JPS63238024A - Gel composition for external use containing sparingly water-soluble medicines - Google Patents

Abstract

PURPOSE:To obtain the title composition by adding necessary ingredients to a sparingly water-soluble medicament, as an active ingredient, further incorporating alginic acid or the like. CONSTITUTION:The subject gel composition for external use is obtained by formulating 0.05-1.5wt.%, based on the whole weight of the composition, of a medicament sparingly soluble in water, as an active ingredient, 0.5-1.5wt.% of a carboxyl polymer as a gelling agent, 40-95wt.% of water, further as desired ingredients, 0.01-3wt.% of alginic acid, its salt such as sodium alginate or propylene alginate. Additives, for example, solubilizer such as ethanol, absorption auxiliary, emulsifier, stabilizer and neutralizer may be incorporated. No gel collapse happens and the composition does not leak from the gaps between fingers, when it is applied.

Description

[Detailed Description of the Invention] [Industrial Field of Application] The present invention comprises a poorly water-soluble drug as an active ingredient, a carboxyvinyl polymer and water as necessary ingredients, and other commonly used additives added thereto. Regarding an external gel composition containing a poorly water-soluble drug, which further contains alginic acid, an alginate salt, or propylene glycol alginate in the external gel preparation,
More specifically, the present invention relates to a gel composition for external use containing a poorly water-soluble drug that prevents the gel from disintegrating upon application and falling off from hands and fingers.

[Prior art and its problems] External gel compositions containing carboxyvinyl polymer and water have been used in medical products, cosmetic products, and the like. These have the advantages of less stickiness on the coated surface and good spreadability. When adding a poorly water-soluble drug to a topical gel composition containing carboxyvinyl polymer and water, additives such as solubilizers, absorption aids, and emulsifiers are added along with the poorly water-soluble drug to improve skin permeability. can of course be considered. However, as a characteristic of carboxyvinyl polymer, when these solubilizers, absorption aids, emulsifiers, etc. are added to the gel composition, the stability of the gel deteriorates, and the gel disintegrates due to salt in the hands, etc. The problem arises that it falls off. To solve these problems, add sodium chloride or
Alternatively, a method has been proposed in which polyacrylic acid or a salt thereof is blended (Japanese Patent Application Laid-open No. 61-68413). but,
If sodium chloride, polyacrylic acid, or a salt thereof is added, the gel may collapse or the viscosity of the product may significantly decrease, so these methods cannot be said to be sufficiently effective.

[Characteristics of the Invention] The present inventors blended a poorly water-soluble drug as an active ingredient with a carboxyvinyl polymer and water as necessary ingredients,
In an external gel preparation made by adding this and other commonly used additives, we conducted extensive research to prevent the gel from disintegrating during application and from falling off from the hands and fingers. As a result, by blending alginic acid, alginate, or propylene glycol alginate into an external gel preparation, which is made by blending a poorly water-soluble drug with carboxyvinyl polymer and water as necessary ingredients, and other commonly used additives, It has been found that the above objectives can be achieved.

[Structure of the Invention] The topical gel composition containing a poorly water-soluble drug according to the present invention includes a poorly water-soluble drug in an amount of 05 to 1.5% by weight based on the entire composition, and a carboxyvinyl polymer as a gelling agent in the entire composition. 0.5-1.5% by weight of water, 40-1.5% by weight of the total composition.
95% by weight and alginic acid, alginate or propylene glycol alginate from 0.01% to 0.01% by weight of the total composition.
It contains 3% by weight.

The alginate is one or a mixture of two or more selected from sodium alginate, potassium alginate, and ammonium alginate.

The amount of alginic acid, alginate, or propylene glycol alginate may need to be increased or decreased depending on the type and amount of poorly water-soluble drugs and additives to be added, but it is 0.01 to 3% by weight of the entire composition, preferably 0.1 to 3%. 1% by weight can be used. The amount of alginic acid, alginate or propylene glycol alginate is 0.0
If the content is less than 1% by weight, the gel tends to slide off, and if it is more than 3% by weight, the gel becomes unstable when using alginate, and when using alginic acid or propylene glycol alginate, the viscosity of the composition increases. Note that if the drug is unstable in an aqueous solution, such as indomethacin, it is advantageous to incorporate propylene glycol alginate.

In the present invention, poorly water-soluble drugs include steroidal anti-inflammatory drugs such as dexamethasone, triamcinolone, and prezonisolone, non-steroidal anti-inflammatory drugs such as indomethacin, ketoprofen, piroxicam, and felbinac, and anti-allergic drugs such as tranilast and ketotifen. .

As a carboxyvinyl polymer, the molecular weight is 1000.
000 to 3,000,000, specifically Wako Pure Chemical's Hibiswako-103, 1O4,105, and Gutdrich Chemical's Carboball 934.940.94.
1 etc. can be blended.

In addition, the external gel composition containing the water B-soluble drug according to the present invention may optionally contain other commonly used additives as necessary.

Commonly used additives include, but are not particularly limited to, solubilizing agents for poorly water-soluble drugs, absorption aids, emulsifiers, stabilizers, neutralizing agents, anti-slip agents, coloring agents, fragrances, and the like.

Examples of dissolving agents for poorly water-soluble drugs include alcohols such as ethanol, propatool, benzyl alcohol, glycerin, stearyl alcohol, and heptyl alcohol; glycols such as propylene glycol, butylene glycol, and polyethylene glycol; medium-chain fatty acid triglycerides; Examples include glycerides such as chain fatty acid monoglycerides and medium chain fatty acid diglycerides. Examples of absorption aids include menthol, diisopropyl adipate, diethyl sebacate, isopropyl myristate, ethyl caproate, and ethyl laurate. As an emulsifier, Tween 20, Tween 60, Tween 8
0, Span 60, Span 80, Abcel C, Arasel 6
Examples include surfactants such as 0, BRIDGE 30, BRIDGE 35, and the like.

Zarani stabilizer 1. There are no restrictions on the types and amounts of neutralizing agents, anti-slip agents, coloring agents, fragrances, etc., and they can be used as desired.

In the present invention, there are no particular limitations on the method for producing the gel composition for external use containing a poorly water-soluble drug, and the gel composition can be produced by a conventional method.

Next, the present invention will be specifically explained with reference to Examples and Comparative Examples.

Example 1 Benzyl alcohol 5.0g, diisopropyl adipate 5.0g, glycerin 5.0g, Tween 80
(Product name) 3.0g and propylene glycol
5. 1.0 g of indomethacin was dissolved. To this, 0.5 g of Hibiswako-104 (trade name) and 0.1 g of sodium alginate were mixed in advance, and a solution of the mixture was dispersed and hydrated with purified water, and then 0.2 g of diisopropanolamine was added. The mixture was thoroughly stirred and the total amount was made up to 100 g with purified water.

Example 2 A product was produced in the same manner as in Example 1 except that Hivis Wako-104 (trade name) of Example 1 was replaced with Carboball 934 (trade name) and sodium alginate was replaced with propylene glycol alginate.

Example 3 Benzyl alcohol 1.7 g, diisobrobyl adipe) 4.5 g and polyethylene glycol 300 4
．． Mix 7g, dissolve 1.0g of indomethacin,
Furthermore, 40.0 g of ethanol was mixed. to this,
Hibiswako 104 (product name) 1.0 in advance
g, 0.5 g of hydroxypropyl methylcellulose and 0.7 g of sodium alginate were mixed, dispersed and hydrated with purified water, then 0.4 g of diisopropanolamine was added, stirred thoroughly, and purified water was mixed. The total amount was set to 100g.

Example 4 0.7 g of sodium alginate from Example 3 was mixed with propylene glycol alginate 1. It was manufactured in the same manner as in Example 3.

Example 5 Hensyl alcohol 2.5g, diisoprobil adipe) 2.5g and Tween 20 (trade name) 3.0
Mix g and tranilast l.

Og was suspended. To this, Arakashime Hibiswako 1
03 (trade name) 0.5g and potassium alginate 0.1g were mixed, dispersed and hydrated with purified water, then 0.2g of diisopropanolamine was added, stirred thoroughly and purified water was mixed. The total amount was set to 100g.

Example 6 Hibiswako-103 (trade name) of Example 5 was added to Carboball 941 (trade name) and potassium alginate 0.1
It was produced in the same manner as in Example 5 except that g was 1.0 g of alginic acid.

Example 7 1.7 g of benzyl alcohol, 3.3 g of diisobrobyl adipes) and 45.0 g of ethanol were mixed, and 1.0 g of tranillas) was suspended. Add 1.0g of Hibiswako-103 (product name) to this in advance.
, 0.5 g of hydroxypropyl methylcellulose and 0.7 g of potassium alginate were mixed, dispersed and hydrated with purified water, and then 0.4 g of diisopropanolamine was added, stirred thoroughly and dissolved with purified water. The total amount was 100g.

Example Day A product was produced in the same manner as in Example 7 except that 0.7 g of potassium alginate in Example 7 was replaced with 1.0 g of alginic acid.

Comparative example 1 It was produced from Example 1 except that sodium alginate was removed.

Comparative Example 2 A product was produced from Example 2 except that propylene glycol alginate was removed.

Comparative example 3 It was produced from Example 3 except that sodium alginate was removed.

Comparative example 4 Except for potassium alginate from Example 5! ! I left it behind.

Comparative example 5 It was produced from Example 6 except that alginic acid was removed.

Comparative example 6 It was produced from Example 7 except that potassium alginate was removed.

Based on the above results, the effects of preventing shedding of external gel compositions containing poorly water-soluble drugs produced in Examples and Comparative Examples? ,F
The residual rate (%) of the drug when left at 50°C for 3 months is shown in the table. The gel composition was evaluated for its anti-shedding effect according to the following gel-shedding prevention effect evaluation criteria.

Gel fall-off prevention effect evaluation standard 0: When picked up, the gel does not collapse and does not slip off the fingers.

Δ: When you pick it up, it slowly slips from your fingers.

×: When picked up, the gel collapses and immediately slips from the fingers.

[Effects of the Invention] The external gel composition containing a poorly water-soluble drug provided in the present invention is characterized by containing a water-B soluble drug as an active ingredient, a carboxyvinyl polymer and water as necessary ingredients, and further containing alginic acid and an alginate salt. Another possibility is to incorporate propylene glycol alginate. As a result, the stability of the gel is improved, the gel does not collapse during application, and it is possible to effectively prevent it from falling off from fingers.

(Patent applicant: Towa Pharmaceutical Co., Ltd.) (Agent: Patent attorney Yasu Kasuya)

Claims (3)

[Claims] (1) In a gel preparation for external use, which contains a poorly water-soluble drug as an active ingredient, a carboxyvinyl polymer and water as necessary ingredients, and other commonly used additives, which are further combined with alginic acid, alginate or propylene alginate. 1. A gel composition for external use containing a poorly water-soluble drug, which is characterized by containing glycol. (2) The amount of alginic acid, alginate or propylene glycol alginate is 0.01 to 3 of the total composition.
An external gel composition containing the poorly water-soluble drug according to claim 1 in a range of % by weight. (3) The amount of poorly water-soluble drug is 0.0 based on the weight of the entire composition.
5-1.5% by weight, carboxyvinyl polymer 0.
3. A gel composition for external use containing a poorly water-soluble drug according to claims 1 and 2, wherein the content of water is 5 to 1.5% by weight and the content of water is 40 to 95% by weight.