Injector for pre-sealing hydrogen peroxide solution having excellent hydrogen peroxide storability due to oil-based composition containing silicone oil

Abstract

The present invention provides a syringe capable of suppressing decomposition of hydrogen peroxide. The present invention provides a syringe in which a hydrogen peroxide solution is pre-filled, at least a syringe barrel of the syringe is made of a material having high hydrogen peroxide decomposition ability, and the inner wall of the syringe barrel is coated with an oily composition containing a silicone oil.

Description

[0001] This application is a divisional application based on the Chinese invention patent application with application number: 202080021242.2, application date: March 27, 2020, and invention name: "Pre-filled hydrogen peroxide solution syringe with excellent hydrogen peroxide preservation due to silicone oil (oily composition containing silicone oil)". [Technical field]

[0002] The present invention relates to a syringe, which is a syringe pre-filled with a hydrogen peroxide solution using an oily composition containing silicone oil. [Background technology]

[0003] Hydrogen peroxide solution is used as a bleaching agent in industry and as a disinfectant in the food industry. Hydrogen peroxide solution containing 2.5 to 3.5 w / v% hydrogen peroxide (also called oxyethanol in the Japanese Pharmacopoeia) is used as a disinfectant in medicine. A hydrogen peroxide solution can be mixed with hyaluronic acid (or its salt (e.g., sodium hyaluronate)) at a predetermined ratio just before irradiation, and the mixture can be applied to a tumor for use as a radiation sensitizer (Patent Document 1). The liquid temperature of hydrogen peroxide increases due to the heat of decomposition, accelerating decomposition. Non-Patent Document 1 discloses materials suitable for hydrogen peroxide. Prior art literature Patent Literature

[0004] Patent Document 1: International Publication No. 2008 / 041514

Non-patent literature

[0005] [Non-patent document 1] Kusakabe Ryo, “Manufacturing, properties and handling of hydrogen peroxide”, Journal of the Pulp Technology Association, Vol. 52, No. 5, May 1998 [Summary of the invention] Problem that the invention aims to solve

[0006] As disclosed in Non-Patent Document 1, the materials of a storage container that can be used to store a hydrogen peroxide solution are limited, and the material of the storage container cannot be freely selected.

[0007] As described in Patent Document 1, when a hydrogen peroxide solution is used as a radiation sensitizer, since hydrogen peroxide decomposes rapidly when taken out from a special light-shielded storage container, it is necessary to take out an appropriate amount or mass and mix it with a sodium hyaluronate solution before injection. This requires the hospital pharmacy to take out the hydrogen peroxide solution and mix it with the sodium hyaluronate, or the doctor needs to perform the operation at the patient's bedside, which places an unnecessary burden on the medical staff treating the patient. In the former case, the pharmacy staff is burdened and there is a risk that the speed of delivering the injection mixture from the pharmacy to the patient's bedside will be delayed. In the latter case, the burden needs to be borne by the medical staff at the patient's bedside. In either case, the complicated process of weighing and mixing the solution increases the risk of errors, which can damage the quality of medical care and endanger patients.

[0008] In addition, if the hydrogen peroxide solution is prefilled using a conventional glass syringe (made of borosilicate glass, etc.), problems such as swelling during storage and the gasket being pushed back may occur, making long-term storage impossible. Solutions for solving problems

[0009] After careful research, the inventors found that an oily composition containing silicone oil has the effect of stabilizing the storage of hydrogen peroxide, thus completing the present invention. The present invention relates to an oily composition used to stabilize the storage of hydrogen peroxide, and a syringe pre-filled with a hydrogen peroxide solution using the oily composition.

[0010] The object of the present invention is to provide a syringe, wherein the syringe is pre-filled with a hydrogen peroxide solution, at least the syringe barrel in the syringe is made of a material with a high ability to decompose hydrogen peroxide, and the inner wall of the syringe barrel is coated with an oily composition containing silicone oil.

[0011] By using the oily composition, hydrogen peroxide can be stably stored in a hydrogen peroxide solution, and by applying the oily composition to the inner wall of a syringe, even a syringe prefilled with a hydrogen peroxide solution can be stored for a long time.

[0012] Another object of the present invention is to provide an oily composition containing silicone oil for the purpose of stably preserving hydrogen peroxide, and the use of the oily composition.

[0013] By using the oily composition, hydrogen peroxide can be stably stored in the hydrogen peroxide solution regardless of the material of the container storing the hydrogen peroxide solution, and the hydrogen peroxide solution can be stored for a long time. Effects of the Invention

[0014] According to the present invention, a prefilled syringe can be provided, which can store hydrogen peroxide solution for a long time until it is used as a radiosensitizer.

Brief Description of the Drawings

[0015] Figure 1 A schematic diagram showing a prefilled syringe filled with hydrogen peroxide solution according to the present embodiment. Figure 2 This is a graph showing the residual rate of hydrogen peroxide in each container in Examples. [Specific implementation method]

[0016] definition For convenience, specific terms used in this application are gathered here. Unless otherwise defined, all technical terms and scientific terms in this application have the same meaning as commonly understood by those skilled in the art to which the invention belongs. Unless otherwise indicated by the context, the singular forms "a", "an" and "the" include plural forms.

[0017] The numerical ranges and parameters shown in the present invention are approximate values, but the numerical values ​​given in the specific examples are recorded as accurately as possible. However, any numerical value substantially includes inevitable specific errors, which are caused by the standard deviations that can be seen in each experimental determination. In addition, the term "about" used in this specification generally refers to within 10%, 5%, 1% or 0.5% of the specified value or range. Alternatively, the term "approximately" refers to within an acceptable standard error considered by a person skilled in the art.

[0018] Oily composition The oily composition involved in this embodiment contains silicone oil and is an oily composition for the purpose of stabilizing the storage of hydrogen peroxide. The above-mentioned oily composition can be used as a drug for stabilizing the storage of hydrogen peroxide. The above-mentioned oily composition may include pharmaceutically acceptable ingredients (sterile water, etc.) other than silicone oil. The above-mentioned oily composition may be applied to the inner wall of a container or a syringe. The above-mentioned oily composition may suppress the decomposition of hydrogen peroxide by being made of a material with high decomposition ability of hydrogen peroxide (for example, glass, plastic with high decomposition ability of hydrogen peroxide (for example, polyethylene terephthalate) and stainless steel). Therefore, the material of the container or the syringe may be the above-mentioned material with high decomposition ability of hydrogen peroxide.

[0019] As the silicone oil, one having a kinematic viscosity at 25° C. of 20 to 40,000 cSt, preferably 500 to 30,000 cSt, more preferably 800 to 20,000 cSt, and even more preferably 1,000 to 15,000 cSt can be used.

[0020] The kinematic viscosity of silicone oil at 25°C can be measured in accordance with JIS Z8803.

[0021] As the silicone oil, it is preferable to use a linear silicone represented by the following formula (1).

[0022]

Chemistry 2

[0023] In the above formula (1), R independently represents an organic functional group such as an alkenyl group and / or a SiH group that does not contain a functional group participating in a hydrosilylation reaction, a monovalent hydrocarbon group or a hydroxyl group, and each R may be the same or different. x represents an integer of 10 to 1200. R preferably represents an alkyl group or an aryl group, and more preferably represents a methyl group, an ethyl group or a phenyl group.

[0024] The linear silicone represented by the above formula (1) may be a polydiorganosiloxane terminated at both ends by triorganosilyl groups, preferably a polydialkylsiloxane, a polydiarylsiloxane, a polyalkylarylsiloxane or a copolymer thereof, more preferably a polydimethylsiloxane or a polymethylphenylsiloxane, and particularly preferably a polydimethylsiloxane in which all R groups are methyl groups.

[0025] syringe Figure 1 1 is a schematic diagram showing a prefilled syringe 1 filled with a hydrogen peroxide solution 50 according to the present embodiment. In the present embodiment, the shape of the syringe 10 (particularly the syringe barrel 20) is generally cylindrical, one end of the syringe 10 is provided with a needle mounting portion 30 for discharging the hydrogen peroxide solution 50, and the other end of the syringe 10 is provided with a rod insertion portion 80 for inserting a plunger rod 70, and a flange 90 is provided around the rod insertion portion 80. Figure 1 The prefilled syringe 1 shown has silicone oil applied to the inner wall of the syringe 10. In order to seal the filled hydrogen peroxide solution 50, Figure 1 The prefilled syringe 1 shown in the figure includes a cap 40 on a needle mounting portion 30 , and a plunger rod 70 including a gasket 60 is inserted from a rod insertion portion 80 .

[0026] In this embodiment, the syringe for hydrogen peroxide solution means a syringe having a low ability to decompose hydrogen peroxide in the hydrogen peroxide solution. In this embodiment, the hydrogen peroxide solution means a solution obtained by dissolving hydrogen peroxide in a solvent (e.g., water), and may contain additives (e.g., phosphoric acid and phenacetin) as needed. In this embodiment, the syringe may be made of a single material or may be composed of multiple materials (including a multilayer structure such as a coating). In the case of a syringe made of a single material, the entire syringe may be composed of a material having a high ability to decompose hydrogen peroxide (e.g., glass, a plastic having a high ability to decompose hydrogen peroxide (e.g., polyethylene terephthalate) and stainless steel). In the case of a syringe composed of multiple materials, the inner wall of the syringe may be composed of glass, and the other parts may be composed of a material having a high ability to decompose hydrogen peroxide. In addition, not all parts in contact with the hydrogen peroxide solution are composed of a material having a high ability to decompose hydrogen peroxide, as long as the main parts, including the inner surface of the syringe barrel of the syringe body, are composed of a material having a high ability to decompose hydrogen peroxide. That is, other components that may come into contact with the hydrogen peroxide solution, such as the plunger rod, Luer lock, cap, and gasket, do not need to be made of a material that has a high ability to decompose hydrogen peroxide. The syringe according to this embodiment can be used for radiosensitizers.

[0027] The ratio of the concentration of hydrogen peroxide in the hydrogen peroxide solution before the start of storage to the concentration of hydrogen peroxide in the hydrogen peroxide solution after a specific storage period under specific temperature conditions (hydrogen peroxide residual rate) determines the decomposition ability of hydrogen peroxide. Storage is carried out in a sealed state. The temperature conditions are not particularly new and can be 35°C, 37°C, 40°C or 60°C. The storage period is not particularly limited and can be 1 week, 2 weeks, 3 weeks or 4 weeks, or more than 4 weeks. The concentration of hydrogen peroxide in the hydrogen peroxide solution before the start of storage can be tested at any concentration in the range of, for example, 0.01 to 40% (w / v). In the embodiment, the decomposition ability of hydrogen peroxide of the above-mentioned resin can be lower than that of glass. Under the condition that a solution containing 2.5 to 3.5 w / v% of hydrogen peroxide is sealed and stored at 60°C for 4 weeks, the hydrogen peroxide residual rate of the above-mentioned resin can be 70% or more, preferably 75% or more, more preferably 78% or more, and further preferably 80% or more. According to the quantitative method of hydrogen peroxide in the Japanese Pharmacopoeia, the amount of hydrogen peroxide in the hydrogen peroxide solution is determined by titration with potassium permanganate solution.

[0028] This embodiment provides a syringe that is pre-filled with a hydrogen peroxide solution. The syringe pre-filled with the hydrogen peroxide solution has a gasket that can be slidably mounted on the syringe. In addition, the needle mounting portion of the syringe pre-filled with the hydrogen peroxide solution is sealed (for example, by a cap, etc.).

[0029] In this embodiment, the concentration of hydrogen peroxide in the hydrogen peroxide solution in the prefilled syringe is, for example, 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%, and can also be within the range between any two of the numerical values ​​exemplified here, for example, 0.01 to 40% (w / v), preferably 0.05 to 30% (w / v).

[0030] The oily composition of this embodiment can be applied using a sprayer or the like. When applied, the oily composition can be dissolved in an appropriate solvent. When the oily composition is applied to the inner wall of the syringe, the oily composition can be applied at a rate of 0.02 to 0.2 mg / cm 2 After the coating of the inner wall of the syringe is completed, the thickness of the oily composition can be made uniform by using a squeegee or other tools, or the thickness of the oily composition can be made uniform by softening the silicone oil in the oily composition by heating (for example, autoclaving).

[0031] The present invention includes the following embodiments: Item 1. A syringe, the syringe being pre-filled with a hydrogen peroxide solution, In the syringe, at least the syringe barrel is made of a material with high decomposition ability of hydrogen peroxide. The inner wall of the syringe barrel is coated with an oily composition containing silicone oil. Item 2. A syringe according to Item 1, wherein: The silicone oil is a straight-chain silicone represented by the following formula (1):

Chemistry 1

[0032] Stability test of hydrogen peroxide solution The stability test of hydrogen peroxide solution was conducted using glass containers coated with silicone oil and glass containers not coated with silicone oil. Silicone oil was purchased from Dow Corning (product name: Dow Corning 360 Medical Fluid (12,500 cSt)). Hydrogen peroxide solution was added to each container and sealed, and stored at 60°C for 4 weeks. The residual rate of hydrogen peroxide in the hydrogen peroxide solution after storage was measured. Hydrogen peroxide "Kenei" manufactured by Kenei Pharmaceutical Co., Ltd. (containing 2.5 to 3.5 w / v% hydrogen peroxide, phosphoric acid, phenacetin) was used as the hydrogen peroxide solution. The amount of hydrogen peroxide in the hydrogen peroxide solution was measured by titration with potassium permanganate solution according to the hydrogen peroxide quantitative method of the Japanese Pharmacopoeia. Figure 2 Indicates the result.

[0033] The residual rate of hydrogen peroxide in the glass container without silicone oil coating was about 70%. The residual rate of hydrogen peroxide in the glass container with silicone oil coating was more than 78%. The above results show that the glass container with silicone oil coating can inhibit the decomposition of hydrogen peroxide compared with the glass container without silicone oil coating.

Explanation of symbols

[0034] 1 Prefilled Syringe 10 Syringes 20 Syringe barrel 30-pin mounting section 40 Blocked 50 Hydrogen peroxide solution 60 Gasket 70 Plunger rod 80 Opening 90 Flange

Claims

1. Use of an oily composition containing silicone oil for stabilizing the storage of hydrogen peroxide, characterized in that: The oily composition is applied to the inner wall of a container or a syringe.

2. The use according to claim 1, wherein: The silicone oil is a straight-chain silicone represented by the following formula (1): In the formula (1), R independently represents an organic functional group, a monovalent hydrocarbon group or a hydroxyl group that does not contain a functional group that participates in the hydrosilylation reaction, and each R is the same or different. x represents an integer from 10 to 1200.

3. The use according to claim 2, wherein: R each independently represents an alkyl group or an aryl group.

4. The use according to claim 3, wherein: R each independently represents a methyl group, an ethyl group or a phenyl group.

5. The use according to claim 2, wherein: The linear silicone represented by the above formula (1) is a polydiorganosiloxane having both ends capped with triorganosilyl groups.

6. The use according to claim 5, wherein: The polydiorganosiloxane is polydialkylsiloxane, polydiarylsiloxane, polyalkylarylsiloxane or a copolymer thereof.

7. The use according to claim 6, wherein: The polydiorganosiloxane is polydimethylsiloxane or polymethylphenylsiloxane.

8. The use according to claim 7, wherein: The polydiorganosiloxane is a polydimethylsiloxane in which all R are methyl groups.

9. The use according to claim 1, wherein: The concentration of hydrogen peroxide in the hydrogen peroxide solution is 0.01 w / v% to 40 w / v%.

10. The use according to claim 1, wherein: The oily composition inhibits decomposition of hydrogen peroxide caused by the material of the container or the syringe.

11. The use according to claim 10, wherein: The material is glass.

12. The use according to any one of claims 1 to 11, wherein: Used as a radiosensitizer.

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