KR20030055571A - Development of microsphere using carboxymethylcellulose - Google Patents

Abstract

PURPOSE: Microsphere formulations obtained by coating microspheres of a drug and carboxy methyl cellulose with a non-aqueous material are provided. The formulations retain the activity of antigen material in the body and sustainingly release the antigen material to the body. CONSTITUTION: Formulations having a size of 0.1 to 200 microns are prepared by coating a non-aqueous material on the surface of microspheres of a drug and carboxy methyl cellulose or an inorganic salt thereof. The formulations use carboxy methyl amylose, gelatin, collagen, chitosan and alginate instead of the carboxy methyl cellulose. The non-aqueous material is selected from the group consisting of lipid such as lecithin, phosphatidylcholine, phosphatidyl ethanol amine, phosphatidyl inositol, a derivative thereof, fatty acid such as myristic acid, palmitic acid and stearic acid, etc.

Description

Development of Sustained-Release Microspheres Using Carboxymethyl Cellulose {Development of microsphere using carboxymethylcellulose}

The present invention relates to a sustained-release preparation formulated to continuously release the drug, and many excellent drugs have a short period of time in which the drug is maintained in the body.

In the case of vaccines, formulations adsorbed on aluminum gel have been approved and marketed, but there is much debate about the safety of aluminum gel.

In addition, microspheres are manufactured using polyester-based polylactide, polyglycolide, and the like, which are biocompatible and biodegradable, so that protein drugs are gradually released as the polymer material is hydrolyzed.

In the case of such synthetic polymer formulations, since the decomposition rate is slow, it takes a long time to release the drug.

It is an object of the present invention to provide an agent that maintains the activity of a vaccine antigen in the body and continuously exposes the antigen to the body, thereby providing a sufficient titer in a single inoculation.

In the present invention, a microsphere containing a vaccine antigen in carboxymethyl cellulose is coated with a non-aqueous substance, and a preparation which can exert a long-term effect with a single inoculation by continuously exposing the antigen during injection into the body. to provide.

In order to prepare the microsphere of the present invention, after preparing a solution in which the vaccine antigen is contained in carboxy methyl cellulose, a micro powder having a size of 1 to 20 μm is prepared by spray drying.

The prepared microspheres are hydrophilic particles, which are easily dissolved when dissolved in water, and the surfaces thereof are coated using non-aqueous materials such as lecithin, stearic acid, stearyl alcohol, cetostearyl alcohol, polyethylene glycol, gelusir, or mixtures thereof. .

Drugs that can be used in the microspheres of the present invention include vaccine antigens such as hepatitis B vaccine, Japanese encephalitis vaccine, typhoid vaccine, growth hormone, granulocyte colony stimulating factor, erythropoietin, interferon, insulin, and urochiase. .

As stabilizers of the drug, sucrose, lactose, gelatin hydrolysates, glycine or mixtures thereof can be used.

Example 1: Japanese encephalitis vaccine antigen-containing microspheres

After dissolving high viscosity carboxymethylcellulose at a concentration of 5 mg / ml in a 10 mM phosphate buffer in which the Japanese encephalitis vaccine was dissolved at a concentration of 20 ug / ml, a 5 um microsphere was prepared using a spray dryer.

10 g of the dried microspheres were evenly dispersed in 1 l of ethanol in which 20 mg / ml of non-aqueous lecithin was dissolved at a concentration of 20 mg / ml.

After dispersing 500 mg of these particles in 1 ml of cottonseed oil, 9 ml of physiological saline solution was added and shaken to a white opaque solution of 50 ug / ml, and then inoculated into mice to confirm neutralizing antibody titer.

The reference product was a vaccine product that passed the national test, and experimental mice were inoculated into 4 groups at 10 logarithmic intervals with 10 male and female 4 weeks old.

The reference product was collected after 2 inoculations at 1 week intervals and the product was compared at the same time after 1 inoculation.

As a result, in the case of the present invention it can be seen that even one inoculation shows a superior titer than the existing product.

division Invention Reference Neutralizing antibody 10 ^ 4 10 ^ 2.5

Microspheres using carboxymethylcellulose are coated with a non-aqueous material on the surface of the particles, making them excellent in dispersibility in non-aqueous solutions, making them less viscous non-aqueous injections. Redispersing in solution can make the injection more viscous.

Development of sustained-release vaccine formulations using the same has the advantage of increasing the effectiveness of existing vaccines, as well as the development of mixed vaccines by making microspheres by mixing several vaccine antigens.

Claims (3)

0.1 ~ 200um size formulation coated with non-aqueous material on the surface of drug and microspheres of carboxymethyl cellulose or its inorganic salts The method of claim 1 Formulations using carboxy methyl amylose, gelatin, collagen, chitosan, alginate with similar properties in place of carboxy methyl cellulose The method of claim 1 The non-aqueous substances are lipids such as lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidyl inositol, derivatives of these lipids, fatty acids such as myritic acid, palmitic acid and stearic acid, salts of these fatty acids, glyceryl stearate, Formulations characterized in that it is selected from the group consisting of ester derivatives of fatty acids such as sorbate palmitate and sorbitan stearate, surfactants such as poloxamer and waxes