Prefilled injection device for delivering multiple medications

Abstract

A prefilled injection device comprising a container body configured to deliver two or more medication fluids, wherein the container body has one or more bypass channel extending from the external surface of the open front end toward to the rear end of the container body for a predetermined length along the container body; two or more piston plungers forming substantially fluid-tight seals with the internal surface of the container body, except the portion of the container body with the bypass channel; and a front cap disposed at the open front end of the container body, wherein the front cap has a liquid communication channel configured to be in fluid communication with the bypass channel on the container body. The prefilled injection device is used to deliver formulations treating different diseases as well as containing different therapeutic modalities, different therapeutic molecules and different fluid media.

Description

PREFILLED INJECTION DEVICE FOR DELIVERING MULTIPLE MEDICATIONSBACKGROUND OF THE INVENTION

[0001] The present invention relates to a prefilled injection device for delivering of two or more medications in fluid dosage forms, such as solution dosage form, suspension dosage form, emulation dosage form or other forms in fluid state.

[0002] Currently, injectable drugs account for more than half of all therapeutic drug candidates in pharmaceutical development pipelines. As the injectable drugs become more and more popular, medication delivery devices are expected to be widely used by patients and health care professionals. Prefilled injection devices, for example, prefilled syringe or prefilled cartridge, are current forms commonly used for injectable drugs. For healthcare industry, the advantages of prefilled injection devices are easy-to-use by patients, lower contamination risk, minimized drug waste and increased product life span.

[0003] The common prefilled syringe or prefilled cartridge generally have a hollow tubular container body closed at one end and a piston plunger inserted through the opposite end so as to form a single closed chamber into which a dose of a medication fluid is filled so that the user will not need to draw the medication fluid into the syringe or cartridge. Examples of prefilled syringes and the related manufacturing and packaging processes can be found in U.S. Pat. No. 6,189,292; U.S. Pat. No. 7,428,807; U.S. Pat. No. 7,431 ,157 and U.S. Pat. No. 8,196,741 . In use, the medical solution can be injected by moving the piston plunger to the other end. Thus, most of prefilled syringe or prefilled cartridge based injection devices are very easy to deliver single medication and can be sanitarily maintained before use, but, cannot be used to deliver two or more medications.

[0004] Although not as common as the single chamber prefilled syringe or prefilled cartridge, prefilled syringes or prefilled cartridges of the dual-chamber type are well-known in the medical field. Such prefilled containers are primarily intended to be used when the liquid pharmaceutical composition to be injected is not stable forany extended period of time. In such cases, the composition to be injected is provided as two separate components, one solid component comprising the active pharmaceutical component in a dry state, and one liquid component comprising a solvent or dispersing agent for the solid component. These two components are enclosed in an injection container body of the dual-chamber type. The solid component is usually enclosed in a chamber, while the liquid component is enclosed in another chamber. For example, dual chamber prefilled injection devices with container bodies as described above are known from prior art: DE 37 36 343, DE 38 16 961 , EP 0 599 649 A1 , EP 0 328 699, DE 42 04 309 A1 , US 8,002,734 and are described in an article by H. Vetter (Lyophilization of Substances in Prefillable Syringes) in: Die Pharmazeutische Industrie, Vol. 46 (1984), No. 10, pp. 1045-1049.

[0005] Existing container bodies of the dual-chamber type are generally shaped as a barrel with a substantially rotationally symmetric cylindrical internal surface, which is divided into two chambers by means of a piston plunger placed in the middle of the container body. When the injectable medication is to be prepared, pressure is applied on one of the pistons to move it forward. This pressure is transmitted through the essentially incompressible liquid to the piston plunger in the middle of the container body, such that this piston plunger is also moved forward because there is a large amount of compressible air in the chamber storing solid component. By this forward movement, the piston plunger activates a bypass channel that is also disposed in the middle of the container bodies, such that the liquid component in one of the two chambers can flow over into another chamber by the action of the forward movement of the piston plunger, to be mixed with the solid component of the injectable medication. However, this mechanism will not function well if the medications in both chambers are incompressible liquid.

[0006] In summary, the prefilled syringe or prefilled cartridge devices discussed above (either single chamber or dual chamber types) are not ideally designed for delivering more than one medications in liquid dosage form. On the other hand, it’s becoming increasingly apparent that treatments for complex diseases such as cancer, autoimmune diseases, and neurodegenerative diseases are unlikely to be controlled by a single molecule in the pathological pathway. Drug developers are turning to new ways to exploit more than one drug target at a time. Perhaps themost well-established approach to exploiting multiple targets is the use of combination therapies - where treatments are expected to act synergistically, providing an additive response over either drug alone. Nowadays, thousands ongoing clinical trials are registered in the US alone investigating combination therapies for complex diseases, and there are even more preclinical-research articles on drug combinations. For example, combination therapy, a treatment that combines two or more therapeutic agents, has become a cornerstone of cancer therapy. The combination of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. Moreover, for aging population, medical treatment has become more complex because of multiple comorbidities. In the US, large amount of medical spending is devoted to patients with 4 or more chronic conditions, with costs increasing exponentially as the number of chronic conditions increases. It isn't uncommon that a patient has multiple chronic diseases at the same time, such as hypertension, diabetes mellitus, dyslipidemia, peripheral arterial diseases, and chronic osteomyelitis. It will be very beneficial to these patient if there is a device capable of delivering multiple injectable medications through one needle based injection or intravenous infusion, therefore, reducing total number of needle injections, vascular intervention or targeted tissue injection, for example, intratumoral injection.

[0007] Therefore, in the medical field, what is needed is a new design for delivering more than one medications in liquid / liquid combination.SUMMARY OF THE INVENTION

[0008] In one form thereof, the present invention provides a prefilled medication delivery device having a container body with a cylindrical internal surface, for delivering of two or more liquid medication fluids. This prefilled medication device include: a container body with an open front end and a rear end, the open front end is meant to refer to the end of the medication delivery device where medication is delivered into the patient tissue, whereas the rear end is meant to refer to the endopposite to the front end along the longitudinal axis of the device body, characterized in that the container body is provided with one or more bypass channels extending from the external surface of the open front end toward to the rear end of the container body for a predetermined length along the container body; two or more piston plungers that fit into the container body; a front cap with a delivery outlet, for covering the open front end of the container body, characterized in that the front cap provides a liquid communication channel or passage between the bypass channel on the container body and the delivery outlet on the front cap. The liquid medications herein might be solution, suspension, emulation or other forms in incompressible fluid state.

[0009] According to the prefilled injection device presented here, a process of injection will be explained briefly. By pushing a plunger rod of the injection device, the piston plungers are forced to move toward to the front end by sliding so that a first medical fluid in the front chamber is pushed out through the delivery outlet on the front cap. All the first medical solution in the front chamber is pushed out when the front piston is brought into contact with the front cap. Then, the rear chamber is communicated with the delivery outlet through the bypass channel and the liquid communication channel on the front cap. By further pushing the plunger rod, the second fluid in the rear chamber is pushed out through the bypass channel, liquid communication channel and the injection port.

[0010] Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

[0011] One advantage of the present invention is that the bypass channel is located at the open front end of the container body and extended from the external surface toward to the rear end of the container body. Therefore, the present invention can be applied to deliver two liquid medications, which are incompressible. In contrast, the other dual chamber containers have the bypass channel located inthe middle of the container barrel. Because the liquid is incompressible, the design with the bypass channel in the middle will not work well for delivering two liquid formulations sequentially.

[0012] Another advantage of the present invention is that the device is well suitable to be used in situations where two separate drugs are unsuitable for coformulation or have reduced stability / shelf life when mixed together.

[0013] Another advantage of the present invention is Increased convenience for the user, with no need for multiple needles or transfer systems for multiple medications.

[0014] Still another advantage of the present invention is that the front end of the container body is open. In contrast to the dual chamber syringe or cartridge with tapered off or closed front end, this open front end design makes manufacturing of the container body much simpler. In the case that the container body is made of plastic material by injection molding process, the container body can be readily stripped off from the molding core. In the case that the container body is made of glass material, a forming tool can be placed at the front end of the container body to form the bypass channel and be easily removed afterward. Moreover, because the the front end of the container body is open, the container body can be filled with medication fluid from the front end rather than from rear end for the container body in the prior arts.BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The figures are schematic and simplied for clarity, and they just show details, which are essential to the understanding of the invention, while other details are left out. Throughout, the same reference numerals are used for identical or corresponding parts. Some embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings in which:

[0016] FIG. 1 is a perspective view of an exemplary prefilled injection device according to the invention;

[0017] FIG. 2 is an exploded view of the exemplary prefilled injection device according to the invention;

[0018] FIGS. 3-5 show cross-sectional views of the exemplary prefilled injection device at different operational steps, according to the invention;

[0019] FIG. 6 is a perspective view of a front cap of the exemplary prefilled injection device according to the invention;

[0020] FIG. 7 is a perspective view of a piston plunger of the exemplary prefilled injection device according to the invention;

[0021] FIG. 8 is a perspective view of a container body of the exemplary prefilled injection device according to the invention;

[0022] FIG. 9 is a perspective view of the first alternative prefilled injection device according to the invention;

[0023] FIG. 10 is an exploded view of the first alternative prefilled injection device according to the invention;

[0024] FIGS. 11-14 show cross-sectional views of the first alternative prefilled injection device at different operational steps, according to the invention;

[0025] FIG. 15 is a perspective view of a front cap of the first alternative prefilled injection device according to the invention;

[0026] FIG. 16 is a perspective view of a container body of the first alternative prefilled injection device according to the invention;

[0027] FIG. 17 is a perspective view of the second alternative prefilled injection device according to the invention;

[0028] FIG. 18 is an exploded view of the second alternative prefilled injection device according to the invention;

[0029] FIGS. 19-20 show cross-sectional views of the second alternative prefilled injection device at different operational steps, according to the invention;

[0030] FIG. 21 is a perspective view of the third alternative prefilled injection device according to the invention;

[0031] FIG. 22 is a cross-sectional view of the third alternative prefilled injection device according to the invention;

[0032] FIGS. 23-25 are perspective views of the manufacturing processes for the container body in the third alternative prefilled injection device according to the invention;

[0033] FIG. 26 shows a packaging design for filling medication fluid into the container body of the third alternative prefilled injection device according to the invention;

[0034] FIG. 27 is a perspective view of the fourth alternative prefilled injection device according to the invention;

[0035] FIG. 28 is a cross-sectional view of the fourth alternative prefilled injection device according to the invention;

[0036] FIG. 29 is a perspective view of the fifth alternative prefilled injection device according to the invention;

[0037] FIG. 30 is a cross-sectional view of the fifth alternative prefilled injection device according to the invention;

[0038] FIG. 31 is an exploded view of the fifth alternative prefilled injection device according to the invention;

[0039] FIG. 32 is a perspective view of the fifth alternative prefilled injection device assembled with a double-ended needle, according to the invention.DETAILED DESCRIPTION OF THE INVENTION

[0040] The present invention will become more fully understood from the detailed description given hereinbelow and the accompanying drawings which aregiven by way of illustration only, and thus, are not limitive of the present invention, and wherein:

[0041] The apparatus and methods presented herein can be used for delivering any of a variety suitable therapeutic agents or substances, such as medication, into a patient. Initially it may be convenient to define that, the term "front end" is meant to refer to the end of the prefilled injection device where medication is delivered into the patient, whereas the term “rear end” is meant to refer to the end opposite to the "front end" along the longitudinal axis of the prefilled injection device. The words "upper", "lower", “right” and “left” designate directions in the drawings to which reference is made. The words “internal” and “external” refer to inside and outside, respectively. The words “inward” and “outward” refer to directions toward and away from, respectively.

[0042] FIGS. 1 -8 illustrate the construction and function mechanism of an exemplary prefilled injection device 10 according to the invention. With reference to FIGS. 1 and 2, in this prefilled injection device 10, a prefilled syringe barrel 101 , as the container body, can be made of either glass or plastic materials. The syringe barrel 101 may be a substantially rotationally symmetric cylindrical shell with internal surface, or may include a substantially rotationally symmetric cylindrical internal surface with a non circular external shape. There is a bypass channel 101a extending from the external surface of the open front end toward to the rear end of the container body for a predetermined length along the longitudinal axis of the syringe barrel 101 . A front cap 102 is disposed at the front end of the syringe barrel 101 . The front cap 102 is in fluid communication with the medication fluid contents of the syringe barrel 101 and has a design with a luer lock injection port 102a at its front end. With reference to FIG. 2, an elastomeric seal member 105 is used to keep the fluid-tight seal between the syringe barrel 101 and the front cap 102. In the case that the syringe barrel 101 is assembled with the front cap 102 through bonding, for example, gluing or ultrasound welding, there is no need to use the elastomeric seal member 105. A tip cap 103 is disposed at the front end of the front cap 102 to seal the medication in the prefilled injection device 10. Piston plungers 106 and 107 may be made from rubber, silicone or other suitable resiliently deformable materials. The external shape of piston plungers 106 and 107 may be substantially rotationallysymmetric about an axis through the piston plungers. The piston plungers 106 and 107 may include one or more circumferential ribs around an external surface of the piston. The piston plungers 106 and 107 and ribs are dimensioned such that the piston plungers form substantially fluid-tight seals with the internal surface of the syringe barrel 101 , except the portion of the syringe barrel with the bypass channel 101 a. The front surface of the piston plungers 106 and 107 may be any suitable shape, for example, substantially planar. The bypass channel 101 a is extended in the longitudinal direction thereof and have a length longer than the thickness of the piston plunger 106, but shorter than the sum of the thickness of the piston plungers 106 and 107 combined to avoid blockage of the bypass channel 101 a by the piston plunger 106 as well as to keep the sealing condition between the internal surface of the syringe barrel 101 and the piston plunger 107.

[0043] FIGS. 3-5 show cross-sectional views of the prefilled injection device 10 at different operational steps, according to the invention. With reference to FIG. 3, medication fluid A in a lower chamber and medication fluid B in an upper chamber of the prefilled syringe barrel 101 are sealed and separated by the piston plungers 106 and 107. The medication fluid A and B may be in solution dosage form, suspension dosage form or emulation dosage form. According to certain embodiments, the medication fluid A and B may be formulations to treat different diseases, for example, medication fluid A contains therapeutic drug treating diabetes and medication fluid B contains therapeutic drug treating cardiovascular disease. According to certain embodiments, the medication fluid A and B may be the formulations containing different therapeutic modalities, for example, medication fluid A contains therapeutic protein drug and medication fluid B contains therapeutic small molecule drug; or, medication fluid A contains gene therapy drug and medication fluid B contains therapeutic small molecule drug. According to certain embodiments, the medication fluid A and B may be the formulations containing different drug substances within the same therapeutic modality, for example, medication fluid A contains PD-1 inhibitor monoclonal antibody and medication fluid B contains CTLA-4 inhibitor monoclonal antibody; or, medication fluid A contains CD4+ T cells and medication fluid B contains CD8+ T cells. According to certain embodiments, the medication fluid A and B may be formulated in different fluid media, for example, the medication fluid A maybe the formulated in aqueous fluid media and medication fluid B may be formulated in non-aqueous fluid media, such as sesame oil. Other differences in fluid media may include but not limit to, pH value, buffer type, concentration, excipient content, viscosity, etc. For example, the medication fluid A has pH value 4 and the medication fluid B has pH value 8. Or, the medication fluid A contains sodium acetate buffer and the medication fluid B contains phosphate buffer.

[0044] Before injection, the tip cap 103 is removed, shown in FIG. 4. Then, a luer lock needle or luer lock connector (not shown) are connected for injection or infusion. During injection or infusion, the plunger rod 104 is pushed downward to deliver medications. The piston plunger 107 is pushed downward accordingly. Because the medication fluid B is incompressible, the piston plunger 106 is also forced to move downward so that the medication fluid A in the lower chamber is first delivered out of the syringe barrel 101 through the injection port 102a on the front cap 102. The dash line in FIG. 4 shows the flow path of the medication fluid A. With reference to FIG. 5, after the medication fluid A is delivered out of the syringe barrel 101 , the piston plunger 106 is brought into contact with the front cap 102. At this moment, the medication fluid B in the upper chamber is communicated with the injection port 102a, through the bypass channel 101 a and the liquid communication channel 102b. Thus, the medication fluid B in the upper chamber is pushed out through the bypass channel 101 a, the liquid communication channel 102b and the injection port 102a. The dash line in FIG. 5 shows the flow path of the medication fluid B.

[0045] FIG. 6 shows the perspective view of the front cap 102. Preferably, the front cap 202 is made of plastic material. The retention edge 102c is designed for assembling the front cap 102 with the syringe barrel 101 . The flat portion 102d is designed to align the front cap 102 and the syringe barrel 101 . The liquid communication channel 102b is connected with the injection port 102a. FIG. 6 shows the perspective view of the piston plunger 106. The piston plunger 106 has a substantially planar front face 106a. When the piston plunger 106 is in contact with the front cap 102, the substantially planar front fact 106a will not block the liquid communication channel 102b. FIG. 8 shows the perspective view of the container body 101 . An outward flange 101 b is designed to be assembled with the retentionedge 102c on the front cap 102. The flat portion 101 ba on outward flange 101 b of the syringe barrel 101 is designed to form the orientation alignment with the flat portion 102c on the front cap 102 so that the bypass channel 101a will be aligned and in fluid communication with the liquid communication channel 102b. The finger flange 101d on the syringe barrel 101 is designed for easy injection.

[0046] FIGS. 9-16 illustrate the construction and function mechanism of the first alternative prefilled injection device 20 according to the invention. With reference to FIGS. 9 and 10, in this prefilled injection device 20, a prefilled syringe barrel 201 , as the container body, can be made of either glass or plastic materials. The syringe barrel 201 may be a substantially rotationally symmetric cylindrical shell with internal surface, or may include a substantially rotationally symmetric cylindrical internal surface with a non circular external shape. There is a bypass channel 201a extending from the external surface of the open front end toward to the rear end of the container body for a predetermined length along the longitudinal axis of the syringe barrel 201 . A front cap 202 is disposed at the front end of the syringe barrel 201 . The front cap 202 is in fluid communication with the medication fluid contents of the syringe barrel 201 and has a design with a luer lock injection port 202a at its front end. An elastomeric seal member 205 is used to keep the fluid-tight seal between the syringe barrel 201 and the front cap 202. In the case that the syringe barrel 201 is assembled with the front cap 202 through bonding, for example, gluing or ultrasound welding, there is no need to use the elastomeric seal member 205. The tip cap 103 is disposed at the front end of the front cap 202 to seal the medication in the prefilled injection device 20.

[0047] FIGS. 11-14 show cross-sectional views of the prefilled injection device 20 at different operational steps, according to the invention. With reference to FIG.11 , medication fluid A in a lower chamber, the medication fluid B in a middle chamber and medication fluid C in an upper chamber of the prefilled syringe barrel 201 are sealed and separated by piston plungers 206, 207 and 208. The medication fluid A, B and C may be in solution dosage form, suspension dosage form or emulation dosage form. The piston plungers 206, 207 and 208 may be made from rubber, silicone or other suitable resiliently deformable materials. The external shape of the piston plungers 206, 207 and 208 may be substantially rotationally symmetricabout an axis through the piston plungers. The piston plungers 206, 207 and 208 may include one or more circumferential ribs around an external surface of the piston plungers. The piston plungers 206, 207 and 208 as well as ribs are dimensioned such that the piston plungers form substantially fluid-tight seals with an internal surface of the syringe barrel 201 , except the portion of the syringe barrel with the bypass channel 201 a. The front surface of the piston plungers 206, 207 and 208 may be any suitable shape, for example, substantially planar. The bypass channel is extended in the longitudinal direction thereof and have a length longer than the sum of the thickness of the piston plunger 206 and 207 combined, but shorter than the sum of the thickness of the piston plungers 206, 207 and 208 combined to avoid blockage of the bypass channel 201a by the piston plunger 206 and 207 as well as to keep the sealing condition between the internal surface of the syringe barrel 201 and the piston plunger 208. Before injection, the tip cap 103 is removed, shown in FIG. 12. Then, a luer lock needle or luer lock connector (not shown) are connected for injection or infusion. During injection or infusion, the plunger rod 104 is pushed downward to deliver medications. The piston plunger 208 is pushed downward accordingly. Because the medication fluid B and C are incompressible, the piston plunger 206 and 207 is also forced to move downward so that the medication fluid A in the lower chamber is first delivered out of the syringe barrel 201 through the injection port 202a on the front cap 202. After the medication fluid A is delivered out of the syringe barrel 201 , the piston plunger 206 is brought into contact with the front cap 202. At this moment, the medication fluid B in the middle chamber is communicated with the injection port 202a, through the bypass channel 201 a and the liquid communication channels 202b. Thus, the medication fluid B in the middle chamber is pushed out through the bypass 201a, the liquid communication channels 202b and the injection port 202a. With further pushing down the plunger rod 104, the medication fluid B is delivered. The dash line in FIG. 12 shows the flow path of the medication fluid B. With reference to FIG. 13, after the medication fluid B is delivered out of the syringe barrel 201 , the piston plunger 207 is brought downward into contact with the piston plunger 206. At this moment, the medication fluid C in the upper chamber is communicated with the injection port 202a, through the bypass channel 201a and the liquid communication channels 202b. Thus, the medication fluid C in the upper chamber is pushed out through the bypass 201a, the liquidcommunication channels 202b and the injection port 202a. With even further pushing down the plunger rod 104, the medication fluid C is delivered. The dash line in FIG. 13 shows the flow path of the medication fluid C. FIG. 14 shows the completion of the delivery of the medication fluid A, B and C. At the completion of the medication delivery, all the three piston plungers, 206, 207 and 208 have reached to the most downward position and stack together to each other.

[0048] FIG. 15 shows the perspective view of the front cap 202. Preferably, the front cap 202 is made of plastic material. The retention edge 202c is designed for assembling the front cap 202 with the syringe barrel 201 . A plurality of the communication channels 202b are radially distributed around the axis of the front cap 202. All the liquid communication channels 202b are connected with and in fluid communication with the injection port 202a. Therefore, the orientation alignment between the front cap 202 and the syringe barrel 201 is not required. FIG. 16 shows the perspective view of the container body 201 . An outward flange 201 b is designed to be assembled with the retention edge 202c on the front cap 202. The bypass channel 201a will be aligned and in fluid communication with one or more of the liquid communication channels 202b in the assembly. The finger flange 201c on the syringe barrel 201 is designed for easy injection.

[0049] FIGS. 17-20 illustrate the construction and function mechanism of the second alternative prefilled injection device 30 according to the invention. With reference to FIGS. 17 and 18, in this prefilled injection device 30, a prefilled syringe barrel 301 , as the container body, can be made of either glass or plastic materials. The syringe barrel 301 may be a substantially rotationally symmetric cylindrical shell with internal surface, or may include a substantially rotationally symmetric cylindrical internal surface with a non circular external shape. There is a bypass channel 301 a extending from the external surface of the open front end toward to the rear end of the container body for a predetermined length along the longitudinal axis of the syringe barrel 301 . A front cap 302 is disposed at the front end of the syringe barrel 301 . The front cap 302 is in fluid communication with the medication fluid contents of the syringe barrel 301 and has a design with liquid communication channels 302a.

[0050] FIGS. 19 and 20 show cross-sectional views of the prefilled injection device 30 at different operational steps, according to the invention. With reference to FIG. 19, medication fluid A in the lower chamber and medication fluid B in the upper chamber of the prefilled syringe barrel 301 are sealed and separated by the piston plungers 306 and 307. An elastomeric seal member 305 is used to keep the fluid- tight seal between the syringe barrel 301 and the front cap 302. In the case that the syringe barrel 301 is assembled with the front cap 302 through bonding, for example, gluing or ultrasound welding, there is no need to use the elastomeric seal member 305. An injection needle 308 is staked at the front end of the front cap 302. Before injection, a needle shield 303 is used to seal the steel needle 308 and the medication fluids in the prefilled injection device 30, shown in FIG. 19. Right before injection, the needle shield 303 is removed. During injection, the plunger rod 104 is pushed downward to deliver medications. The piston plunger 307 is pushed downward accordingly. Because the medication fluid B is incompressible, the piston plunger 306 is also forced to move downward so that the medication fluid A in the lower chamber is first delivered out of the syringe barrel 301 through the injection needle 308 on the front cap 302. With reference to FIG. 20, after the medication fluid A is delivered out of the syringe barrel 301 , the piston plunger 306 is brought into contact with the front cap 302. At this moment, the medication fluid B in the upper chamber is communicated with the injection needle 308, through the bypass channel 301 a and the liquid communication channels 302a. Thus, the medication fluid B in the upper chamber is pushed out through the bypass channel 301 a, the liquid communication channels 302a and the injection needle 308. The dash line in FIG. 20 shows the flow path of the medication fluid B. The design of the liquid communication channels 302a are substantially the same as the design of the liquid communication channels 202a.

[0051] FIGS. 21 and 22 illustrate the construction and function mechanism of the third alternative prefilled injection device 40 according to the invention. The prefilled injection device 40 may be used as a sub-assembly in other injection devices, such as the injection devices disclosed in U.S. Pat. No. 10,603,444. With reference to FIG. 21 , in this prefilled injection device 40, a prefilled cartridge 401 , as the container body, can be made of either glass or plastic materials. The prefilledcartridge 401 may be a substantially rotationally symmetric cylindrical shell with internal surface, or may include a substantially rotationally symmetric cylindrical internal surface with a non circular external shape. There is a bypass channel 401 a extending from the external surface of the open front end toward to the rear end of the container body for a predetermined length along the longitudinal axis of the cartridge 401 . The front cap 202 is disposed at the front end of the cartridge 401 . An outward flange 401 b is designed to be assembled with the front cap 202. The front cap 202 is in fluid communication with the medication fluid contents of the cartridge 401 and has a design with liquid communication channels 202a. The elastomeric seal member 205 is used to keep the fluid-tight seal between the cartridge 401 and the front cap 202. In the case that the cartridge 401 is assembled with the front cap 202 through bonding, for example, gluing or ultrasound welding, there is no need to use the elastomeric seal member 205. The tip cap 103 is disposed at the front end of the front cap 202 to seal the medication in the prefilled injection device 40.Medication fluid A in the lower chamber and medication fluid B in the upper chamber of the prefilled cartridge 401 are sealed and separated by the piston plungers 406 and 407.

[0052] FIGS. 23 and 24 illustrate the injection molding manufacturing process for the cartridge 401 . In this exemplary manufacturing process, the prefilled cartridge is made of plastic material and manufactured through injection molding process. In contrast to the container body with closed front end and disclosed in the prior arts, the cartridge 401 has an open front end. The open front end design makes the injection molding manufacturing process much easier for the cartridge 401 . With reference to FIG. 23, the cartridge 401 is formed by a flowing molten plastic material around a molding core 410. There is a projection 410a on the molding core 410 to form the bypass channel 401 a on the cartridge 401 . With reference to FIG. 24, after the cartridge 401 is formed, the molding core 410 with the project 410a may be directly and readily separated from the cartridge 401 , along the longitudinal axis of the cartridge 401 and along the direction indicated by arrowed dash line in FIG. 24. There is no undercut situation in manufacturing the cartridge 401 made of plastic material. With regard to the container body made of plastic material with closed front end and disclosed in the prior arts, the molding core along the feature to form thebypass channel has to be removed from the open rear end, this creates an undercut situation for manufacturing process and makes the manufacturing process much more difficult. In the case that the cartridge 401 is made of glass materials, it is also much easier to form the bypass channel 401 a at the open front end of the cartridge 401 , based on the glass forming / converting manufacturing process. FIG. 25 shows an exemplary solid glass forming tool 420 utilized to form the bypass channel 401 a when the cartridge 401 is made of glass. On the glass forming tool 420, there is a projection feature 420a. When the project feature 420a is put in contact with the cartridge 401 at its front end, the bypass channel 401 a can be formed while the glass is soften by heat. After the bypass channel 401 a is formed, the glass forming tool 420 with the project feature 420a may be directly and readily separated from the cartridge 401 , along the longitudinal axis of the cartridge 401 . With regard to the container body made of glass material with closed front end and disclosed in the prior arts, pressured gas may be used to form the bypass channel. In contrast, there is no need to use pressured gas to manufacture the cartridge 401 made of glass.

[0053] FIG. 26 shows a packaging design for filling medication fluid into the cartridge 401 . This packaging design is similar to the standard prefilled syringe packaging design, i.e., nest-tub package, existed in prior art. This demonstrates that the device may be filled and assembled using existing filling, assembly and packaging processes for the standard prefilled syringe. In FIG. 26, a nest 430 for the cartridge 401 is provided being a panel with a plurality of spaced-apart openings 430a and container body holding features 430aa and 430ab for holding the cartridge 401 in place. In the embodiment illustrated, openings 430 and holding features 430aa / 430ab are arranged in a series of rows and columns and are uniformly spaced apart. The holding features 430aa and 430ab are further optimized, compared with the standard prefilled syringe packaging nest. The feature 430aa supports the outward flange 401 b on the cartridge 401 , and the feature 430ab is designed to fit with the bypass channel 401a on the cartridge 401 . Here, the filling process happens at the front end of the cartridge 401 . As an example, the medication fluid A is filled through a filling needle 450 into the catridge 401 .

[0054] FIGS. 27 and 28 illustrate the construction and function mechanism of the fourth alternative prefilled injection device 50 according to the invention. Theprefilled injection device 50 may be used as a sub-assembly in other injection devices, such as the injection devices disclosed in U.S. Pat. No. 10,603,444. In this prefilled injection device 50, a prefilled cartridge 501 , as the container body, can be made of either glass or plastic materials. The prefilled cartridge 501 may be a substantially rotationally symmetric cylindrical shell with internal surface, or may include a substantially rotationally symmetric cylindrical internal surface with a non circular external shape. Instead of one bypass channel 401a for the prefilled cartridge 401 , there are two bypass channels 501 a extending from the external surface of the open front end toward to the rear end of the container body for a predetermined length along the longitudinal axis of the cartridge 501 . The front cap 202 is disposed at the front end of the cartridge 501 . The front cap 202 is in fluid communication with the medication fluid contents of the cartridge 501 through the two bypass channels 501 a, and has the design with liquid communication channels 202b.

[0055] FIGS. 29-32 illustrate the construction and function mechanism of the fifth alternative prefilled injection device 60 according to the invention. The prefilled injection device 60 may be used as a sub-assembly in other injection devices, such as the drug delivery devices disclosed in U.S. Pat. No. 11 ,040,137. In this prefilled injection device 60, the prefilled cartridge 401 is used as the container body. A front cap 602 is disposed at the front end of the cartridge 401 . The front cap 602 is in fluid communication with the medication fluid contents of the cartridge 401 through the bypass channels 401 a, and has the design with liquid communication channels 602b. During injection or infusion, the medication fluid will flow out of the prefilled cartridge 401 through the injection port 602a on the front cap 602. In the cross-sectional view and the exploded view of the prefilled injection device 60 shown in FIGS. 30 and 31 , at the front end of the front cap 602, there is a pierceable septum closure 604, and a crimp seal 603 for firmly sealing the septum closure 604 with the front cap 602. FIG. 32 shows that during injection, the prefilled injection device may be assembled with a double-ended steel needle 610. One end of the double-ended steel needle can pierce through the septum closure 604 to establish the fluid pathway. The other end of the double-ended steel needle can penetrate skin at injection site for delivering the medication fluids to targeted tissue.

[0056] All the features in the above embodiments and design concepts herein can be inter-changed and combined to generate new device designs. Those of skill in the art will understand that modifications (additions and / or removals) of various components of the apparatuses, methods and / or systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

Claims

CLAIMS1 . A prefilled injection device comprising: a container body configured to provide at least two medication fluids, wherein the container body has an internal surface, an external surface, a rear end, an open front end, and a bypass channel extending from the external surface of the open front end toward to the rear end of the container body for a predetermined length along the container body; at least two piston plungers disposed inside the container body, and a front cap disposed at the open front end of the container body, wherein the front cap has a liquid communication channel configured to be in fluid communication with the bypass channel on the container body.

2. The prefilled injection device as in claim 1 , wherein the medication fluid provided by the container body is in solution dosage form, suspension dosage form or emulation dosage form.

3. The prefilled injection device as in claim 1 , wherein the medication fluids provided by the container body are formulations to treat different diseases.

4. The prefilled injection device as in claim 1 , wherein the medication fluids provided by the container body are formulations containing different therapeutic modalities.

5. The prefilled injection device as in claim 1 , wherein the medication fluids provided by the container body are formulations containing different drug substances within the same therapeutic modality.

6. The prefilled injection device as in claim 1 , wherein the medication fluids provided by the container body are the same drug substance formulated in different fluid media.

7. The prefilled injection device as in claim 1 , wherein the container body having an outward flange at the open front end, and the container body is assembled with the front cap through the outward flange at the open front end of the container body.

8. The prefilled injection device as in claim 1 , wherein the container body forms orientation alignment with the front cap so that the liquid communication groove on the front cap is in fluid communication with the bypass channel on the container body.

9. The prefilled injection device as in claim 1 , wherein the container body is made of plastic material and manufactured without undercut situation.

10. The prefilled injection device as in claim 1 , wherein the container body is made of glass material and manufactured without using pressured gas.1 1 . The prefilled injection device as in claim 1 further comprising a seal member placed between the container body and the front cap.

12. The prefilled injection device as in claim 1 , wherein the front cap having a luer lock injection port.

13. The prefilled injection device as in claim 1 , wherein the front cap having a staked injection needle.

14. The prefilled injection device as in claim 1 , wherein the front cap having a pierceable septum closure.

15. A packaging assembly for a prefilled injection device configured to deliver at least two medication fluids, comprising: a container body having an internal surface, a rear end, an open front end with an outward flange, and at least one bypass channel extending from the open front end along the longitudinal axis of the container body; a panel; and a plurality of openings defined in the panel, wherein the panel and the plurality of openings are integrally formed as a unitary structure and each of the openings configured to removeably receive each of the container body; wherein the outward flange at the open front end of the container body prevent the container body from passing through each of the openings defined in the panel.

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