Stable fat emulsion containing prostaglandin e1

Abstract

Disclosed is a fat emulsion containing a compound having prostaglandin E1 activity, which fat emulsion is hermetically sealed in a glass container and then heat sterilized. The residual amount of prostaglandin E1 activity after 16-month storage at 5 DEG C is not less than 65% but not more than 100% of the prostaglandin E1 activity at the beginning of storage.

Description

technical field

[0001] The present invention relates to containing prostaglandin E 1 stable fat emulsion. Background technique

[0002] Prostaglandin E 1 (hereinafter, sometimes referred to as "PGE 1 ") The general name is that Alprostadil (Alprostadil) has a strong vasodilator effect and inhibits platelet aggregation, and is effective for improving chronic arterial occlusions (Buerger's disease, obliterative arteriosclerosis) when extremity ulcers and quiet It is effective in improving the pain of the patient, the improvement of the skin ulcer of the mobile systemic cured disease, the improvement of the skin ulcer of the diabetes, etc., so it is used in clinical practice. As a product containing prostaglandin E 1 formulations known to require dissolution of PGE in fine fat particles 1 So-called lipidation preparations (for example, "Liple Injection", manufactured and sold by Mitsubishi Tanabe Pharmaceutical Co., Ltd.). This preparation is based on the fact that fat par...

Examples

example 1

[0032] Dissolving alprostadil (PGE) in refined soybean oil 1 ), oleic acid, and egg yolk lecithin from which phosphatidylethanolamine (PE) has been removed, add a mixture of glycerin and distilled water for injection prepared separately, stir with a homogenizer, and prepare a suspension. The resulting suspension was emulsified by a Manton-Gaulin type emulsifier (manufactured by Manton-Gaulin), and the pH was adjusted to 4.90 using sodium hydroxide and hydrochloric acid. The formulated emulsion is filled into Silicoat ampoules (manufactured by Fuji Glass, and the thickness of the ampoule is 70 to 100 In the glass ampoule with a silicon oxide protective film), the void part of the ampoule was replaced with nitrogen, and sealed by fusing. The obtained ampoule was sterilized at 125° C. for 2.2 minutes using a high-pressure steam sterilizer to obtain the fat emulsion of the present invention.

example 2

[0034] An emulsion was formulated in the same manner as in Example 1, adjusted to pH 5.01 with sodium hydroxide, filled and sealed in a Silicoat ampoule and sterilized in the same manner as in Example 1 to obtain the fat emulsion of the present invention.

example 3

[0036] An emulsion was formulated in the same manner as in Example 1, and the pH was adjusted to 5.15 using sodium hydroxide. Then, it was filled and sealed in a Silicoat ampoule in the same manner as in Example 1, and sterilized to obtain the fat emulsion of the present invention.

technical field

[0001] The present invention relates to containing prostaglandin E 1 stable fat emulsion. Background technique

[0002] Prostaglandin E 1 (hereinafter, sometimes referred to as "PGE 1 ") The general name is that Alprostadil (Alprostadil) has a strong vasodilator effect and inhibits platelet aggregation, and is effective for improving chronic arterial occlusions (Buerger's disease, obliterative arteriosclerosis) when extremity ulcers and quiet It is effective in improving the pain of the patient, the improvement of the skin ulcer of the mobile systemic cured disease, the improvement of the skin ulcer of the diabetes, etc., so it is used in clinical practice. As a product containing prostaglandin E 1 formulations known to require dissolution of PGE in fine fat particles 1 So-called lipidation preparations (for example, "Liple Injection", manufactured and sold by Mitsubishi Tanabe Pharmaceutical Co., Ltd.). This preparation is based on the fact that fat par...

Examples

example 1

[0032] Dissolving alprostadil (PGE) in refined soybean oil 1 ), oleic acid, and egg yolk lecithin from which phosphatidylethanolamine (PE) has been removed, add a mixture of glycerin and distilled water for injection prepared separately, stir with a homogenizer, and prepare a suspension. The resulting suspension was emulsified by a Manton-Gaulin type emulsifier (manufactured by Manton-Gaulin), and the pH was adjusted to 4.90 using sodium hydroxide and hydrochloric acid. The formulated emulsion is filled into Silicoat ampoules (manufactured by Fuji Glass, and the thickness of the ampoule is 70 to 100 In the glass ampoule with a silicon oxide protective film), the void part of the ampoule was replaced with nitrogen, and sealed by fusing. The obtained ampoule was sterilized at 125° C. for 2.2 minutes using a high-pressure steam sterilizer to obtain the fat emulsion of the present invention.

example 2

[0034] An emulsion was formulated in the same manner as in Example 1, adjusted to pH 5.01 with sodium hydroxide, filled and sealed in a Silicoat ampoule and sterilized in the same manner as in Example 1 to obtain the fat emulsion of the present invention.

example 3

[0036] An emulsion was formulated in the same manner as in Example 1, and the pH was adjusted to 5.15 using sodium hydroxide. Then, it was filled and sealed in a Silicoat ampoule in the same manner as in Example 1, and sterilized to obtain the fat emulsion of the present invention.

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