Drug injection device, system and method

Abstract

This disclosure relates to systems, methods, and apparatuses for storing, transporting, mixing, and injecting drugs in solutions. In some embodiments, the drug injection apparatuses and systems are designed for mixing a pre-measured amount and dose of drug with a liquid such as water as needed, and for injecting the drug mixture using an integrated hypodermal needle assembly. Methods for using such apparatuses and systems are also provided.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 62 / 981,811, filed on February 26, 2020, which is incorporated herein by reference in its entirety. Technical Field

[0003] The present disclosure relates to a device including a needle for administering an active agent to a subject, wherein the active agent is an active agent in solid or liquid form in one compartment, separated from a diluent or a pharmaceutically acceptable carrier in another compartment, and the device is capable of exposing the active agent to the diluent or pharmaceutically acceptable carrier for mixing or dissolving prior to administration. The present disclosure also relates to systems, methods and devices for storing, transporting, mixing and injecting drugs in solutions, and in some embodiments, the drug injection devices and systems involved are intended to be used to mix pre-measured amounts and doses of drugs with liquids such as water as needed, and inject the drug mixture using an integrated subcutaneous injection needle assembly. Methods of using such devices and systems are also provided. Background Art

[0004] Emergency injections have long been utilized in response to any form of extremely time-sensitive, life-threatening events, including overdose, anaphylaxis, angioedema, or adrenal insufficiency (AI). The immediate need and essential requirements of the active ingredient necessitate accurate and rapid drug delivery. In fact, naloxone auto-injectors are widely used in the medical field. and an auto-injector containing epinephrine ( and ) provide a dosing system that is easier to manipulate and administer, however, steroid syringes (Solu- and Solu- ) due to its reliance on reconstitution, which, while equally important, still suffers from bulky delivery systems, thus providing a suboptimal drug delivery device in terms of drug preparation and delivery.

[0005] At this point, the emergency injection of steroids, i.e., hydrocortisone, is still the drug of choice for adrenal insufficiency, which is manifested by the inability of the adrenal glands to produce sufficient amounts of the glucocorticoid cortisol. Corticosterone itself is released in response to both stress and hypoglycemia, where this necessary steroid is responsible for the production of glucose and immunosuppression, in addition to other processes such as glycogen production, electrolyte balance, and secretion of gastric acid, and can affect sleep, mood, and stress levels. Conversely, a reduction (or absence) of cortisol can lead to weakness, fatigue, weight loss, and depression, while a complete absence of cortisol can lead to adrenal shock or adrenal crisis, in which the body lacks the ability to maintain its own homeostatic function, and the patient can show severe drowsiness, confusion, psychosis, cramps, diarrhea, vomiting, spasms, hypoglycemia, and other life-threatening sequelae, until death.

[0006] Until now, patients with congenital adrenal hyperplasia (CAH), Addison's disease, and idiopathic adrenal insufficiency have faced challenges in taking medication. Conventionally, to prepare cortisol for intramuscular (IM) administration, individuals inject bacteriostatic water or bacteriostatic sodium chloride into a sterile bottle containing dry cortisol powder, or use Act-o- A system in which a diluent in an upper bottle is attached to a lower bottle containing the active dry cortisol component. Similarly, both require laborious manipulation of different or connected bottles to mix, extract and administer the reconstituted mixture, all of which need to be done in a very short time when life is at stake. Even the relatively simpler Act-o- For drug mixing systems, an average of 12 user steps are required to perform an injection, including (1) obtaining a needle and diluent / drug container, (2) pressing the plastic cap onto 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 cap, (5) sterilizing the needle plug, (6) inserting the needle through the center of the plug, (7) extracting the dose, and finally, (8) injecting the appropriate dose into the muscle. Due to the complexity of the system, Act-o- Delivery systems require trained medical personnel to ensure proper access and administration of potentially life-saving medications. The delivery system is not designed for use by lay persons or individuals suffering from adrenal insufficiency. Summary of the invention

[0007] The present disclosure relates to systems, methods and devices for delivering, storing, mixing and injecting medications to a patient, such as for administering a single dose of medication to a patient by transporting, storing, mixing and injecting medications using a medication injection device.

[0008] The emergency injection of steroids, i.e., cortisol, remains the drug of choice for adrenal insufficiency, a condition characterized by the inability of the adrenal glands to produce adequate amounts of the glucocorticoid cortisol. Reduced or absent cortisol can lead to a variety of conditions, including weakness, fatigue, weight loss, and depression, while a complete absence of cortisol can lead to adrenal shock or adrenal crisis, which can be life-threatening. It is against this background that the importance of immediate administration of exogenous cortisol, i.e., cortisol, becomes necessary and mandatory. Until now, cortisol has been available to hospitalized patients either intravenously or by intramuscular injection (IM), but only to non-hospitalized patients specifically for acute short-term illnesses via a prepared reconstituted intramuscular injection from a dose typically between 100 mg and 500 mg.

[0009] Designed 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 is intended to improve the administration of life-saving injectable drugs using twist-to-mix delivery systems and devices to benefit the millions of patients worldwide suffering from congenital adrenal hyperplasia (CAH), Addison's disease, and idiopathic adrenal insufficiency. Exemplary embodiments of the disclosed systems and devices require as few as four injection steps and can be designed for people experiencing adrenal crisis and their caregivers.

[0010] The present disclosure is directed primarily to filling the gap in the field of emergency injectable steroids. The present disclosure is also directed to further advancing the efficient and effective administration of other emergency drugs (e.g., epinephrine and naloxone) and non-emergency drugs, including but not limited to non-emergency steroids, antibiotics, analgesics, disease-specific therapeutic agents (e.g., MS treatment, psoriasis treatment), insulin, glycoproteins, immunomodulators, G-CSF, erythropoietin Biological products, antihypertensive drugs, vaccines, hormones (including contraceptives), anti-hormones, sedatives, anti-epileptic drugs, anti-neoplastic drugs, pesticides (e.g., dobutamine), antipsychotics, antidotes, cosmetics, selective serotonin reuptake inhibitors (SSRI), proton pump inhibitors (PPI), anesthetics, diuretics, antidiuretics, blood thinners (e.g., low molecular weight heparin), streptokinase, etc., used alone or in combination, whether in liquid form, reconstitutable form or other forms. In some embodiments, the systems and devices of the present disclosure can be used to deliver drugs that were previously used with Act-o- In some embodiments, the systems and devices of the present disclosure are used to deliver drugs used in the delivery of methylprednisolone for multiple sclerosis, certain cancers, and autoimmune diseases. In some embodiments, the systems and devices of the present disclosure are used to deliver glucagon for use in hypoglycemia emergencies. In some embodiments, the systems and devices of the present disclosure are used to deliver hydroxythiazolidine for the treatment of high-morbidity infections. In some embodiments, the systems and devices of the present disclosure are used to deliver chlordiazepoxide for the treatment of alcohol withdrawal. In some embodiments, the systems and devices of the present disclosure are used to deliver deoxycorticosterone trimethylacetate for use in veterinary emergencies. In some embodiments, the systems and devices of the present disclosure are used in in vitro fertilization processes.

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

[0012] One or more best modes envisioned for carrying out the various embodiments disclosed herein are set forth in the present disclosure to enable those skilled in the art to practice the present disclosure. However, the preferred embodiments are not intended to be limiting, but on the contrary, they are non-limitingly included within the spirit and scope of the present disclosure and the appended claims, and changes and modifications may be made thereto.

[0013] According to one aspect of the present disclosure, a device for transmitting, storing, mixing and injecting a drug into a patient is disclosed, wherein the device includes: a transmission component, a storage component, a mixing component and an injection component. The transmission component is suitable for providing a simple mode of transmitting the drug before administering the drug to the patient. The storage component is suitable for storing the drug and mixing the components in the transmission component before mixing the drug and mixing the components to create the drug in solution when the mixture is about to be injected into the patient. The mixing component is suitable for correctly mixing the drug and mixing the components to create the drug in solution in the transmission component when the mixture is ready to be injected into the patient. The injection component is suitable for correctly injecting the drug in solution into the patient once the mixture is obtained.

[0014] According to one aspect of the present disclosure, a method of using a device for transferring, storing, mixing and injecting a drug into a patient is disclosed, wherein the device comprises: a transfer component, a storage component, a mixing component and an injection component, and wherein the method comprises: providing the device, engaging the mixing component to mix the drug and create the drug in solution when the drug is ready to be administered to the patient, and engaging the injection component to inject the drug in solution into the patient. In some embodiments, the method also includes removing a safety device before engaging the injection component to inject the drug in solution into the patient.

[0015] According to one aspect of the present disclosure, a method for assembling a device for transmitting, storing, mixing and injecting drugs into a patient is disclosed, wherein the device includes: a transmission component, a storage component, a mixing component and an injection component, and wherein the method includes: providing and assembling the transmission component, providing and assembling the storage component, providing and assembling the mixing component, and providing and assembling the injection component.

[0016] According to one aspect of the present disclosure, a system for assembling a device for transferring, storing, mixing and injecting drugs into a patient is disclosed, wherein the device comprises: a transfer component, a storage component, a mixing component and an injection component, and wherein the system comprises: a device for assembling the transfer component, a device for assembling the storage component, a device for assembling the mixing component, and a device for assembling the injection component.

[0017] Thus, the present disclosure provides a device comprising: (a) a first compartment and a second compartment, each of which defines a first cavity and a second cavity, respectively, the first compartment and the second compartment being in fluid communication with a first opening and separated from each other at the first opening; (b) a needle assembly; and (c) an insertion rod positioned in the first compartment, the insertion rod being operably connected to a movable element, wherein the first opening is covered by a seal; in some embodiments, the insertion rod of the disclosed device comprises two oppositely oriented faces, the first face being in physical contact with the movable element, and the second face being positioned within the first cavity; wherein the second face comprises a protrusion and at least one valve positioned away from the protrusion. In some embodiments, the protrusion of the second face of the insertion rod has an inclined surface. In some embodiments, the movable element of the disclosed device is physically positioned adjacent to the insertion rod, and wherein the insertion rod is capable of moving in a direction along a longitudinal axis when the movable element is pressed, the longitudinal axis being parallel to the first compartment and the second compartment and being located within the first compartment and the second compartment.

[0018] In some embodiments, the second compartment of the disclosed device contains an active agent, and the first compartment contains a pharmaceutically acceptable carrier. In some embodiments, the second compartment contains a pharmaceutically acceptable carrier, and the first compartment contains an active agent. In some embodiments, the first compartment and the second compartment each contain one or more active agents. In some embodiments, the first compartment and the second compartment each contain: one or more active agents or one or more pharmaceutically acceptable carriers. In some embodiments, the second compartment contains an active agent in solid or semi-solid form, and the first compartment contains a pharmaceutically acceptable carrier in liquid form. In some embodiments, the second compartment contains an active agent in liquid form, and the first compartment contains a pharmaceutically acceptable carrier in liquid form. In some embodiments, the active agent of the disclosed device is lyophilized.

[0019] In some embodiments, the disclosed device further comprises a third compartment defining a third cavity, and the third compartment is adjacent to the second compartment and is separated from the second compartment by a second opening covered by a second seal. In some embodiments, the second seal is a removable stopper operably connected to the removable element, and wherein the removable stopper is allowed to be displaced when the removable element is pressed to achieve fluid communication between the second compartment and the third compartment. In some embodiments, the removable stopper and the insertion rod are allowed to be displaced when the removable element is pressed to achieve fluid communication between the second compartment and the third compartment.

[0020] In some embodiments, the third compartment of the disclosed device contains the needle assembly; the needle assembly includes a spring and a needle operably connected to the spring; wherein the needle includes a first fluid opening located within the third cavity and a second fluid opening oppositely located away from the first cavity and the second cavity. In some embodiments, the first fluid opening and the second fluid opening are covered by a movable seal operably connected to the movable element, so that when the movable element is pressed to a first predetermined position and a second predetermined position, displacement of the first seal and the second seal is caused, respectively.

[0021] In some embodiments, the disclosed device is in a first operable condition and includes a first compartment, a second compartment, and a third compartment, wherein the first compartment and the second compartment are fluidically connected to each other through a first opening including a first seal; the second compartment and the third compartment are fluidically connected to each other through a second opening covered by a second seal; wherein the second compartment is positioned between the first compartment and the third compartment located on opposite sides of the second compartment; wherein the movable element is located in a fully extended position relative to the lateral direction of the device, wherein the first compartment contains a pharmaceutically acceptable carrier, the second compartment contains one or more active agents, the third compartment contains a needle assembly, and wherein the first seal and the second seal covering each of the first opening and the second opening are intact, thereby preventing fluid from flowing from one compartment to another. In some embodiments, the disclosed device is in a second operable condition and includes a first compartment, a second compartment, and a third compartment, wherein the first compartment and the second compartment are fluidically connected to each other through a first opening; the second compartment and the third compartment are fluidically connected to each other through a second opening covered by a second seal; wherein the second compartment is positioned between the first compartment and the third compartment located on opposite sides of the second compartment; wherein the movable element is located in a position pressed in relative to a lateral portion of the device, wherein the first compartment and the second compartment contain a pharmaceutically acceptable carrier and one or more active agents; wherein the third compartment contains a needle assembly, and wherein the second seal covering the second opening prevents fluid from flowing from the third compartment to the first compartment or the second compartment. In some embodiments, the disclosed device is in a third operable condition and includes a first compartment, a second compartment, and a third compartment, wherein the first compartment, the second compartment, and the third compartment are fluidically connected to each other; wherein the second compartment is positioned between the first compartment and the third compartment located on opposite sides of the second compartment; wherein the movable element is located in a position pressed in relative to a lateral portion of the device so that the insertion rod has caused the second seal to be punctured, wherein the first compartment, the second compartment, and the third compartment contain a pharmaceutically acceptable carrier and one or more active agents; wherein the third compartment contains the needle assembly, and wherein the second seal has been punctured or has been moved relative to its position covering the second opening, and the needle assembly is exposed to the active agent and the pharmaceutically acceptable carrier.In some embodiments, the disclosed device is in a fourth operable condition and comprises a first compartment, a second compartment, and a third compartment, wherein the first compartment, the second compartment, and the third compartment are in fluid communication with each other; wherein the second compartment is positioned between the first compartment and the third compartment on opposite sides of the second compartment; wherein the movable element is in a fully depressed position relative to the lateral direction of the device, and the needle of the needle assembly is exposed. In embodiments where the disclosed device is in the second position, the third position, or the fourth position, the active agent contained in 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 any one or a combination of the active agents selected from Table 1. In some embodiments, the active agent is any one or a combination of the active agents selected from Table 1 and has a dosage identified in Table 1. In some embodiments, the active agent is corticosterone or a corticosterone derivative thereof. In some embodiments, the corticosterone derivative is hydrocortisone sodium succinate, wherein the content of the derivative as an active agent in a solution of a pharmaceutically acceptable carrier per unit volume is about 50 mg / mL to 250 mg / mL by weight, or about 25 mg / mL to 150 mg / mL.

[0023] In some embodiments, the first compartment and the second compartment of the disclosed device contain a pharmaceutically acceptable carrier in fluid form having a viscosity of about 1 cP to about 150 cP.

[0024] In some embodiments, the present disclosure provides a method for treating and / or preventing a disease or disorder in a subject in need thereof, comprising administering one or more active agents to the subject by any of the devices described herein. In some embodiments, the present disclosure provides a method for treating a subject in need of administering one or more active agents, comprising administering a pharmaceutically effective amount of the one or more active agents by any of the devices described herein. In some embodiments, the present disclosure provides a method for treating cortisol depletion in a subject in need thereof, comprising administering corticosterone or a corticosterone derivative thereof to the subject by any of the devices described herein. In some embodiments, the cortisol depletion is caused by: Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenal myeloneuropathy, adrenoleukodystrophy, adrenal tumors, Schmidt's syndrome, hyperaldosteronism, pituitary tumors, pituitary cysts, and / or corticosteroid insufficiency associated with critical illness. In some embodiments, the present disclosure provides a method for treating cortisol disorder in a subject in need thereof, comprising administering cortisol or a cortisol derivative thereof to the subject using any device described herein. In some embodiments, the administering step in any of the disclosed treatment methods comprises: pressing the movable element of the disclosed device to a first predetermined position, a second predetermined position, and a third predetermined position; wherein the device comprises: a first compartment, a second compartment, and a third compartment, each of the first compartment, the second compartment, and the third compartment defining a first cavity, a second cavity, and a third cavity, respectively; the first compartment and the second compartment are respectively connected to the first opening fluid and separated from each other at the first opening; and the second cavity and the third cavity are respectively connected to the second opening fluid and separated from each other at the second opening; wherein the first opening is covered by a first seal, and the second opening is covered by a second seal; wherein the third compartment comprises a needle assembly, and the needle assembly comprises The invention relates to a needle assembly comprising a spring and a needle operably connected to the spring; wherein the movable element is pressed to a first predetermined position so that the insertion rod causes the first seal to move away from the first opening and expose the first opening between the first compartment and the second compartment, thereby causing fluid communication between the first compartment and the second compartment; and wherein the movable element is pressed to a second predetermined position so that the insertion rod causes the second seal to move away from the second opening and expose the second opening between the second compartment and the third compartment, thereby causing fluid communication between the second compartment and the third compartment; and wherein the movable element is pressed to a third predetermined position so that the contents of the third compartment are injected through the needle assembly.In some embodiments, the disclosed method further comprises the step of unlocking the needle assembly prior to causing the movable element to be depressed 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, comprising administering corticosterone or a corticosterone derivative thereof to the subject via any device according to any one of the devices described herein.

[0026] The present disclosure provides a method for manufacturing any device described herein, comprising placing one or more of the active agents in a sterile or sterilized environment. In some embodiments, the method further comprises weighing the one or more active agents. In some embodiments, the method further comprises attaching the first compartment and the second compartment. In some embodiments, the method comprises attaching the first compartment and the second compartment to each other in a sterile environment by compression or threading into a fastener.

[0027] The present disclosure provides a method of administering an active agent to a subject in need thereof by any device described herein, comprising: (a) causing the movable element to be pressed to a first predetermined position; and (b) causing the movable element to be pressed to a second predetermined position; wherein the first predetermined position causes the insertion rod to be sufficiently displaced to pierce the first seal so that the first compartment and the second compartment are in fluid communication; and wherein the displacement produced by the second predetermined position is sufficient to cause the movable seal to be displaced, thereby allowing fluid communication between the second compartment and the third compartment. In some embodiments, the displacement produced by the second predetermined position is sufficient to cause the spring in the third compartment to be loaded with a force of about 0 Newtons 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 which defines a first cavity, a second cavity and a third cavity, respectively, and the second compartment is positioned adjacently between the first compartment and the third compartment; (b) a needle shield assembly, operably functioning in the third cavity and at least partially contained in the third cavity, and comprising a needle operably attached to a spring; and (c) an insertion rod positioned in the first compartment, the insertion rod operably connected to a movable element, the insertion rod and the movable element being movable along the longitudinal axis of the first compartment, the second compartment and the third compartment; wherein the first compartment and the second compartment are fluidically connected through a first opening, and the second compartment and the third compartment are fluidically connected through a second opening; the first opening is covered by a first seal and the second opening is covered by a second seal. In some embodiments, the first compartment contains one or more active agents and the second compartment contains one or more pharmaceutically acceptable carriers. In some embodiments, the first compartment contains one or more pharmaceutically acceptable carriers and the second compartment contains one or more active agents. In some embodiments, the cylindrical peripheries of the first compartment, the second compartment, and the third compartment are aligned along the longitudinal axis of the three cavities. In some embodiments, the needle guard assembly includes a spring, a needle sheath, and an inner surface, the inner surface including one or more guide rail elements operably connected to the needle, the guide rail element being capable of guiding the needle to move through the needle sheath after the spring moves. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Referring to the accompanying drawings showing exemplary embodiments of the present disclosure, the detailed description provided below explains in detail various features, advantages and aspects of the present disclosure. Therefore, the features of the present disclosure can be more clearly understood through the following detailed description in conjunction with the accompanying drawings, in which the same reference numerals represent the same, similar or comparable elements throughout the text. The exemplary embodiments shown in the drawings are not necessarily drawn to scale or shape, and are not to be considered as limiting the scope thereof, as the present disclosure may admit other equally effective embodiments having different combinations of the features shown in the drawings.

[0030] Figure 1A A side cross-sectional view of one embodiment of the apparatus disclosed herein is shown. 100: A three chamber system allowing for the containment and mixing of one or more solid or liquid materials. 102: A first chamber containing a liquid or solid material, the first chamber being separated from a second chamber 104 by a barrier. 104: A second chamber containing a liquid or solid material, the second chamber being separated from the first chamber 102 by a barrier.

[0031] Figure 1B Shows Figure 1A 116: A three chamber system that allows for the containment and mixing of one or more solid or liquid materials. 112: A first chamber containing a liquid or solid material, the first chamber being separated from the second chamber 110 by a barrier. 110: A second chamber containing a liquid, solid, semi-solid or gaseous material, the second chamber being separated from the first chamber 112 by a barrier. 114: A compression system, such as a plunger, spring, screw system, or a combination of two or more such systems, to initiate mixing between chambers 112 and 110.

[0032] Figure 2A A side cross-sectional view of another embodiment of the device disclosed herein is shown, which also includes movable components, chamber barriers, seals, and other components associated with an automatic injector. 200: A three-chamber system including a housing, a plunger, a mechanism to separate the three chambers, a compression system to initiate mixing of materials held in the first two chambers and move the materials into the third chamber. 202: An activation system for initiating mixing of materials held in chambers 214 and 208 and moving the materials into chamber 210. 204: An insertion rod that pierces barrier 206 to allow material transfer between chambers 216 and 208. The insertion rod will be pushed into chamber 208 to help push liquid from 216 into 208. The insertion rod 204 may be composed of or surrounded by a sealing material to prevent fluid from flowing behind the insertion rod. 206: A barrier between chambers 216 and 208 that prevents material transfer between the two chambers until the barrier is pierced by the insertion rod 204. 208: A second chamber containing a liquid, solid, semi-solid or gaseous material to mix with the material held in chamber 216 after piercing the seal 206. 210: A third chamber in the device where materials from chambers 208 and 216 mix after the device is activated. 212: A spring that compresses the material transferred into chamber 210 after the barrier 206 is pierced and material mixing occurs. 214: A movable seal assembly that moves through chamber 210 as the materials in chambers 208 and 216 mix. 216: A first chamber in the device that may contain a liquid or solid material to mix with the material in chamber 208 after the insertion rod pierces the barrier 206. 218: A housing that houses the three chambers 216, 218 and 210, and the activation system 202.

[0033] Figure 2BA side cross-sectional view of another embodiment of the device disclosed herein is shown, wherein the insertion rod for piercing the seal includes two components (220, 254) instead of one. 220: Another embodiment of a three-chamber system for mixing two materials. 222: Activation system for initiating mixing of materials held in chambers 254 and 234 and moving the materials into chamber 210. 224: Insertion rod assembly that pierces barrier 232 to allow mixing of materials of chambers 254 and 234. 226: Sealing component that prevents fluid from moving back through the device. 228: Fluid outlet that allows fluid transfer between chambers 254 and 234. 230: Fluid path that passes through insertion rod 224 to allow fluid transfer between chambers 254 and 234. 232: Barrier between chambers 254 and 234, preventing material transfer between the two chambers until the barrier is pierced by insertion rod 224. 234: A second chamber containing a liquid or solid material to be mixed with the material held in chamber 254 after piercing seal 232. 236: A housing for chamber 234 which may be closed at its sides or ends by a material transfer barrier. 238: A slidable seal for a movable assembly 246 which prevents fluid from passing around its edges. 240: A third chamber in the device where materials from chambers 254 and 234 are mixed after the device is activated. 242: A needle for injecting the combined materials. 244: A spring which compresses when filling chamber 240 and subsequently moves assembly 246 through chamber 240. 246: A sealing assembly which acts as a barrier to chamber 234 before the device is activated, after which the seal is the wall of chamber 240 and is the compression mechanism that pushes the mixed material out of the device.

[0034] 248: Seal preventing material from entering syringe 242 until the seal is pierced by movement of assembly 246 when the device is activated. 250: Sealing material on chamber 236. 252: Entry point for insertion rod into chamber 234. 254: First chamber containing material to mix with material in chamber 234. 256: Housing containing mixing chamber, material and all device components. 258: Housing for insertion rod 224 allowing the rod to move inwardly and may contain seal. 260: Insertion rod assembly. 262: Needle guide and spring attachment.

[0035] Figure 3A A side cross-sectional view of another embodiment of the device disclosed herein is shown, wherein the needle assembly has a needle guard 302 attached to a main device 300. 300: Device assembly for mixing two materials. 302: Needle assembly and needle guard for injecting the mixed two materials. A more detailed view of the needle assembly and needle guard of this embodiment is shown in FIG. Figure 3B304: Needle guard assembly that prevents fluid from leaving the device and prevents accidental injection. In this state, the guard extends over the needle. 306: Needle guard housing that hides the needle 308 and can be retracted to allow injection. 308: Injection needle. 310: Safety clip that prevents the needle guard from being activated until it is removed. 312: Compression spring that holds the needle guard 306 in place and pushes the guard 306 back over the needle once the injection is complete. 314: Seal that prevents fluid from entering the needle 308. Figure 3C It shows Figure 3A 316: needle guard assembly that prevents fluid from leaving the device and prevents accidental injection. In this state, the guard shell is retracted to allow injection. 318: injection needle. 320: needle guard shell that hides needle 318 and can be retracted to allow injection. 322: seal that prevents fluid from entering needle 308. A more detailed view of the needle assembly and needle guard of this embodiment is shown in FIG. Figure 3D 323: Needle guard assembly that prevents fluid from leaving the device and prevents accidental injection. In this state, the guard extends over the needle. 324: Needle guard housing that hides the needle 342 and can be retracted to allow injection. 326: Guide that allows the needle guard to be slid into place using the guard guide 328. 328: Needle guard guide that cooperates with the guide 326. 330: Needle stabilizer and accessories. 338: Safety clip that prevents the needle guard housing 324 from retracting before intended use. 340: Connection between the needle guard assembly and the injection device. 342: Injection needle. 344: Compression spring that pushes the needle guard into place around the needle. 346: Seal that prevents fluid from entering or leaving the needle before injection. Figure 3E Another embodiment of a needle assembly and needle guard is shown. 348: Another embodiment of a needle guard assembly that prevents fluid from leaving the device and prevents accidental injection. In this state, the guard covers and extends over the needle. 350: Needle guard housing that hides the needle and can be retracted to allow injection. 352: Device housing that can also act as a needle guard guide. 354: Needle exit port that can contain a seal to prevent fluid from entering or leaving the injection needle.

[0036] Figure 4A side cross-sectional view of an embodiment with a device body, needle assembly, and attached guard is shown. 400: Needle guard assembly that prevents fluid from leaving the device and prevents accidental injection. In this state, the guard covers and extends over the needle. 402: Guide rails that allow the needle guard to be slid into place using guard guide 446. 404: Needle guard assembly attachment point to the main device. 406: Needle stabilizer and accessories. 408: Spring that compresses when filling cavity 444 and then moves assembly 410 through cavity 444. 410: Movable seal assembly. 412: Seal that prevents material from entering syringe 448. 414: Sealing material on cavity 438. 416: Beveled entry point for insertion rod 428. 418: First cavity in the device. 420: Main device housing. 422: Fluid outlet that allows fluid transfer between cavities 418 and 436. 424: Embodiment of a three chamber system for mixing two materials with a needle assembly and guard. 426: Actuation system for actuating the mixing of the materials. 428: Insertion rod. 430: Seal surrounding the insertion rod. 434: Pierceable seal between chambers 418 and 436. 436: Second chamber in the device. 438: Housing for the second chamber. 440: Slidable seal for movable assembly 246. 442: Safety clip that prevents needle guard from being activated until it is removed. 444: Third chamber in the device. 448: Needle for performing an injection. 450: Seal to prevent fluid from entering needle 448. 452: Exit point for needle to extend from needle guard.

[0037] Figure 5A A side cross-sectional view of a first operable condition of the device disclosed herein is shown. 500: First operable condition of the device before it is activated. 502: Needle guard housing extending around the needle. 504: In this state, the mixing chamber is empty. 506: Removable sealing assembly acting as a barrier between chambers 508 and 504. 508: Chamber 508 contains material to be mixed with material in chamber 510. 510: Chamber 510 contains material to be mixed with material in chamber 508. 512: Insertion rod for piercing barrier 516 and pushing material from chamber 510 into chamber 508. 514: Activation assembly, which may be a plunger, a screw system, or some other type of mechanism, for compressing the device and moving the material to be mixed into chamber 504. 516: Barrier between chambers 510 and 508. 518: Safety clip preventing retraction of needle guard 502.

[0038] Figure 5BA side cross-sectional view showing a second operable condition of the device disclosed herein. 542: Insertion rod, partially inserted into cavity 546. 544: Actuation assembly, which may be a plunger, screw system, or some other type of mechanism, for compressing the device and moving the material to be mixed. 546: First cavity in the device. 548: Pierced seal, allowing cavities 550 and 546 to be in fluid contact. 550: Second cavity in the device.

[0039] Figure 5C A side cross-sectional view of a third operable condition of the device disclosed herein is shown. 520: Third operable condition, wherein the device has been activated and materials have been mixed but not injected. 522: Mixing chamber containing materials from the first two chambers. 524: Compression assembly, activated to allow materials in the first two chambers to mix. 526: Insertion rod, fully moved through the first chamber to push all of the material through the second chamber and into chamber 522. 528: Seal assembly, moved away from the input end of the material from the first two chambers to create a space in chamber 522 for the materials to mix. 530: Compression spring, now loaded, allows the mixed material to be injected once the needle guard 532 is retracted. 532: Needle guard, in an unretracted position, prevents the mixed material in chamber 522 from being removed from chamber 522 through the needle. 534: Seal to prevent the material in chamber 522 from being removed from the needle.

[0040] Figure 5D A side cross-sectional view of a fourth operable condition of the device disclosed herein is shown. 536: Fourth operable condition, wherein the needle guard has been retracted and the mixed material has been extruded from the mixing chamber. 538: The needle guard, retracted to expose the needle and allow the mixed liquid to be extruded from the device. 540: The sealing assembly, moved back into the device to extrude the mixed liquid from the device through the needle. 542: The compression spring, moved back into the device to extrude the mixed liquid from the device. 544: The injection needle.

[0041] Figure 6 A side cross-sectional view showing the three main operable conditions of the device disclosed herein and a final state in which the device has been removed from the injection site. 600: Operable condition before removal of the safety pin. The device has been activated and, due to the presence of a movable sealing assembly near the bottom of the third chamber, the material for injection is mixed as shown. 602: The safety pin has been removed and the device can now be pressed against a surface, such as the skin of a patient, for injection. 604: The device has been pushed onto the patient or other surface, causing the needle guard to retract and the needle to enter the injection volume. The device is held in place until the injection is complete. 606: After all the liquid has been injected, the device is moved upwards, causing the needle guard to extend and cover the needle again. With the movable sealing assembly moved to a position away from the bottom of the device, the completion of the injection is indicated.

[0042] Figure 7 A side cross-sectional view showing the internal components of the second chamber 722 of one embodiment of the device disclosed herein and how they are distributed between the other two chambers 714 and 728. 700: The internal components of the second chamber and associated components. 702: Compression spring that holds the seal assembly 724 in place and allows mixed material from chamber 728 to be squeezed out of the device during injection. 704: Seal that prevents material from chamber 722 from transferring to chamber 728 and prevents liquid from entering needle 726. 706: Housing of chamber 722. 708: Entry point for insertion rod 714 into chamber 722. 710: Seal surrounding chamber 710 that prevents fluid flow. 712: Barrier that prevents material transfer between chambers 714 and 722. 714: The first chamber in the device, containing material to be mixed with material in chamber 722. 716: Insertion rod for piercing barrier 712 and expelling material from 714 to 722. 718: Fluid path allowing fluid transfer between chambers 720 and 714. 720: Piercing point allowing piercing of barrier 712. 722: Chamber 722 contains material to be mixed with material in 714. 724: Seal assembly, acts as a barrier between 728 and 722 and pushes fluid out of the device during injection. 726: Injection needle. 728: Mixing chamber, containing mixed material from 714 and 722 waiting to be injected.

[0043] Figure 8 A side cross-sectional view of one embodiment of the device disclosed herein using a screw mechanism to drive the piston downward is shown. 800: Another embodiment of the priming assembly, where the device is twisted and the screw mechanism pushes the piston downward. This is the state of the device before priming. 802: The priming assembly, in a state after priming, the piston has been pushed downward to cause mixing of the two materials. DETAILED DESCRIPTION

[0044] The present disclosure relates to systems, methods and devices for storing, transporting, mixing and injecting drugs in solutions. The disclosed systems, methods and devices may be better understood with reference to the following detailed description of specific embodiments and examples included herein, and with reference to the accompanying drawings and their previous and following descriptions.

[0045] 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.

[0046] It must be noted that, as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "a nucleic acid sequence" includes a plurality of nucleotides formed, reference to a "nucleic acid sequence" refers to one or more nucleic acid sequences and their equivalents known to those skilled in the art, and so forth.

[0047] Range can be expressed as "about" a specific value and / or to "about" another specific value in this article. When representing such range, it is also particularly envisioned that the range from a specific value and / or to another specific value is considered as the disclosed range, unless the context specifically indicates other situations. Similarly, when a value is expressed as an approximation, by using the antecedent "about", it will be understood that the specific value forms another particularly envisioned embodiment and it should be considered as disclosed content, unless the context specifically indicates other situations. It will be further understood that the two endpoints of each range are both important relative to the other endpoint and independent of the other endpoint, unless the context specifically indicates other situations. When referring to measurable values ​​such as quantity, duration, etc., the term "about" as used herein is intended to cover ± 20%, ± 10%, ± 5%, ± 1%, ± 0.5% or ± 0.1% changes, because such changes are suitable for performing the disclosed method.

[0048] “Optional” or “optionally” means that the subsequently described event, circumstance or material may or may not occur, exist or not exist, and that the description includes instances where said event, circumstance or material occurs or exists, and instances where it does not occur or does not exist.

[0049] As used in the specification and claims herein, the term "and / or" should be understood to mean "either or both" of the elements so combined, i.e., elements that are present in a combined form in some cases and in an uncombined manner in other cases. In addition to the elements explicitly identified by the "and / or" term, other elements may optionally be present, whether related or unrelated to these explicitly identified elements, unless otherwise expressly indicated to the contrary. Thus, as a non-limiting example, when used in conjunction with open language such as "comprising", in some embodiments, reference to "A and / or B" refers to A without B (optionally including elements other than B); in another embodiment, reference to "A and / or B" refers to B without A (optionally including elements other than A); in yet another embodiment, reference to "A and / or B" refers to A and B (optionally including other elements).

[0050] As used in the specification and claims herein, "or" should be understood to have the same meaning as "and / or" as defined above. For example, when separating the items in a list, "or" or "and / or" should be interpreted as inclusive, i.e., including at least one of a plurality of elements or a list of elements, and may also include more than one, and optionally also include additional unlisted items. Only terms that clearly indicate the opposite meaning, such as "only one of them" or "exactly one of them", or when used in the claims, "consisting of..." will refer to containing exactly one of a plurality of elements or a list of elements. In general, the term "or" used herein should be interpreted as referring to an exclusive alternative (i.e., "one or the other, but not both at the same time") only when it is preceded by an exclusive term such as "any one", "one of them", "only one of them", or "exactly one of them". When used in the claims, "mainly consisting of..." will have the ordinary meaning used in the field of patent law.

[0051] As used herein, the term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable diluent" is intended to refer to an excipient, carrier or diluent that can be administered to a subject together with the formulation or pharmaceutical composition disclosed herein, and the excipient, carrier or diluent is inert or cannot eliminate the pharmacological activity of the active agent of the pharmaceutical composition. In some embodiments, the pharmaceutically acceptable carrier does not destroy or eliminate the pharmacological activity of the active agent / vaccine, and the carrier is non-toxic when the dose administered is sufficient to deliver a therapeutic dose of the active agent. As used herein, the term "pharmaceutically acceptable salt" can be an acid salt or base salt that is generally considered suitable for contact with human or animal tissues in the art without excessive toxicity, irritation, allergic reaction, or other problems or complications. Such salts include mineral salts and organic acid salts such as amine salts with basic residues, and alkali salts or organic salts such as carboxylates with acidic residues. Specific pharmaceutically acceptable salts include, but are not limited to, salts of acids such as hydrochloric acid, phosphoric acid, hydrobromic acid, malic acid, gluconic acid, fumaric acid, sulfuric acid, sulfamic acid, sulfonic acid, formic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanedisulfonic acid, 2-hydroxyethylsulfonic acid, nitric acid, benzoic acid, 2-acetylbenzoic acid, citric acid, tartaric acid, lactic acid, stearic acid, salicylic acid, glutamic acid, ascorbic acid, pantothenic acid, succinic acid, fumaric acid, maleic acid, propionic acid, hydroxymaleic acid, hydroiodic acid, phenylacetic acid, alkanoic acids such as acetic acid, HOOC-(CHZ)n-COOH wherein n is 0-4, etc. Similarly, pharmaceutically acceptable cations include, but are not limited to, sodium, potassium, calcium, aluminum, lithium, and ammonium. Those of ordinary skill in the art will recognize from this disclosure and common knowledge in the art that additional pharmaceutically acceptable salts for aggregated virus-specific antigens or polynucleotides are provided herein, including those listed in the 17th edition of Remington's Pharmaceutical Sciences (Mack Publishing Company, Easton.PA, page 1418 (1985)). In general, pharmaceutically acceptable acid or base salts can be synthesized from parent compounds containing a basic or acidic portion that can be obtained by conventional chemical methods. Simply put, such salts can be prepared by reacting the free acid or base form of these compounds with a certain stoichiometric amount of an appropriate base or acid component in an appropriate solvent.

[0052] As used herein, the term "prevent" or "preventing" is intended to mean reducing the likelihood of a disease or condition occurring in a subject who does not have the disease but is at risk of or susceptible to the disease or condition.

[0053] As used herein, the terms "subject", "individual", "host" and "patient" are used interchangeably herein and refer to a vertebrate individual in need of diagnosis, treatment or cure, including but not limited to mammals or humans, particularly humans. Mammals include but are not limited to rodents, apes, humans, farm animals, cows, pigs, goats, sheep, horses, dogs, sports animals and pets. The methods described herein are suitable for human treatment and veterinary applications. In some cases, in the description of the present disclosure, the term "patient" refers to a human patient suffering from a specific disease or disorder. In some embodiments, the subject is an animal, and in other embodiments, the subject is a human.

[0054] As used herein, the term "treat", "treated", "treating", "treatment", etc. refers to the reduction or alleviation of diseases and / or symptoms associated therewith (such as viral infection). "Treatment" may refer to the injection of the DNA vaccine described herein into a subject after the onset of the disease or suspected onset of viral infection. "Treatment" includes the concept of "relief", which refers to reducing the frequency or severity of the occurrence, recurrence, or severity of any symptoms or other adverse reactions related to the virus and / or side effects associated with viral treatment. The term "treatment" also covers the concept of "management", which refers to reducing the severity of a patient's particular disease or condition or delaying its recurrence, such as prolonging the remission period for patients who already have the disease. It is worth understanding that, although it cannot be excluded, the treatment of a disease or condition does not require the complete elimination of the disease, condition, or symptom associated therewith.

[0055] For the therapeutic agents described herein, the therapeutically effective amount can be initially determined from preliminary in vitro studies and / or animal models. The therapeutically effective dose can also be determined from human data. The dose applied can be adjusted based on the relative bioavailability and potency of the administered formulation. It is within the capabilities of a person of ordinary skill in the art to adjust the dose to achieve maximum efficacy based on the above methods and other well-known methods. The general principles for determining therapeutic effectiveness found in Chapter 1 of Goodman and Gilman's Pharmacological Basis of Therapy, 10th Edition, McGraw-Hill (New York) (2001) are summarized below, which is incorporated herein by reference. Pharmacokinetic principles provide a basis for adjusting the dosage regimen to obtain the desired degree of therapeutic effect and the least unacceptable adverse reactions. In cases where the plasma concentration of the drug can be measured and correlated with the therapeutic time window, additional guidance for dosage adjustment can be obtained. Drugs are considered pharmaceutically equivalent if they contain the same active ingredient and the drugs are identical in strength or concentration, dosage form, and route of administration. Two pharmaceutically equivalent drug products are considered bioequivalent if the rate and extent of bioavailability of the active ingredients in the two products do not differ significantly under appropriate test conditions.

[0056] As used herein, the terms "comprising" (and any forms of "including," such as "comprise," "comprises," and "comprised"), or "containing" (and any forms of "comprising," such as "contains" and "contain") are inclusive or open-ended, and do not exclude additional, unrecited elements or method steps.

[0057] As used herein, the term "about" means that the value is approximate and that small changes will not significantly affect the implementation of the disclosed embodiments. When referring to measurable values ​​such as quantities, durations, etc., the term "about" as used herein is intended to cover changes of ±10%, ±5%, ±1%, or ±0.1% around a particular value, because such changes are suitable for performing the disclosed methods. If a numerical limitation is used, unless the context indicates otherwise, "about" means that the value can vary by ±10%, ±5%, ±4%, ±3%, ±2%, or ±1%, while still remaining within the scope of the disclosed embodiments.

[0058] References in the specification and summary claims to parts by weight of a particular element or component in a composition represent the weight relationship of that element or component to any other elements or components in the composition or article expressed in parts by weight. Thus, in a compound comprising two parts by weight of X and five parts by weight of Y, the weight ratio of X to Y is 2:5, and this ratio exists regardless of whether additional components are present in the compound.

[0059] Unless otherwise specifically stated, the weight percent (wt. %) of a component is based on the total weight of the formulation or composition in which the component is included.

[0060] As used herein, the terms "administering" and "administration" refer to any method of providing a pharmaceutical preparation to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral, transdermal, by inhalation, nasal, topical, vaginal, ophthalmic, aural, intracerebral, rectal, and parenteral administration, including injectables such as intravenous, intraarterial, intramuscular, and subcutaneous. Administration may be continuous or intermittent. In various embodiments, the preparation may be administered therapeutically; that is, administered to treat an existing disease or condition. In other various embodiments, the preparation may be administered prophylactically; that is, administered to prevent a disease or condition. As used herein, the terms "parenteral administration" and "administered parenterally" refer to modes of administration other than enteral and topical administration, usually by injection, including but not limited to intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcorneal, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injections.

[0061] 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 where said event or circumstance occurs and instances where it does not occur.

[0062] As used herein, the term "diagnosed" means that the patient has been physically examined by a skilled artisan, such as a physician, and found to have a condition that can be diagnosed or treated by the compounds, compositions or methods disclosed herein.

[0063] The present disclosure relates to systems, methods and devices for storing, transporting, mixing and injecting drugs in solutions. The disclosed systems, methods and devices are more easily understood by referring to the following detailed description of specific embodiments and examples included in the specific embodiments and referring to the drawings and the previous and following descriptions thereof.

[0064] As used herein, the term "contacting" refers to placing a disclosed compound with a cell, target receptor, or other biological entity in such a way that the compound can directly affect the activity of the target (e.g., receptor, cell, etc.), i.e., by interacting with the target itself; or such that the compound can indirectly affect the target, i.e., by interacting with another molecule, co-factor, factor, or protein on which the activity of the target depends.

[0065] As used herein, the term "compartment" refers to a space defined by one or more continuous surfaces to form an internal volume separated from the external environment by the one or more surfaces. In some embodiments, the compartment is defined by one or more surfaces and can be a volume of any shape, such as a rectangular prism or a cylindrical space. The present invention generally relates to a device comprising a first compartment, a second compartment, and / or a third compartment, which compartments include a cylindrical or substantially cylindrical cavity or a space with sequentially aligned walls, so that at least one end of the cylindrical or substantially cylindrical space is adjacent to or close to at least one end of another compartment, and such cylindrically aligned compartments define the interior of the device. In some embodiments, the compartment is a part of a closed system once aligned and fixed to each other via a physical connection between one or more exteriors or interiors of one or more surfaces thereof.

[0066] As used herein, the term "active agent" refers to a drug or other substance that treats a subject when administered. In some embodiments, the active agent or derivative thereof is selected from one or a combination of the following:

[0067]

[0068]

[0069] *Doses are expressed as approximate amounts. Any dosage should be interpreted as meaning "from about X to about Y." For example, the dosage of cortisol sodium succinate should be from about 50 mg per ml to about 150 mg per ml.

[0070] The term "movable element" refers to a shaft, plunger, rod, fastener or other part or element of a device that can move in any direction relative to the longitudinal axis of the device. In the case of a cylindrical device, the longitudinal axis defines the center point of a circle around the device.

[0071] "Derivatives" of the compounds disclosed herein are pharmaceutically acceptable salts, prodrugs, deuterated forms, radiolabeled forms, isomers, solvents, and combinations thereof. "Combinations" mentioned in the context refer to derivatives that fall within the range of at least two of the following: pharmaceutically acceptable salts, prodrugs, deuterated forms, radiolabeled forms, isomers, and solvents. Examples of radiolabeled forms include compounds labeled with tritium, phosphorus-32, iodine-129, carbon-11, fluorine-18, and the like.

[0072] As used herein, the term "disease" refers to an ailment of a subject that causes a malfunction of the body. In some embodiments, the disease is one or a combination of diseases selected from Table 2.

[0073]

[0074] As used herein, the term "carrier" refers to a diluent, adjuvant or excipient with which a compound is administered. Pharmaceutical carriers may be liquids, such as water and oils, including oils of petroleum, animal oils, vegetable oils or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc. Pharmaceutical carriers may also be saline, gum arabic, gelatin, starch paste, talc, keratin, colloidal silica, urea, etc. In addition, adjuvants, stabilizers, thickeners, lubricants and colorants may be used. Pharmaceutical compositions include compounds carried in pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers refer to sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injections or dispersions prior to use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.), carboxymethyl cellulose and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters, such as ethyl oleate. The compound can be formulated using a pharmaceutically acceptable carrier or diluent and any other known adjuvants and excipients according to conventional techniques such as those disclosed in Remington's Science and Practice of Pharmacy (19th edition, edited by Gennaro, published by Mack Publishing Company, Easton. Pa, 1995). The term "pharmaceutically acceptable carrier" is recognized in the art and includes pharmaceutically acceptable materials, compositions or vehicles suitable for administering the compounds of the present invention to mammals. The carrier includes a liquid or solid filler, diluent, excipient, solvent or encapsulating material for transporting the drug formulation from one organ or body part to another. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formula and not harmful to the patient. Some examples of materials that serve as pharmaceutically acceptable carriers include: sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerol, 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; alcohol; phosphate buffer; and other nontoxic compatible substances employed in pharmaceutical formulations. Suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by EW Martin, which is incorporated herein by reference in its entirety.

[0075] Wetting agents, emulsifiers and lubricants, such as sodium sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening agents, flavoring agents, infusing agents, preservatives and antioxidants can also be present in the compositions.

[0076] Examples of pharmaceutically acceptable antioxidants include: water-soluble antioxidants, such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, etc.; oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, etc.; and metal chelators, such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, etc.

[0077] The amount of active ingredient that can be combined with carrier materials to produce a single dosage form is generally the amount of the compound that can produce a therapeutic effect. Generally, relative to 100% of the total amount, the range of the amount of active ingredient is from about 1% to about 99%, preferably from about 5% to about 70%, more preferably from about 10% to about 30%. The method for preparing these preparations or compositions includes the step of mixing the compound of the present invention with a carrier and one or more optional auxiliary ingredients. Generally, the preparation is prepared by consistently and closely mixing the compound of the present invention with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, the product is molded.

[0078] In the solid dosage forms for oral administration of the present invention (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, polyvinyl pyrrolidone, sucrose and / or acacia; humectants, such as glycerol; disintegrants, such as agar, calcium carbonate, potato starch or tapioca starch, alginic acid, certain silicates and sodium carbonate; solution retarders, such as paraffin; absorption promoters, such as quaternary ammonium compounds; wetting agents, such as, for example, cetyl alcohol and glyceryl monostearate; adsorbents, such as kaolin and bentonite clay; lubricating oils, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof; and coloring agents. In the case of capsules, tablets and pills, the pharmaceutical compositions may also include buffering agents. Solid compositions of a similar type may also employ such excipients as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like as fillers in soft and hard-filled gelatin capsules.

[0079] Tablets can be made by compression or molding, preferably with one or more adjuvants. Compressed tablets are prepared using a binder (e.g., gelatin or hydroxypropyl methylcellulose), a lubricating oil, an inert diluent, a preservative, a disintegrant (e.g., sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), a surfactant or a dispersant. Molded tablets can be made by molding a mixture of powdered compounds moistened with an inert liquid diluent in a suitable machine.

[0080] Tablets and other solid dosage forms of the pharmaceutical composition of the present invention, such as sugar pills, capsules, pills and granules, can optionally be scored or prepared using coatings and shells such as enteric coatings and other coatings known in the field of pharmaceutical formulations. They can also be prepared in various proportions using, for example, hydroxypropyl methylcellulose, so as to provide a slow or controlled release of the active ingredient, to provide a desired release curve, other polymer matrices, liposomes, vesicles and / or microspheres. For example, they can be filtered through a filter that retains bacteria, or by adding a sterilizing agent to form a form of a sterile solid composition that can be dissolved in sterile water, or disinfected with some other sterile injection media when about to use. These compositions can also optionally include an opacifier, and can be a composition that releases one or more active ingredients only or preferentially in a specific part of the gastrointestinal tract, optionally in a delayed manner. Examples of usable embedded compositions include polymeric substances and waxes. If appropriate, the active ingredient can also be used in microcapsule form with one or more of the above-mentioned excipients.

[0081] Liquid dosage forms for oral administration of the compounds of the present invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage form may contain an inert diluent commonly used in the art, such as, for example, water or other solvents, solubilizers and emulsifiers, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oil (particularly cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofuran methanol, polyethylene glycol and fatty acid esters of sorbitol, and mixtures thereof.

[0082] In addition to inert diluents, the oral composition may include adjuvants such as wetting agents, emulsifying and suspending agents, sweeteners, flavoring agents, coloring agents, aromatics and preservatives. Suspensions, in addition to the active compounds, may contain suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and xanthan gum, and mixtures thereof.

[0083] It should be understood that all individual values ​​and sub-ranges of values ​​contained within the explicitly disclosed ranges are also specifically contemplated and should be considered disclosed herein unless the context indicates otherwise. The foregoing applies regardless of whether some or all of the embodiments are explicitly disclosed in a particular case.

[0084] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the disclosed methods and compositions belong. Although any methods and materials similar or equivalent to the methods and materials described herein can be used for the implementation or testing of the present methods and compositions, particularly useful methods, devices and materials are described herein. The publications cited herein and the materials to which they are cited are specifically incorporated herein by reference. Nothing herein can be interpreted as admitting that the present disclosure is not entitled to be disclosed earlier than such disclosure by virtue of the prior disclosure. It is not admitted that any reference cited herein constitutes prior art. The discussion of the references states the claims of their authors, and the applicant reserves the right to challenge the accuracy and relevance of the cited documents. It will be clearly understood that although some publications are cited herein, such references do not constitute a part of the common general knowledge in the art to admit that any of the documents in these documents form.

[0085] In the detailed description and claims of this specification, the word "include" and variations of the word, such as "comprising" and "comprises", mean "including but not limited to", and are not intended to exclude, for example, other additives, ingredients, integers or steps. Specifically, in a method stated as including one or more steps or operations, it is particularly considered that each step includes the listed content (unless the step contains a restrictive term, such as "consisting of"), which means that each step is not intended to exclude, for example, other additives, ingredients, integers or steps not listed in the step.

[0086] A number of possible embodiments of the present disclosure are contemplated and described in greater detail herein. Without departing from the meaning of the present disclosure and remaining within the disclosed purpose and functional scope of the present disclosure, minor changes may be made to the physical properties of the components to design commercial products for a variety of objectives, including cost control, chemical compatibility, ease of use, manufacturing cost and convenience, a variety of drugs and target disease indications. For example, the disclosed device may be utilized with a variety of drugs, including but not limited to for Solu- Corticosterone, methylprednisolone for multiple sclerosis, chemotherapy for certain cancers, chronic treatment medications for autoimmune diseases, biological therapies, glucagon for hypoglycemic emergencies, ticarcillin for high-incidence infections, chlordiazepoxide for alcohol withdrawal symptoms, and deoxycorticosterone trimethylacetate for veterinary emergencies, among others.

[0087] Some embodiments of the present disclosure may be beneficial to patients with congenital adrenal hyperplasia (CAH), Addison's disease, and idiopathic adrenal insufficiency during the administration of their medications, such as during periods of adrenal crisis. For example, for the 144 million patients worldwide who suffer from CAH, Addison's disease, and idiopathic adrenal insufficiency, some embodiments of the present disclosure are expected to improve the administration of life-saving injectable medications. Some exemplary embodiments of the present disclosure require as few as four injection steps and can be designed specifically for patients experiencing adrenal crisis and their caregivers. For example, exemplary embodiments of the present disclosure may specifically improve Solu- The efficacy of the drug is mainly used in patients with CAH.

[0088] In some embodiments, the present disclosure provides a device comprising: (1) a transmission assembly comprising: a main tube and a handle fixed at a mixing end of the main tube opposite to the injection end of the main tube; (2) a storage assembly adapted to fit within the tube bore of the main tube and comprising a first seal, a liquid-impermeable plunger adapted to fit within the first seal, a liquid-injection piston adapted to couple the first seal and the liquid-impermeable plunger together, a drug container adapted to contain unmixed drug, a foil seal attached to the liquid-injection side of the drug container, a second seal adapted to be coupled to the injection side of the drug container opposite to the liquid-injection side, and an optional air filter adapted to be placed between the second seal and the injection side of the drug container; (3) a mixing assembly adapted to be attached to the handle and partially fit within the tube bore of the main tube, adapted to engage the storage assembly, and comprising a twist cap including an internal thread and rotatably engaged with the handle, a piston guide engaged with the twist cap, and a mixing spring engaged with the guide, wherein the guide has a flange located within the internal thread, The guide head passes through the cover hole of the twist cover, the handle hole of the handle and the tube hole of the main tube in sequence, and the mixing spring is suitable for being adapted in the tube hole of the main tube and being located between the guide head and the first seal of the storage assembly; and (4) an injection assembly, suitable for engaging the injection end of the main tube and partially adapting in the tube hole of the main tube, suitable for engaging the storage assembly, and comprising a protective cap, a cap spring, a hollow needle, a needle driver and an injection spring, wherein the protective cap is suitable for movably covering the injection tip of the needle, the cap spring is suitable for being positioned between the protective cap and the needle driver and is suitable for being compressed to remove the protective cap to expose the injection tip of the needle, the needle passes through the needle driver and is integrated in the needle driver, the needle passes through the tube closure at the injection end of the tube hole of the main tube, and the injection spring is suitable for being positioned between the tube closure and the second seal of the storage assembly, wherein the needle is suitable for piercing the second seal when the protective cap is fully compressed against the needle driver and the needle driver is fully compressed against the injection end of the tube hole of the main tube.

[0089] In some embodiments, the device or apparatus of the present disclosure is used to conveniently transport and appropriately store medicine in the device or apparatus until the patient needs the medicine, at which time the device is used to administer the medicine to the patient. To administer the medicine to the patient, the medicine must be mixed with a liquid such as water to prepare a medicine mixture in the solution. In order to use the mixing assembly to mix the medicine, the user twists the twist cap relative to the handle so that the flange of the piston guide rotates in the thread, so that the guide moves toward the mixing spring and compresses the mixing spring, so that the mixing spring applies pressure to the first seal and pushes the liquid ejection piston toward the medicine container. When the liquid ejection piston moves toward the medicine container, the liquid ejection piston pierces the foil seal and enters the container hole of the medicine container, so that the liquid stored in the main tube between the first seal and the foil seal enters the medicine container and is mixed with unmixed medicine to form the medicine in the solution. The movement of the liquid ejection piston toward the medicine container and against the medicine container generates a liquid pressure that pushes the medicine in the solution to move through the medicine container to the injection end of the main tube, and pushes the second seal toward the tube closure, thereby compressing the injection spring. The displacement of the second seal toward the tube closure forms a cavity between the second seal (near the injection end) and the drug container (near the mixing end), and the drug in the solution contained in the cavity is under the pressure of the injection spring against the second seal. The injection assembly optionally also includes a safety device suitable for attachment to the needle driver, the protective cap and / or the main tube, such as a removable safety clip, to prevent the protective cap and the needle driver from moving and causing the compression cap spring to expose the injection tip of the needle, and to prevent the needle driver from moving toward the main tube and causing the second seal to be pierced. The safety device can be disengaged such as by removing the safety clip to allow the injection assembly to be engaged. After the removable safety clip is removed, the device is ready to press the protective cap against the patient such as against the patient's exposed skin. In the case where the removable safety clip has been removed, the protective cap is pressed against the patient, so that the protective cap is retracted toward the needle driver, the needle driver is retracted toward the main tube, and the needle driver drives the needle inward into the tube hole of the main tube. In the case where the drug has been mixed using the mixing assembly, the drug in solution is located in the cavity, awaiting injection into the patient, and driving the needle inward causes the input tip of the needle to pierce the second seal. The input tip of the needle then enters the cavity, allowing the drug in solution to enter the needle hole of the hollow needle and extract the drug in solution from the cavity. The drug in solution enters the input tip of the needle, passes through the needle hole, and exits the needle at the injection tip. The injection spring, which has been compressed by the mixing step using the mixing assembly, applies pressure to the second seal to move the second seal backward toward the drug container, thereby reducing the cavity volume of the cavity and pushing the drug in solution out of the cavity, through the needle, out of the injection tip and into the patient.

[0090] Other aspects of the disclosure are set forth herein. Details of exemplary embodiments of the disclosure are set forth in the drawings and description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings and from the claims.

[0091] In some embodiments, in the disclosed device: (1) a transmission assembly comprising a main tube and a spring piston fixed at a mixing end of the main tube opposite to the injection end of the main tube and screwed into the main tube; (2) a storage assembly adapted to fit within the tube bore of the main tube and comprising a first seal, a liquid-impermeable plunger adapted to fit within the first seal, a liquid-jet piston adapted to couple the first seal and the liquid-impermeable plunger together, a drug container adapted to contain unmixed drug, a foil seal attached to the liquid-jet side of the drug container, a second seal adapted to be coupled to the injection side of the drug container opposite to the liquid-jet side, and an optional air filter adapted to be placed between the second seal and the injection side of the drug container; (3) a mixing assembly adapted to be attached to the main tube and partially fit within the tube bore of the main tube, adapted to engage the storage assembly, and comprising a push rod having an annular groove and slidably engaging the main tube, wherein the push rod extends through the tube bore of the main tube. the tube opening, the push rod being adapted to fit into the tube hole of the main tube and abutting against the first seal of the piston and the storage assembly, and when the push rod is further pushed into the tube hole of the main tube and is pushed from the unpushed position to the pushed position so that the drug and the liquid are mixed, the spring piston of the transmission assembly is adapted to engage the annular groove; and (4) an injection assembly, adapted to engage the injection end of the main tube and partially fit into the tube hole of the main tube, adapted to engage the storage assembly, and comprising a hollow needle, a needle driver, a tube plunger and an injection spring, wherein the needle passes through the needle driver and is integrated in the needle driver, the needle driver is adapted to slide on the injection end of the main tube, the needle passes through the tube plunger, the tube plunger comprises a tube closure at the injection end of the tube hole of the main tube, and the injection spring is adapted to be positioned between the tube closure and the second seal of the storage assembly, wherein the needle is adapted to pierce the second seal when the needle driver is fully compressed against the injection end of the main tube. In some embodiments, the second seal may include a cavity piston having an inner cavity with a piston center hole proximate to the drug container, a diaphragm placed in the inner cavity and covering the piston center hole, and a spring guide located in the inner cavity and covering the diaphragm, wherein the spring guide includes an injection spring that guides the center hole and engages the injection assembly.

[0092] In some embodiments, the device or apparatus of the present disclosure is used to conveniently transport and appropriately store the drug in the device or apparatus until the patient needs the drug, at which time the device is used to administer the drug to the patient. In some embodiments, the needle driver is suitable for being transported and stored separately relative to the rest of the device until the device is used. The separated needle driver may optionally include a tip protector at the injection tip and the input tip to protect the tip and protect the user from accidental needle sticks. When administering the drug to the patient, the drug must be mixed, the needle driver is ready to use (e.g., remove any tip protector and sterile packaging), the needle driver is held by its side wall, the injection end of the needle is inserted into the patient's body (preferably the patient's skin is flush with the surface of the needle driver close to the injection tip), and the needle driver is slid onto the injection end of the main tube so that the input tip of the needle pierces the second seal and the drug in the solution is discharged from the cavity. In some embodiments, before the injection tip of the needle is inserted into the patient's skin, the needle driver slides onto the main tube to start releasing the drug in the solution.

[0093] Before administration to the patient, the medicine must be mixed with liquid such as water to prepare the drug mixture in the solution. In the second specific embodiment, in order to use the mixing assembly to mix the medicine, the user pushes the push rod relative to the main pipe until the annular groove reaches the spring plunger, so that the spring plunger extends into the annular groove and locks the push rod in place. Pushing the push rod makes the liquid ejection piston move forward, to apply pressure to the first seal and push the liquid ejection piston towards the medicine container. When the liquid ejection piston moves towards the medicine container, the liquid ejection piston pierces the foil seal and enters the container hole of the medicine container, so that the liquid stored between the first seal and the foil seal in the main pipe enters the medicine container, and is mixed with unmixed medicine to produce the medicine in the solution. The liquid ejection piston pushes the medicine in the solution towards and against the movement of the medicine container through the liquid pressure that the injection end of the medicine container moves towards the main pipe, and pushes the second seal towards the tube closure, thereby compressing the injection spring. The displacement of the second seal toward the tube closure creates a cavity between the second seal (near the injection end) and the drug container (near the mixing end), and the drug in the solution contained in the cavity is under the pressure of the injection spring against the second seal. The injection assembly optionally also includes a safety device suitable for attaching to the main tube to protect the tube closure at the injection end, such as a removable safety cap. The safety device can be disengaged such as by removing the safety cap to allow the injection assembly to be engaged. After the removable safety device is removed, the device is ready to press the needle driver against the patient such as flush with the patient's bare skin, wherein the needle pierces the patient's skin to a desired depth determined by the length of the needle extending beyond the needle driver, which is equal to the distance from the injection tip to the surface of the needle driver near the injection tip. Pressing the needle driver against the patient can be accompanied by and cause the needle driver to slide onto the main tube, so that the needle driver drives the needle inwardly into the tube hole of the main tube. Assuming that the mixing assembly has been used to mix drugs, the drug in the solution is located in the cavity, waiting to be injected into the patient, and at this time, driving the needle inward will cause the input end of the needle to pierce the second seal. The input end of the needle then enters the cavity, allowing the drug in the solution to enter the needle hole of the hollow needle and discharge the drug in the solution from the cavity. The drug in the solution enters the input end of the needle, passes through the needle hole, and leaves the needle at the injection tip. The injection spring, which has been compressed by the mixing step using the mixing assembly, applies pressure to the second seal to move the second seal backward toward the drug container, thereby reducing the cavity volume of the cavity and pushing the drug in the solution out of the cavity, through the needle, out of the injection tip and into the patient's body. Alternatively, before the injection tip of the needle is inserted into the patient's skin, the needle drive can be slid onto the main tube to start releasing the drug in the solution.

[0094] Other aspects of the disclosure are set forth herein. Details of exemplary embodiments of the invention are set forth in the drawings and description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings and from the claims.

[0095] See now Figure 1A and Figure 1B . Figure 1A A side cross-sectional view of one embodiment of the apparatus disclosed herein is shown. Assembly 100 includes two chambers, a first chamber 102 and a second chamber 104, separated by a seal in an unactivated state to prevent material transfer between the two chambers. First chamber 102 contains a liquid, solid, semi-solid, or gaseous material to be mixed with another material contained in second chamber 104. Upon activation, the material located in first chamber 102 is pushed through second chamber 104, whereby the material located in second chamber 104 is mixed with the material from first chamber 102. The materials are mixed by the action of compression mechanism 114, such as Figure 1B The compression mechanism 114 moves the material from the first chamber 112 (equivalent to Figure 1A 102) moves to the second chamber 110 (equivalent to Figure 1A 104 in ).

[0096] See now Figure 2A , Figure 2A Shown is a side cross-sectional view of another embodiment of the apparatus disclosed herein. Figure 2A The device in the embodiment also includes movable parts, cavity barriers, seals and other parts associated with the automatic injector. The device assembly 200 is composed of a housing 218 containing three cavities and associated parts. The device includes a compression assembly 202 that interacts with an insertion rod 204. The insertion rod is pushed through the first cavity 216 to pierce the cavity seal 206. The cavity seal 206 is an impermeable membrane that prevents material from being transferred between the first cavity 216 and the second cavity 208. When the device is activated and the compression assembly 202 is subsequently pressed, the insertion rod 204 pierces the barrier 206 and pushes the material from the first cavity 216 through the pierced seal 206 and into the second cavity 208. The material from the first cavity 216 moves into the second cavity 208, thereby mixing with the material in the second cavity 208 and moving together into the third cavity 210. When the mixed material moves into the third cavity 210, these mixed materials jointly push the sealing assembly 214 into the third cavity 210. As the sealing assembly 214 is pushed inwardly into the third chamber 210, the spring 212 is compressed, which stores energy that will subsequently be used to drive material out of the device through the needle for injection.

[0097] See now Figure 2B, which shows a side cross-sectional view of another embodiment of the device disclosed herein, wherein the insertion rod that pierces the seal is two parts (220, 254) instead of one. The device assembly 220 includes a housing 256, three chambers (a first chamber 254, a second chamber 234, and a third chamber 240), an insertion rod assembly 260 composed of multiple parts including an internal insertion rod 224, an external housing 258, and a seal 226. The internal insertion rod 224 also includes a fluid path 230 and a fluid outlet 228 that allow fluid to be transferred between the first chamber 254 and the second chamber 234. When the compression mechanism 222 is pressed inwardly onto the assembly 260, the internal assembly rod pushes into and pierces the barrier 232. After the barrier 232 is pierced, the fluid can enter the fluid outlet 228 and be transmitted through the fluid path 230 into the second chamber 234, or the fluid can move from the second chamber 234 in the opposite direction through the fluid path 230 and move out of the fluid outlet 228. Once the inner insertion rod 224 has pierced the barrier 232 and has become flush with the outer assembly 258 on the rear side, the entire assembly 260 is compressed by the compression mechanism 222 into the second cavity 234. The insertion part of the inner rod will move into the second cavity 234 and the outer assembly as a whole, and the large end of the insertion rod will be flush with the outside of the second cavity 234. During the compression, the material from the first cavity 254 moves through the first cavity 254 and mixes with the material in the second cavity 234. The optional seal 250 around the cavity housing 236 prevents the material from flowing out of the cavity. The mixed material is pushed inwardly into the third cavity 240. When the mixed material is pushed into the third cavity 240, the movable seal assembly 246 moves inwardly into the third cavity 240, thereby creating a space for accommodating the mixed material. The movable seal assembly 246 includes a seal 238 and a housing 262 that serves as an attachment point for the needle guide and the spring 244.

[0098] As assembly 246 moves into third chamber 240, seal 248 is pierced by the non-injection end of injection needle 242. This allows fluid to enter injection needle 242, provided that the injection end of needle 242 is open. As assembly 246 moves inwardly into third chamber 240, spring 244 is compressed. The compression force of spring 244 will be used to inject the mixed material.

[0099] See now Figure 3A , shows a side cross-sectional view of another embodiment of the device disclosed herein, wherein the needle assembly has a needle guard 302 attached to a main device 300. In some embodiments, the needle assembly and guard are attached to the device by a threaded connection system, but they can also be attached by gluing, welding, snapping, press-fitting fittings, or other attachment methods known in the art.

[0100] A more detailed view of the needle assembly and shield of this embodiment is shown in Figure 3B 308 is shown in . In this state, the device has not been activated and no mixing of components has occurred. The needle guard 304 includes a housing 306 held in an extended position covering the needle 308 by a spring 312. The injection end of the needle is covered by a seal 314 that prevents fluid from entering or leaving the needle until the guard 304 is retracted and the needle 308 is exposed through the seal 314. To activate the needle guard 304, the safety pin 310 is removed from the device, which allows the housing 306 to retract on the device housing, thereby exposing the needle 308. When the needle guard 316 is retracted, as in Figure 3C As shown in FIG. 3 , when the needle housing 320 is retracted and the needle 318 has pierced the seal 322, the needle 318 is exposed, thereby allowing the material to be injected. Figure 3C In the state shown in , the device has been activated and the components have been mixed, but the injection operation has not yet started.

[0101] Figure 3D Yet another more detailed embodiment of a needle guard 328 and assembly 322 is shown. The guard housing 324 is guided in motion by a guide 328 that is aligned with and seated in a guide track 326. The needle 342 is held in place by a needle attachment 330. The needle 342 is sealed at the injection end by a seal 346 that prevents fluid from entering or leaving the device until the needle guard housing 322 is retracted to expose the needle 342. To activate the needle guard, the safety pin 338 is removed to allow the assembly 322 to retract and expose the needle through the seal 346. After the injection, the spring 344 pushes the needle guide back into place to hide the needle.

[0102] See now Figure 3E , which shows another embodiment of the needle assembly and needle guard, wherein the needle guard 348 is formed by a housing 350 and guided for movement by the body of the device 352. The injection end of the needle is sealed by a seal 354.

[0103] See now Figure 4, a side cross-sectional view of another embodiment with a device body, needle assembly and shield attached is shown. The needle assembly and shield 400 are attached to the main device body 424 via an attachment point 404. The attachment may be a thread, adhesive, weldment, press fit, snap fit or other means known in the art. The device body consists of a trigger mechanism 426 and three chambers (first chamber 418, second chamber 436 and third chamber 444) all located within the housing 420. An insertion rod 428 is contained within the first chamber 418 and optionally contains a seal 430. A fluid path 432 and a fluid outlet 422 are contained within the insertion rod 428. The end of the insertion rod 428 is adjacent to a barrier 434 that separates the first chamber 418 and the second chamber 436. The second chamber 436 is contained within a housing 438, which may contain a seal 414 or may be a component of the housing itself. The second chamber 436 is maintained separate from the third chamber 444 by the movable sealing assembly 410 and an optional seal 440. The seal 412 is attached to the movable sealing assembly 410 to prevent material from entering the needle 448 prior to activation of the device.

[0104] Upon activation of the device, the compression mechanism 426 pushes the insertion rod 428 through the barrier 434 and into the second chamber 436. The insertion rod 428 enters the second chamber 436 through the opening 416, which allows material transfer and possible seating of the insertion rod 428. The material from the second chamber 436 and the first chamber 418 moves through the second chamber 436, and the movable sealing assembly 410 moves into the third chamber 444 to compress the spring 408. The mixed material resides inside the third chamber 444 until the needle guard assembly 400 is retracted for injection.

[0105] To allow injection after activation of the device, the safety clip is removed, allowing the needle guard 400 to retract and expose the needle 400. Before the needle guard 400 is retracted, the injection end of the needle is sealed by a seal 450 that prevents material from entering or leaving the needle 448. After retraction, the needle 448 is exposed through the needle port 452. During retraction, the needle guide 446 follows the needle guide track 402 to allow movement of the appropriate needle guard assembly. The needle 448 is attached by the needle attachment 406.

[0106] The device disclosed herein can be used FIG. 5A to FIG. 5D The four different operable conditions shown in are maintained. Figure 5A, the first operable condition 500 is a state prior to device activation in which no mixing of materials occurs. The compression mechanism 514 has not yet been activated and the insertion rod 512 is not depressed. The first chamber 510 contains the first material to be mixed, and the seal 516 has not yet been pierced. The second chamber 508 contains all of the material to be mixed. The movable seal assembly 506 acts as a barrier between the second chamber 508 and the third chamber 504, and no material enters the third chamber 504. The safety pin 518 is still located on the device, and the needle guard has not yet been retracted.

[0107] See also Figure 5B In the second operable condition, the compression assembly 544 has been partially activated. The insertion rod has penetrated into the first chamber 546 by piercing the seal 548. The first chamber 546 and the second chamber 550 are in fluid communication, but the materials have not yet been completely mixed.

[0108] See also Figure 5C , in the third operable condition 520, the compression assembly 524 has been fully activated and has pushed the insertion rod 526 into the first chamber 527. The material has been mixed and moved into the second chamber 522. The movable seal 528 has retracted and compressed the spring 530. The safety pin 529 is still in place, the needle guard 532 has not been retracted, and the seal 534 has not been pierced by the injection needle.

[0109] See also Figure 5D In the fourth operable condition 536, the safety pin has been removed and the needle guard 538 has been retracted, exposing the injection needle 544. The spring 542 has been pushed back into the device and fluid has been driven out of the needle 544. The movable seal 540 has been pushed back to the middle of the device.

[0110] See now Figure 6 , which shows three main operational conditions, and a final state where the device has been removed from the injection site. Prior to injection (state 600), the device is brought close to a surface for injection. Once at or near the injection surface (state 602), the pin is removed, and the device is then pushed downward (state 604), pushing the needle through the injection surface. After the injection is complete (state 606), the device is lifted and the needle guard hides the needle again.

[0111] See now Figure 7, which shows an embodiment of the internal components of the second cavity 722 and how they are distributed between the other two cavities (the first cavity 714 and the third cavity 728). The second cavity 722 is contained in the housing 706, which is itself contained in the housing 700 and is optionally surrounded by a seal 710. The insertion rod 716 is initially held adjacent to the barrier 712. The insertion rod 716 includes a fluid path 718 and a piercing end for piercing the barrier 712. The piercing end 720 may have one or more pointed or blunt protrusions to allow easy piercing of the seal 712. Once the seal 712 is pierced, the insertion rod is pushed into the second cavity 722 through the opening 708, which may be beveled or otherwise shaped to facilitate easy entry of the insertion rod and transfer of material from the first cavity 714 to the second cavity 722. The material from the first chamber 714 is pushed into and through the second chamber 722, and the movable seal assembly 724 and the needle seal 704 move into the third chamber 728 to allow the material to be transferred into the third chamber 728. After the above components move into the third chamber 728, the spring 702 is compressed and the needle seal 704 is pierced by the non-injection end of the needle 726, allowing the material to enter the needle during injection.

[0112] See now Figure 8 , which shows a side cross-sectional view of one embodiment of the device disclosed herein, which uses a screw mechanism to drive the piston downward. Assembly state 800 shows an unactivated device, while when turned in assembly state 802, the assembly drives the piston into the device to compress the components and activate the device.

[0113] The apparatus described herein may be implemented as specific articles of manufacture of various sizes and using components of various sizes, and applied to its use according to various operating parameters and for various purposes.

[0114] These dimensional characteristics and use parameters may be the subject of selection for a particular purpose and may include the force applied to the injection site in order to inject the active agent, the volume of the drug to be delivered, the size of the internal passage through the needle, the injection depth determined by the length of the needle protruding from the device, the spring force applied to the needle to expel the drug, and the time interval required to inject the drug when the device is activated. It is believed that these factors, in various combinations and possibly other circumstances, individually and / or collectively contribute to the effectiveness of the device in delivering the drug into the patient's body and dispersing the drug from the initial injection site into the surrounding body tissues, which may be referred to as the "uptake" of the drug.

[0115] The force applied to the injection site is ultimately determined by the force selected by the user to press the device against the user's body, but the minimum level of this force is determined by the design of the device itself and the force required to drive the device. In some embodiments, the driving force to release the active agent is between 4 pounds and 8 pounds. In some embodiments, the driving force to release the active agent is between 2 pounds and 8 pounds. In some embodiments, the driving force to release the active agent is between 4 pounds and 6 pounds. In some embodiments, the driving force to release the active agent is between 2 pounds and 6 pounds. In some embodiments, the driving force to release the active agent is between 2 pounds and 6 pounds. In some embodiments, the force actually applied by the user is at least about 2 pounds. In some embodiments, the force actually applied by the user is at least about 3 pounds. In some embodiments, the force actually applied by the user is at least about 4 pounds. In some embodiments, the force actually applied by the user is at least about 5 pounds. In some embodiments, the force actually applied by the user is at least about 6 pounds. In some embodiments, the force actually applied by the user is at least about 7 pounds. In some embodiments, the force actually applied by the user is at least about 8 pounds.

[0116] The force required for the active agent to be injected into the patient can also vary depending on the viscosity of the fluid mixture obtained by the active agent and a pharmaceutically acceptable carrier. In some embodiments, the fluid mixture of the active agent and a pharmaceutically acceptable carrier with a viscosity of about 1cP (centipoise) to about 150cP will be injected by the disclosed device. In some embodiments, the fluid mixture of the active agent and a pharmaceutically acceptable carrier with a viscosity of about 5cP (centipoise) to about 125cP will be injected by the disclosed device. In some embodiments, the fluid mixture of the active agent and a pharmaceutically acceptable carrier with a viscosity of about 10cP (centipoise) to about 100cP will be injected by the disclosed device. In some embodiments, the fluid mixture of the active agent and a pharmaceutically acceptable carrier with a viscosity of about 15cP (centipoise) to about 75cP will be injected by the disclosed device. In some embodiments, the fluid mixture of the active agent and a pharmaceutically acceptable carrier with a viscosity of about 20cP (centipoise) to about 60cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 25 cP (centipoise) to about 50 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 1 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 5 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 10 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 25 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 50 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 75 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier with a viscosity of about 100 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier with a viscosity of about 110 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier with a viscosity of about 120 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier with a viscosity of about 130 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier with a viscosity of about 140 cP will be injected by the disclosed device.In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity of about 150 cP will be injected by the disclosed device. In some embodiments, a fluid mixture of an active agent and a pharmaceutically acceptable carrier having a viscosity greater than about 150 cP will be injected by the disclosed device.

[0117] After injection, the time interval that the needle is held in place against the injection site is typically determined based on the manufacturer's recommendations as printed on the autoinjector label. In some embodiments, it is recommended to be held in place for a time interval of at least about 2 seconds. In some embodiments, it is recommended to be held in place for a time interval of at least about 3 seconds. In some embodiments, it is recommended to be held in place for a time interval of at least about 4 seconds. In some embodiments, it is recommended to be held in place for a time interval of at least about 5 seconds.

[0118] The volume of the drug to be delivered depends on the internal dimensions of the device, which is selected by the manufacturer to administer the desired volume of the active agent. For example, when adrenaline is administered using an automatic syringe, an injection volume of about 0.15mL or about 0.30mL can be used. A larger volume of injection can also be administered. In some embodiments, depending on viscosity and other factors, a volume of about 0.50mL to about 3.0mL can be rapidly injected using any device in the disclosed device. In these embodiments, the injection volume or dispersion volume of the active agent mentioned refers to the total volume of the liquid injected into the patient, and these references are independent of the amount of the active ingredient contained in the injection volume. However, in some embodiments, the device of the present disclosure can be used to deliver a predetermined amount or dose of the active agent to the patient. In some embodiments, when corticosterone or a corticosterone derivative is used, the corticosterone or corticosterone derivative with a dosage of about 5mg to about 500mg is used together with the disclosed device. In some embodiments, the corticosterone or corticosterone derivative with a dosage of about 10mg to about 400mg is used together with the disclosed device. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dose of about 25 mg to about 300 mg. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dose of about 50 mg to about 250 mg. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dose of about 60 mg to about 200 mg. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dose of about 75 mg to about 150 mg. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dose of about 5 mg / mL to about 300 mg / mL of the active agent in a pharmaceutically acceptable carrier. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dose of about 10 mg / mL to about 250 mg / mL of the active agent in a pharmaceutically acceptable carrier. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dosage of about 15 mg / mL to about 200 mg / mL of the active agent in a pharmaceutically acceptable carrier by weight per unit volume of solution. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dosage of about 20 mg / mL to about 175 mg / mL of the active agent in a pharmaceutically acceptable carrier by weight per unit volume of solution.In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dosage of about 25 mg / mL to about 150 mg / mL of the active agent in a pharmaceutically acceptable carrier by weight per unit volume of solution. In some embodiments, the corticosterone or corticosterone derivative is used with the disclosed device at a dosage of about 30 mg / mL to about 125 mg / mL of the active agent in a pharmaceutically acceptable carrier by weight per unit volume of solution.

[0119] It should be understood that the amount of the activating agent such as corticosterone or corticosterone derivative in the medicine of injection volume can be changed.The amount of the activating agent in the injection volume can be changed according to the dosage prescribed to the patient.The dosage prescribed of corticosterone or corticosterone derivative can be, for example, about 1mg, about 5mg, about 10mg, about 25mg, about 50mg, about 75mg, about 100mg, about 125mg, about 150mg, about 175mg, about 200mg, about 225mg, about 250mg, about 275mg or about 300mg.The activating agent of these dosages can be prepared with other components such as pharmaceutically acceptable carriers, to include the medicine of 0.15mL to about 0.6mL volume.The amount of activating agent need not be directly related to the volume of the medicine to be injected, because the volume can be diluted as required.For example, the medicine of the injection of 0.30mL can include the activating agent of about 1mg to about 25mg.

[0120] The size of the internal passage through the needle is determined by the manufacturer by selecting the tubing of the appropriate specification of the needle. Small diameter stainless steel tubing commonly used for hypodermic needles can be obtained in various standard sizes called specifications. The specification determines the nominal outer diameter of the tubing. Then, for each specification, the tubing can generally obtain various wall thicknesses called regular wall (RW), thin wall (TW), ultra-thin wall (ETW) and ultra-thin wall (UTW). The thinner the wall of the tubing of a given specification, the larger the inner diameter or hole of the tubing will be. And for each standard tubing size, such as, for example, 22-spec RW tubing, the applicable standard specifies the minimum value, nominal value and maximum value of each size such as inner diameter. For the device disclosed in the present invention, the needle can be constructed from RW stainless steel tubing with specifications as large as 18 specifications and as small as 24 specifications. Wall thicknesses other than RW can also be selected. The following table shows the standard minimum inner diameter, nominal inner diameter and maximum inner diameter of RW stainless steel tubing from 18 specifications to 24 specifications. All dimensions are given in inches.

[0121] Specification type Minimum inner diameter Nominal inner diameter Maximum inner diameter 18 R 0.0315 0.0330 0.0345 19 R 0.0255 0.0270 0.0285 20 R 0.0230 0.0238 0.0245 21 R 0.0195 0.0203 0.0210 22 R 0.0155 0.0163 0.0170 23 R 0.0125 0.0133 0.0140 24 R 0.0115 0.0123 0.0130

[0122] Therefore, selecting the minimum of these inner diameters, the minimum inner diameter of 24 gauge RW tubing is about 0.0115 inches. In the case of selecting 23 gauge RW tubing, its inner diameter will be at least about 0.0125 inches. In the case of selecting 22 gauge RW tubing, its inner diameter will be at least about 0.0155 inches. For all of the selections shown in the table above, the inner diameter of the needle will be no greater than about 0.0345 inches, which is the maximum inner diameter that forms 18 gauge RW tubing.

[0123] The injection depth is determined by the needle length protruding from the disclosed device, for example in Figure 6 . Those dimensions determined by the dimensions of the various internal components are appropriate for the specific active agent to be injected. For example, for subcutaneous injection of an active agent, the device can provide an injection in the subcutaneous region, wherein, in some embodiments, the depth of the injection is about 0.15 inches to about 0.30 inches. In other embodiments, the depth of the injection into the subject is about 0.2 inches to about 0.25 inches. For intramuscular injection of an active agent, the disclosed device can provide an injection in the muscle region, wherein, in some embodiments, the depth of the injection is about 0.4 inches to about 0.7 inches. In other embodiments, the depth of the injection into the subject is about 0.6 inches. In some embodiments, the depth of intramuscular injection that the disclosed device can provide is a depth of up to about 1.25 inches into the subject.

[0124] The spring force applied to discharge the active agent is determined by the manufacturer's selection of the force spring and by the design of various internal components, which will affect how much available spring force is actually applied. A given spring will have a certain static force applicable to the surrounding structure when compressed, which keeps the spring in a compressed state. When the spring is released, some of its potential energy will be lost due to friction and moving the needle and collapsing the needle sheath, so that the spring is actually applied to the plunger to discharge the force of the active agent, that is, the dynamic force applied to the plunger, less than the initial static force output of the spring. For example, when compressed, the spring can have a nominal static force output of about 100 Newtons. Due to manufacturing tolerances, the actual static force output of the spring may be in the range of about 0 Newton to about 100 Newtons. Then, the spring is actually applied to the plunger to discharge the dynamic force of the active agent in the range of about 10 Newtons to about 75 Newtons. The dynamic force can be described as at least about 10 Newtons, about 20 Newtons, about 30 Newtons, about 40 Newtons, about 50 Newtons, about 60 Newtons, about 70 Newtons, about 80 Newtons, about 90 Newtons, or about 100 Newtons.

[0125] Devices according to the present disclosure can be used to deliver a wide range of active agents into a subject. Of particular interest is providing the active agents in Table 1 in the dosages listed herein.

[0126] Table 1. Active agents suitable for use in the devices of the present disclosure and corresponding dosages

[0127]

[0128] In some embodiments, the disclosed device is used to deliver one or more of the active agents selected from Table 1 to a patient. In some embodiments, the disclosed device is used to deliver one or more of the active agents selected from Table 1 to a patient at a dose identified in Table 1. In some embodiments, the disclosed device is used to deliver corticosterone to a patient. In some embodiments, the disclosed device is used to deliver a corticosterone derivative to a patient. In some embodiments, the disclosed device is used to deliver hydrocorticosterone sodium succinate to a patient. In some embodiments, one or more of the active agents are delivered to a patient using the disclosed device accompanied by one or more of the pharmaceutically acceptable carriers. In some embodiments, the pharmaceutically acceptable carrier used is water for injection. In some embodiments, the pharmaceutically acceptable carrier used is sterile water for injection. In some embodiments, the pharmaceutically acceptable carrier used is bacteriostatic water for injection. In some embodiments, the pharmaceutically acceptable carrier used is sodium chloride in water. In some embodiments, the pharmaceutically acceptable carrier used is sodium bicarbonate in water. In some embodiments, the pharmaceutically acceptable carrier used is a dimethyl sulfoxide solution in water.

[0129] method

[0130] The present disclosure provides a method for treating and / or preventing a disease or condition of a patient, including administering one or more active agents by any of the devices disclosed herein. The present disclosure further provides a method for treating a subject who needs to administer one or more active agents, including administering a pharmaceutically effective amount of one or more active agents by any of the devices disclosed. In some embodiments, the subject is diagnosed with or suspected of having a cortisol disorder. "Cortisol disorder" as used herein refers to a disease or condition that causes a disorder in cortisol secretion to reach an abnormal level. In some embodiments, the cortisol disorder is Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenal myeloneuropathy, adrenoleukodystrophy, adrenal tumors, Schmidt's syndrome, hyperaldosteronism, pituitary tumors, pituitary cysts, or corticosteroid deficiency associated with critical illness. In some embodiments, the subject is diagnosed with or suspected of having a cortisol depletion disorder. In some embodiments, the subject's cortisol depletion disorder is caused by Addison's disease, congenital adrenal hyperplasia, autoimmune adrenalitis, adrenalectomy, adrenal neuropathy, adrenoleukodystrophy, adrenal tumor, Schmidt's syndrome, hyperaldosteronism, pituitary tumor, pituitary cyst, or corticosteroid insufficiency associated with critical illness.

[0131] In addition to corticosterone or corticosterone derivatives, the disclosed devices can also be used to deliver other non-urgent active agents to a subject in need thereof for a desired treatment. Examples of such non-urgent active agents include, but are not limited to, non-urgent steroids, antibiotics, analgesics, disease-specific treatments (e.g., MS treatments, psoriasis treatments), insulin, glycoproteins, immunomodulators, G-CSF, erythropoietin, Biological agents, antihypertensive drugs, vaccines, hormones (including contraceptives), anti-hormones, sedatives, anti-epileptic drugs, anti-neoplastic drugs, pesticides (e.g., dobutamine), antipsychotics, antidotes, cosmetics, selective serotonin reuptake inhibitors (SSRI), proton pump inhibitors (PPI), anesthetics, diuretics, antidiuretics, blood thinners (e.g., low molecular weight heparin), streptokinase, etc., used alone or in combination, whether in liquid form, reconstitutable form or other form. In some embodiments, the device of the present disclosure can be used to deliver drugs that have been previously used Act-o- In some embodiments, the devices of the present disclosure are used to deliver drugs that are delivered by the system, namely, methylprednisolone for multiple sclerosis, certain cancers, and autoimmune conditions. In some embodiments, the devices of the present disclosure are used to deliver glucagon for hypoglycemia emergencies. In some embodiments, the devices of the present disclosure are used to deliver ticarcillin for the treatment of high incidence infections. In some embodiments, the devices of the present disclosure are used to deliver chlorodiazepine epoxide for the treatment of alcohol withdrawal symptoms. In some embodiments, the devices of the present disclosure are used to deliver deoxycorticosterone trimethylacetate for veterinary emergencies. In some embodiments, the devices of the present disclosure are used for in vitro fertilization treatments.

[0132] The equipment of the present disclosure can be manufactured by any device known to the technicians in the field of related fields, particularly automatic syringes. In some embodiments, the first compartment, the second compartment and the third compartment are physically attached to the shell by friction fit, rivet, plug or plastic welding such as radio frequency welding or ultrasonic welding. These compartments can also be attached to the shell or attached to each other via the same technology or by projections such as snap fit. The parts of the equipment can be plastic, rubber, glass or metal. Most (if not all) sealing materials will be made of plastic or rubber, and the cavity will be made of plastic, glass or metal. The insertion rod will be plastic or metal, and by being attached to any seal based on groove for the interlocking mechanism attached, or by spiral thread attachment. In the embodiment where the movable system is attached to the insertion rod, the movable system will be attached by friction. The seal attached to the cavity will be pressed into place using friction, attached by an interlocking groove system, or threaded in place. In some embodiments, these compartments are cylindrical or substantially cylindrical, with projections for fastening on both ends. In some embodiments, there are one or more fasteners on each side of the compartment and on each side of the device component.

[0133] Methods according to various aspects of the present disclosure include methods of using a device for transporting, storing, mixing, and injecting a drug into a patient, for example, wherein the device includes: a transport component, a storage component, a mixing component, and an injection component, and wherein the method includes: providing the device, engaging the mixing component to mix the drug and create the drug in solution when ready to administer the drug to the patient, and engaging the injection component to inject the drug in solution into the patient. The method may also include disengaging a safety device before engaging the injection component to inject the drug in solution into the patient.

[0134] Another method according to various aspects of the present disclosure includes, for example, a method of assembling a device for transporting, storing, mixing and injecting a drug into a patient, wherein the device includes: a transmission component, a storage component, a mixing component and an injection component, and wherein the method includes: providing and assembling the transmission component, providing and assembling the storage component, providing and assembling the mixing component, and providing and assembling the injection component.

[0135] Systems according to various aspects of the present disclosure include, for example, systems for assembling a device for transporting, storing, mixing and injecting a drug into a patient, wherein the device includes: a transmission component, a storage component, a mixing component and an injection component, and wherein the system includes: a device for assembling the transmission component, a device for assembling the storage component, a device for assembling the mixing component, and a device for assembling the injection component.

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

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

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

[0139] Preparation method

[0140] The devices described herein include active agents to be injected into the body and therefore must be manufactured using aseptic sterilization techniques. The general techniques used for manufacturing include sterilization of the device components, filling of active agents and carrier agents, assembly of active agents for contact components, and assembly of inactive agents for contact components. Filling of active agents and carrier agents and assembly of some active agents for contact components must be completed in a sterile processing manufacturing facility commonly referred to as a sterile core.

[0141] Component sterilization techniques are known in the art. Filling of the agent depends on the characteristics of the device and whether the active agent is a solid or liquid. Liquids can be filled using dispensing techniques by volumetric or flow measurement. Powders and other solids can be filled by inserting the powder or solid material using a density or weight-based measurement system for determining the total fill amount.

[0142] In a manufacturing method of the device, the cavity is capped at the distal end using a movable seal, and the capped cavity is then inserted into a sterile kernel. The active agent is inserted into the cavity by a powder filling method or a liquid filling method. The liquid may be freeze-dried or not, depending on the active agent type and device requirements. The filled cavity is then capped on the proximal end and inserted into the main device tube for injection. Then, a second medicament is filled into the first cavity using a powder or liquid filling method, an insertion rod is added, and the exposed end of the second filled cavity is sealed. A needle is added to the device, and a complete subassembly is removed from the sterile kernel. The remaining components are assembled onto the device outside the sterile kernel.

[0143] In another manufacturing method, the device components are sterilized outside the sterile core. The needle assembly, removable seal and a chamber are inserted into the main device housing outside the sterile core, and the assembled subassembly is then transferred to the sterile core, where the active agent is inserted into the exposed cavity using a liquid or powder filling method. The cavity is capped and a second active agent is added on top of the first active agent, also using a liquid or powder filling method. The insertion rod and seal are added above the newly filled cavity, 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.

[0144] In another manufacturing method, the components are sterilized. The main device tube and needle are assembled and inserted into the sterile core. The device cavity is sealed at the distal end with a removable seal and placed into the same sterile core. The active agent is inserted into the cavity using a powder filling method or a liquid filling method. If necessary, the liquid is lyophilized. Once the filling is completed, the cavity is sealed at the proximal end. The filled and sealed cavity is inserted into the main device tube. The liquid or powder is then filled on top of the previous cavity. The insertion rod and seal are added above the newly filled cavity, 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.

[0145] In some embodiments, the first compartment, the second compartment and the third compartment are physically attached to the housing by friction fit, rivets, plugs or plastic welding such as radio frequency welding or ultrasonic welding. These compartments can also be attached to the housing or each other via the same technology or by projections such as snap fits. The parts of the equipment will be plastic, rubber, glass or metal. In some embodiments, the sealing material will be made of plastic or rubber, and the cavity will be made of plastic, glass or metal. In some embodiments, the insertion rod will be plastic or metal, and by being attached to any seal based on a groove for attachment of an interlocking mechanism, or by a spiral thread attachment. In the embodiment in which the removable system is attached to the insertion rod, the removable system will be operably attached by friction. The seal attached to the cavity will be pressed into place using friction, attached by an interlocking groove system, or threaded in place. In some embodiments, these compartments are cylindrical or substantially cylindrical, with projections for fastening at both ends. In some embodiments, there are one or more fasteners on each side of the compartment and on each side of the device component.

[0146] The foregoing description discloses exemplary embodiments of the present disclosure. Although the invention disclosed herein has been described by its specific embodiments and applications thereof, it is apparent to those skilled in the art that various modifications and variations may be made thereto without departing from the scope of the invention as described in the claims. Modifications to the above disclosed apparatus and methods that fall within the scope of the claimed invention will be apparent to those of ordinary skill in the art. Therefore, other embodiments may also fall within the spirit and scope of the claimed invention, as defined by the claims below.

[0147] The present disclosure relates to a method for treating a subject in need of administering one or more active agents by using a device. In some embodiments, the administration method includes compressing a movable element to a first predetermined position so that the insertion rod pierces a seal on the first opening for separating the first compartment and the second compartment. In some embodiments, the method also includes waiting for a period of time to pass to allow the active agent and diluent in the first compartment and the second compartment to mix and dissolve and / or activate the active agent. In some embodiments, the method also includes a step of pressing the movable element to a second predetermined position at a second sequential time after the first pressing step so that the insertion rod is displaced and pierces a seal for separating the second compartment and the third compartment. In some embodiments, the method also includes a step of allowing a second period of time to pass so that the active agent and a pharmaceutically acceptable carrier or diluent contact the end of the needle. In some embodiments, the method also includes a step of pressing the movable element to a fully compressed position for the third time so that the spring of the needle assembly is released and the distal end of the needle is deployed into the patient's body. In some embodiments, the method also includes unlocking the needle assembly before the movable element is fully compressed. In some embodiments, the first predetermined distance is about 1 cm to about 5 cm during the movement toward the needle assembly. In some embodiments, the second predetermined distance is about 1 cm to about 5 cm during the movement toward the needle assembly. In some embodiments, the third predetermined distance is about 2 cm to 6 cm.

[0148] In some embodiments, the method of administering the drug does not include a third depression of the movable element, and the final release of the spring of the needle assembly is accomplished by applying pressure only to the end of the device proximal to the needle assembly. In this case, the application of pressure to the device in the longitudinal direction by the patient or operator releases the spring and unsheathes the needle with a certain force, thereby injecting the drug composition into the subject.

[0149] The therapeutically effective amount or dosage of a compound can vary within a wide interval. Such dosages can be adjusted according to the individual requirements of each particular situation, including the administration of one or more specific compounds, the route of administration, the condition being treated, and the patient being treated. Generally speaking, in the case of oral administration or parenteral administration, the daily dosage of an adult with a body weight of about 70Kg or more is about 10mg to 10000mg, preferably about 200mg to 1000mg should be suitable, although the upper limit may also be exceeded. The daily dosage can be administered in a single dose or multiple doses, or for parenteral administration, continuous injection can be used. A single dose composition can include such a quantity or multiple times of the compound or composition to constitute a daily dosage. The dosage can be adjusted by each doctor according to the situation of any contraindications. In one day or several days, the dosage can vary, and can be administered in a single dose or multiple doses every day.

[0150] In the above description, many specific details are set forth in order to provide a more thorough understanding of the embodiments of the present invention. However, it is obvious to those of ordinary skill in the art that the present invention can be implemented without combining all aspects of the specific details described herein. Not all possible embodiments of the present invention are set forth verbatim herein. Multiple combinations of various aspects of the present invention can be formed to create different embodiments falling within the scope of the claims described below. In addition, specific details well known to those of ordinary skill in the art will not be described in detail to avoid causing the present invention to become obscure. The reader should note that although examples of the present invention are set forth herein, the full scope of the claims and any equivalents thereof is the scale and limit used to define the scope of protection of the present invention.

[0151] The foregoing description discloses exemplary embodiments of the present disclosure. Although the disclosure disclosed herein has been described by specific embodiments and applications thereof, it is apparent to those skilled in the art that various modifications and variations may be made thereto without departing from the scope of the present disclosure set forth in the claims. Modifications to the above disclosed apparatus and methods that fall within the scope of the claimed subject matter will be apparent to those of ordinary skill in the art. Therefore, other embodiments may also fall within the spirit and scope of the claimed subject matter, as defined by the claims below.

[0152] In the above description, many specific details are described in order to provide a more thorough understanding of the embodiments of the present disclosure. However, it is obvious to those of ordinary skill in the art that the present disclosure can be implemented without combining all aspects of the specific details described herein. Not all possible embodiments of the present disclosure are described verbatim herein. Multiple combinations of various aspects of the present disclosure can be formed to create different embodiments that fall within the scope of the claims described below. In addition, for the specific details known to those of ordinary skill in the art, no further detailed description is given to avoid causing the present disclosure to become obscure. The reader should note that although the examples of the present disclosure are described herein, the full scope of the claims and any equivalents thereof is the scale and limit used to limit the scope of the protection required.

Claims

1. An injection device comprising: (a) a first compartment and a second compartment, each of the first compartment and the second compartment defining a first cavity and a second cavity, respectively, the first compartment and the second compartment being in fluid communication with a first opening and being separated from each other at the first opening, the first opening being covered by a first movable seal; (b) needle assembly; (c) an insertion rod positioned in the first compartment, the insertion rod operably connected to the movable element; and (d) a third compartment defining a third cavity, the third compartment being adjacent to the second compartment and separated from the second compartment by a second opening covered by a second movable seal of a movable stopper, wherein the movable element allows displacement of the insertion rod and the movable stopper when depressed, wherein displacement of the movable stopper provides fluid communication between the second compartment and the third compartment; wherein the third compartment contains the needle assembly; the needle assembly comprises a spring and a needle operably connected to the spring; wherein the needle comprises a first fluid opening within the third cavity and an opposing second fluid opening positioned away from the first cavity and the second cavity.

2. The injection device according to claim 1, wherein: The insertion rod includes two oppositely oriented faces, a first face in physical contact with the movable element and a second face positioned within the first cavity; wherein the second face includes a protrusion and at least one valve positioned away from the protrusion.

3. The injection device according to claim 2, wherein: The protrusion has an inclined surface.

4. The injection device according to claim 1, wherein: The movable element is physically positioned adjacent to the insertion rod, and wherein the insertion rod is movable in a direction along a longitudinal axis parallel to and within the first and second compartments when the movable element is depressed.

5. An injection device according to any one of claims 1 to 4, wherein: The second compartment contains an active agent, and the first compartment contains a pharmaceutically acceptable carrier; or wherein the second compartment contains a pharmaceutically acceptable carrier, and the first compartment contains an active agent; or Wherein, the first compartment and the second compartment each contain one or more active agents.

6. The injection device according to claim 5, wherein: The first compartment and the second compartment each contain: one or more active agents and one or more pharmaceutically acceptable carriers.

7. The injection device of claim 1, wherein: The second compartment contains an active agent in solid or semi-solid form; and wherein the first compartment contains a pharmaceutically acceptable carrier in liquid form.

8. The injection device of claim 1, wherein: The second compartment contains an active agent in liquid form; and wherein the first compartment contains a pharmaceutically acceptable carrier in liquid form.

9. The injection device according to claim 5, wherein: The active agent is lyophilized.

10. The injection device of claim 1, wherein: The insertion rod includes a fluid path extending between two oppositely oriented faces, a first face being in physical contact with the movable element and a second face being positioned within the first cavity, wherein the second face includes a pointed protrusion and at least one valve positioned away from the pointed protrusion.

11. The injection device of claim 1, wherein: In a first operable condition, the movable element is in a fully extended position relative to the lateral direction of the injection device, wherein the first compartment contains a pharmaceutically acceptable carrier, the second compartment contains one or more active agents, the third compartment contains a needle assembly, and wherein the first movable seal and the second movable seal covering each of the first opening and the second opening are intact, thereby preventing fluid from flowing from one compartment to the other compartment.

12. The injection device of claim 11, wherein: In a second operable condition, the movable element is in a depressed position relative to a lateral portion of the injection device, wherein the first compartment and the second compartment contain a pharmaceutically acceptable carrier and one or more active agents; wherein the third compartment contains a needle assembly, and wherein the second movable seal covering the second opening prevents fluid from flowing from the third compartment to the first compartment or the second compartment.

13. An injection device according to claim 12, wherein: In a third operable condition, the movable element is in a depressed position relative to a lateral portion of the injection device such that the insertion rod has caused the second movable seal to be pierced, wherein the first compartment, the second compartment, and the third compartment contain a pharmaceutically acceptable carrier and one or more active agents; wherein the third compartment contains the needle assembly, and wherein the second movable seal has been pierced or has been moved relative to its position covering the second opening, and the needle assembly is exposed to the active agent and the pharmaceutically acceptable carrier.

14. An injection device according to claim 13, wherein In a fourth operable condition, the movable element is in a fully depressed position relative to the side of the injection device and the needle of the needle assembly is exposed.

15. An injection device according to any one of claims 11 to 14, wherein The active agent is dissolved in one or more pharmaceutically acceptable carriers.

16. The injection device of claim 5, wherein: The active agent is any one or a combination of the following active agents: hydrocortisone sodium succinate; certolizumab pegol; etanercept; risperidone; olanzapine pamoate; aripiprazole; human chorionic gonadotropin; follicle-stimulating hormone; gonadotropin-releasing hormone analog; azacitidine; metreleptin; various antivenoms, including Italian honey bees, wasp white spot venom protein, wasp snow fungus, Vespa chlorella, Pompeu species, wasp white spot venom protein, Vespa chlorella venom protein; various antibiotics; chlorimiperazole; pembro chloride; ziprasidone mesylate; homoharringtonine; caneluzumab; deferoxamine mesylate; sodium methotrexate; corticotropin; peginterferon α-2b; bortezomib; canakinumab; rilonacept; telluride.

17. An injection device according to claim 16, wherein The active agent is any one or a combination of the active agents selected from the following and has a dosage as indicated below: 50mg / ml to 150mg / ml of cortisol sodium succinate; 100 mg / ml to 300 mg / ml of certolizumab; 10 mg / ml to 100 mg / m of etanercept; 2.5 mg / ml to 200 mg / ml of risperidone; 1 mg / ml to 200 mg / ml of olanzapine pamoate; 100 mg / m to 250 mg / ml of aripiprazole; 250 IU / ml to 1000 IU / ml human chorionic gonadotropin; 300 IU / ml to 1000 IU / ml of follicle-stimulating hormone; 10 mg / ml to 50 mg / ml of a gonadotropin-releasing hormone analog; 10 mg / ml to 100 mg / ml of azacitidine; 1 mg / ml to 50 mg / ml of metreleptin; Various antivenoms ranging from 0.001mg / ml to 1mg / ml, including Apis mellifera, Wasp venom protein, Wasp snow fungus, Vespa chlorella, Polistes species, Wasp venom protein, Vespa chlorella venom protein; various antibiotics in various doses based on the patient's weight and treatment; 0.1mg / ml to 1mg / ml of chlorpromazine; 100mg / ml to 500mg / ml of pembroyl chloride; 5 mg / ml to 10 mg / ml of ziprasidone mesylate; 1 mg / ml to 50 mg / ml of homoharringtonine; 10 mg / ml to 200 mg / ml of caneluzumab; 50 mg / ml to 500 mg / ml of deferoxamine mesylate; 5mg / ml to 100mg / ml of methotrexate sodium; 0.1 mg / ml to 1 mg / ml of corticotropin; 0.1 mg / ml to 1 mg / ml of peginterferon alfa-2b; 0.1 mg / ml to 4 mg / ml of bortezomib; 25 mg / ml to 300 mg / ml of canakinumab; 30mg / ml to 200mg / ml of rilonacept; 1 mg / ml to 25 mg / ml of telluride.

18. The injection device of claim 16, wherein: The active agent is corticosterone or a corticosterone derivative thereof.

19. An injection device according to claim 18, wherein The corticosterone derivative is hydrocortisone sodium succinate, wherein the content of the derivative as an active agent in a unit volume of a solution of a pharmaceutically acceptable carrier is 50 mg / mL to 250 mg / mL by weight, or 25 mg / mL to 150 mg / mL.

20. The injection device of claim 1, wherein: The first compartment or the second compartment contains a pharmaceutically acceptable carrier in a fluid form having a viscosity of 1 cP to 150 cP.

21. A method of manufacturing an injection device according to any one of claims 1 to 20, comprising placing one or more active agents in a sterile or sterile environment.

22. The method of claim 21, further comprising weighing the one or more active agents.

23. The method of claim 21 or 22, further comprising attaching the first compartment and the second compartment.

24. The method according to claim 21, wherein: The first compartment and the second compartment are attached to each other in a sterile environment by compression or threading into a fastener.

25. An injection device comprising: (a) a first compartment, a second compartment, and a third compartment, each of the first compartment, the second compartment, and the third compartment defining a first cavity, a second cavity, and a third cavity, respectively, and the second compartment being adjacently positioned between the first compartment and the third compartment; (b) a needle guard assembly operatively active in and at least partially contained within the third chamber and comprising a needle operatively attached to a spring that compresses upon filling of the third compartment; as well as (c) an insertion rod positioned in the first compartment, the insertion rod operably connected to a movable element, wherein the insertion rod and the movable element are movable along the longitudinal axes of the first compartment, the second compartment, and the third compartment; wherein the first compartment and the second compartment are in fluid communication via a first opening; wherein the second compartment and the third compartment are in fluid communication via a second opening; the first opening is covered by a first seal and the second opening is covered by a second seal; displacement of the movable element provides fluid communication between the second compartment and the third compartment; wherein the third compartment contains a needle assembly; the needle assembly includes a spring and a needle operably connected to the spring; wherein the needle includes a first fluid opening located within the third chamber and an opposing second fluid opening located away from the first chamber and the second chamber; and (i) wherein the first compartment contains one or more active agents and the second compartment contains one or more pharmaceutically acceptable carriers; or (ii) wherein the first compartment contains one or more pharmaceutically acceptable carriers and the second compartment contains one or more active agents.

26. An injection device according to claim 25, wherein The cylindrical peripheries of the first, second and third compartments are aligned along the longitudinal axes of the three chambers.

27. An injection device according to claim 25 or 26, wherein The needle guard assembly includes a spring, a needle sheath, and an interior surface containing one or more guide elements operably connected to the needle, the guide elements being capable of guiding movement of the needle through the needle sheath after movement of the spring.

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