dose can be adjusted based on the relative bioavailability and potency of the administered agent. Adjusting the dose to achieve maximum efficacy based on the above and other well-known methods is within the ability of one of ordinary skill in the art. The general principles for determining therapeutic efficacy found in Chapter 1 of Goodman and Gilman, "The Pharmacological Basis of Therapeutics," 10th ed., McGraw-Hill, New York, 2001, incorporated herein by reference, are summarized below. Pharmacokinetic principles provide a basis for modifying dosage regimens to achieve the desired therapeutic effect while minimizing unacceptable side effects. Plasma concentrations of drugs can be measured and correlated with a therapeutic window, providing further guidance for modifying dosages. Pharmaceuticals are considered pharmaceutically equivalent if they contain the same active ingredient, have the same strength or concentration, dosage form, and route of administration. Two pharmaceutically equivalent drug products are considered to be bioequivalent if, under suitable test conditions, there are no significant differences in the rate and extent of bioavailability of the active ingredient in the two products.

[0043] As used herein, the terms "consisting of" (and any form of "consisting of" such as "consisting of" and "consisted of"), "having" (and any form of "having" such as "and having"), "including" (and any form of "including" such as "include"), or "containing" (and any form of "containing" such as "containing") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0044] As used herein, the term "about" means that a numerical value is approximate and that small variations do not significantly affect the practice of the disclosed embodiments. As used herein, the term "about," when referring to a measurable value, such as an amount, duration, etc., is intended to encompass variations of ±10%, ±5%, ±1%, or ±0.1% from the specified value, where such variations are appropriate for carrying out the disclosed methods. When limiting a numerical value, unless the context dictates otherwise, "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.

[0045] In this specification and in the concluding claims, references to parts by weight of a particular element or component in a composition indicate the weight relationship between that element or component and the other elements or components in the composition or article to which the parts by weight are expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight of component Y, X and Y are present in a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are included in the compound.

[0046] Weight percent (wt.%) of an ingredient is based on the total weight of the formulation or composition in which it is included, unless specifically stated to the contrary.

[0047] As used herein, the terms "administer" 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 oral, transdermal, inhalation, nasal, topical, vaginal, ophthalmic, intraaural, intracerebral, rectal, and parenteral administration, and include, but are not limited to, injection, such as intravenous, intraarterial, intramuscular, and subcutaneous administration. Administration can be continuous or intermittent. In various embodiments, the preparation can be administered therapeutically, i.e., to treat an existing disease or condition. In further various embodiments, the preparation can be administered prophylactically, i.e., to prevent a disease or condition. As used herein, the terms "parenteral administration" and "administering parenterally" refer to modes of administration other than enteral administration 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, intrathecal, intraspinal, and intrasternal injection.

[0048] As used herein, the terms "optional" or "optionally" mean that the subsequently described event or circumstance may or may not occur, and that the description includes instances in which the event or circumstance occurs and instances in which it does not occur.

[0049] As used herein, the term "diagnosed" means subjected to a physical examination by a person skilled in the art, e.g., a physician, and found to have a condition that can be diagnosed or treated by the compounds, compositions, or methods disclosed herein.

[0050] The present disclosure relates to systems, methods, and devices for storing, transporting, mixing, and injecting drugs as solutions. The disclosed systems, methods, and devices may be more readily understood by reference to the following detailed description of specific embodiments and examples included therein, as well as the figures and accompanying description.

[0051] As used herein, the term "contacting" refers to the bringing together of a disclosed compound and a cell, target receptor, or other biological entity in such a way that the compound can affect the activity of the target (e.g., receptor, cell, etc.), either directly, i.e., by interacting with the target itself, or indirectly, i.e., by interacting with another molecule, cofactor, factor, protein on which the activity of the target depends.

[0052] As used herein, the term "compartment" refers to a space defined by one or more contiguous surfaces that form an internal volume isolated from the external environment by one or more surfaces. In some embodiments, a compartment can be defined by one or more surfaces and be a volume of any shape, such as a rectangular prism or cylindrical space. The present disclosure generally relates to devices comprising first, second, and / or third compartments that comprise cylindrical or approximately cylindrical cavities or spaces having sequentially aligned walls, where at least one end of the cylindrical or approximately cylindrical space is adjacent or proximate to at least one end of another compartment, such that the cylindrically aligned compartments define the interior of the device. In some embodiments, the compartments, once aligned, are part of a closed system attached via a physical connection between the interior or exterior, or between a portion of a surface or surfaces.

[0053] As used herein, the term "active agent" refers to a drug or other substance that, when administered, treats a subject. In some embodiments, the active agent or derivative thereof is selected from one or a combination of the following active agents:

[0054] [Table 1] *Dosages are approximate. Dosage should be interpreted as "about X to about Y." As an example, the dosage of hydrocortisone sodium succinate should be interpreted as about 50 milligrams per milliliter to about 150 milligrams per milliliter.

[0055] The term "movable element" means a shaft, plunger, rod, fastener, or other part or element of a device that is movable in any direction relative to the longitudinal axis of the device. If the device is cylindrical, the longitudinal axis defines the center point of the circumference of the device.

[0056] "Derivatives" of the compounds disclosed herein include pharmaceutically acceptable salts, prodrugs, deuterated forms, radiolabeled forms, isomers, solvates, and combinations thereof. A "combination" in this context refers to derivatives that fall into at least two of the following groups: pharmaceutically acceptable salts, prodrugs, deuterated forms, radiolabeled forms, isomers, and solvates. Examples of radiolabeled forms include compounds labeled with tritium, phosphorus-32, iodine-129, carbon-11, fluorine-18, etc.

[0057] As used herein, the term "disease" refers to an illness in a subject that causes a dysfunctional process in the body. In some embodiments, the disease is one or a combination of diseases selected from Table 2.

[0058] [Table 2]

[0059] As used herein, the term "carrier" refers to a diluent, adjuvant, or excipient for administration of a compound. Pharmaceutical carriers can be liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, and sesame oil. Pharmaceutical carriers also include saline, acacia gum, gelatin, starch paste, talc, keratin, colloidal silica, urea, and the like. Additionally, auxiliary substances, stabilizers, thickeners, lubricants, and coloring agents can be used. Pharmaceutical compositions comprise the present compound in a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers refer to sterile aqueous or non-aqueous solutions, dispersions, suspensions, or emulsions, as well as sterile powders to be reconstituted into sterile injectable solutions or dispersions immediately 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.), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters such as ethyl oleate. The compounds can be formulated with pharmaceutically acceptable carriers or diluents, as well as any other known adjuvants and excipients, according to conventional techniques, such as those disclosed in Remington, Gennaro (ed.), "The Science and Practice of Pharmacy," 19th ed., Mack Publishing, Easton, PA, 1995. The phrase "pharmaceutically acceptable carrier" is art-recognized and includes any pharmaceutically acceptable substance, composition, or vehicle suitable for administering the compounds of the present invention to a mammal. Carriers include liquid or solid fillers, diluents, excipients, solvents, or encapsulating materials involved in carrying or transporting the subject drug from one organ or part of the body 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.Examples of substances that can function 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 carboxymethylcellulose, ethylcellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository wax; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerin, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solution; and other non-toxic compatible substances used in pharmaceutical formulations. Suitable pharmaceutical carriers are reported in E.W. Martin, "Remington's Pharmaceutical Sciences," which is incorporated herein by reference in its entirety.

[0060] Wetting agents, emulsifiers, and lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening agents, flavoring and perfuming agents, preservatives, and antioxidants can also be added to the compositions.

[0061] Examples of pharmaceutically acceptable antioxidants include: water-soluble antioxidants such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, and sodium sulfite; oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, and α-tocopherol; and metal chelating agents such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, and phosphoric acid.

[0062] The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will generally be that amount which produces a therapeutic effect of the compound. Generally, out of 100%, this amount will range from about 1% to about 99% of the active ingredient, preferably from about 5% to about 70%, and most preferably from about 10% to about 30%. Methods of preparing these formulations or compositions include the step of bringing into association a compound of the present invention with the carrier and, optionally, one or more additional ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the present invention with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product.

[0063] In solid dosage forms of the present invention for oral administration (capsules, tablets, pills, dragees, powders, granules, etc.), the active ingredient is mixed with one or more pharmaceutically acceptable carriers such as sodium citrate or dicalcium phosphate, and / or any of the following: fillers or extenders such as starch, lactose, sucrose, glucose, mannitol, and / or silicic acid; binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and / or gum arabic; humectants such as glycerol; disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicic acids, and sodium carbonate; solution retarding agents such as paraffin; absorption accelerators such as quaternary ammonium compounds; wetting agents such as, for example, cetyl alcohol and glycerol monostearate; absorbents such as kaolin and bentonite clay; lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and colorants. In the case of capsules, tablets, and pills, the pharmaceutical composition may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft- and hard-filled gelatin capsules using such excipients as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like.

[0064] Tablets may be made by compression or molding, optionally with one or more additional ingredients. Compressed tablets may be prepared using binders (e.g., gelatin or hydroxypropylmethylcellulose), lubricants, inert diluents, preservatives, disintegrants (e.g., sodium starch glycolate or cross-linked sodium carboxymethylcellulose), surface active agents, or dispersing agents. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.

[0065] Tablets and other solid dosage forms of the pharmaceutical compositions of the present invention, such as sugar-coated tablets, capsules, pills, and granules, may optionally be obtained or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical formulation art. These pharmaceutical compositions may also be formulated for sustained or controlled release of the active ingredient therein, for example, using hydroxypropylmethylcellulose, other polymer matrices, liposomes, cationic vesicles, and / or microspheres, with proportions varied to provide the desired release profile. These pharmaceutical compositions may be sterilized, for example, by filtration through a bacteria-retaining filter or by incorporating a sterilizing agent in the form of a sterile solid composition that can be dissolved in sterile water or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be composed to release the active ingredient(s) only, or preferentially, in a certain part of the gastrointestinal tract, optionally in a sustained manner. Examples of implantable compositions that can be used include polymeric substances and waxes. The active ingredient can also be in microencapsulated form, if appropriate, with one or more of the above-mentioned excipients.

[0066] The liquid dosage form for oral administration of the compound of the present invention includes pharmaceutically acceptable emulsion, microemulsion, solution, suspension, syrup and elixir.In addition to active ingredients, liquid dosage form may contain inert diluents commonly used in the art, such as water or other solvents, solubilizers and emulsifiers, for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofuryl alcohol, polyethylene glycol and fatty acid esters of sorbitan, and mixtures thereof.

[0067] Besides inert diluents, oral compositions can also contain adjuvants such as wetting agents, emulsifying agents, suspending agents, sweeteners, flavoring agents, coloring agents, perfuming agents, and preservatives. Suspensions may contain suspending agents in addition to the active compounds, such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, and tragacanth, and mixtures thereof.

[0068] Unless the context specifically dictates otherwise, it should be understood that each and every individual value and subrange of values ​​falling within an expressly disclosed range is also specifically contemplated and disclosed. The foregoing applies regardless of whether any or all of these embodiments are expressly disclosed in any particular instance.

[0069] 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 belong. Any methods and materials similar or equivalent to those described herein can be used in the practice of the methods and testing of the compositions, with particularly useful methods, devices, and materials being as described. Publications cited herein and the materials for which they are cited are specifically incorporated herein by reference. Nothing herein should 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 constitutes prior art. The description of a cited reference states what its author asserts, and the applicant reserves the right to challenge the accuracy and pertinence of the cited reference. Although a number of publications are referenced herein, it is expressly understood that such citation does not constitute an admission that any of these documents form part of the common general knowledge in the art.

[0070] Throughout this specification and the claims, the terms "consisting of" and variations thereof, such as "consisting of" and "consisting of (third person singular)," mean "including but not limited to," and are not intended to exclude, for example, other additives, ingredients, integers, or steps. In particular, for methods described as consisting of one or more steps or operations, each step is specifically contemplated to consist of what is listed (unless the step includes a limiting term such as "consisting only"), meaning that each step is not intended to exclude, for example, other additives, ingredients, integers, or steps not listed in that step.

[0071] Many possible embodiments of the present disclosure are contemplated and are described in more detail herein. Commercially available products may be designed with minor variations in the physical attributes of components for various goals, including cost containment, chemical compatibility, ease of use, manufacturing cost and convenience, and various pharmaceuticals and target indications, without departing from the spirit of the present disclosure and remaining within the scope of the disclosed purpose and function of the present disclosure. For example, the disclosed devices may be used with a variety of pharmaceuticals, including, but not limited to, Solu-cortef®, hydrocortisone, and methylprednisolone for multiple sclerosis; chemotherapy for certain cancers; chronic medications for autoimmune conditions; biologic treatments; glucagon for hypoglycemic emergencies; ticarcillin for severe infections; chlordiazepoxide for alcohol withdrawal; and desoxycorticosterone pivalate for veterinary emergencies.

[0072] Some embodiments of the present disclosure are useful for administering medications during adrenal crises, such as those in patients with congenital adrenal hyperplasia (CAH), Addison's disease, and idiopathic adrenal insufficiency. Some embodiments of the present disclosure are designed to improve the efficacy of life-saving injectable medications for the 144 million people worldwide who suffer from CAH, Addison's disease, and idiopathic adrenal insufficiency. Some exemplary embodiments of the present disclosure require only four injection steps and can be designed for people suffering from adrenal crises and their caregivers. For example, exemplary embodiments of the present disclosure can improve the efficacy of the drug Solu-cortef®, which is specifically indicated for use in patients with CAH.

[0073] In some embodiments, the present disclosure provides a device comprising: (1) a transport assembly, the transport assembly comprising a main tube and a handle secured to a mixing end of the main tube opposite an injection end of the main tube; and (2) a storage assembly, the storage assembly configured to fit within a lumen of the main tube and comprising: a first sealing member, a liquid-impermeable stopper configured to fit within the first sealing member, a liquid-dispensing plunger configured to connect the first sealing member and the liquid-impermeable stopper, a medication container configured to contain an unmixed medication, a foil sealing member attached to the liquid-dispensing side of the medication container, a second sealing member configured to connect to an injection side of the medication container opposite the liquid-dispensing side, and optionally an air filter configured to be disposed between the second sealing member and the injection side of the medication container. (3) A mixing assembly, the mixing assembly being configured to attach to the handle, to fit partially within the lumen of the main pipe, and to engage with the storage assembly, comprising a twist cap having internal threads and rotatably engaging the handle, a plunger initiator engaging the twist cap, and a mixing spring engaging the initiator, wherein the initiator has a flange disposed within the internal threads and passes through a cap aperture in the twist cap, a handle aperture in the handle, and a lumen of the main pipe, and the mixing spring is configured to fit within the lumen of the main pipe and between the primer and a first sealing member of the storage assembly. (4) An injection assembly, the injection assembly configured to engage with the injection end of the main tube and partially fit within the lumen of the main tube and engage with the storage assembly, comprising a protective cap, a cap spring, a hollow needle, a needle propellant, and an injection spring, wherein the protective cap is configured to movably cover the injection tip of the needle, the cap spring is disposed between the protective cap and the needle propellant and configured to be compressed to displace the protective cap and expose the injection tip of the needle, the needle passes through and is integrated into the needle propellant, the needle passes through a tube seal at the injection end of the lumen of the main tube, and the injection spring is configured to be disposed between the tube seal and a second sealing member of the storage assembly, and the needle is configured to pierce the second sealing member when the protective cap is fully compressed against the needle propellant and when the needle propellant is fully compressed against the injection end of the main tube.

[0074] In some embodiments, the disclosed device or appliance allows for convenient transport and proper storage of medication within the device or appliance until a patient needs the medication, at which time the appliance is used to administer the medication to the patient. To administer a medication to a patient, the medication must be mixed with a liquid, such as water, to prepare a medication solution mixture. To mix a medication using the mixing assembly, a user twists the twist cap relative to the handle, rotating the plunger starter flange within the threads, moving and compressing the starter toward the mixing spring, which applies pressure to the first sealing member and advances the liquid dispensing plunger toward the medication container. As the liquid dispensing plunger moves toward the medication container, it pierces the foil sealing member and enters the container hole of the medication container, allowing the liquid stored in the main tube between the first sealing member and the foil sealing member to enter the medication container and mix with the unmixed medication, creating a medication solution. As the liquid dispensing plunger moves toward and presses against the medication container, hydraulic pressure is generated, forcing the medication solution through the medication container toward the injection end of the main tube and pushing the second sealing member toward the tube seal, thereby compressing the injection spring. Displacement of the second sealing member toward the tube seal creates a chamber between the second sealing member (proximate the injection end) and the medication container (proximate the mixing end), which contains the medication solution under pressure of the injection spring against the second sealing member. The injection assembly optionally further comprises a safety device, such as a removable safety clip, attached to the needle propeller, protective cap, and / or main tube, configured to prevent the protective cap and needle propeller from moving and pressing against the cap spring, exposing the injection tip of the needle, and to prevent the needle propeller from moving toward the main tube and puncturing the second sealing member. The safety device may be disengaged, such as by removing the safety clip, to engage the injection assembly. When the removable safety clip is removed, the device is ready to press the protective cap against the patient, such as against the patient's bare skin. Without the removable safety clip, pressing the protective cap against the patient would cause the protective cap to retract toward the needle propeller, which would retract toward the main lumen, causing the needle propeller to propel the needle into the lumen of the main lumen.When using the mixing assembly to mix a drug, the drug solution is contained in the chamber awaiting injection into a patient, and when the needle is advanced inward, the injection tip of the needle pierces the second sealing member. The injection tip of the needle then enters the chamber, and the drug solution flows into the hollow needle bore and is expelled from the chamber. The drug solution flows into the injection tip of the needle, passes through the needle bore, and exits the needle at the injection tip. The injection spring, compressed by the mixing process using the mixing assembly, applies pressure to the second sealing member, causing it to return to the drug container, reducing the chamber volume of the chamber and forcing the drug solution out of the chamber, through the needle, and out the injection tip to the patient.

[0075] Further aspects of the present disclosure are described herein. Details of exemplary embodiments of the present disclosure 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.

[0076] In some embodiments, the disclosed device includes: (1) a transport assembly comprising a main tube and a spring plunger threadably engaging the main tube at a mixing end of the main tube opposite the injection end of the main tube; (2) a storage assembly configured to fit within the lumen of the main tube and comprising a first sealing member, a liquid-impermeable stopper configured to fit within the first sealing member, a liquid-dispensing plunger configured to connect the first sealing member and the liquid-impermeable stopper, a medication container configured to contain unmixed medication, a foil sealing member attached to the liquid-dispensing side of the medication container, a second sealing member configured to connect to an injection side of the medication container opposite the liquid-dispensing side, and optionally an air filter configured to be disposed between the second sealing member and the injection side of the medication container. (3) The mixing assembly is attached to the main tube, partially fits within the lumen of the main tube, and is configured to engage with the storage assembly, and comprises a push rod having a concave annular cavity and slidably engaging with the main tube, the push rod passes through an opening in the lumen of the main tube, the push rod fits within the lumen of the main tube and pushes the plunger and first sealing member of the storage assembly, and the spring plunger of the transport assembly engages with the concave annular cavity when the push rod is further pushed into the lumen of the main tube from the non-push position to the push position, thereby mixing the drug and the liquid. (4) An injection assembly configured to engage the injection end of the main tube and partially fit within the lumen of the main tube and engage the storage assembly, comprising a hollow needle, a needle propellant, a tube stopper, and an injection spring, wherein the needle passes through and is integrated within the needle propellant, the needle propellant is configured to slide over the injection end of the main tube, the needle passes through the tube stopper, the tube stopper comprises a tube seal at the injection end of the lumen of the main tube, the injection spring is configured to be positioned between the tube seal and a second sealing member of the storage assembly, and the needle is configured to pierce the second sealing member when the needle propellant is fully compressed against the injection end of the main tube. In some embodiments, the second sealing member may comprise a chamber piston having an internal cavity with a central hole of the piston adjacent to the drug container, a septum disposed in the internal cavity and covering the piston central hole, and a spring guide disposed in the internal cavity and covering the septum, the spring guide having a guide central hole and engaging with the injection spring of the injection assembly.

[0077] In some embodiments, the disclosed devices or instruments allow for convenient transport and proper storage of the medication within the device or instrument until the patient needs the medication, at which time the medication can be administered to the patient. In some embodiments, the needle propeller is configured to be detached from the rest of the device for transport and storage until the device is ready for use. The detached needle propeller may optionally include tip guards at the injection and injection tips to protect the tip and protect the user from accidental needlesticks. When administering a medication to a patient, the medication must be mixed, and the needle propeller is prepared for use (e.g., any tip guards and sterile packaging are removed), the needle propeller is held by its sidewall, the injection tip of the needle is inserted into the patient (preferably with the patient's skin in close contact with the surface of the needle propeller adjacent the injection tip), and the needle propeller is slid into the injection end of the main tube, causing the injection tip of the needle to pierce the second sealing member and expel the medication solution from the chamber. In some embodiments, the needle pusher is slid into the main tube to initiate the release of the drug solution before the injection tip of the needle is inserted into the patient's skin.

[0078] Before administering a drug to a patient, the drug must be mixed with a liquid, such as water, to prepare a drug solution mixture. In a second specific embodiment, to mix a drug using the mixing assembly, the user presses the push rod against the main tube until the concave annular cavity reaches the spring plunger, extending the spring plunger into the concave annular cavity and locking the push rod in place. Pressing the push rod moves the liquid dispensing plunger in a direction that applies pressure to the first sealing member and advances it toward the drug container. As the liquid dispensing plunger moves toward the drug container, it pierces the foil sealing member and flows into the container hole of the drug container. Liquid stored in the main tube between the first sealing member and the foil sealing member flows into the drug container and mixes with the unmixed drug, creating a drug solution. As the liquid dispensing plunger moves toward the drug container and pushes against the drug container, hydraulic pressure is generated, forcing the drug solution through the drug container toward the injection end of the main tube and pushing the second sealing member toward the tube seal, thereby compressing the injection spring. Displacement of the second sealing member toward the tube seal forms a chamber between the second sealing member (proximal to the injection end) and the drug container (proximal to the mixing end), which contains the drug solution under pressure of the injection spring against the second sealing member. The injection assembly optionally further comprises a safety device, such as a removable safety clip, configured to attach to the main tube and protect the tube seal at the injection end. The safety device may be disengaged, such as by removing the safety cap, to engage the injection assembly. Upon removal of the removable safety device, the device is ready to press the needle propeller against the patient, e.g., against the patient's bare skin, and the needle penetrates the patient's skin to a desired depth determined by the length of the needle extending beyond the needle propeller from the injection tip to the surface of the needle propeller proximal to the injection tip. Pressing the needle propeller against the patient may be coupled with sliding the needle propeller into the main tube, causing the needle propeller to propel the needle into the lumen of the main tube. Assuming the mixing assembly is used to mix drugs, the drug solution is contained within the chamber awaiting injection into a patient, and when the needle is advanced inward, the injection tip of the needle pierces the second sealing member.The injection tip of the needle then enters the chamber, causing the drug solution to flow into the bore of the hollow needle and then exit the chamber. The drug solution enters the injection tip of the needle, passes through the bore, and exits the needle at the injection tip. The injection spring, compressed by the mixing process using the mixing assembly, applies pressure to the second sealing member, causing it to return to the drug container, reducing the chamber volume of the chamber and forcing the drug solution out of the chamber, through the needle, and out the injection tip to the patient. Alternatively, the needle propeller may be slid into the main tube to initiate the release of the drug solution before the injection tip of the needle is inserted into the patient's skin.

[0079] Further aspects of the present disclosure are described herein. Details of exemplary embodiments of the present disclosure 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.

[0080] Reference is made to FIGS. 1A and 1B. FIG. 1A is a side cross-sectional view of one embodiment of a device disclosed herein. The three-chamber system (assembly) 100 includes two chambers, a first chamber 102 and a second chamber 104, separated by a sealing member that prevents material transfer between the two chambers in an unactivated state. The first chamber 102 contains a liquid, solid, semi-solid, or gaseous substance that combines with another substance contained in the second chamber 104. The substance contained in the second chamber 104 may also be a liquid, solid, semi-solid, or gaseous substance. Upon actuation, the substance in the first chamber 102 is forced into the second chamber 104, thereby combining with the substance in the second chamber 104 from the first chamber 102. These substances combine due to the action of an actuation assembly (compression mechanism) 114, shown in FIG. 1B. An actuation assembly (compression mechanism) 114 moves the substance from a first chamber 112 (equivalent to first chamber 102 in FIG. 1A) to a second chamber 110 (equivalent to second chamber 104 in FIG. 1A).

[0081] Reference is now made to FIG. 2A, which is a side cross-sectional view of another embodiment of a device disclosed herein. The device of FIG. 2A further comprises moving parts, chamber barriers, sealing members, and other components associated with an auto-injector. A three-chamber system (device assembly) 200 comprises a housing 218 containing three chambers and associated components. The device includes an actuation assembly (compression assembly) 202 that interacts with an insertion rod 204. The insertion rod 204 is advanced within a first chamber 216, penetrating a sealing member 206. The sealing member 206 is an impermeable membrane that prevents material transfer between the first chamber 216 and the second chamber 208. Upon actuation of the device and subsequent compression of the actuation assembly (compression assembly) 202, the insertion rod 204 penetrates the sealing member 206, forcing material from the first chamber 216, through the pierced sealing member 206, and into the second chamber 208. As the substance from first chamber 216 moves into second chamber 208, it combines with the substance in second chamber 208 and moves together into third chamber 210. As the combined substances move into third chamber 210, they together push movable seal member assembly 214 into third chamber 210. As movable seal member assembly 214 is pushed into third chamber 210, spring 212 is compressed, storing energy that is later used to force the substance out of the device through the needle for injection.

[0082] 2B, which illustrates a cross-sectional side view of another embodiment of the device disclosed herein, in which the insertion rod that breaches the sealing member is two pieces rather than one. The three-chamber system 220 includes a housing 256, a multi-piece insertion rod assembly 260 including three chambers (first chamber 254, second chamber 234, and third chamber 240), an insertion rod (inner insertion rod) 224, an outer housing 258, and a sealing member 226. The insertion rod 224 further includes a fluid passage 230 and a fluid vent 228 that allow fluid transfer between the first chamber 254 and the second chamber 234. When the actuation assembly (compression mechanism) 222 pushes the insertion rod assembly 260 inward, the insertion rod 224 is forced into and penetrates the sealing member 232. Upon penetration of sealing member 232, fluid can enter fluid vent 228, pass through fluid pathway 230, and enter second chamber 234, or fluid can flow in the opposite direction, from second chamber 234, through fluid pathway 230, and out fluid vent 228. Once insertion rod 224 penetrates sealing member 232 and its backside is flush with outer housing 258, the entire insertion rod assembly 260 is compressed by actuation assembly (compression mechanism) 222 into second chamber 234. The insertion portion of insertion rod 224 moves completely into second chamber 234, with outer housing 258 and the larger part of insertion rod 224 resting against the outside of second chamber 234. During this compression, material from first chamber 254 moves within first chamber 254 and combines with material in second chamber 234. An optional sealing member 250 around the housing (chamber housing) 236 prevents the substance from flowing outside the chamber. The combined substance is forced into the third chamber 240. As the combined substance is forced into the third chamber 240, a movable sealing member assembly 246 moves into the third chamber 240 to create a space for the combined substance. The sealing member assembly 246 consists of the sealing member 238 and a housing 262, which is the attachment point for the needle guide and spring 244.

[0083] As the movable seal member assembly 246 moves into the third chamber 240, the seal member 248 is pierced by the non-injection side of the needle 242. This allows fluid to enter the needle 242, provided that the injection end of the needle 242 is open. As the movable seal member assembly 246 moves into the third chamber 240, the spring 244 is compressed. The compressive force of the spring 244 is used to inject the compounded substance.

[0084] 3A, which is a side cross-sectional view of another embodiment of the device disclosed herein, including a needle assembly having a needle guard 302 attached to a main device 300. In some embodiments, the needle assembly and guard are attached to the device via a threaded system, although attachment via adhesives, welding, a snap fit, a compression fit, or other attachment methods known in the art is also possible.

[0085] A more detailed view of the needle assembly and guard of this embodiment is shown in Figure 3B. In this state, the device is not activated and no compounding of the components has occurred. The needle guard assembly 304 consists of a needle guard housing 306 held in an extended position by a spring 312 that covers a needle 308. The injection end of the needle is covered by a sealing member 314, preventing fluid from entering or exiting the needle until the needle guard assembly 304 is retracted, exposing the needle 308 through the sealing member 314. To activate the needle guard assembly 304, a safety clip 310 is removed from the device, causing the needle guard housing 306 to retract over the device housing, thereby exposing the needle 308. As shown in Figure 3C, upon retraction of the needle guard assembly 316, the needle guard housing 320 retracts, exposing the needle 318 as it penetrates the sealing member 322, exposing the needle 318 and injecting the substance. In the state shown in Figure 3C, the device is activated and the components are compounding, but injection has not yet begun.

[0086] 3D shows yet another detailed embodiment of the needle assembly and needle guard. The needle guard housing 324 is guided by the movement of guard guide 328 aligned with and positioned within guide track 326. The needle 342 is held in place by needle attachment 330. The needle 342 is sealed at the injection end by sealing member 346, preventing fluid from entering or exiting the needle 342 until the needle guard housing 324 is retracted, exposing the needle 342. To activate the needle guard, safety clip 338 is released, which retracts the needle guard assembly 323, exposing the needle from sealing member 346. After injection, a compression spring 344 pushes the needle guide back into place, concealing the needle.

[0087] 3E, which illustrates another embodiment of the needle assembly and needle guard. Here, the needle guard assembly 348 consists solely of a needle guard housing 350, which is guided by the movement of a device housing 352. The injection end of the needle is sealed with a sealing member 354.

[0088] Reference is now made to FIG. 4, which shows a side cross-sectional view of another embodiment with the device body, needle assembly, and guard attached. The needle assembly and needle guard assembly 400 attaches to a three-chamber system (main device body) 424 via attachment points 404. Attachment may be by screws, adhesive, welding, press fit, snap fit, or other methods commonly known in the art. The device body consists only of an actuation assembly (actuation mechanism) 426 and three chambers (first chamber 418, second chamber 436, and third chamber 444), all contained within a housing 420. An insertion rod 428 is contained within the first chamber 418 and optionally includes a sealing member 430. A fluid pathway 432 and a fluid vent 422 are contained within the insertion rod 428. The end of the insertion rod 428 abuts a sealing member 434, which is a barrier separating the first chamber 418 from the second chamber 436. Second chamber 436 is contained within housing 438 and may include a sealing member 414, or may be part of the housing itself. Second chamber 436 is maintained isolated from third chamber 444 via movable sealing member assembly 410 and optional sealing member 440. Sealing member 412 is attached to movable sealing member assembly 410 and prevents material from entering needle 448 prior to device activation.

[0089] Upon actuation of the device, actuation assembly (compression mechanism) 426 forces insertion rod 428 through seal member 434 and into second chamber 436. Insertion rod 428 enters second chamber 436 through opening 416, displacing the material and allowing accommodation of insertion rod 428. Material from second chamber 436 and first chamber 418 moves within second chamber 436, and movable seal member assembly 410 moves into third chamber 444, compressing spring 408. The combined material remains in third chamber 444 until needle guard assembly 400 is retracted for injection.

[0090] To allow for an injection after device activation, safety clip 442 is released and needle guard assembly 400 is retracted, exposing needle 448. Before needle guard assembly 400 is retracted, the injection end of needle 448 is sealed with sealing member 450 to prevent substances from entering or exiting needle 448. Upon retraction, needle 448 is exposed through needle port 452. During retraction, needle guard guide 446 follows guide track 402 to facilitate proper movement of needle guard assembly 400. Needle 448 is attached via needle attachment 406.

[0091] The device of the present disclosure can be maintained in four different operable states, as shown in Figures 5A-5D. Referring to Figure 5A, the first operable state 500 is the state before the device is actuated, and no material combination has occurred. The actuation assembly (compression mechanism) 514 is not actuated and does not compress the insertion rod 512. The first chamber 510 contains the first material to be combined, and the sealing member 516 is not penetrated. The second chamber 508 contains all of the material to be combined. The movable sealing member assembly 506 acts as a barrier between the second chamber 508 and the third chamber 504, and no material is flowing into the third chamber 504. The safety clip (safety pin) 518 is still in place on the device, and the needle guard is not retracted.

[0092] 5B, in the second operational state, the actuation assembly (compression assembly) 544 is partially actuated to a first predetermined position. The insertion rod 542 penetrates into the second chamber 550 by breaking the sealing member 548. The first chamber 546 and the second chamber 550 are in fluid communication, but the substances are not fully combined.

[0093] 5C, in the third operational state 520, the actuation assembly (compression system) 524 is fully actuated through the second predetermined position to the third predetermined position, forcing the insertion rod 526 into the second chamber. The substances combine and move into the third chamber 522. The movable seal member assembly 528 is retracted, compressing the spring 530. The safety clip (safety pin) 529 is in place, the needle guard 532 is not retracted, and the seal member 534 is not pierced by the injection needle.

[0094] 5D, in the fourth operable state 536, the safety clip is released and the needle guard 538 is retracted, exposing the needle 544. The compression spring 542 is forced back into the device, and fluid is forced outward from the needle 544. The movable seal member assembly 540 is forced back toward the center of the device.

[0095] Reference is now made to Figure 6, which shows the three main operational states, plus the final state when the device is removed from the injection site. Operational state 600: The device is brought close to the injection surface prior to injection. State 602: Once the device is at or near the injection surface, the safety clip (safety pin) is released, then State 604: The device is pushed downwards, pushing the needle into the injection surface. State 606: After the injection is complete, the device is lifted and the needle guard again hides the needle.

[0096] Reference is now made to FIG. 7 , which illustrates one embodiment of the internal components of second chamber 722. This figure shows how second chamber 722 is positioned between two other chambers (first chamber 714 and third chamber 728). Second chamber 722 is housed within housing 706, which is itself housed within housing assembly 700 and optionally surrounded by sealing member 710. An insertion rod 716 is initially held adjacent to sealing member 712. Insertion rod 716 includes a fluid passageway 718 and a piercing end 720 for penetrating sealing member 712. Piercing end 720 may include one or more sharp or blunt protrusions to more easily penetrate sealing member 712. Once sealing member 712 is penetrated, insertion rod 716 is pushed through opening 708 into second chamber 722. Opening 708 may be chamfered or otherwise shaped to facilitate entry of insertion rod 716 and facilitate material transfer from first chamber 714 to second chamber 722. As material from first chamber 714 is forced into and through second chamber 722, movable seal member assembly 724 and sealing member 704 move into third chamber 728, transferring the material to third chamber 728. Upon moving into third chamber 728, spring 702 is compressed, causing the non-injection side of needle 726 to pierce sealing member 704 and allow material to enter needle 726 during injection.

[0097] 8, which illustrates a side cross-sectional view of one embodiment of a device disclosed herein that uses a screw mechanism to urge a plunger downward. Actuation assembly 800 is the unactuated device, and upon rotation of actuation assembly 802, actuation assembly 802 urges the plunger into the device, compressing the components and actuating the device.

[0098] The devices described herein may be configured into specific articles of various dimensions using components of various sizes and adapted in use for various purposes and according to various operating parameters.

[0099] Dimensional characteristics and parameters of use, which may be selected for a particular purpose, may include the force applied to the injection site to inject the active agent, the amount of medication to be delivered, the size of the internal passageway through the needle, the injection depth determined by the length of the needle protruding from the device, the spring force applied to the needle to expel the medication, and the time interval required to inject the medication upon activation of the device. These factors, individually and / or collectively in various combinations, and possibly other factors, are believed to contribute to the effectiveness of the device in delivering the medication into the patient's body, also referred to as "uptake" of the medication, and in dispersing the medication from the initial injection site into surrounding body tissues.

[0100] The amount of force applied to the injection site is ultimately determined by the user's choice of how much pressure the device must exert against their body, but the minimum level of force is determined by the device design and the force required to activate the device. In some embodiments, the activation force to release the active agent is about 4 to about 8 pounds. In some embodiments, the activation force to release the active agent is about 2 to about 8 pounds. In some embodiments, the activation force to release the active agent is about 4 to about 6 pounds. In some embodiments, the activation force to release the active agent is about 2 to about 6 pounds. In some embodiments, the actual force applied by the user is at least about 2 pounds. In some embodiments, the actual force applied by the user is at least about 3 pounds. In some embodiments, the actual force 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.

[0101] The force required to inject an active agent into a subject may also vary depending on the viscosity of the resulting fluid mixture of the active agent and pharmaceutically acceptable carrier. In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is between about 1 milliPascal-second (mPa·s) (centipoise (cP)) and about 150 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is between about 5 and about 125 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is between about 10 and about 100 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is between about 15 and about 75 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 20 to about 60 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 25 to about 50 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 1 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 5 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 10 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 25 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 50 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 75 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 100 mPa·s (cP).In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 110 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 120 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 130 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 140 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is about 150 mPa·s (cP). In some embodiments, the viscosity of a fluid mixture of an active agent and a pharmaceutically acceptable carrier injected by a disclosed device is greater than about 150 mPa·s (cP).

[0102] The time the needle is held in place against the injection site after injection is typically based on the manufacturer's recommendations printed on the auto-injector label. In some embodiments, at least about 2 seconds is recommended. In some embodiments, at least about 3 seconds is recommended. In some embodiments, at least about 4 seconds is recommended. In some embodiments, at least about 5 seconds is recommended.

[0103] The volume of medication delivered depends on the internal dimensions of the device selected by the manufacturer to administer the desired volume of active agent. For example, when administering epinephrine with an auto-injector, the injection volume used may be about 0.15 mL or about 0.30 mL. Larger injection volumes may also be administered. In some embodiments, the volume for rapid injection using one of the disclosed devices may be about 0.50 mL to about 3.0 mL, depending on viscosity and other factors. In these embodiments, references to injection volume or dispense volume of an active agent refer to the total volume of liquid injected into the patient, and these references do not relate to the amount of active ingredient contained in that injection volume. However, in some embodiments, the disclosed devices may be used to deliver a predetermined amount or dose of active agent to a subject. In some embodiments, when cortisone or a cortisone derivative is used, the cortisone or cortisone derivative is used in a dosage of about 5 mg to about 500 mg by weight in the disclosed devices. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 10 mg to about 400 mg by weight. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 25 mg to about 300 mg by weight. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 50 mg to about 250 mg by weight. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 60 mg to about 200 mg by weight. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 75 mg to about 1500 mg by weight. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 5 mg / mL to about 300 mg / mL by weight, based on the volume of solution of the active agent in a pharmaceutically acceptable carrier. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 10 mg / mL to about 250 mg / mL by weight of solution volume of the active agent in a pharmaceutically acceptable carrier.In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 15 mg / mL to about 200 mg / mL by weight based on the volume of solution of the active agent in the pharmaceutically acceptable carrier. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 20 mg / mL to about 175 mg / mL by weight based on the volume of solution of the active agent in the pharmaceutically acceptable carrier. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 25 mg / mL to about 150 mg / mL by weight based on the volume of solution of the active agent in the pharmaceutically acceptable carrier. In some embodiments, cortisone or a cortisone derivative is used in the disclosed devices at a dosage of about 30 mg / mL to about 1250 mg / mL by weight based on the volume of solution of the active agent in the pharmaceutically acceptable carrier.

[0104] It is understood that the amount of active agent, such as cortisone or a cortisone derivative, in an injection volume of a medication may vary. The amount of active agent in that injection volume may vary depending on the dosage prescribed for the patient. The prescribed dosage of cortisone or a cortisone derivative may 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 active agent may be formulated with other ingredients, such as a pharmaceutically acceptable carrier, to comprise a volume of medication between 0.15 mL and about 0.6 mL. The amount of active agent does not necessarily correlate directly with the volume of medication injected, as the volume of medication injected can be diluted as needed. For example, a 0.30 mL injection of a medication may contain about 1 mg or about 25 mg of active agent.

[0105] The size of the internal passageway through the needle is determined by the manufacturer by selecting the appropriate gauge of the needle's tubing. Small-diameter stainless steel tubing, typically used for hypodermic needles, is available in a variety of standard sizes, referred to as gauges. The gauge determines the tubing's nominal outer diameter. Within each gauge, the tubing is then typically available in a variety of wall thicknesses, referred to as standard wall (RW), thin wall (TW), extra thin wall (ETW), and ultra thin wall (UTW). The thinner the wall of a given gauge of tubing, the larger the tubing's inner diameter and / or bore. For each standard tubing size, such as 22-gauge RW tubing, the applicable standard specifies minimum, nominal, and maximum values ​​for each dimension, such as the inner diameter. For the devices of the present disclosure, the needle may be constructed from RW stainless steel tubing with gauges greater than or equal to 18 gauge and less than or equal to 24 gauge. Wall thicknesses other than RW are also possible. The table below shows the standard minimum, nominal, and maximum inner diameters for 18-24 gauge RW stainless steel tubing. All dimensions are in millimeters (inches).

[0106] [Table 3]

[0107] Therefore, if you choose the smallest of these internal diameters, the minimum internal diameter for 24 gauge RW tubing is 0.0115 inches. If you choose 23 gauge RW tubing, the internal diameter must be at least 0.0125 inches. If you choose 22 gauge RW tubing, the internal diameter must be at least 0.0155 inches. For all of the options in the table above, the internal diameter of the needle will not exceed the maximum internal diameter of 0.0345 inches for 18 gauge RW tubing.

[0108] The injection depth, determined by the length of the needle protruding from the disclosed device, is shown, for example, in FIG. 6. The dimensions are determined by the dimensions of various internal components to suit the particular active agent being injected. For example, for subcutaneous injection of an active agent, the device may inject into the subcutaneous region, and in some embodiments, the injection depth is 0.15 inches to 0.30 inches. In other embodiments, the injection depth is 0.2 inches to 0.25 inches within the subject. For intramuscular injection of an active agent, the disclosed device may inject into the intramuscular region, and in some embodiments, the injection depth is 0.4 inches to 0.7 inches. In other embodiments, the injection depth is 0.6 inches within the subject. In some embodiments, the disclosed device may inject intramuscularly to a depth of up to 1.25 inches within the subject.

[0109] The spring force applied to expel the activator is determined by the choice of the power spring manufacturer and the design of various internal components, which affect the amount of available spring force actually applied. When a given spring is compressed, it exerts a certain static force on the surrounding structure that holds the spring in its compressed state. However, when the spring is released, some of its potential energy is lost due to friction, needle movement, and needle sheath collapse, so the actual dynamic force the spring exerts on the plunger to expel the activator is less than the initial static force output of the spring. For example, when the spring is compressed, the nominal static force output of the spring may be approximately 100 Newtons. Due to manufacturing tolerances, the actual static force output of the spring may range from approximately 0 to approximately 100 Newtons. The actual dynamic force the spring exerts on the plunger to expel the activator may then range from approximately 10 to approximately 75 Newtons. The dynamic force may be described as being 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.

[0110] The devices of the present disclosure can be used to deliver a variety of active agents to a subject. The active agents set forth in Table 1, and the dosages listed therein, are of particular interest.

[0111] [Table 4]

[0112] In some embodiments, the disclosed devices are used to deliver one or more active agents selected from Table 1 to a subject. In some embodiments, the disclosed devices are used to deliver one or more active agents selected from Table 1 to a subject at the dosages specified in Table 1. In some embodiments, the disclosed devices are used to deliver cortisone to a subject. In some embodiments, the disclosed devices are used to deliver a cortisone derivative to a subject. In some embodiments, the disclosed devices are used to deliver hydrocortisone sodium succinate to a subject. In some embodiments, the one or more active agents are delivered to a subject using the disclosed devices in the presence of one or more 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 aqueous sodium chloride solution. In some embodiments, the pharmaceutically acceptable carrier used is aqueous sodium bicarbonate. In some embodiments, the pharmaceutically acceptable carrier used is aqueous dimethyl sulfoxide.

[0113] method The present disclosure provides methods for treating and / or preventing a disease or disorder in a subject, the method comprising administering one or more active agents via any of the devices disclosed herein. The present disclosure also provides methods for treating a subject in need of administration of one or more active agents, the method comprising administering a pharmaceutically effective amount of one or more active agents via any of the devices disclosed herein. In some embodiments, the subject has been diagnosed with or is suspected of having a cortisol disorder. As used herein, "cortisol disorder" refers to any disease or disorder that causes dysfunction in abnormal levels of cortisol secretion. In some embodiments, the cortisol disorder is Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenomyeloneuropathy, adrenoleukodystrophy, adrenal tumor, Schmidt's syndrome, hyperaldosteronism, pituitary tumor, pituitary cyst, or severely related corticosteroid deficiency. In some embodiments, the subject has been diagnosed with, is suspected of having, or is suffering from a cortisol deficiency. In some embodiments, the cortisol deficiency in the subject is caused by Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenomyeloneuropathy, adrenoleukodystrophy, adrenal tumor, Schmidt's syndrome, hyperaldosteronism, a pituitary tumor, a pituitary cyst, or severe related corticosteroid insufficiency.

[0114] In addition to cortisone or cortisone derivatives, the disclosed devices can also be used to deliver other non-acute active agents to a subject in need thereof for necessary treatment. Examples of such non-acute active agents include, but are not limited to, non-acute steroids, antibiotics, analgesics, disease-specific treatments (e.g., MS medications, psoriasis medications), insulin, glycoproteins, immunomodulators, G-CSF, erythropoietin (Epogen®, Procrit®), biologics, antihypertensives, vaccines, hormones (including birth control), antihormones, sedatives, antiepileptics, antineoplastics, insecticides (e.g., Dobutrex), antipsychotics, antidotes, cosmetics, selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors (PPIs), anesthetics, diuretics, antidiuretics, blood thinners (e.g., low molecular weight heparin), streptokinase, and the like, whether administered alone or in combination, whether in liquid, reconstitutable, or other dosage form. In some embodiments, the disclosed device is used to deliver drugs previously used with the Act-o-vial® system, namely methylprednisolone for multiple sclerosis, certain cancers, and autoimmune diseases. In some embodiments, the disclosed device is used to deliver glucagon for use in hypoglycemic emergencies. In some embodiments, the disclosed device is used to deliver ticarcillin for use in treating high-morbidity infectious diseases. In some embodiments, the disclosed device is used to deliver chlordiazepoxide for use in treating alcohol withdrawal. In some embodiments, the disclosed device is used to deliver desoxycorticosterone pivalate for use in veterinary emergencies. In some embodiments, the disclosed device is used for in vitro fertilization treatments.

[0115] The devices of the present disclosure may be manufactured by any means known to those skilled in the relevant art, particularly in the field of auto-injectors. In some embodiments, the first, second, and third compartments are physically attached to the housing by friction fit, rivets, plugs, or plastic welding, such as radio frequency or ultrasonic welding. The compartments may also be attached to the housing or to each other by the same techniques or via protrusions, such as snap fittings. The device components can be plastic, rubber, glass, or metal. Most, if not all, seals are made of plastic or rubber, while the chamber is made of plastic, glass, or metal. The insertion rod is either plastic or metal and attaches to any sealing member via an interlocking mechanism based on an attachment groove or by helical threading. In embodiments using a movable system attached to the insertion rod, the movable system is attached by friction. The sealing member attached to the chamber is press-fit into place using friction, attached via an interlocking groove system, or screwed into place. In some embodiments, the compartments are cylindrical or approximately cylindrical and have fastening protrusions on their ends. In some embodiments, each side of the compartment and each side of the device piece may be provided with one or more fasteners.

[0116] Methods according to aspects of the present disclosure include, for example, a method of using an apparatus for transporting, storing, mixing, and injecting drugs into a patient, the apparatus comprising: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, the method comprising providing the apparatus, mixing the drugs to form a drug solution in preparation, engaging the mixing assembly to administer the drug to the patient, and engaging the injection assembly to inject the drug solution into the patient. The method may further comprise disengaging a safety device prior to engaging the injection assembly to inject the drug solution into the patient.

[0117] Further methods according to aspects of the present disclosure include, for example, a method of assembling an apparatus for transporting, storing, mixing, and injecting a drug into a patient, the apparatus comprising: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, the method comprising: 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.

[0118] Systems according to aspects of the present disclosure include, for example, a system for assembling an apparatus for transporting, storing, mixing, and injecting drugs into a patient, the apparatus comprising: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, the system comprising: a means for assembling the transport assembly, a means for assembling the storage assembly, a means for assembling the mixing assembly, and a means for assembling the injection assembly.

[0119] Methods according to aspects of the invention include, for example, a method of using a device for transporting, storing, mixing, and injecting a drug into a patient, the device comprising: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, the method comprising: providing the device, mixing the drugs to form a drug solution in preparation, engaging the mixing assembly to administer the drug to the patient, and engaging the injection assembly to inject the drug solution into the patient. The method may further comprise disengaging a safety device prior to engaging the injection assembly to inject the drug solution into the patient.

[0120] Further methods according to aspects of the invention include, for example, a method of assembling an apparatus for transporting, storing, mixing, and injecting a drug into a patient, the apparatus comprising: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, the method comprising: 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.

[0121] Systems according to aspects of the invention include, for example, a system for assembling an apparatus for transporting, storing, mixing, and injecting drugs into a patient, the apparatus comprising: a transport assembly, a storage assembly, a mixing assembly, and an injection assembly, the system comprising: a means for assembling the transport assembly, a means for assembling the storage assembly, a means for assembling the mixing assembly, and a means for assembling the injection assembly.

[0122] Manufacturing method The devices described herein comprise an active agent that is injected into the body and therefore must be manufactured using sterile and aseptic techniques. Typical techniques for manufacturing include sterilization of device components, filling with the active agent and carrier agent, assembly of active agent-contacting components, and assembly of non-active agent-contacting components. Filling with the active agent and carrier agent, as well as assembly of some active agent-contacting components, must be completed in an aseptic processing manufacturing facility, often referred to as a sterile core.

[0123] Component sterilization techniques are well known in the art. Drug loading depends on the device characteristics and whether the active agent is a solid or liquid. Liquids can be loaded by dispensing techniques using volumetric or flow measurements. Powders and other solids can be loaded by inserting the powder or solid material using a density- or weight-based measuring system to determine the total load.

[0124] One method of manufacturing this device involves capping the chamber at the distal end with a movable sealing member and then inserting the capped chamber into a sterile core. An active agent is inserted into the chamber using either a powder or liquid filling method. The liquid may or may not be lyophilized, depending on the type of active agent and device requirements. The filled chamber is then capped at the proximal end and inserted into the main device tube. A second agent is then filled into the first chamber using either a liquid or powder filling method, and an insertion rod is added to seal the exposed end of the second-agent-filled chamber. A needle is added to the device, and the completed subassembly is removed from the sterile core. The remaining components are assembled into the device outside of the sterile core.

[0125] In another manufacturing method, the components are sterilized outside the sterile core. The needle assembly, movable sealing member, and one chamber are inserted into the main device housing outside the sterile core. This subassembly is then transferred to the sterile core, and an active agent is inserted into the exposed chamber using a liquid or powder filling method. This chamber is then capped, and a second active agent is added on top of the first active agent using a liquid or powder filling method. An insertion rod and sealing member are added on top of the newly filled chamber, and the assembly is removed from the sterile core. Any final manufacturing assembly steps are completed, and the device is packaged and labeled for distribution.

[0126] In another manufacturing method, the components are sterilized. The primary device tube and needle are assembled and inserted into a sterile core. The device chamber is sealed at the distal end with a movable sealing member and placed within the same sterile core. The active agent is inserted into the chamber using a powder or liquid filling method. If necessary, the liquid is lyophilized. Once filling is complete, the chamber is sealed at the proximal end. The filled and sealed chamber is inserted into the primary device tube. The liquid or powder is then filled on top of the previous chamber. An insertion rod and sealing member are added on top of the newly filled chamber and the assembly is removed from the sterile core. Any final manufacturing assembly steps are completed and the device is packaged and labeled for distribution.

[0127] In some embodiments, the first, second, and third compartments are physically attached to the housing by friction fit, rivets, plugs, or plastic welding, such as radio frequency or ultrasonic welding. The compartments may also be attached to the housing or to each other by the same techniques or via protrusions, such as snap fittings. The device components are plastic, rubber, glass, or metal. In some embodiments, the seal is made of plastic or rubber, while the chamber is made of plastic, glass, or metal. In some embodiments, the insertion rod is either plastic or metal and is attached to any sealing member via an interlocking mechanism based on an attachment groove or by helical threading. In some embodiments using a movable system attached to the insertion rod, the movable system is attached operably by friction. The sealing member attached to the chamber is press-fit into place using friction, attached via an interlocking groove system, or screwed into place. In some embodiments, the compartment is cylindrical or approximately cylindrical and has protrusions on the ends for fastening. In some embodiments, one or more fasteners may be provided on each side of the compartment and each side of the device component.

[0128] The foregoing description discloses exemplary embodiments of the present invention. While the invention disclosed herein has been described in terms of particular embodiments and applications thereof, numerous modifications and variations thereto may be made by those skilled in the art without departing from the scope of the invention as set forth in the claims. Modifications of the above-disclosed apparatus and methods which fall within the scope of the claimed invention will be readily apparent to those skilled in the art. Accordingly, other embodiments may fall within the spirit and scope of the claimed invention, as defined by the claims which follow.

[0129] The present disclosure relates to methods for treating a subject in need thereof by administering one or more active agents through the use of a device. In some embodiments, the administration method comprises depressing a movable element to a first predetermined position such that an insertion rod pierces a sealing member at a first opening separating a first and second compartment. In some embodiments, the method further comprises allowing a time period for the active agent and diluent in the first and second compartments to mix and dissolve and / or activate the active agent. In some embodiments, the method further comprises, after a second continuous period of time following the first step of depressing the movable element to the second predetermined position, depressing the movable element so that the insertion rod displaces or pierces a sealing member separating a second and third compartment. In some embodiments, the method further comprises allowing a second period of time to pass such that the active agent and pharmaceutically acceptable carrier or diluent contact the end of the needle. In some embodiments, the method further comprises fully depressing the movable element to the depressed position a third time to release the spring of the needle assembly and place the distal end of the needle within the subject. In some embodiments, the method further comprises unlocking the needle assembly before fully depressing the movable element. In some embodiments, the first predetermined distance of movement toward the needle assembly is between about 1 cm and about 5 cm. In some embodiments, the second predetermined distance of movement toward the needle assembly is between about 1 cm and about 5 cm. In some embodiments, the third predetermined distance is between about 2 cm and about 6 cm.

[0130] In some embodiments, the method of administration does not involve depressing the movable element a third time, and the final release of the needle assembly spring is achieved by simply applying pressure to the end of the device adjacent to the needle assembly. In such cases, longitudinal pressure applied to the device by the subject or operator releases the spring, dislodging the needle sheath with a force that places the pharmaceutical composition within the subject.

[0131] The therapeutically effective amount or dosage of a compound can vary within wide limits. Such dosage will be tailored to the individual requirements of each particular case, including the specific compound(s) administered, the route of administration, the condition being treated, and the patient being treated. Generally, for oral or parenteral administration to adult humans weighing at least about 70 kg, a daily dosage of about 10 mg to about 10,000 mg, preferably about 200 mg to about 1,000 mg, is appropriate, although the upper limit may be exceeded. The daily dosage can be administered as a single dose or in divided doses, or, for parenteral administration, as a continuous infusion. A single-dose composition may contain such amounts or submultiples of such amounts of the compound or composition that constitute the daily dose. In the event of any contraindications, the dosage can be adjusted by the individual physician. The dosage is variable and can be administered in one or more doses per day for one or several days.

[0132] In the above description, numerous specific details are set forth to provide a more thorough understanding of embodiments of the present invention. However, it will be apparent to one skilled in the art that the present invention may be practiced without incorporating all of the specific details set forth herein. Not all possible embodiments of the present invention are described verbatim herein. Multiple aspects of the present invention may be combined to form various embodiments within the scope of the following claims. Additionally, specific details well known to those skilled in the art have not been described in detail so as not to obscure the present invention. While examples of the present invention are described herein, the reader should bear in mind that the claims, and the full scope of any equivalents, define the metes and bounds of protection of the present invention.

[0133] The foregoing description discloses exemplary embodiments of the present disclosure. While the disclosure herein has been described in terms of specific embodiments and applications thereof, numerous modifications and variations may be made to the embodiments and applications thereof by those skilled in the art without departing from the scope of the disclosure as set forth in the claims. Modifications of the above-disclosed apparatus and methods that fall within the scope of the claimed subject matter will be readily apparent to those skilled in the art. Accordingly, other embodiments may be within the spirit and scope of the claimed subject matter, as defined in the claims that follow.

[0134] In the above description, numerous specific details are set forth to provide a more thorough understanding of embodiments of the present disclosure. However, it will be apparent to one skilled in the art that the present disclosure may be practiced without incorporating all of the specific details set forth herein. Not all possible embodiments of the present disclosure are described verbatim herein. Multiple aspects of the present disclosure may be combined to form various embodiments within the scope of the following claims. Furthermore, specific details well known to those skilled in the art have not been described in detail so as not to obscure the disclosure. While examples of the present disclosure are described herein, the reader should bear in mind that the claims, and the full scope of any equivalents, define the metes and bounds of protection. [Explanation of symbols]

[0135] 102 First compartment, first chamber 104 Second compartment, second chamber 110 Second compartment, second chamber 112 First compartment, first chamber 114 Moving element actuation assembly 202 Moving element actuation assembly 204 Insertion Rod 206 Sealing member which is the first sealing member 208 Second compartment, second chamber 210 Third compartment, third chamber 212 Spring 216 First compartment, first chamber 222 Actuating assembly, which is a moving element 224 Insertion Rod 232 sealing member which is the first sealing member 234 Second compartment, second chamber 240 Third compartment, third chamber 242 needles 244 Spring 248 Sealing member which is a second sealing member 254 First compartment, chamber 1 308 needles 318 needles 342 needles 408 Spring 412 sealing member which is a second sealing member 416 First Aperture 418 First compartment, first chamber 426 Working assembly, which is a moving element 428 Insertion Rod 434 a sealing member which is a first sealing member 436 Second compartment, second chamber 444 The third compartment, the third chamber 448 needles 504 Third compartment, third chamber 508 Second compartment, second chamber 510 First compartment, first chamber 512 Insertion Rod 514 Actuating assembly, which is a moving element 516 a sealing member which is a first sealing member 522 Third compartment, third chamber 524 Actuating assembly, which is a moving element 526 Insertion Rod 530 Spring 542 Insertion Rod 546 First compartment, first chamber 548 a sealing member which is a first sealing member 550 Second compartment, second chamber 702 Spring 704 sealing member which is the second sealing member 708 First Aperture 712 a sealing member which is a first sealing member 714 First compartment, first chamber 716 Insertion Rod 722 Second compartment, second chamber 726 needles 728 Third compartment, third chamber

Claims

1. 1. A method of discharging material from an apparatus, comprising: the device comprises a first compartment, a second compartment, and a third compartment, each of the first, second, and third compartments defining a first, second, and third cavity, respectively; the first and second compartments are fluidly communicable through a first opening and separated by a first sealing member covering the first opening; the second and third compartments are fluidly communicable through a second opening and separated by a second sealing member covering the second opening; and the third compartment comprises a needle assembly having a spring and a needle; depressing a movable element of the device to a first predetermined position, causing an insertion rod to displace the first sealing member from the first opening to allow fluid communication between the first compartment and the second compartment; depressing the movable element to a second predetermined position, causing the insertion rod to displace the second sealing member from the second opening to allow fluid communication between the second compartment and a third compartment; Depressing the movable element to a third predetermined position causes the needle assembly to expel the substance through the needle.

2. 10. The method of claim 1, wherein the first compartment contains a pharmaceutically acceptable carrier in liquid form and the second compartment contains an active agent in solid or semi-solid form, and fluid communication between the first and second compartments results in the active agent being dissolved in the pharmaceutically acceptable carrier.

3. 2. The method of claim 1, wherein the displacement occurs such that the spring in the third compartment is loaded with a force between 0 and 100 Newtons at the second predetermined position.

4. The method of claim 1 , further comprising the step of unlocking the needle assembly before depressing the movable element to the third predetermined position.

5. 10. The method of claim 1, wherein depressing the movable element to the third predetermined position releases energy stored in the spring and expels the material through the needle.

6. 1. A method of operating an injection device, comprising: depressing a movable element of the injection device to a first predetermined position, a second predetermined position, and a third predetermined position; the injection device comprises a first compartment, a second compartment, and a third compartment, each of the first, second, and third compartments defining a first, second, and third cavity, respectively; the first and second compartments are fluidly communicable through a first opening and separated by a first sealing member covering the first opening; the second and third compartments are fluidly communicable through a second opening and separated by a second sealing member covering the second opening; and the third compartment comprises a needle assembly having a spring and a needle operably connected to the spring; In the step of depressing the movable element to the first predetermined position, an insertion rod displaces the first sealing member from the first opening to expose the first opening between the first compartment and the second compartment and establish fluid communication between the first compartment and the second compartment; In the step of depressing the movable element to the second predetermined position, the insertion rod displaces the second sealing member from the second opening to expose the second opening between the second compartment and the third compartment and establish fluid communication between the second compartment and the third compartment; The step of depressing the movable element to the third predetermined position causes the substance in the third compartment to be expelled from the needle assembly.

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

8. 7. The method of claim 6, wherein depressing the movable element to the third predetermined position releases energy stored in the spring and expels material through the needle.

9. 7. The method of claim 6, wherein the spring in the third compartment stores a force that, when activated, is used to expel material through the needle.

10. 1. A method of removing a substance from a device comprising a first compartment, a second compartment, and a third compartment, comprising: each of the first, second, and third compartments defining a first, second, and third cavity, respectively; the first and second compartments are fluidly communicable through a first opening and separated by a first sealing member covering the first opening; the second and third compartments are fluidly communicable through a second opening and separated by a second sealing member covering the second opening; and the third compartment contains a needle assembly having a spring and a needle; a first step in which a movable element of the device is moved to a first predetermined position and an insertion rod displaces the first sealing member from the first opening to allow fluid communication between the first compartment and the second compartment; a second step in which the movable element moves to a second predetermined position and the insertion rod displaces the second sealing member from the second opening to allow fluid communication between the second compartment and the third compartment; and a third step of moving the movable element to a third predetermined position to expel the substance in the third compartment from the needle assembly.

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