JPH02124813A - Injection suppository - Google Patents

Abstract

PURPOSE:To obtain an injection suppository having good retaining properties and excellent absorption properties of drug by blending a drug with a base comprising a composition prepared by blending mineral fats and oils and/or vegetable fats and oils with fixed amounts of dextrin fatty acid ester and a nonionic surfactant. CONSTITUTION:A base consisting essentially of a composition obtained by blending mineral fats and oils such as liquid paraffin or vaseline and/or vegetable fats and oils such as soybean oil or sesame oil with 1-15wt.%, preferably 2-10wt.% based on the fats and oils of dextrin fatty acid ester (e.g., ester of dextrin and palmitic acid) and 0.1-6wt.%, preferably 0.1-2wt.% nonionic surfactant (e.g., polyoxyethylene sorbitan fatty acid ester) is mixed with a drug (e.g., anti-inflammatory drug, analgesic or styptic) to give an injection suppository having good retaining properties from the lower part of the rectum to the anus and excellent absorption properties of drug. The suppository is a viscous liquid or semisolid at room temperature and injected and administered from the anus by using an insufflator.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a halved drug, and more particularly to an injected halved drug that has excellent retention properties and drug absorption from the lower rectum to the anus.

2. Description of the Related Art Conventionally, most of the halved drugs are solid types based on solid fats and oils, but solid types take time to absorb the drug and require strict temperature control for product storage.

On the other hand, injection halves based on viscous liquid oils or semi-solid oils have become popular in recent years because they are easy to manufacture, have rapid drug absorption, and do not require very strict temperature control for product storage. It became so.

Problems to be Solved by the Invention However, once injected into the rectum, the injectable halved liquid immediately becomes liquid and spreads to the sigmoid colon, so it is not suitable for hemorrhoid-affected areas from the lower rectum to the vicinity of the anus, such as hemorrhoids. It is difficult to get the drug to work properly.

An object of the present invention is to provide an injectable halved drug that has good retention properties from the lower part of the rectum to the anal region and has excellent drug absorption.

Means for Solving the Problems As a result of extensive research into solving the above problems, the present inventors found that
When administered into the rectum, half of the base is a combination of mineral oil and/or vegetable oil, a certain amount of dextrin fatty acid ester, and a nonionic surfactant, and it remains in the area from the lower rectum to the anus. The present invention was completed based on the discovery that the absorption of the drug into this region is improved.

The present invention relates to mineral oils and/or vegetable oils.
It is an injection half-split made by blending a drug into a base whose main component is a composition containing 15% by weight of dextrin fatty acid ester and 0.1 to 6% of a nonionic surfactant.

In the present invention, mineral oil is a liquid or semi-solid oil derived from petroleum that can be used as a component of a halved base, such as liquid paraffin.
・This is Vaseline.

Vegetable oils and fats are oils and fats derived from plants that can be used as a component of the halved base, such as soybean oil and sesame oil.

Text Phosphorus fatty acid Nisdel is Dex I phosphorus and
Lauric acid, myristic acid, valmitic acid, stearic acid, arachic acid, hebenic acid, etc., particularly preferably nisdel with fatty acids such as valmitic acid and stearic acid, and one or more of them are combined with mineral oils and fats. and/or 1 to 15% by weight, preferably 2 to 10% by weight of vegetable oil or fat. The nonionic surfactant is a nonionic surfactant with HLBIQ or higher, and one or more of them are added in an amount of 0.05 to 5% by weight, preferably 1% by weight, of mineral oil and/or vegetable oil. It is blended in an amount of 0.1 to 2% by weight.

As the nonionic surfactant, for example, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkyl ether, polyethylene glycol fatty acid Nisdel, polyoxyethylene hydrogenated castor oil, etc. can be used.

Drugs are commonly used medicinal ingredients, such as anti-inflammatory agents (hydrocortisone acetate, prednisolone acetate, indomethacin, ibuprofen, lysozyme chloride, glycyrrhetinic acid, etc.), analgesics (dibucaine hydrochloride, aminobenzoic acid, etc.) ethyl, lidocaine, etc.), hemostatic agents (
Zinc oxide, dffi-methylnibnidoline hydrochloride, tannic acid, etc.), wound healing promoters (allantoin, aluminum chlorohydroxyallantoinate, etc.), bactericidal agents (chlorhexidine hydrochloride, furanomycin sulfate, etc.)
, antipruritic agents (diphenhydramine hydrochloride, isothipendyl hydrochloride, etc.), vitamins (vitamin E acetate, vitamin B, etc.), and cooling agents (coumenthol, dR-camphor, etc.).

The halving of the present invention also contains water-soluble thickeners (carboxymethylhyulose sodium, carboxyvinyl polymer sodium alginate, etc.) and solubilizing agents (isopropyl myrisdate, sorbitan monomer, etc.), which are usually used in halving, as necessary. ate, glycerin oleate, etc.) can be used.

The halving method of the present invention is obtained by heating the fusible component to 70 to 90°C, preferably 75 to 85°C to melt it, then dispersing the infusible component therein, and cooling it to room temperature while stirring. can be manufactured.

The halves of the present invention are viscous or semi-solid at room temperature, and are administered by injection through the anus using a syringe.

Effects of the Invention According to the present invention, it is possible to provide an injectable half-split that has good retention properties from the lower rectum to the anus and has excellent drug absorption.

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples and Test Examples.

Example 1 Vitamin E acetate-1-160g, white 1 Nohirin 16
0g2 Dextrin Palmitate Nisder 20&, Boxoxyethylene (20) Sorbitan Monostearate [Nilacol TS-10, Trade Name, El
120g manufactured by Hikari Chemical Co., Ltd., liquid paraffin 1560
After heating and melting g to 75 to 85°C, stirring was continued while maintaining this temperature (J).

To this were added 4 g of micronized hydrocordisone acetate, 4 g of dibucaine hydrochloride, 28 g of diphenhydramine hydrochloride, 4 g of chlorhexidine hydrochloride, and 40 g of sodium alginate, and the mixture was thoroughly stirred and mixed at the above temperature.

This was cooled to room temperature while stirring, and half of the mixture was prepared.

Example 2 (Formulation) Lysozyme chloride Glycyrrhetinic acid Chlorhexidine White petrolatum Dextrin Stearate polyoxyethylene (60) Hydrogenated castor oil [Nitsukol HCO-60. Product name.

Nikko Chemical Co., Ltd.] Carboxymethyl cellulose sodium 7g g 00g 0g 0g Total 2. 000 g Based on the above formulation, an injection suppository was prepared by processing according to Example 1.

Example 3 (Formulation) Lysozyme chloride Glycyrrhetinic acid Chlorhexidine White petrolatum Dextrin Valmitic acid ester Polyoxyethylene (20) Sorbitan monooleate [Niracol TO-10, trade name, manufactured by Nikko Chemical Co., Ltd.] Sodium carboxymethyl cellulose 7 g g 00g 00g 0g Liquid paraffin 00g Total 2,000g Based on the above recipe, an injection supplementary agent was prepared by processing according to Example 1.

Example 4 (Formulation) Hydrocortisone acetate 4g Dipcaine hydrochloride 4g Diphenhydramine hydrochloride 28g Chlorhexidine hydrochloride
4g white petrolatum
160g dextrin palmitate ester
100g polyoxyethylene (40) monostearate [Niracol MMS-40, trade name.

Nikko Chemical Co., Ltd. 5g carboxyvinyl polymer vitamin E acetate 160g total 2
．． 000 g Based on the above formulation, an injection suppository was prepared by processing according to Example 1.

Test Example 1 Injection top preparations were prepared according to Example 1 according to the formulation shown in Table 1, and 0.1 part by weight of blue aluminum lake was added to each 100 parts by weight, and the mixture was thoroughly mixed to make it homogeneous. Samples 1 to 17 were used, respectively.

Table 1 Three domestic rabbits (male, weight 2.5-3 kg) were grouped together, and 2 g of each sample was injected into the anus of the rabbits in the separate group, and the anus was sealed.

4 hours after injection, remove the rectum and remove the lower part of the rectum (1 minute from the anus).
0cm) was cut out, and the half existing in this part was scraped off, dissolved in 50d of 0°IN nitric acid methanol solution, and filtered to obtain a sample solution.

Separately, accurately weigh 0.1 g of blue No. 1 aluminum rake, and IN
Dissolve in 1.00 arll of nitric acid methanol solution, collect 2d of this solution accurately, put it in a 50-volume flask, and add
, adjusted to 5M with IN nitric acid methanol solution and used as a standard solution.

The absorbance of each sample solution and standard solution at 627 nm was measured using a spectrophotometer, and the weight of the half remaining in the rectal t' region was calculated using the following formula.

The results are shown in Table 2.

Test Example 2 After washing the lower rectum obtained in Test Example 1 with water and thoroughly washing half of it, it was placed in a 50 d centrifuge tube and mixed with 10 m of methanol.
Homogenization was performed by adding N and water. This was centrifuged (3000 rpm, 10 minutes), and the supernatant was taken into a 50 mg volumetric flask. Add 10 d of methanol and 2 LI of water to the residue! ! The mixture was shaken for 10 minutes, centrifuged (3000 rpm, 10 minutes), and the supernatant was added to a MIF 50d volumetric flask and diluted with an aqueous methanol solution (10:2).

Accurately take 10 d of this solution, put it in a volumetric flask and evaporate it, and the residue is used as an eluent for liquid chromatography [methanol-water-phosphoric acid (40:60:
1) Mixed liquid] Dissolved in 1d to prepare a sample solution.

Separately, accurately weigh 50 mg of hydrocordesin into a 20 d volumetric flask, add methanol to adjust to 20 mg,
Hydrocordesin was dissolved. Accurately weigh 2 d of this solution, put it in a 50 d volumetric flask, and add the methanol aqueous solution (
10:2) to make a standard solution.

The sample solution and standard solution were subjected to high-performance liquid chromatography [filling material: TSK-Gel LS410 (trade name, manufactured by Tosoh Corporation, color 150 mm x 4 m).
mφ, flow rate 10 d/min, eluent: methanol-water-nonacid (40:60:0.1) mixture, column temperature 50
℃, and ultraviolet absorption at 240 nm was measured to measure drocortisone content in the lower rectal tissue.

The results are shown in Table 2.

No. table

Claims (1)

[Claims] (1) Mineral oils and/or vegetable oils 1 to 15
An injection suppository prepared by blending a drug into a base whose main component is a composition containing dextrin fatty acid ester at % by weight and a nonionic surfactant at 0.1 to 6% by weight.