JPH0338244B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a poultice with excellent water retention and shape retention. A poultice using an aqueous plaster suppresses inflammation and relieves pain by absorbing heat (compress) for local acute inflammation accompanied by fever such as bruises and sprains, and the action of the water contained in it suppresses the inflammation. It is a useful dosage form that promotes skin penetration of medicinal ingredients and enhances therapeutic effects. Such poultices should have excellent water retention, high water content, no solidification, syneresis, bleeding, etc., excellent shape retention, no dripping, and appropriate adhesiveness. However, it is desirable that the adhesive has characteristics such as being able to be used immediately by simply pasting it on at the appropriate time. Conventional poultices are made by kneading kaolin, gelatin, and glycerin as a base with other water-soluble polymeric substances such as sodium polyacrylate and sodium carboxymethylcellulose, active ingredients, and water, and forming them into a paste or rice cake. It is a paste applied to a support such as cloth, and usually contains polyhydric alcohols such as glycerin, propylene glycol, sorbitol, urea, etc. to increase water retention.
In addition to incorporating alkaline earth metal salts such as magnesium chloride with high hygroscopicity and deliquescent properties into the plaster, water-soluble polymeric substances are mixed with polyvalent metal ions, aldehydes, epoxy compounds, etc. to improve shape retention. Crosslinking is performed. However, water retention and shape retention are mutually contradictory; increasing water retention reduces shape retention, and conversely, increasing shape retention decreases water retention, resulting in solidification, syneresis, and There is a tendency for bleeding to occur and adhesive strength to decrease, making it difficult to improve both water retention and shape retention in a well-balanced manner. Moreover, when a water-soluble polymer substance is crosslinked with a polyvalent metal salt to improve shape retention, the reaction of metal ions in the polymer substance (electrolyte) generally belongs to an inorganic reaction, and its speed is extremely fast. (Especially in the case of soluble salts) Since a reaction occurs simultaneously with the addition, partially non-uniform crosslinking gelation (flocculation) may occur, making it impossible to obtain a uniform paste or coating the paste on the support. There is a problem that the viscosity increases significantly during the process, making it impossible to apply it uniformly. Further, since conventional plasters have a pH of 6 or more, usually 7 to 9, they have problems such as poor stability of active ingredients such as salicylic acid esters and skin irritation. For this reason, acidic plasters are desired, but in conventional poultices, organic acids such as tartaric acid and citric acid or mineral acids such as hydrochloric acid are added to stabilize the active ingredients and alleviate skin irritation to lower the pH. When made acidic, the viscosity of the compounded polymer substances (especially gelatin and anionic polymer substances) decreases significantly, causing sag and bleed. However, in conventional technology, when the pH is lower than 6, the reaction of dialdehyde starch and urea does not proceed, and metal crosslinking has little crosslinking effect.
The more crosslinking agent is added, the harder the paste itself becomes, but more bleed may occur, making it extremely difficult to obtain an acidic poultice. In view of the above circumstances, the inventors of the present invention have developed a plaster that has excellent water retention and shape retention properties, and is capable of maintaining appropriate moisture content, consistency, and consistency over a long period of time without being affected by changes in temperature and humidity associated with seasonal changes. It has a texture, viscoelasticity, and adhesiveness, and its moisture content does not increase or decrease in a short period of time due to body temperature, perspiration, etc. even during application, so it may dry out or become soft after absorbing moisture, causing so-called sagging. As a result of intensive research to obtain a poultice that does not cause stickiness, we have found that polyvalent metal derivatives of amino acids and/or polyvalent metal salts of amino acids have been added to plasters containing water-soluble polymeric substances. It has been found that the above object can be effectively achieved by incorporating the following. That is, the present inventors added polyvalent metal derivatives of amino acids and/or polyvalent amino acids as metal ion donors to poultices containing water-soluble polymeric substances such as gelatin, sodium carboxymethyl cellulose, and sodium polyacrylate. When a valent metal salt is blended, the functional groups of the water-soluble polymer substance such as amino groups and carboxyl groups bond or chelate with the polyvalent metal ion, and the water-soluble polymer substance is crosslinked to create a more stable structural arrangement. In addition, unlike when using an inorganic crosslinking agent such as potassium alum, the reaction is gradual,
There is no rapid cross-linking reaction with polymeric substances during the production of the plaster, which prevents partial hardening and unevenness of the plaster, or a sudden increase in viscosity that prevents the plaster from being kneaded. Furthermore, unlike when dialdehyde starch is used as a crosslinking agent, the crosslinking reaction with the polymer substance proceeds even in an acidic region, making it possible to obtain an acidic paste. In addition, unlike plasters that use aluminum hydroxide as a crosslinking agent, the pH of the plaster does not gradually increase due to heat deterioration or storage and become weakly alkaline. It also maintains acidity, contributing to the stabilization of active ingredients such as salicylic acid esters and alleviation of skin irritation, and does not affect or impose restrictions on other ingredients. We have discovered that there is no such thing, and have come up with the present invention. The present invention will be explained in more detail below. The plaster according to the present invention contains a polyvalent metal derivative of an amino acid and/or a plaster containing a water-soluble polymeric substance.
Or it is made by blending a polyvalent metal salt of an amino acid. In this case, the water-soluble polymer substances include gelatin, pectin, polyacrylic acid, polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate copolymer, polyethylene oxide, sodium carboxymethylcellulose, hydroxypropylcellulose, and methylcellulose. , ethyl cellulose, alginate, xanthan gum, gum arabic, gum tragacanth, gum karaya, methyl vinyl ether/maleic anhydride copolymer, etc. In the present invention, any water-soluble polymeric substance that reacts with and crosslinks with polyvalent metal ions can be used. can be used. The amount of water-soluble polymer substance to be used is not particularly limited, but usually 1 part of the entire poultice is used.
~20% (weight%, same hereinafter). In addition, examples of polyvalent metals in polyvalent metal derivatives of amino acids or polyvalent metal salts of amino acids include calcium,
Magnesium, aluminum, iron, barium, bismuth, etc. can be used. The amino acid derivative or amino acid is not particularly limited, but α-amino acids can be preferably used. Here, the type of polyvalent metal derivative of amino acid is not particularly limited, but dihydroxyaluminum aminoacetate can be particularly preferably used. Further, the type of polyvalent metal salt of an amino acid is not particularly limited, but magnesium potassium aspartate can be particularly preferably used. In addition, in the present invention, each of the polyvalent metal derivatives of amino acids and the polyvalent metal salts of amino acids may be used alone, or two or more types may be used in combination. In addition, there is no limit to the amount of polyvalent metal derivatives of amino acids and/or polyvalent metal salts of amino acids, but it is usually 0.01 to 10% of the entire plaster.
It is preferably 0.02 to 2%. Furthermore, as other components of the present invention, appropriate components commonly used are used, such as one or more polyhydric alcohols such as propylene glycol, polyethylene glycol, glycerin, and sorbitol (in the amount usually 5-60% of the total.5%
If it is less than 60%, the moisturizing effect will be insufficient, and although there is no particular upper limit, if it is more than 60%, the solubility of the polymer and the amount of water mixed may decrease. ), kaolin,
One or more inorganic powders such as bentonite, montmorillonite, zinc oxide, titanium oxide, and silicic anhydride (compounding amount is usually 0 to 30%. If it exceeds 30%, the paste becomes too hard and does not fit well to the skin. ), water (compounding amount is usually 10 to 80%).
%. If it is less than 10%, the compressive effect will be insufficient, and if it is more than 80%, the plaster may become soft and sag. ), methyl salicylate, glycol salicylate, indomethacin, l-menthol, peppermint oil, eucalyptus oil, dl-camphor, nonylic acid vanillylamide, vitamin E, diphenhydramine, chlorpheniramine maleate, thymol, flufenamic acid and its derivatives , mefenamic acid and its derivatives, diclofenac sodium, aspirin,
ibuprofen, sulindac, naproxen, piroxicam, thiaramide hydrochloride, fenbufuene,
One or more active ingredients such as chili pepper extract, chili powder, chili tincture, capsaicin, etc. (compounding amount usually 0-20%), as an agent for adjusting the physical properties of the plaster (flexibility, adhesiveness, shape retention, etc.) Polymeric substances such as guar gum, xanthan gum, gum arabic, starch derivatives, polybutene, latex, vinyl acetate emulsion, acrylic resin emulsion, lanolin, liquid paraffin as a stabilizing agent for active ingredients,
Vegetable oil, lard, beef tallow, higher alcohol, higher fatty acid, activator, etc. are appropriately blended as necessary. The poultice of the present invention is prepared by thoroughly kneading the above-mentioned components into a paste, which is applied to a support (backing) such as paper, woven fabric, non-woven fabric, or plastic film, and if necessary, a paste such as polyethylene film. It is obtained by coating facings. Therefore, the poultice according to the present invention has improved water retention and shape retention by blending a polyvalent metal derivative of an amino acid and/or a polyvalent metal salt of an amino acid into a plaster containing a water-soluble polymeric substance. It has excellent adhesiveness, no bleeding of the paste onto the support, high adhesiveness, excellent stability of active ingredients, and reduced skin irritation. Next, examples and comparison columns will be shown to specifically explain the present invention. Example 1, Comparative Example 1 1 part of dihydroxyaluminum aminoacetate (glycinal) (parts by weight, same hereinafter), 7 parts of kaolin (JP), 2 parts of sodium polyacrylate (Aronbis S), and sodium carboxymethyl cellulose (CMC Dial 1380) )3
1 part into a mixer, and gradually add 25 parts of concentrated glycerin (Japanese Pharmacopoeia) to this, stirring thoroughly to disperse and mix until it becomes a paste. Separately, gelatin 3
1 part is swollen with 54.5 parts of water to form a homogeneous liquid at 50 to 60°C, and this is added to the above paste and kneaded until uniform. This is cooled to 35-40℃, and then a surfactant (polysorbate 80, JP) 0.5
1 part and 4 parts of the medicinal ingredient and knead thoroughly until the whole is homogeneous. The 4 parts of the medicinal ingredients are 1 part of methyl salicylate (Japanese Pharmacopoeia), 1 part of l-menthol (Japanese Pharmacopoeia), 1 part of dl-camphor (Japanese Pharmacopoeia), 0.5 part of chlorpheniramine maleate (Japanese Pharmacopoeia), and acetic acid. It consists of 0.5 parts of tocopherol (Japanese version).
Next, this was spread on a non-woven fabric to a certain thickness using a spreading machine, the surface was covered with a polyethylene film, the patch of the present invention was cut to a certain area, and this was sealed in an aluminum foil laminated bag. It was made into a product. In each of the above steps, the base material was easily made uniform, and the kneading was not hindered.
In addition, the resulting poultices do not easily soften even when stored at high temperatures, and do not easily soften due to sweating during application, so they do not lose their shape, sag, or become sticky, and can be used for long periods of time. It did not lose its cooling sensation, adhesion, elasticity, or flexibility, and neither solidification nor separation occurred even after exposure to water. Next, in order to investigate the effect of adding dihydroxyaluminum aminoacetate (amino acid polyvalent metal derivative) in the poultice of Example 1, a comparative example was prepared in which dihydroxyaluminum aminoacetate was removed from the above composition and the remaining amount was supplemented with purified water. 1
The following tests were conducted to compare the plaster of Example 1 and the plaster of Comparative Example 1. Furthermore, a product containing 1 part of aluminum acetate instead of 1 part of dihydroxyaluminum aminoacetate in Example 1 (Comparative Example 2) and a product containing 1.6 parts of aluminum citrate (Comparative Example 3) were produced in the same manner. Its properties are shown in Table 2. Test method: Each bag of each poultice was placed in a constant temperature and humidity chamber adjusted to 40±2℃ and RH75%, and after two weeks, it was taken out and brought to room temperature. bleed), adhesion of plaster to the polyethylene film when removed,
The adhesion of the paste to the skin when it was applied to human skin and removed was evaluated by a sensory test. The results are shown in Table 1 below. The evaluation criteria are as follows. Evaluation criteria -: Not at all ±: Slightly present +: A small amount present: A large amount present: Quite a large amount present

[Table] From the results in Table 1, it is clear that the plaster of the present invention containing an amino acid polyvalent metal derivative has better cohesiveness and shape retention than the comparative plaster that does not contain an amino acid polyvalent metal derivative. It was recognized that it has excellent properties such as high water retention.

[Table] Example 2, Comparative Example 4 In the composition of the poultice of Example 1, 1 part of magnesium potassium aspartate was added instead of 1 part of dihydroxyaluminum aminoacetate, and the poultice of Example 2 was obtained in the same manner. Ta. In addition, a comparative poultice was prepared by removing magnesium potassium aspartate from the above composition and supplementing it with purified water. 2
It was compared with a poultice. The results are shown in Table 3.

[Table] From the results in Table 3, it is clear that the plaster of the present invention containing an amino acid polyvalent metal salt has better cohesiveness and shape retention than the comparative plaster containing no amino acid polyvalent metal salt. It was recognized that it has excellent properties such as high water retention. Example 3 Dihydroxyaluminum aminoacetate (glycinal) 0.2 parts, kaolin (JP) 5
1 part titanium oxide, polyvinylpyrrolidone (K
-90), 1 part of sodium polyacrylate (Viscomate), and 4 parts of sodium carboxymethyl cellulose (CMC Daicel 2200) are placed in a mixer, and this is mixed with 20 parts of concentrated glycerin (Japanese Pharmacopoeia) and 70% sorbitol solution (Japanese Pharmacopoeia). ) and mix until uniformly dispersed into a paste. Next, a solution obtained by swelling and dissolving 3 parts of polyacrylic acid (Dyurimer AC) in 52.45 parts of water is added to the above paste and kneaded well. Thereafter, 1 part of a surfactant (Polysorbate 80, Japanese Pharmacopoeia) and 1.35 parts of a medicinal ingredient are added to the mixture, and the mixture is kneaded until it becomes uniformly cake-like. In addition, 1.35 parts of medicinal ingredients include 0.5 parts of glycol salicylate (Salimento), 0.2 parts of DL-camphor (Japanese Pharmacopoeia), 0.3 parts of peppermint oil (Japanese Pharmacopoeia), and tocopheryl acetate (Japanese Pharmacopoeia).
0.3 part and diphenhydramine hydrochloride (JP) 0.05
It consists of several parts. Next, this is spread on a nonwoven fabric to a certain thickness using a spreading machine, the surface is covered with a polyethylene film, and cut into a certain area to obtain the poultice of the present invention, which is enclosed in an aluminum foil laminated bag. It was made into a product. The poultice of Example 3 above was used in Example 1 and Comparative Example 1.
As a result of the same tests as in the above, it was found that the plaster had excellent properties such as high cohesiveness, shape retention, and water retention. In addition, the pH of the plaster is
When commercially available poultices that are acidic with a pH of 4.5 and contain the same medicinal ingredients in the same content as the poultices of Example 3 and Example 3 are each stored at 50°C for 10 weeks, the pH of the commercially available poultices is The pH of the poultice in Example 3 increased from 5.3 to 6.3 or higher before storage, and glycol salicylate decomposed and its residual rate was only 10%, indicating a significant decrease in content. 4.5 remained unchanged, and the residual rate of glycol salicylate was 93%, with almost no decomposition observed.The active ingredient is stabilized by maintaining the poultice in an acidic state both during manufacturing and storage. It was recognized that this could be done. Example 4 Dihydroxyaluminum aminoacetate 1% Magnesium potassium aspartate 0.2% Kaolin 5.5% Titanium oxide 0.5% Polyvinyl alcohol 2% Sodium polyacrylate 5% Polyvinylpyrrolidone/vinyl acetate copolymer 6% Carboxyvinyl polymer 1% Concentrated glycerin 24 % Citric acid 0.5% Gelatin 5% Sorbitan monooleate 1% Polyoxyethylene sorbitan monooleate (Polysorbate 80) 2% Isostearic acid 2% Isopropyl myristate 3% Squalane 1% Eucalyptus oil 2% Indomethacin 1% Water Residual total 100.0% Example 5 Dihydroxyaluminum aminoacetate
0.5% Kaolin 12% Zinc oxide 6% Polyvinyl alcohol 5% Sodium polyacrylate 9% Polyvinylpyrrolidone/vinyl acetate copolymer 4% Sodium alginate 1% Polyethylene glycol 400 5% 70% Sorbitol solution 16% Urea 1% Gelatin 8 % Polysorbate 80 1% Horse chestnut extract 0.6% Horse chestnut extract 0.2% Hyaluronic acid 1% Methyl salicylate 1% L-menthol 1% Water Total remaining 100.0% Example 6 Dihydroxyaluminum aminoacetate
0.3% Magnesium potassium aspartate 1% Zinc oxide 1% Polyvinyl alcohol 1% Sodium polyacrylate 4% Polyvinylpyrrolidone/vinyl acetate copolymer 2% Hydroxypropyl cellulose 3% Cyclodextrin 1% Concentrated glycerin 18% Castor oil 1% Propylene Glycol 4% Citric acid 2% Gelatin 9% Polyoxyethylene hydrogenated castor oil 0.6% Polysorbate 80 0.5% Methyl salicylate 1% Glycol salicylate 0.5% Water Remaining total 100.0% Example 7 Magnesium potassium aspartate 0.5% Kaolin 8% Titanium oxide 0.5% Zinc oxide 1.5% Sodium polyacrylate 3% Polyvinylpyrrolidone/vinyl acetate copolymer 8% Carboxymethyl cellulose 1.8% Gelatin 7% Sorbitan monooleate 0.5% Polysorbate 80 0.2% Isopropyl myristate 1% Indomethacin 1% Methyl salicylate 0.5 % dl-menthol 0.5% water Remaining total 100.0% Example 8 Dihydroxyaluminum aminoacetate 4% Methyl vinyl ether/maleic anhydride copolymer
12% Kaolin 8% Polyvinyl alcohol 1% Methyl cellulose 1% Polyacrylic acid 4% Concentrated glycerin 15% 70% Sorbitol solution 3% Propylene glycol 7% Gelatin 3% Polybutene 2% Polyoxyethylene hydrogenated castor oil 1% Polysorbate 80 0.5% Isostearin Acid 1% Indomethacin 1% Hyaluronic acid 1% Peppermint oil 1% Water Remaining total 100.0% Example 9 Magnesium potassium aspartate 5% 1N-NaOH aqueous solution 30ml Methoxyethylene/maleic anhydride copolymer 5% Kaolin 10% Titanium oxide 0.5% Zinc oxide 0.5% Polyvinylpyrrolidone 1.5% Concentrated glycerin 12% 70% Sorbitol 4% Polyoxyethylene hydrogenated castor oil 0.5% Polysorbate 80 1% Methyl salicylate 2% Glycyrrhizin 0.5% Water Remaining total 100.0% Example 10 Dihydroxy aluminum amino Acetate 3% Magnesium Potassium Aspartate 1.5% Xanthan Gum 1.5% Sodium Polyacrylate 4% Carboxyvinyl Polymer 4% Concentrated Glycerin 5% 70% Sorbitol Solution 12% Propylene Glycol 3% Urea 5% Polyoxyethylene Sorbitan Trioleate
1% Polysorbate 80 0.2% Methyl salicylate 1% Tocopheryl acetate 1% Water Total remaining 100.0%

Claims (1)

[Scope of Claims] 1. A poultice comprising a plaster containing a water-soluble polymer substance and a polyvalent metal derivative of an amino acid and/or a polyvalent metal salt of an amino acid. 2. The poultice according to claim 1, wherein the polyvalent metal derivative of amino acid is dihydroxyaluminum aminoacetate. 3. The poultice according to claim 1, wherein the polyvalent metal salt of an amino acid is potassium magnesium aspartate. 4. The poultice according to any one of claims 1 to 3, wherein the amount of the polyvalent metal derivative of an amino acid and/or the polyvalent metal salt of an amino acid is 0.01 to 10% by weight of the entire plaster.