JP2008068122A - Syringe preparation - Google Patents

Abstract

An object of the present invention is to provide a novel injection that can reduce the time from drug ampule cutting to filling a syringe and reduce the time required for drug administration, and to improve the stability of the drug solution of the syringe preparation. Make it.
Means for Solving the Problems The present invention provides a container in which a syringe preparation containing a drug solution is sealed and a syringe preparation in which an aqueous solution containing dopamine or a pharmacologically acceptable salt thereof is enclosed in a syringe.
[Selection figure] None

Description

  The present invention relates to a container in which a syringe preparation containing a drug solution used in the medical field is sealed and a syringe preparation in which a solution containing dopamine or a pharmacologically acceptable salt thereof is enclosed in a syringe.

  Dopamine is an acute circulatory insufficiency-improving agent and exhibits an effect of enhancing cardiac contractility, an effect of increasing renal blood flow, and an effect of increasing blood pressure. Clinically, it has been found useful for improving acute circulatory failure such as cardiogenic shock and hemorrhagic shock, and is supplied mainly as a solution enclosed in an ampoule.

In general, when using a drug sealed in an ampoule, it is necessary to perform ampoule cutting work, sucking the drug solution into a syringe, etc. Is a problem. In addition, syringe preparations are known for some chemical solutions, but syringes are less hermetic than containers such as ampoules, reducing the stability of syringe preparations.

  An object of this invention is to improve the stability of the chemical | medical solution in a syringe formulation. It is another object of the present invention to provide a novel injection that can reduce the time required for drug administration by omitting the operation from the ampoule cutting operation to filling the syringe with a normal injection.

  The present invention relates to a container in which a syringe preparation formed by enclosing a drug solution is sealed and a syringe preparation in which an aqueous solution containing dopamine or a pharmacologically acceptable salt thereof is enclosed in a syringe.

  The syringe preparation of the present invention saves labor such as ampoule cutting work and suctioning of the drug solution into the syringe, and mixes glass fragments into the drug solution or amputation of contaminants from the outside air into the drug solution during ampoule cutting. Can be prevented. Furthermore, an unstable chemical | medical solution can be preserve | saved stably by enclosing a syringe formulation with an airtight container.

  The drug solution of the present invention may be any drug that can be administered using a syringe, but an aqueous solution containing dopamine or a pharmacologically acceptable salt thereof is preferred. Examples of the pharmacologically acceptable salt include acid addition salts. Examples of the acid addition salt include inorganic acid salts such as hydrochloride, sulfate and phosphate, and organic acid salts such as acetate, maleate, fumarate, tartrate, citrate and lactate.

  Examples of the aqueous solution include distilled water, physiological saline, glucose solution, and amino acid solution. The solution may contain components that can be used for injection, for example, a buffer, an antioxidant, an isotonic agent, and the like, if desired. Examples of the buffer include citric acid, lactic acid, potassium dihydrogen phosphate, acetic acid, tartaric acid and the like. Examples of the antioxidant include sodium pyrosulfite, ascorbic acid, sodium hydrogen sulfite, erythorbic acid, tocopherol, potassium dichloroisocyanurate and the like. Examples of the isotonic agent include sodium chloride, glycerin, glucose, D-mannitol and the like.

There is no restriction | limiting in particular as a syringe used for this invention, The syringe of any shape and material may be sufficient. Examples of the material include glass, resin, rubber, and metal. As the resin, polyethylene, polystyrene, polycarbonate, polypropylene, polyvinyl chloride, 6-nylon, polyethylene terephthalate and the like can be used, but a resin having a low oxygen permeability coefficient is preferable from the viewpoint of the stability of the chemical solution. Examples of the resin having a low oxygen permeability coefficient include resins having an oxygen permeability coefficient of less than 0.1 × 10 ⁻¹¹ cm ³ (STP) cm ⁻¹ s ⁻¹ cmHg ⁻¹ , such as polyvinyl alcohol, polyacrylonitrile, and polyvinylidene chloride. .

For the purpose of reducing the sliding resistance between the barrel of the syringe and the gasket, for example, a resin such as polyolefin can be used.
Although the shape of the container which seals the syringe preparation used for this invention is not specifically limited, A bag shape is preferable. The container is a container having an oxygen permeability coefficient of less than 0.1 × 10 ⁻¹¹ cm ³ (STP) cm ⁻¹ s ⁻¹ cmHg ⁻¹ . As the material of the container, any material can be used as long as it can restrict the permeation of oxygen. For example, metal, glass, aluminum, resin and the like can be mentioned, and resin is preferable.

As the resin, in addition to the above-described resin having a low oxygen permeability coefficient, a resin obtained by depositing an inorganic oxide such as silicon oxide or aluminum oxide is also preferably used.
As a bag-like container having a low oxygen permeability coefficient, for example, a copolymer film of vinylidene chloride resin and ethylene-vinyl alcohol, a tolyl film on polyacryl, and an inorganic oxide such as silicon oxide or aluminum oxide on a resin film are deposited. Film.

The oxygen scavenger is not particularly limited as long as it has an action of absorbing oxygen, and examples thereof include an antioxidant, a reducing substance, and a metal compound.
Of these oxygen scavengers, oxygen scavengers containing metal powder such as ascorbic acid or salts thereof, isoascorbic acid or salts thereof or iron powder are preferred, and oxygen scavengers containing iron powder are particularly preferred.

  Examples of deoxidation materials containing metal powder such as iron powder include AGELESS (registered trademark) [manufactured by Mitsubishi Gas Chemical Co., Ltd.], anti-mold (registered trademark) [manufactured by Freund Corporation], Oxyguard (registered trademark) [Toyo Etc.] can be obtained as a commercial product. The syringe used in the present invention has a tip for attaching an injection needle or cannula sealed with a rubber, plastic, or metal part, and one end is made of a rubber, plastic, or metal gasket. Or it can produce as a kit by sealing with a plunger rod.

When preparing the syringe preparation of the present invention, in the above-described syringe, after filling the drug solution from either the tip portion or the plunger rod portion for attaching the injection needle or cannula, the filled site is sealed.
Further, the syringe preparation is sealed with the aforementioned container. At this time, it is preferably performed in a nitrogen gas atmosphere. Moreover, when sealing the syringe preparation with the container, it is preferable to enclose an oxygen scavenger at the same time.

  When using the syringe preparation of the present invention, the tip sealing part is removed, an injection needle, a cannula or the like is attached to the tip, and the plunger rod is operated to perform the injection operation.

Test example 1
Cut the ampoule of Inoban Injection (manufactured by Kyowa Hakko Kogyo Co., Ltd.), suck the solution from the ampoule using a 10 ml disposable syringe (manufactured by Terumo) equipped with an injection needle, and then 50 ml physiological saline (plastic bottle; Otsuka Pharmaceutical Co., Ltd.) After aspirating the solution from the plastic bottle using a 50 ml disposable syringe (Terumo) equipped with an injection needle, replacing the injection needle with a winged needle (Nipro), and removing air It was mounted on a Terumo syringe pump STC-525. The entire process took 5 minutes. However, it took 1 minute for the syringe preparation produced in Example 1 to be mounted on the syringe pump STC-525 manufactured by Terumo. By using an injection container having a specific structure that itself becomes a syringe instead of an ampule as a container, rapid administration may be possible.

Test example 2
The syringe produced in Example 1 was set in a Terumo syringe pump STC-525 and operated at 5.0 ml / h.
The flow rate is 4.97 ± 0.04 ml for the syringe pump flow rate setting value of 5.0 ml / h, and its accuracy (CV) is 0.8%. Therefore, it can operate stably and at a constant speed even when connected to a syringe pump. It was.

  According to the present invention, by providing an injection container having a specific structure that itself becomes a syringe instead of an ampule as a container, stable administration can be achieved in a sterile state.

Test example 3
The formulations prepared in Example 1 and Example 2 were stored under conditions of 40% and 60 ° C. under conditions of 75% relative humidity. Table 1 shows the residual ratio of dopamine hydrochloride, and Table 2 shows the absorbance of the liquid preparation at 430 nm.

  The stability of the liquid preparation can be improved by sealing with an oxygen barrier film. Examples of the present invention are shown below.

  A solution containing 150 mg of dopamine hydrochloride, 400 mg of NaCl, 10.5 mg of citric acid monohydrate, 15 mg of sodium pyrosulfite in 50 ml is prepared, and after aseptic filtration, 51 ml is aseptically filled into a Terumo 50 ml disposable syringe and sealed. A syringe formulation was produced.

  A syringe prepared in the same manner as in Example 1 was packaged with an oxygen barrier film containing oxygen guard (manufactured by Toyo Co., Ltd.) substituted with nitrogen using a vacuum packaging machine (manufactured by Mutual Co., Ltd.) to produce a film-packed syringe preparation.

Claims (7)

A syringe preparation packaged with a sealed medicinal solution,
Syringe preparations that contain a drug solution are placed in a container that is a resin bag with an oxygen permeability coefficient of less than 0.1 x 10 ^-11 cm ³ (STP) cm ^-1 s ^-1 cmHg ^-1 together with an oxygen scavenger. A syringe preparation packaged by a packaging method comprising a step and a step of sealing the container. A syringe preparation packaged with a sealed medicinal solution,
Syringe preparation containing a drug solution is a resin bag containing an oxygen scavenger and an oxygen permeability coefficient of less than 0.1 x 10 ^-11 cm ³ (STP) cm ^-1 s ^-1 cmHg ^-1 A syringe preparation packaged by a packaging method comprising a step of placing in a container and a step of sealing the container.   3. The syringe preparation according to claim 1 or 2, wherein the packaging method is a packaging method wherein the container is sealed in a nitrogen gas atmosphere. The syringe preparation according to any one of claims 1 to 3, wherein the material of the syringe is a resin having an oxygen permeability coefficient of less than 0.1 x 10 ^-11 cm ³ (STP) cm ^-1 s ^-1 cmHg ^-1 .   The syringe preparation according to any one of claims 1 to 4, wherein the drug solution is an aqueous solution containing dopamine or a pharmacologically acceptable salt thereof.   6. The syringe preparation according to claim 5, wherein dopamine or a pharmacologically acceptable salt thereof is dopamine hydrochloride.   7. The syringe preparation according to claim 5 or 6, wherein the aqueous solution further contains sodium chloride, citric acid monohydrate and sodium pyrosulfite.