Drug administration device and kit

Abstract

A support for mixing at least two solutions, a drug delivery device and kit. Mixing a low-viscosity solution and a high-viscosity solution was difficult. An objective of the present invention is to provide a support for mixed administration of at least two types of solutions to enhance the radiation or anticancer therapeutic effect on a tumor, wherein the support is capable of simultaneously discharging each solution in a constant proportion from the respective syringes containing each solution.

Description

1 / 14 Medication Administration Device and Technical Field Kit

[0001] The present invention is a support for mixing and administering at least two solutions, in particular a support capable of simultaneously ejecting each solution in a fixed proportion from each syringe containing each solution. PRIOR ART

[0002] Surgery is the most common local treatment method for malignant tumors, and radiotherapy is the second most common treatment method. The number of patients treated with radiotherapy has increased dramatically in recent years due to its applicability in elderly patients and its ability to preserve normal organs and tissues. However, high-energy X-rays and electron beams from linear accelerators, which are commonly used in these radiotherapies, are low linear energy transfer (LET) radiation and have relatively lower biological efficacy. Therefore, linear accelerator radiotherapy for tumors such as malignant melanoma, various types of sarcomas, and pleomorphic glioblastoma is ineffective.Locally advanced cancers that have grown to more than a few centimeters in size are less effective for linear accelerator radiotherapy due to the high number of hypoxic tumor cells and the large amount of antioxidant enzymes they contain, which makes them radioresistant.

[0003] Patent document 1 discloses a technique in which hydrogen peroxide is combined with hyaluronic acid or a salt thereof to effectively exert a Petition 870260022342, dated 11 / 03 / 2026, pages 22 / 23 2 / 14 radiation sensitization effect and an anticancer chemotherapy sensitization effect. Patent document 2 discloses a technique in which hydrogen peroxide is combined with a hydrogel containing a crosslinked gelatin gel prepared from acid gelatin to effectively exert a radiation sensitization effect and an anticancer chemotherapy sensitization effect. Previous artwork Patent Documents Patent document 1: WO2008 / 041514 Patent document 2: WO2014 / 126222 SUMMARY OF THE INVENTION Problem to be Solved by the Invention

[0004] However, the technologies disclosed by patent documents 1 and 2 take a long time to mix hyaluronic acid or hydrogel with hydrogen peroxide solution due to its high viscosity. Furthermore, when hyaluronic acid or hydrogel is mixed with hydrogen peroxide solution in advance, the hydrogen peroxide decomposes. WAYS TO SOLVE THE PROBLEM

[0005] The inventors developed a technique that makes it possible to easily mix low and high viscosity solutions at the time of use and to easily change the ratio of low and high viscosity solutions in the mixture, and then the invention was completed.

[0006] It is an object of the present invention to provide a support for mixing and administering at least two solutions to increase the effectiveness of treatment of Petition 870210106484, dated 11 / 18 / 2021, page 59 / 96 3 / 14 tumors with radiation or anticancer agents, where the support is capable of simultaneously ejecting each solution in a fixed proportion from each syringe containing each solution.

[0007] This support allows the plunger rods of each syringe to be pushed simultaneously, so that each solution can be ejected simultaneously in a fixed proportion from each syringe containing each solution.

[0008] The present invention also provides the support including a housing section for housing the syringes, a connection section for connecting the syringes to the support, an ejection section for ejecting the solution and a flow channel in fluid communication with the ejection section and the connection section.

[0009] Another object of the present invention is to provide a drug administration device, including syringes and the holder.

[0010] The present invention also provides a drug delivery device in which the cross-sectional areas of the filling spaces in each syringe differ from one another.

[0011] The present invention also provides the drug delivery device, including an adapter, wherein each syringe is fitted with a plunger rod and the adapter is connected to the plunger rods.

[0012] The present invention also provides a drug delivery device in which each syringe is pre-filled with a different desired solution.

[0013] The present invention also provides a drug delivery device in which at least Petition 870210106484, dated 11 / 18 / 2021, pp. 60 / 96 4 / 14 One of the syringes is pre-filled with a hydrogen peroxide solution, and the material of one syringe barrel containing the hydrogen peroxide solution is a cycloolefin polymer (COP) or a cycloolefin copolymer (COC).

[0014] Another object of the present invention is to provide a kit including syringes and the holder.

[0015] The present invention also provides a kit in which each syringe is pre-filled with a different desired solution.

[0016] The present invention also provides a kit in which at least one of the syringes is pre-filled with a hydrogen peroxide solution and the material of a syringe barrel containing the hydrogen peroxide solution is a cycloolefin polymer (COP) or a cycloolefin copolymer (COC). BRIEF DESCRIPTION OF THE DRAWING

[0017] FIG. 1 illustrates a drug delivery device 1 according to the present embodiment.

[0018] FIG. 2 shows a graph of the residual rate of hydrogen peroxide remaining in each syringe due to the difference in the material of each syringe barrel in the example. DESCRIPTION OF THE METHODS OF IMPLEMENTATION Definition

[0019] For convenience, certain terms used in the context of this disclosure are collected herein. Unless otherwise defined, all technical and scientific terms used in this document have the same meaning. Petition 870210106484, dated 11 / 18 / 2021, pp. 61 / 96 5 / 14 meaning as commonly understood by a man of the art to which this invention pertains. The singular forms a, e, and e are used in this document to include plural referents, unless the context clearly dictates otherwise.

[0020] Although the numerical ranges and parameters that establish the broad scope of the invention are approximations, the numerical values ​​set forth in the specific examples are described to the greatest extent possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in the respective test measurements. Furthermore, as used in this document, the term approximately generally means within 10%, 5%, 1%, or 0.5% of a given value or range. Alternatively, the term approximately means within an acceptable standard error of the mean when considered by a person of the art.

[0021] To avoid redundancy, the explanation for similar content is not repeated.

[0022] As an embodiment, a support is provided for mixing and administering at least two solutions to increase the effectiveness of tumor treatment with radiation or anticancer agents, wherein the support is capable of simultaneously ejecting each solution in a fixed proportion from each syringe containing each solution.

[0023] As another embodiment, a drug administration device including syringes and the stand is provided. Medication Administration System

[0024] FIG. 1 shows a drug delivery device 1. The device of Petition 870210106484, dated 11 / 18 / 2021, pp. 62 / 96 The drug administration device 1 includes a holder 100, syringes 200 and 300 housed and connected to the holder 100, and an adapter 400 connected to a plunger rod 202 of syringe 200 and a plunger rod 302 of syringe 300. The drug administration device 1 is manually operated but can also be used in conjunction with an appropriate electrical dosing device or mechanical dosing device. In this specification, the holder side 100 of the drug administration device 1 can be described as distal and the adapter side 400 of the drug administration device 1 can be described as proximal. For example, it can be described as the distal end of the plunger rods 202 and 302 being provided with gaskets 203 and 303, respectively. The drug delivery device may be one that mixes at least two solutions (e.g., a solution of hydrogen peroxide and hyaluronic acid). Support

[0025] Support 100 has a hosting section Section 110 is for housing the syringes; connecting sections 120 and 130 are for connecting syringes 200 and 300 to the holder 100; an ejection section 140 is for ejecting the solution; and a flow channel 150 is in fluid communication with connecting sections 120 and 130 and the ejection section 140. Connecting section 120 is in fluid communication with the flow channel 150. Connecting section 130 is in fluid communication with the flow channel 150. Ejection section 140 is in fluid communication with the flow channel 150. Therefore, connecting section 120, connecting section 130, and ejection section 140 are in fluid communication with each other through the flow channel 150. The channel of Petition 870210106484, dated 11 / 18 / 2021, pp. 63 / 96 7 / 14 Flow 150 can be a T-shaped flow channel or a Y-shaped flow channel. When flow channel 150 is a T-shaped channel, the flow direction of the solution from connecting section 120 is opposite to the flow direction of the solution from connecting section 130, resulting in a more uniform mixing of the solutions. When flow channel 150 is a Y-shaped flow channel, the confluence of the solution from connecting section 120 and the solution from connecting section 130 is smooth, resulting in smooth ejection of the mixed solution.

[0026] Housing section 110 of holder 100 is capable of housing a plurality of syringes (syringe groups). In housing section 110, each syringe is preferably configured to be arranged parallel to each other. Housing section 110 can retain or secure the syringes. Housing section 110 can be configured to retain and / or secure a group of syringes that have the same outside diameter, or it can be configured to retain or secure a group of syringes where the outside diameter of at least one of the plurality of syringes is different from the outside diameter of the other syringes (i.e., a group of syringes including a group of syringes having various outside diameters). Housing section 110 of holder 100 has a plurality of sub-housing sections, and each sub-housing section can retain a single syringe or a plurality of syringes. Each sub-housing section can be configured to retain or secure syringes that have different outside diameters from each other.The housing section 110 does not need to cover the entire syringe barrel and can be configured to cover part of the syringe barrels.

[0027] Support materials 100 can Petition 870210106484, dated 11 / 18 / 2021, pp. 64 / 96 8 / 14 include, but are not limited to, metals (e.g., stainless steel), resins (e.g., cycloolefin polymers (COPs), cycloolefin copolymers (COCs), polypropylene, and polycarbonate), and glass. The holder 100 may be manufactured from a single material or from a plurality of materials. The holder 100 may include a plurality of parts (composed of the same or different materials) or may be made of a single piece. The flow channel 150 may be a tunnel within the holder 100 or may be a flexible tube (e.g., a silicone tube). The ejection section 140 may be fitted with a needle when in use, but an extension component (e.g., a silicone tube) may also be fitted between the ejection section 140 and the needle.

[0028] Support 100 may have an opening (window) to check connection sections 120 and 130. The proximal end of support 100 may be provided with a flange 160 for stable injection. Syringe

[0029] Syringes 200 and 300 include cylinders 201 and 301 and plunger rods 202 and 302 with gaskets 203 and 303, respectively, wherein cylinders 201 and 301 have tips 204 and 304 that eject the solutions into syringes 200 and 300, respectively. In FIG. 1. Syringes 200 and 300 are housed in housing section 110 of holder 100. Syringe 200 is detachably connected to connection section 120 of holder 100 via tip 204 of syringe 200. Syringe 300 is detachably connected to connection section 130 of holder 100 via tip 304 of syringe 300. Syringes 200 and 300 may be cartridge-type syringes in which the Petition 870210106484, dated 11 / 18 / 2021, pp. 65 / 96 9 / 14 plunger rods and gaskets are not fixed. Each syringe may also contain a different desired solution. Solutions may be pre-filled in each syringe and may be filled in each syringe as needed. The cross-sectional areas of the filling space in each syringe may be the same or different from each other. The cross-sectional area of ​​the filling space in at least one of the plurality of syringes may be different from the cross-sectional area of ​​the filling space in the other syringes. The expression "the cross-sectional area of ​​the filling space in each syringe" means the cross-sectional area of ​​the filling space relative to an axis extending in the direction of plunger rod slide. When the cross-sectional area of ​​the filling space in the syringe is disc-shaped, the inner diameter of the syringe may be used instead of the cross-sectional area of ​​the filling space in the syringe.The syringe filling space refers to the area of ​​the syringe where the solution is filled.

[0030] Syringes 200 and 300 can be manufactured from a single material or can be configured from multiple materials (including a multi-layered structure, such as a coating). For a syringe manufactured from a single material, the entire syringe can be made from one resin (e.g., cycloolefin polymer (COP), cycloolefin copolymer (COC), and polypropylene). As discussed in the following example, a syringe that contains or may contain a hydrogen peroxide solution is preferably made from cycloolefin polymer (COP), cycloolefin copolymer (COC), or Petition 870210106484, dated 11 / 18 / 2021, pp. 66 / 96 10 / 14 polypropylene. In the case of a syringe composed of more than one material, one part of the syringe in direct contact with the solution may be made of the aforementioned resin, while the other part may be made of glass or metal. It is not necessary for all parts in contact with the solution to be made of the above resin, but only if the main part of the syringe body, including the inner surface of the syringe body cylinder, is made of the above resin. The plunger rod, luer lock, cap, gasket, and the like do not need to be made of the above resin. Adapter

[0031] Adapter 400 can be detachably connected to plunger rods 202 and 302 and can be molded as a single piece with plunger rods 202 and 302. Adapter 400 can be connected to the proximal end of plunger rods 202 and 302, or it can be connected to the distal side of plunger rods 202 and 302 instead of the proximal end of plunger rods 202 and 302. When these are close enough to each other that plunger rod 202 and plunger rod 302 can be pushed at the same time, adapter 400 cannot be used. Adapter 400 can be connected to support 100 by means of a sliding mechanism (e.g., a rail) or a wire (e.g., a metal wire and a plastic wire). Solution(s)

[0032] In this embodiment, a solution is mixed with one or more other solutions after use. If necessary, the mixed solution can be injected (for example, using adapter 400 connected to the proximal end of plunger rods 202 and 302) after one of the Petition 870210106484, dated 11 / 18 / 2021, pp. 67 / 96 11 / 14 multiple solutions have been injected first. One of the two solutions may be a hydrogen peroxide solution and the other solution may be selected from the group consisting of hyaluronic acid, hydrogel, and combinations thereof. In another embodiment, at least one of the above syringes is pre-filled with a hydrogen peroxide solution. When the hydrogen peroxide solution is pre-filled in the syringe, the material of the syringe barrel for the hydrogen peroxide solution is preferably a cycloolefin polymer (COP) or a cycloolefin copolymer (COC). When more than three solutions are used, a solution other than the above may be used (e.g., Hank's solution, Ringer's solution, physiological saline, acetate buffer (to reduce discomfort at the injection site), suspension, stabilizer, and dispersant).

[0033] Hydrogen peroxide solution means a solution of hydrogen peroxide dissolved in a solvent (e.g., water) and may contain additives (e.g., phosphoric acid and phenacetin) as required. The concentration of hydrogen peroxide in the hydrogen peroxide solution is from 0.01 to 40% (w / v), for example, it may be 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.5, 1, 5, 10, 15, 20, 25, 30, 35 or 40%, or a value within a range between any two of the above values, preferably from 0.05 to 30% (p / v).

[0034] Hyaluronic acid includes its salts. The characteristics of hyaluronic acid (molecular weight, degree of cross-linking, etc.) used in the treatment of tumors by radiation or as an anticancer agent may be those known in the art (see, for example, WO2008 / 041514). Petition 870210106484, dated 11 / 18 / 2021, pp. 68 / 96 12 / 14 Hydrogel containing gelatin gel may be composed of, as a main component, a gelatin gel that is produced by crosslinking gelatin with a chemical crosslinking agent, heat treatment, or UV irradiation or electron beam irradiation. The gelatin gel may be an acidic gelatin gel. The characteristics of the hydrogel containing gelatin gel used in radiation or anticancer tumor treatment (such as gelatin type, isoelectric point, content, degree of crosslinking, etc.) may be those known in the art (see, for example, WO2014 / 126222). Solution Ratio

[0035] The respective solutions in each syringe 200 or 300 flow into the flow channel 150 by pushing the adapter 400 towards the support 100. The solutions are mixed in the flow channel 150. The mixed solutions are ejected from the ejection section 140. Using the adapter 400, the movement speed of the syringe plunger rod 202 is controlled. 200 is the same as that of the plunger rod 302 of syringe 300, allowing each solution to be ejected in a fixed proportion. The proportion of each solution in the mixed solution is the proportion of the cross-sectional area in the filling space of each syringe. In other words, the proportion of each solution in the mixed solution depends on the proportion of the cross-sectional areas in the filling spaces of each syringe. Kit

[0036] As yet another embodiment, a kit is provided including the above syringes and the above support. Petition 870210106484, dated 11 / 18 / 2021, pp. 69 / 96 13 / 14

[0037] The kit may include a plurality of containers, each of which may hold the required quantity of the desired solution. The kit may include a 400 adapter. The kit may include one or more needles for the syringe and / or holder. The kit may include additional elements (e.g., instructions or dosage plan) for the treatment of tumors with radiation or an anticancer agent. If the solution is pre-filled in the 200 and 300 syringes, the 204 and 304 syringe tips are covered with caps. EXAMPLE Stability test of hydrogen peroxide solution

[0038] The stability test of a hydrogen peroxide solution was performed using a glass syringe, a COP syringe, and a COC syringe. 1 ml of hydrogen peroxide solution was added to each syringe, sealed, and then stored at 60 °C for 4 weeks. Residual hydrogen peroxide levels in the hydrogen peroxide solutions after storage were measured. The hydrogen peroxide solution used was Oxydol KENEI (containing 2.5 to 3.5% (w / v) hydrogen peroxide, phosphoric acid, and phenacetin) manufactured by Kenei Pharmaceutical Co., Ltd. The amount of hydrogen peroxide in the hydrogen peroxide solution was detected by titration with a potassium permanganate solution according to the oxidol determination method described in the Japanese Pharmacopoeia.

[0039] The results are shown in FIG. 2. In the case of the glass syringe, the residual rate of hydrogen peroxide was less than 70%, while the residual rate Petition 870210106484, dated 11 / 18 / 2021, pp. 70 / 96 14 / 14 regarding the COP or COC syringe was 70% or more. As a result, the COP syringe and the COC syringe were able to suppress hydrogen peroxide decomposition more than the glass syringe. EXPLANATION OF REFERENCES 1 Medication administration system 100 Support 110 Housing section 120, 130 Connection section 140 Ejection section 150 Flow channel 160 Flange 200, 300 Syringe 201, 301 Cylinder 202, 302 Plunger rod 203, 303 Gasket 204, 304 Tip 400 Adapter Petition 870210106484, dated 11 / 18 / 2021, pp. 71 / 96

Claims

1 / 2 CLAIMS 1. MEDICATION ADMINISTRATION DEVICE (1), comprising at least two syringes (200,300) and a holder (100) for mixing at least two solutions, wherein the holder (100) is capable of simultaneously ejecting the solution containing each solution in a fixed ratio from each syringe (200, 300), characterized in that: at least one of the syringes (200,300) is pre-filled with a hydrogen peroxide solution, and the material of a syringe barrel containing the hydrogen peroxide solution is a cycloolefin polymer (COP) or a cycloolefin copolymer (COC).

2. MEDICATION ADMINISTRATION DEVICE (1), according to claim 1, characterized in that the cross-sectional areas of the filling spaces in each syringe (200,300) differ from each other.

3. MEDICATION ADMINISTRATION DEVICE (1), according to claim 1 or 2, characterized in that it further comprises an adapter (400), wherein each syringe (200,300) is fitted with a plunger rod (202,302) and the adapter (400) is connected to the plunger rods (202,302).

4. MEDICATION ADMINISTRATION DEVICE (1), according to any one of claims 1 to 3, characterized in that each syringe (200, 300) is pre-filled with a different desired solution from the other.

5. MEDICATION ADMINISTRATION DEVICE Petition 870260076011, dated 07 / 30 / 2026, page 15 / 16 2 / 2 (1), according to any one of claims 1 to 4, characterized in that it comprises a housing section for housing the syringes, a connection section for connecting the syringes to the holder, an ejection section for ejecting the solution and a flow channel in fluid communication with the ejection section and the connection section.

6. KIT, characterized in that it comprises the drug administration device (1) according to claim 1.

7. KIT, according to claim 6, characterized in that each syringe (200, 300) is pre-filled with a different desired solution.

8. A KIT, according to any one of claims 6 or 7, characterized in that it comprises a housing section for housing the syringes, a connection section for connecting the syringes to the holder, an ejection section for ejecting the solution, and a flow channel in fluid communication with the ejection section and the connection section. Petition 870260076011, dated 07 / 30 / 2026, p. 16 / 16

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