JPS62161724A - 3-oxygermylropionic acid drug for external use - Google Patents

Abstract

PURPOSE:The titled drug for external use, obtained by blending 3- oxygermylpropionic acid with a high polymer carrier for formulation as a stabilizer in a specific proportion, capable of very well holding antitumor, antimicrobial and anti-inflammatory activity and having high efficacy for a long period. CONSTITUTION:A drug for external use obtained by blending 0.005-5wt% 3-oxygermylpropionic acid expresses by the formula (n is an integer of >=1) with 0.005-25wt% high polymer carrier for formulation as a stabilizer. The above-mentioned high polymer carrier for formulation is selected from natural high polymers, eg.g gelatin, blood serum albumin, etc., synthetic high polymers, e.g. glycol, cellulosic high polymer, etc., proteinaceous mixtures, e.g. peptone, trypsin, etc. The drug is preferably used in the form of ointment or cream for viral single wart, viral multiple wart, dermal cancer, etc., and in the form of suppository for rectal cancer, herpetic dermatitis, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a 3-oxygermylpropionic acid external preparation.

(Prior art and its problems) Organic germanium compounds (polymers), especially 3-oxygermylpropionic acid, are compounds that have attracted much attention in recent years due to their pharmacological activity, but they are extremely unstable in water. It has certain flaws.

(Purpose of the Invention) The present inventors have focused on the pharmacological activity exhibited by organic germanium polymers, compared polymers with different synthesis conditions, and as a result of intensive research on conditions for maintaining pharmacological activity, have found that He discovered that it was effective to coexist with a polymeric carrier, and filed the original patent application (Japanese Patent Application No. 59-186).
No. 270, JP-A No. 61-65819).

In contrast, the present invention uses 3-oxygermylpropionic acid as an effective substance among the various organic germanium polymers shown in the specification of the original patent application, and has stable pharmacological activity. The object of the present invention is to provide an external preparation that can provide this compound while retaining the following properties.

(Means and Effects for Achieving the Object) According to the present invention, the above object is achieved by 3-oxygermylpropion represented by the formula % (wherein n means an integer of 1 or more). acid 0.00
This is achieved by a topical preparation for 3-oxygermylpropionic acid, which is characterized by containing 5-5% by weight and 0.005-25% by weight of a polymeric carrier for formulation as a stabilizer. .

In the external preparation according to the present invention, the pharmaceutical carrier can be at least one of natural polymeric substances, synthetic polymeric substances, and protein-based formulations. Examples of natural polymeric substances include gelatin, pepsin, serum albumin, globulin, and protamine. Synthetic polymeric substances include glycols, cellulose polymeric substances, vinyl polymeric substances, and acrylic polymeric substances. Among these, glycols include propylene glycol and polyethylene glycol, cellulose-based polymers include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and carboxymethylcellulose, and polyvinyl-based polymers include polyester. Vinyl pyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, etc.
Examples of the acrylic polymer include methacrylic acid, ethyl acrylate copolymer, polyacrylic acid, and polyacrylamide.

On the other hand, examples of protein-based formulations include so-called additive components for medium, such as peptone, polypeptone, yeast extract, tryptone, tryptose, and dextrose.

The amount of addition or blending of the polymeric carrier as a stabilizer is as follows:
It depends on the type of the topical preparation and the type of topical preparation depending on the disease. For example, for inflammatory diseases that require mild sterilization and disinfection properties, such as sunburn, a topical preparation in the form of a lotion is preferable. is 3-oxygermylpropionic acid 0.0
It is advantageous to prepare a polymeric carrier such as polyvinyl pyrrolidone in a range of 0.4-3.0% by weight to 5-3.0% by weight. It is possible to maintain the pharmacological activity of propionic acid in an optimal state, and also to provide long-term storage stability. Diseases that require moderate antibacterial and anti-inflammatory properties such as single viral warts, as well as multiple viral warts,
For diseases that require strong antitumor or bactericidal properties such as skin cancer and malignant moles, external preparations in the form of ointments or creams are preferred; in this case, 0.005-1 3-oxygermylpropionic acid It is advantageous to mix 0.02-1.5% by weight of a polymeric carrier such as albumin with respect to 0.0% by weight, thereby increasing the pharmacological activity of 3-oxygermylpropionic acid. It is possible to optimize the retention state and provide long-term storage stability.

In addition, for diseases that require severe antibacterial and anti-inflammatory properties, such as rectal cancer caused by viral diseases and herpetic dermatitis, a suppository form is preferable, and in this case, 3-oxygermylpropionic acid 0. 5-2.0% by weight of a polymeric carrier such as hydroxypropylcellulose of 1.0-4.0% by weight.
It is advantageous to formulate the 3-oxygermylpropionic acid by blending it within the range of % by weight, which can optimize the retention of the pharmacological activity of 3-oxygermylpropionic acid and provide long-term storage stability. can.

(Effects of the Invention) According to the external preparation according to the present invention, the pharmacological activity of 3-oxygermylpropionic acid, which is the main ingredient, is maintained extremely well, and as a result, the effectiveness hardly decreases even after long-term storage. A topical preparation for 3-oxygermylpropionic acid is provided.

(Examples, etc.) Next, the present invention will be described in further detail with reference to formulation examples and stability test examples thereof as examples.

Reifuranyu (suspension lotion) 1.5g 3-oxygelmylpropionic acid 1.5g gum arabic powder 3.0g polyvinyl pyrrolidone (K 30) 1.5g lime water
5010-s water total volume 100.0ml 3-oxygermylpropionic acid was collected in a dry mortar,
A small amount of ethanol is added and the mixture is lightly ground into a fine powder, and gum arabic powder is added thereto and further ground. After the ethanol has evaporated, add rose water little by little and continue grinding to completely emulsify the whole. Next, continue grinding and gradually add lime water to obtain the desired suspension lotion. as a drug.

1 Goryu (emulsifying lotion) 1 Ryo 3-oxygermylpropionic acid 1.0 g Carboxymethyl cellulose (sodium salt) 0.5 g Stearyl alcohol 2.5 g Light liquid paraffin 25.0 g Sodium lauryl sulfate
1.0g propylene glycol 12.
Og Methyl paraoxybenzoate 0.025g Propyl paraoxybenzoate 0.015g Total amount of purified water 100. hl Dissolve stearyl alcohol on a water bath, add paraffin to it, and then warm to 70°C (oil phase)
On the other hand, methyl paraoxybenzoate and propyl paraoxybenzoate as preservatives and the remaining components carboxymethyl cellulose (Na salt), sodium lauryl sulfate and propylene glycol were added to hot water,
Prepare the aqueous phase by keeping at °C. This aqueous phase is added to the above oil phase, cooled to 45° C. with stirring, and then allowed to cool to form a desired emulsified lotion.

ML3A solution-based lotion) 1 3-oxygermylpropionic acid 0.1 g Polyvinyl pyrrolidone (K 30) 0.5 g Total amount of purified water 100.0 ml Add polyvinyl pyrrolidone and 3-oxygermyl propionic acid to purified water. Add and dissolve to form the desired solution-based lotion.

Shinl'L Soil (Cream) Add 1.5% 3-oxygermylpropionic acid to 4% bovine serum albumin solution. Add and dissolve to achieve Ox concentration,
It was then freeze-dried. This composition was mixed with excipients and the like according to the following formulation to prepare a cream by a conventional method.

Treatment L The above composition 0.5g diethyl sebacate 8.0g 1t wax
5.0g Sodium polyoxyethylene oil ether phosphate 6.0g Sodium benzoate 0.5g Total amount of petrolatum 100.0g AlbL (cream) (Phase A) Polyoxyl stearate 40 50g Glycerin fatty acid ester 100g Beef fatty acid liglyceride
60g cetanol 60
g Butyl oxybenzoate Ig (Phase B) 3-oxygermylpropionic acid 5 g Propylene glycol 5Qg 3% albumin aqueous solution
100g rose methyl oxybenzoate 1
g Total amount of purified water (A + B phase) 1000g Heat the above A and B phases to TO-80℃ respectively.
Phase B is gradually added to the human phase while stirring, stirred under reduced pressure at 45° C., and then allowed to cool to obtain a desired cream.

1! ]1Li (Suppositories) The lyophilized composition obtained in the course of Formulation Example 4 is dispersed in a melt of cacao butter (higher fatty acid glyceride) as an oily base, and formed into a desired suppository by a conventional method. as a drug.

Above composition 60+ag cocoa butter 60I+170 per piece
0ntg Next, we will show the stability tests and results of the external preparation of the present invention obtained from the above formulation example. These results show that the external preparation of the present invention is extremely stable in terms of pharmacological activity and has a long-lasting effect. It is found that it can withstand storage.

An J11 Test JLLI Each of the external preparations of Formulation Examples 1-3 was loaded into a glass bottle and placed in a constant temperature bath at 40°C and stored for 6 months, during which time the pharmacological activity was measured over time. The reduction rate was investigated and the results are shown in Table 1 below.

The external preparations of Shiran m Takuyu formulation examples 4 and 5 were each filled into an aluminum tube and placed in a constant temperature bath at 35°C and stored for 8 months, during which time the pharmacological activity was measured. The reduction rate was investigated and the results are shown in Table 2 below.

The topical preparation of Shijogo XMJfL Yu Formulation Example 6 was placed in a constant temperature bath at 25°C in an FTP package and stored for 8 months, during which time the pharmacological activity was measured and the rate of decrease was determined. The results of the investigation were as shown in Table 3 below.

It is.

table" Shishiji”

Claims (9)

[Claims] (1) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, n means an integer of 1 or more) 3-oxygermylpropionic acid 0.00
5-5% by weight of 3-oxygermylpropionic acid, and 0.005-25% by weight of a polymeric carrier for formulation as a stabilizer. (2) The 3-oxygel according to claim 1, wherein the polymeric carrier for pharmaceutical preparations is at least one of a natural polymeric substance, a synthetic polymeric substance, and a protein-based compound. Milpropionic acid topical preparation. (3) 3-oxygermylpropionic acid according to claim 2, wherein the natural polymeric substance is at least one selected from gelatin, pepsin, serum albumin, globulin, and protamine. Topical preparation. (4) The synthetic polymeric substance according to claim 2, wherein the synthetic polymeric substance is at least one of glycols, cellulose-based polymeric substances, vinyl-based polymeric substances, and acrylic-based polymeric substances. 3-oxygermylpropionic acid external preparation. (5) characterized in that the protein-based formulation is at least one selected from peptone, polypeptone, yeast extract, tryptone, tryptose, and dextrose;
3-oxygermylpropionic acid external preparation according to claim 2. (6) The external preparation for 3-oxygermylpropionic acid according to claim 4, wherein the glycol is selected from propylene glycol and polyethylene glycol. (7) Claim 4, characterized in that the cellulosic polymer material is selected from methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and carboxymethylcellulose.
3-oxygermylpropionic acid external preparation as described in 2. (8) 3-oxygelmylpropion according to claim 4, wherein the polyvinyl polymer substance is selected from polyvinyl pyrrolidone, polyvinyl alcohol, and carboxyvinyl polymer. Acid topical preparation. (9) The 3-oxy acrylic material according to claim 4, wherein the acrylic polymer material is selected from methacrylic acid, ethyl acrylate copolymer, polyacrylic acid, and polyacrylamide. Germylpropionic acid topical preparation.