TW202103713A - Hydrogen peroxide solution-prefilled syringe with excellent hydrogen peroxide preservation due to silicone oil included in oil composition - Google Patents

Abstract

A syringe that suppresses decomposition of hydrogen peroxide is provided. An object of the present invention is to provide a pre-filled syringe having at least a barrel thereof made of a material having high decomposition capability with respect to hydrogen peroxide, including: a hydrogen peroxide solution therein; and an oil composition applied to an inner wall of the barrel, the oil composition containing silicone oil.

Description

Prefilled glass syringe of hydrogen peroxide solution with excellent hydrogen peroxide storage properties due to silicone oil (oily composition containing silicone oil)

The present invention relates to a syringe, which is a glass syringe prefilled with a hydrogen peroxide solution using an oily composition containing silicone oil.

Hydrogen peroxide solution is used as a bleaching agent in industry and as a bactericide in the food industry. A hydrogen peroxide solution (also called oxidized alcohol in the Japanese Pharmacopoeia) containing 2.5 to 3.5 w/v% of hydrogen peroxide is used as a disinfectant in medicine.

The hydrogen peroxide solution can be mixed with hyaluronic acid (or a salt thereof (for example, sodium hyaluronate)) in a predetermined ratio immediately before irradiation, and the mixture can be applied to a tumor for use as a radiation sensitizer (Patent Document 1). Prior art literature [Patent Literature]

Patent Document 1: International Publication 2008/041514

[The problem to be solved by the invention]

As described in Patent Document 1, when hydrogen peroxide solution is used as a radiation sensitizer, the hydrogen peroxide will rapidly decompose when taken out of a special storage container that is shielded from light, so it is necessary to take out an appropriate amount or quality and transparency before injection. Sodium hydrochloride solution is mixed, because the hospital pharmacy needs to take out the hydrogen peroxide solution and mix with the sodium hyaluronate, or the doctor needs to operate at the bedside of the patient, which brings an unnecessary burden to the medical staff who treat the patient. In the former case, the pharmacy staff is heavily burdened and there is a risk that the delivery of the injection mixture from the pharmacy to the bedside of the patient will be delayed. In the latter case, the burden must be borne by the medical staff at the patient's bedside. In either case, the complicated process of weighing and mixing solutions increases the risk of errors, which can compromise the quality of medical care and endanger patients.

In addition, if a conventional glass (made of borosilicate glass, etc.) syringe is used to prefill the hydrogen peroxide solution, problems such as expansion during storage and the gasket being pushed back may occur, making long-term storage impossible. [Solution to solve the problem]

After careful research, the inventor found that the oily composition containing silicone oil has the effect of stabilizing the preservation of hydrogen peroxide, and thus completed the present invention. The invention relates to a syringe, which is a syringe prefilled with a hydrogen peroxide solution, and an oily composition is used in order to stabilize the storage of the hydrogen peroxide.

The object of the present invention is to provide a syringe, wherein the syringe is prefilled with a hydrogen peroxide solution, at least the syringe barrel of the syringe is made of glass, and the inner wall of the syringe barrel is coated with an oily composition containing silicone oil.

By using this oily composition, hydrogen peroxide can be stored stably in a hydrogen peroxide solution. By coating the oily composition on the inner wall of a syringe, even a syringe prefilled with hydrogen peroxide solution can be stored for a long time. . [Effects of the invention]

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

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

The numerical ranges and parameters shown in the present invention are approximate values, but the numerical values given in the specific embodiments are recorded as accurately as possible. However, any numerical value essentially includes unavoidable specific errors, which are caused by the standard deviations that can be seen in the measured values of each test. In addition, the term "about" used in this specification usually means within 10%, 5%, 1%, or 0.5% of a predetermined value or range. Alternatively, the term "approximately" means within an acceptable standard error considered by those skilled in the art.

Oily composition The oily composition according to the present embodiment contains silicone oil, and is an oily composition for the purpose of 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 can suppress the decomposition of hydrogen peroxide caused by glass.

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

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

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

In the above formula (1), R each independently represents an organic functional group, a monovalent hydrocarbon group, or a hydroxyl group that does not contain a functional group participating in the hydrosilation addition reaction, such as an alkenyl group and/or SiH 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.

The linear organosilicon represented by the above formula (1) may be polydiorganosiloxane whose both ends are terminated by triorganosilyl groups, preferably polydialkylsiloxane, polydiarylsiloxane, poly Alkylarylsiloxanes or copolymers of these are more preferably polydimethylsiloxanes or polymethylphenylsiloxanes, and particularly preferably polydimethylsiloxanes in which all R are all methyl groups.

syringe FIG. 1 is a schematic diagram showing a prefilled syringe 1 filled with a hydrogen peroxide solution 50 according to this embodiment. In this embodiment, the shape of the syringe 10 (especially 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 plunger for inserting The rod insertion portion 80 of the rod 70 is provided with a flange 90 around the rod insertion portion 80. The prefilled syringe 1 shown in FIG. 1 is coated with silicone oil on the inner wall of the syringe 10. In order to seal the filled hydrogen peroxide solution 50, the prefilled syringe 1 shown in FIG. 1 is provided with a cap 40 on the needle mounting portion 30, and a plunger rod 70 provided with a gasket 60 is inserted from the rod insertion portion 80.

In the present embodiment, the hydrogen peroxide solution syringe means a syringe with a low decomposition ability of hydrogen peroxide in the hydrogen peroxide solution. In the present embodiment, the hydrogen peroxide solution means a solution obtained by dissolving hydrogen peroxide in a solvent (for example, water), and may contain additives (for example, phosphoric acid and phenacetin) as necessary. In this embodiment, the syringe may be made of a single material, or may be composed of multiple materials (multi-layer structure including plating films). When the syringe is made of a single material, the entire syringe can be composed of glass. When the syringe is composed of multiple materials, the inner wall of the syringe is composed of glass, and the other parts may be composed of a material with high hydrogen peroxide decomposition ability. In addition, not all parts in contact with the hydrogen peroxide solution are made of glass, as long as the main part including the inner surface of the syringe barrel of the syringe body is made of glass. That is, other plunger rods, Luer locks, caps, gaskets, etc. that may come into contact with the hydrogen peroxide solution do not need to be composed of the above-mentioned glass. The syringe according to this embodiment can be used as a radiosensitizer.

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

This embodiment provides a syringe which is prefilled with a hydrogen peroxide solution. The syringe prefilled with hydrogen peroxide solution is equipped with a gasket that can be slid on the syringe. In addition, the needle mounting part of the syringe prefilled with the hydrogen peroxide solution is sealed (for example, by a cap, etc.).

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% can also be within the range between any two of the numerical values exemplified here, such as 0.01 to 40% (w/v), preferably 0.05 to 30%(w/v).

Coating The oily composition according to 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 above-mentioned oily composition is applied to the inner wall of the syringe, the oily composition can be applied to the inner wall of the syringe by spraying the oily composition at a coating amount of 0.02 to 0.2 mg/cm2. After coating the inner wall of the syringe, you can use a squeegee to make the thickness of the oily composition uniform, or heat treatment (for example, autoclaving) to soften the silicone oil in the oily composition to make the thickness of the oily composition uniform . [Example]

Stability test of hydrogen peroxide solution The stability test of the hydrogen peroxide solution was performed using a glass container coated with silicone oil and a glass container not coated with silicone oil. Silicone oil was purchased from Dow Corning (product name: Dow Corning 360 Medical Fluid (12,500 cSt)). The hydrogen peroxide solution was added to each container, sealed, and stored at 60°C for 4 weeks. The residual rate of hydrogen peroxide in the hydrogen peroxide solution after storage was measured. The hydrogen peroxide solution used the hydrogen peroxide "Kenei" manufactured by Jianrong Pharmaceutical Company (containing 2.5 to 3.5 w/v% hydrogen peroxide. Contains phosphoric acid and phenacetin). According to the hydrogen peroxide quantitative method of the Japanese Pharmacopoeia, the amount of hydrogen peroxide in the hydrogen peroxide solution was detected by the potassium permanganate solution titration. Figure 2 shows the results.

In a glass container that is not coated with silicone oil, the residual rate of hydrogen peroxide is approximately 70%. 78% or more of glass containers coated with silicone oil. From the above results, it can be seen that the glass container coated with silicone oil can suppress the decomposition of hydrogen peroxide compared to the glass container not coated with silicone oil.

It should be noted that the above is only a preferred embodiment for explaining the case, and the case is not limited to the described embodiment. The scope of the case is determined by the scope of the patent application attached. And this case can be modified in many ways by those who are familiar with this technology, but none of them deviates from the protection of the scope of the patent application.

1: prefilled syringe 10: Syringe 20: Syringe barrel 30: Needle mounting part 40: Block 50: Hydrogen peroxide solution 60: Gasket 70: Plunger rod 80: opening 90: flange

Fig. 1 shows a schematic diagram of a prefilled syringe filled with hydrogen peroxide solution according to this embodiment.

Fig. 2 is a graph showing the residual rate of hydrogen peroxide in each container in the example.

1: prefilled syringe

10: Syringe

20: Syringe barrel

30: Needle mounting part

40: Block

50: Hydrogen peroxide solution

60: Gasket

70: Plunger rod

80: opening

90: flange

Claims (11)

A syringe, the syringe is prefilled with a hydrogen peroxide solution, at least the syringe barrel in the syringe is made of glass, and the inner wall of the syringe barrel is coated with an oily composition containing silicone oil. Such as the syringe of claim 1, wherein the silicone oil is a linear organosilicon represented by the following formula (1),

In the formula (1), R each independently represents an organic functional group, a monovalent hydrocarbon group, or a hydroxyl group that does not contain a functional group participating in the hydrosilation addition reaction, each R may be the same or different, and x represents an integer of 10 to 1200. Such as the syringe of claim 2, wherein R each independently represents an alkyl group or an aryl group. Such as the syringe of claim 3, wherein R each independently represents a methyl group, an ethyl group or a phenyl group. The syringe according to any one of claims 2 to 4, wherein the linear organosilicon is polydiorganosiloxane whose two ends are capped with triorganosilyl groups. The syringe of claim 5, wherein the polydiorganosiloxane is a polydialkylsiloxane, a polydiarylsiloxane, a polyalkylarylsiloxane, or a copolymer thereof. Such as the syringe of claim 6, wherein the polydiorganosiloxane is polydimethylsiloxane or polymethylphenylsiloxane. Such as the syringe of claim 7, wherein the polydimethylsiloxane is all polydimethylsiloxane in which R is a methyl group. According to the syringe of any one of claims 1 to 8, wherein the concentration of hydrogen peroxide in the hydrogen peroxide solution is 0.01-40% (w/v). The syringe according to any one of claims 1 to 9, wherein the oily composition suppresses the decomposition of hydrogen peroxide caused by glass. The syringe according to any one of claims 1 to 10, wherein the syringe is used for a radiosensitizer.

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