JPH029006B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a skin protective agent mainly composed of an acrylic polymer that is water resistant, alkali soluble, and contains few impurities. [Prior Art] Protective coatings for protecting the skin from chemicals and other irritating substances are known. When applied to the skin surface, it forms a film to protect the skin. In the past, cellulose derivatives dissolved in strong organic solvents such as acetone and ethyl acetate have been used, but organic solvents can irritate the skin and mucous membranes, and can remove the formed film from the skin. There were some problems, such as it was not easy. Recently, a skin protective agent (hereinafter also referred to as the prior art protective agent) whose main ingredients are n-butyl polyester/maleic acid and plasticized ethyl cellulose has been commercially available in the United States, but this In Japan, it has not yet been put into practical use due to problems in its use, such as safety not yet being established. In this prior art protective agent, an extracorporeal catheter,
Creates a protective agent between the skin and the immobilizer, cast, diaper, etc. Another proposed use is to prevent hands from getting dirty with grease. In particular, the present inventors have conducted intensive studies on polymers that can coat the skin of housewives who use neutral detergents, and those who clean equipment in restaurants, hospitals, beauty salons, and the like. Acrylic polymers have long been used in medicine and are known to be highly safe. However, since all known acrylic polymers are manufactured by conventional polymerization methods such as welding polymerization and emulsion polymerization, the resulting polymers contain large amounts of anionic surfactants, chain transfer agents, residual monomers, etc. I'm here. Therefore, not only is it irritating to the skin and poses problems in terms of environmental protection, but the presence of surfactants also makes the film brittle and has poor water resistance. This was not suitable for the main purpose of the present invention. In addition, some research has been conducted on polymer emulsion synthesis that does not use surfactants or similar water-soluble substances, but for example, when this method is used to copolymerize ethyl acrylate and acrylic acid, It has been said that when the amount of acid exceeds 2 to 3 mol%, the resulting polymer emulsion becomes mechanically unstable and tends to gel (Matsumoto et al., Kobunshi Ronshu Vol. 32, No. 9). 1975). Furthermore, known acrylic polymers for pharmaceutical use, such as Eudragit from Ro¨hm Pharma in West Germany, are unsuitable for the purpose of the present invention due to the elongation and tensile strength of the resulting film. It turned out to be. [Problems to be Solved by the Invention] To achieve the objects of the present invention, it is necessary to satisfy the following points in a well-balanced manner, but a polymer that simultaneously satisfies them has not yet been developed. The required performance of the skin protective agent targeted by the present invention is (1) to be able to form a thin film, (2) to be water resistant and alkali soluble, (3) to form a stretchable and flexible film, (4) Contains few impurities such as residual monomers, has no odor or irritation, (5) Does not permeate neutral detergents, (6) Dissolves in alcohol or water-containing alcohol, and ( 7) It must be breathable and moisture permeable, and it must not get stuffy or sticky when covered. [Means for solving the problem] In view of the above points, the present inventors have prepared 75 parts by weight to 95 parts by weight of ethyl acrylate (hereinafter sometimes referred to as EA).
Parts by weight and 25 to 5 parts by weight of methacrylic acid (hereinafter also referred to as MAA) monomer are heated in deionized water, using persulfate as a polymerization initiator, and further peroxidized if desired. It has now been discovered that the use of redox catalyst systems such as hydrogen, ferrous sulfate, and L-ascorbic acid, alone or in combination, and post-treatment, results in the synthesis of preferred polymers that meet the objectives of the present invention, and the present invention has been made in accordance with the present invention. Completed. The monomer unit of the copolymer used in the skin protection agent of the present invention will be explained in more detail. Ethyl acrylate is 75~
It is used in a range of 95 parts by weight, preferably in a range of 80 to 90 parts by weight. The reason I chose EA is that EA
This is because the synthetic copolymer can be easily dissolved in a solvent such as alcohol or hydrous alcohol. Methacrylic acid is used in the copolymer in an amount of 25 to 5 parts by weight, preferably 20 to 10 parts by weight. If the composition ratio of MAA is below the above-mentioned lower limit, alkali solubility will be insufficient, and if the composition ratio of MAA is above the above-mentioned upper limit, elongation and flexibility will decrease, which is not preferable. If the composition ratio of MAA exceeds 35 parts by weight, the polymer becomes unstable and an emulsifier or suspending agent is required to stabilize it. The water resistance of the films obtained from the compositions of the invention was better than that of the prior art protectants. Why did we choose MAA instead of acrylic acid?
This is because MAA is said to be safer and has been found to be better in terms of water resistance and reduction of residual monomers. They also found that when copolymers with EA are made in the absence of emulsifiers, a higher proportion of unsaturated carboxylic acid monomers can be used when MAA is used as a partner than when acrylic acid is used as a partner. This is a strong reason for selection. As a result, a safer acrylic polymer with fewer impurities could be obtained. Compared to the known prior art protective agents, the skin protective agent of the present invention provides a protective film with a better feel without any discomfort or stinging sensation. The various properties required for the above-mentioned polymer for skin protection agents can also be adjusted by changing the monomer composition ratio of ethyl acrylate and methacrylic acid in the acrylic polymer. For example, when intending to make a film with emphasis on water resistance, MAA
When a film with a low composition ratio and an emphasis on alkali solubility is intended, the MAA composition ratio may be increased. A general method for producing the acrylic polymer of the present invention is shown. Deionized water is placed in a closed reactor purged with nitrogen and heated. Persulfate, previously dissolved in deionized water, is added as a polymerization initiator, then EA and
Each monomer of MAA is added over a period of time under stirring. The polymerization progresses and is almost complete by the time the monomer addition is completed. If it is desired to further reduce the monomer concentration, the reaction temperature is maintained as it is, or the temperature is raised further and stirring is continued (hereinafter, this step may be referred to as post-treatment). The reaction solution is cooled to obtain the desired polymer as a dispersion. Examples of the persulfate include ammonium persulfate, sodium persulfate, potassium persulfate, etc., and the total amount may be added at once, or may be added in portions or continuously. The optimum amount of persulfate to be used is selected depending on the final polymer concentration, polymerization temperature, polymerization time, etc., but it is generally about 0.2 to 4 parts by weight, more preferably about 4 parts by weight per 100 parts by weight of monomer. 0.4
~3 parts by weight is used. Below the lower limit, the stability of the polymer dispersion becomes poor and residual monomer increases, while above the upper limit, the water resistance of the coating decreases. If you want to reduce the time required for post-treatment, you can increase the post-treatment temperature, add persulfate during post-treatment, or use a combination of hydrogen peroxide, ferrous sulfate and L-ascorbic acid. It is sufficient to add a small amount of an oxidation-reduction catalyst, etc. If the purpose is simply to complete polymerization and reduce residual monomers, polymerization initiators and redox catalysts other than those mentioned above may be used, but they are not preferred in view of the application to the skin, which is the purpose of the present invention. Although the monomers EA and MAA may be added separately, it is easier to add them as a mixture. Although the addition rate may vary, it is preferable to add at a constant rate because it prevents the formation of coarse particles and facilitates temperature control. Polymerization temperature is about 45-98℃, more preferably 65-95℃
Adjust to a range of ℃. Below the lower limit, coarse particles are likely to be generated. The polymer concentration in the dispersion is not particularly limited, but is preferably 15 to 65%, more preferably 25 to 55%. Below the lower limit, the amount of monomer persulfate required increases or the relative amount of residual monomer increases. Moreover, if it exceeds the upper limit, the polymer dispersion becomes unstable, and coarse particles and deposits on the vessel wall increase. According to the above method, polymers with various degrees of polymerization can be obtained. Although it is not necessary to particularly limit the weight average molecular weight of the polymer, for the purpose of the present invention, it is approximately 100,000 to 100,000.
2,000,000, more preferably about 100,000 to 1,300,000 is preferably used. By adjusting the amount of persulfate used, polymerization temperature, and polymer concentration, the molecular weight of the produced polymer can be freely selected. Furthermore, if alcohol such as ethanol or isopropanol is used as a chain transfer agent, the molecular weight can be reduced. The use of commonly used chain transfer agents such as organic sulfur compounds is not preferred in view of skin safety. The skin protection agent of the present invention is prepared by dissolving the acrylic polymer and hydrophilic cellulose in a suitable medium. As the medium, alcoholic solvents are preferred. Ethanol or aqueous ethanol is the most desirable dissolution medium as a skin protectant from the standpoint of safety, but high ethanol content evaporates quickly;
There are problems such as irritation when the skin is damaged.
Conversely, if there is too much water, the solubility of the polymer will decrease or the evaporation rate will slow down. Isopropanol can also be used instead of ethanol. The preferred mixing ratio is 60/40 to 80/20 alcohol/water. Acrylic polymer in these solvents is about 2~
It is desirable to dissolve at a concentration of 10%, more preferably about 4-7%. If the upper limit is exceeded, a sticky feeling may be felt during use, and adhesion to the skin may be reduced. Below the lower limit, only a thin film is formed and the film becomes brittle, which is not preferable. Examples of cellulose derivatives used in the present invention include methylcellulose, ethylcellulose, and hydroxypropylcellulose. Among them, ethylcellulose is most preferably used. The amount of cellulose added is approximately 0.3
% to 2%, more preferably about 0.7 to 1.5%.
If it is more than the upper limit, the film formed will become brittle, which is not preferable, and if it is less than the lower limit, it will feel sticky during drying, which is also not preferable. The addition of these celluloses significantly improved the tackiness during coating and the elasticity after drying. If desired, the skin protective agent of the present invention may contain appropriate softeners, additives such as polyvinylpyrrolidone, preservatives, coloring agents, or pharmaceutically active ingredients. The skin protective agent of the present invention forms a colorless and transparent thin film, and is therefore very desirable from a cosmetic point of view. However, depending on the purpose of use, it may be designed to add an appropriate coloring agent to confirm the presence or absence of film formation. In the present invention, the formulation packaging form of the skin protective agent should not be particularly limited. Since the protective agent is an alcohol solution, a closed container that can prevent the alcohol from volatilizing is preferable. For example, a glass or plastic bottle or a spray container may be used. The advantages of the acrylic polymer used in the present invention and the advantages in producing the polymer are summarized below. Forms a film that is almost impermeable to neutral detergents and can be easily washed off with weakly alkaline soaps. Forms a thin, highly flexible film with good elongation. When the residual monomer content is 50 ppm or less, there is almost no odor and no irritation. In the conventional emulsion polymerization method, there is a large amount of residual monomer and therefore a strong odor. In order to reduce this residual monomer, a long time is required for post-processing such as vacuum suction and extension of polymerization time. However, in the polymerization method shown in the present invention, since there is little residual monomer, post-treatment is also easy. It is stable at room temperature and can be stored for long periods without using emulsifiers or suspending agents. The present invention will be explained in more detail with reference to the following Examples, but these are not intended to limit the scope of the present invention in any way. Reference Example (Production of Polymer) Reference Example 1 236.1 parts by weight of deionized water was charged into a closed reaction vessel equipped with a stirrer and the air was purged with nitrogen, and the temperature inside the reactor was adjusted to 80°C. Then, 1.2 parts by weight of ammonium persulfate was added. Then, the following monomer mixture, 85 parts by weight of EA and 15 parts by weight of MAA, was added over 8 hours. Stirring was continued for an additional 8 hours while maintaining the inside of the reactor at 80°C to complete the reaction. The solid content of this dispersion was 30%, and as a result of analysis of residual monomers by gas chromatography,
EA was 37ppm and MAA was less than 10ppm. Furthermore, the weight average molecular weight of this copolymer was approximately 840,000. Reference Example 2 237.3 parts by weight of deionized water and 0.5 parts by weight of isopropanol were charged into a closed reaction vessel equipped with a stirrer and replaced with nitrogen, and the inside of the reactor was adjusted to 80°C. Then, 1.7 parts by weight of ammonium persulfate was added, and then the following reaction was carried out. A monomer mixture of 85 parts by weight of EA and 15 parts by weight of MAA was added over a period of 5 hours. The inside of the reactor was maintained at 85° C., hydrogen peroxide, ferrous sulfate, and L-ascorbic acid were added in an amount of 0.1 part by weight, and stirring was continued for 5 hours to complete the reaction. The solids content of this dispersion was 30%;
Analysis of residual monomers by gas chromatography revealed that EA was 12 ppm and MAA was 10 ppm or less. Further, the weight average molecular weight of this copolymer was approximately 180,000. Reference Example 3 237.3 parts by weight of deionized water and 2.0 parts by weight of isopropanol were charged into a nitrogen-substituted airtight reaction vessel equipped with a stirrer, and the temperature inside the reactor was adjusted to 80°C. Then, 1.7 parts by weight of ammonium persulfate was added, and then the following reaction was carried out. A monomer mixture of 80 parts by weight of EA and 20 parts by weight of MAA was added over 8 hours. The inside of the reactor was maintained at 85° C., hydrogen peroxide, ferrous sulfate, and L-ascorbic acid were added in an amount of 0.1 part by weight, and stirring was continued for 5 hours to complete the reaction. The solids content of this dispersion was 30%;
Analysis of residual monomers by gas chromatography revealed that EA was 20 ppm and MAA was 10 ppm or less. Further, the weight average molecular weight of this copolymer was approximately 130,000. Reference Example 4 238.0 parts by weight of deionized water and 3.0 parts by weight of isopropanol were charged into a nitrogen-substituted airtight reaction vessel equipped with a stirrer, and the temperature inside the reactor was adjusted to 80°C. Then, 2.0 parts by weight of ammonium persulfate was added, and then the following reaction was carried out. A monomer mixture of 75 parts by weight of EA and 25 parts by weight of MAA was added over a period of 5 hours. The inside of the reactor was maintained at 85° C., hydrogen peroxide, ferrous sulfate, and L-ascorbic acid were added in an amount of 0.1 part by weight, and stirring was continued for 5 hours to complete the reaction. The solids content of this dispersion was 30%;
Analysis of residual monomers by gas chromatography revealed that EA was 18 ppm and MAA was less than 10 ppmm. Furthermore, the weight average molecular weight of this copolymer was approximately 110,000. Reference Example 5 237.3 parts by weight of deionized water was charged into a closed reaction vessel equipped with a stirrer and the air was replaced with nitrogen, and the inside of the reactor was adjusted to 80°C, and 1.7 parts by weight of potassium persulfate was added.
Then, the following monomer mixture, 85 parts by weight of EA and 15 parts by weight of MAA, was added over 8 hours. The inside of the reactor was maintained at 80 DEG C., hydrogen peroxide, ferrous sulfate and L-ascorbic acid were added in an amount of 0.1 part by weight, and stirring was continued for 5 hours to complete the reaction. The solid content of this dispersion was 30%, and analysis of residual monomers by gas chromatography showed that EA was 15 ppm and MAA was 10 ppm or less. Moreover, the weight average molecular weight of this copolymer was approximately 750,000. Reference Example 6 187.8 parts by weight of deionized water was charged into a closed reaction vessel equipped with a stirrer and the atmosphere was replaced with nitrogen, and the temperature inside the reactor was adjusted to 75°C. Then, 1.1 parts by weight of ammonium persulfate was added, and then the following monomer mixture EA 80 20 parts by weight MAA were added over 5 hours. The inside of the reactor was maintained at 88 DEG C., hydrogen peroxide, ferrous sulfate and L-ascorbic acid were added in an amount of 0.1 part by weight, and stirring was continued for 5 hours to complete the reaction. The solid content of this dispersion was 35%, and analysis of residual monomers by gas chromatography showed that EA was 15 ppm and MAA was 10 ppm or less. Moreover, the weight average molecular weight of this copolymer was approximately 800,000. Reference Example 7 151.7 parts by weight of deionized water was charged into a closed reaction vessel equipped with a stirrer and replaced with nitrogen, and the temperature inside the reactor was adjusted to 70°C. Then, 1.1 parts by weight of ammonium persulfate was added, and then the following monomer mixture EA 85 15 parts by weight MAA were added over 8 hours. The inside of the reactor was maintained at 80 DEG C., hydrogen peroxide, ferrous sulfate and L-ascorbic acid were added in an amount of 0.1 part by weight, and stirring was continued for 5 hours to complete the reaction. The solid content of this dispersion was 40%, and analysis of residual monomers by gas chromatography showed that EA was 20 ppm and MAA was 10 ppm or less. Furthermore, the weight average molecular weight of this copolymer was approximately 1,180,000. Example 1 The dispersion prepared in Reference Example 1 was used as a polymer.
Weigh it into a suitable container so that it weighs 100 g. Add 658 g of isopropanol (hereinafter sometimes referred to as IP) and stir until the polymer is completely dissolved.
Ethyl cellulose (hereinafter referred to as
Gradually add 10g of EC (sometimes called EC) to prepare a uniform dispersion, then add water to bring the total amount to 1Kg. This composition contains 5.0% of the polymer of Reference Example 1 and
Contains EC1.0% in IP. Example 2 Using the polymer prepared in Reference Example 2, a hydrous IP solution containing 5.0% polymer and 1.0% EC is prepared according to the preparation method of Example 1. Example 3 Using the polymer prepared in Reference Example 3, a water-containing IP solution containing 5.0% polymer and 1.0% EC is prepared according to the preparation method of Example 1. Example 4 Using the polymer prepared in Reference Example 4, a water-containing IP solution containing 5.0% polymer and 1.0% EC is prepared according to the preparation method of Example 1. Example 5 Using the polymer prepared in Reference Example 1, a hydrous IP solution containing 3.5% polymer and 1.0% EC is prepared according to the preparation method of Example 1. Example 6 Using the polymer prepared in Reference Example 1, a water-containing IP solution containing 7.0% polymer and 1.0% EC is prepared according to the preparation method of Example 1. Example 7 Using the polymer prepared in Reference Example 1, a hydrous IP solution containing 10.0% polymer and 1.0% EC is prepared according to the preparation method of Example 1. Example 8 Using the polymer prepared in Reference Example 2, a water-containing IP solution containing 7.0% polymer and 1.0% EC is prepared according to the preparation method of Example 1. Test Example 1 The following composition was applied to the back of a person's hand to examine the performance of the composition of the present invention. As controls, an EC-free composition of the polymer of the present invention, a composition of a known acrylic polymer, and a commercially available liquid adhesive plaster were used. The results are shown in Table 1. (Test composition) Composition of the present invention Examples 1 to 7 Control composition (prior art) Reference 1 The following components are contained in the water-containing IP. Polymer of Reference Example 1 3.5% Reference 2 The following components are contained in the water-containing IP. Polymer of Reference Example 1 5.0% Reference 3 The following components are contained in the water-containing IP. Polymer of Reference Example 1 7.0% Reference 4 The following components are contained in the water-containing IP. Polymer of Reference Example 1 10.0% Control 1 Water-containing IP contains the following components. Eudragit E30D 5.0% EC 1.0% Control 2 Water-containing IP contains the following ingredients. Eudragit E30D 10.0% EC 1.0% Control 3 Water-containing IP contains the following ingredients. Eudragit L30D-55 10.0% EC 1.0% Control 4 Commercially available film forming agent (aerosol type) Control 5 Commercially available liquid bandage Results The skin protective agent of the present invention is a skin protective agent using a known acrylic polymer or a commercially available film forming agent. Compared to liquid adhesive plasters, it showed clearly higher sensory properties. Furthermore, the addition of cellulose improved the tackiness during application and the elasticity after drying.

【table】

[Table] (Note) ○: Good, △: Average, ×: Bad.
Test Example 2 A sensory test was conducted on 7 healthy adults while using the skin protectant. The test method is described below. (Method of applying the specimen) Apply the reference specimen to the right hand and the test specimen to the left hand according to the following criteria. 1. Apply 5 drops (approximately 100 mg) of the reference sample to the back of your right hand. 2 Remove the thumb from the center of the back of the right hand with the fingertips of the left hand 4
Apply evenly to the second joint of your finger. 3. Apply 5 drops (approximately 100 mg) of the test sample to the back of your left hand. 4 Remove the thumb from the center of the back of the left hand with the fingertips of your right hand 4
Apply evenly to the second joint of your finger. 5. Perform evaluation immediately after application. 6. Evaluate the specimen after it has dried 10 minutes after dropping. 7 Next, evaluate the use of water. 8 Wipe the specimen with 70% ethanol. 9. Evaluate the above items three times a day with one course. However, there should be at least 3 hours between the end of one evaluation and the next evaluation. (Evaluation items and evaluation criteria) [Evaluation items] Immediately after application 1 Ease of spreading 2 Stickiness 3 Ease of drying 4 Overall evaluation immediately after application After drying 5 Gloss of film 6 Smoothness of film 7 Difficulty in peeling 8 Tightness on skin Feeling 9 Overall evaluation after drying 10 Difficulty in peeling 11 Slimy feeling 12 Overall evaluation when using water Overall rating 13 Comprehensive evaluation of the above overall [Evaluation criteria] The following ratings are given for each of the above items. give,
Analysis of variance was conducted based on a balanced incomplete block design. Rating: Bad: -2, Fairly bad: -1, Same: 0, Fairly good: +1, Good: +2. The organoleptic properties of the following compositions were compared according to the test method described above. The results are shown in Table 2, and the evaluation values shown in the table below indicate that a value greater than 0 indicates a higher evaluation than the reference specimen, and a value smaller than 0 indicates a lower evaluation. (Test Composition) Skin Protective Agent of the Present Invention Examples 1 and 2 Prior Art Skin Protective Agent Control Composition 6 Contains the following ingredients in a hydrated IP. Eudragit E30D 3.5% EC 1.5% Control Composition 7 Contains the following ingredients in a water-containing IP. Eudragit L30D-55 5.0% Propylene glycol 1.0%

【table】

[Table] Results The skin protective agent of the present invention exhibited higher organoleptic properties compared to skin protective agents using known acrylic polymers. Test Example 3 According to the method described in Test Example 2, the preferred concentration of the polymer in the skin protective agent was investigated. Table 3 shows the results. (Test composition) Example 2: Polymer 5.0% Example 8: Polymer 7.0%

【table】

[Table] Item Example 2 Example 8

Claims (1)

[Claims] 1. A skin protective agent consisting essentially of the following basic ingredients. a An acrylic polymer in which the monomer ratio of ethyl acrylate and methacrylic acid is within the range of 75/25 to 95/5, the residual monomer is 50 ppm or less, and substantially no surfactant is contained.
2 to 10%, b cellulose derivative about 0.2 to 2%, and c hydroalcohol residual amount 2. The skin according to claim 1, wherein the acrylic polymer has a weight average molecular weight of about 100,000 to about 1,300,000. Protective agent. 3. The skin protective agent according to claim 1, wherein the cellulose derivative is ethyl cellulose. 4. The skin protective agent according to claim 1, wherein the alcohol is ethanol or isopropanol.