JPS6141926B2 - - Google Patents

Description

[Detailed description of the invention]

This invention relates to a method for producing a new hydrophilic synthetic polymer gel that can be used in a wide range of applications including pharmaceuticals. Conventionally, soluble polymers of aliphatic carboxylic acids or their salts exhibit high viscosity in aqueous solutions mainly due to repulsion due to the negative charge of carboxyl groups within the molecule, so they have been widely used as thickeners in foods, medicines, etc. It has been used in fields such as cosmetics. However, if a certain amount or more of polyvalent metal ions are mixed into a mucus containing this substance under stirring, the substance immediately reacts and forms a non-uniform floc-like precipitate, reducing its usefulness as a thickener. As a result of research on polyvalent metal salts of aliphatic carboxylic acid polymers, the present inventors discovered that aluminum salts have properties suitable for various uses, and were able to complete the present invention. That is, in this invention, 0.5% to 30% (W/W%) of the water-soluble polymer of aliphatic carboxylic acid or its salts
By reacting an aluminum compound with low solubility in the solvent of this solution with an aqueous solution in the presence of an organic acid containing a hydroxyl group in the molecule or its salts in the pH range of 4.0 to 7.0, self-shape retention and retention can be achieved. We succeeded in obtaining a synthetic polymer gel with excellent properties such as water resistance and thermal stability. The gel obtained by the method of this invention has the following properties. (1) Self-shape retention: Although this gel contains a large amount of water, it is not fluid and has strong elasticity, so it does not collapse easily even when pressed. (2) Water-retaining property: Even if it is compressed with about 90% water inside, it will not spit out water, and even if you touch its surface, you will only feel a slight dampness and your hands will not get wet. There isn't. (3) Thermal stability: This gel retains its original shape even after being sealed in an aluminum foil bag and placed in a thermostat at 50°C for two weeks. No resulting leaching of moisture is observed. (4) Transparency: This gel is extremely transparent and homogeneous. (5) Water absorption: Even when it contains a large amount of water, when it comes into contact with water, it swells and absorbs even more water. (6) Moisture release: When the gel that has absorbed water is left indoors,
Water gradually evaporates from the surface. At this time, the latent heat of vaporization is taken away, so the gel itself is always kept at a temperature lower than room temperature. Since the gel obtained by the method of the present invention has the above-mentioned excellent properties, it can be applied to various uses as described below. (1) Pharmaceuticals: Base of prescription drugs. (2) Medical equipment: Cooling the affected area during fever. (3) Cosmetics: Packaging agents. (4) Daily necessities: A. Gel-like fragrance preservative. (b) Shape it as appropriate to prevent eyestroke during flaming heat. Alternatively, it is formed into a belt shape and wrapped around the head for cooling purposes.The aliphatic carboxylic acid polymer referred to in this invention specifically includes acrylic acid, methacrylic acid, maleic anhydride, etc. as a constituent unit. It refers to synthetic polymer compounds, such as polyacrylic acid, polymethacrylic acid, carboxyvinyl polymer, etc. Maleic anhydride can be considered an aliphatic carboxylic acid because it is easily hydrolyzed in water to produce a carboxylic acid. These monomers may form a polymer consisting only of themselves or may combine with other monomers to form a copolymer, and the present invention may be applied to either of these. For example, methoxyethylene/maleic anhydride copolymer is an example. Polymers of aliphatic carboxylic acid esters, aliphatic carboxylic acid amides, and aliphatic nitriles are not included in the invention, but if a part of them is hydrolyzed to form free carboxylic acids or their salts, it is considered that they are water-soluble. Included as long as Soluble salts refer to salts of primary, secondary, and tertiary organic bases such as alkali metal salts, ammonium salts, and mono-, di-, and triethanolamine salts that are soluble in water. means. Furthermore, aluminum compounds include hydroxides such as aluminum hydroxide, normal salts of inorganic or organic acids such as aluminum chloride, aluminum sulfate, aluminum acetate, aluminum stearate, or their basic salts, aluminum alum, etc. double salts such as, aluminates such as sodium aluminate, inorganic aluminum complex salts and organic aluminum chelate compounds. Even if these aluminum compounds are water-soluble, they can be made poorly soluble by appropriate treatment, so the solubility of the aluminum compound itself as a starting material is not a concern. In order to obtain a stable gel by reacting a water-soluble polymer of aliphatic carboxylic acid or its salts with an aluminum compound as listed above, the reaction within the system is not local but global. Preferably it occurs uniformly. In other words, since the carboxylic acid polymer solution has a high viscosity, when the aluminum compound solution is added under stirring, the reaction proceeds at the interface between the two solutions before uniform mixing of the two solutions is achieved. This results in the formation of a floc-like precipitate that is non-uniform and less useful. Although crosslinking of aliphatic carboxylic acids with aluminum has been theoretically predicted for some time, the reason why it has not reached the level of practical use is that it is extremely difficult to overcome this non-uniformity. This problem has been solved according to the invention by using aluminum compounds with low solubility. Even if the aluminum compound has a high solubility, the solution will drop after dissolution.
It can be converted into a sparingly soluble salt through treatments such as adjusting the pH. The reaction rate between the above polymer and the aluminum compound is controlled by the surface area and dissolution area of suspended aluminum compound particles and the pH of the solution. The lower the pH, the faster the reaction, but if it is too low, the gel strength will be weak, and on the other hand, if the pH is around 7, the reaction will be slow. In addition, the amount of aluminum compound blended is 0.15 of the amount of water-soluble heavy weight of aliphatic carboxylic acid or salt.
~15% by weight is adequate to obtain the desired polymeric gel. Furthermore, the present inventor discovered that in the reaction system,
It has been found that the reaction rate can be increased by adding an organic acid or its salt containing an OH group.
These organic acids include glycolic acid, lactic acid,
These include what are generally called oxyacids, such as malic acid, tartaric acid, gluconic acid, and salicylic acid.
The reason why such organic acids act to promote the above reaction is thought to be due to the chelating ability of the OH group within the molecule, and the OH group and carboxylic acid act cooperatively to form a poorly soluble It is presumed that this is due to the gradual dissolution of the aluminum salt in the system. This invention also provides two of the above carboxylic acid polymers.
It can also be carried out by adding a sparingly soluble aluminum compound to a solution in which more than one species is mixed. For example, a gel prepared by adding an aluminum compound to a sodium polyacrylate solution mixed with a carboxyvinyl polymer and crosslinking the gel has high elasticity and water-retaining properties, and is extremely useful as a base for, for example, a prescription drug. When preparing a practically meaningful gel according to the present invention, the amount (W/W%) of the water-soluble polymer of aliphatic carboxylic acid or its salt in water is 0.5 to 30
%, preferably in the range of 2.5 to 25%. If the amount used exceeds or does not reach the above range, a gel-like product cannot be obtained. Since the gel obtained by the method of the present invention has a variety of uses, arbitrary additives can be used as necessary in the manufacturing process to develop delicate properties depending on each purpose. In recent years, many drug pills have been commercialized in the form of a paste-like drug spread on a support cloth, but the gel obtained by the present invention can be prepared in a similar form by adding several kinds of additives. It can be applied to the purpose of making products. In addition, the gel itself can be used as a medical tool or a daily necessity to cool various parts of the body. The cooling effect of this gel is due to the heat of vaporization taken away by the evaporation of water from the gel surface, and compared to other methods currently available on the market, the cooling effect between the gel and the application site is It has a gentle temperature gradient and is highly safe to use on sick patients. And since evaporation continues while water remains, the heat removal capacity and duration are greater than commercially available heat capacity-dependent types. In the field of cosmetics, application as a pack agent is possible. In the case of prescription medicines intended to cool affected areas such as bruises and sprains, the water contained in the ingredients is an important active ingredient because it removes heat from the affected area in the form of latent heat of vaporization. It can be said that it is one of the Furthermore, as mentioned above, water is the source of its usefulness when used as a medical tool or daily necessity for the sole purpose of cooling various parts of the body.
The higher the content, the more effective it is. However, with conventional drug bases, when large amounts of water are added, the consistency of the base decreases and causes problems such as staining the affected area, but the gel of the present invention actually stabilizes more than 90% of water. The usefulness in this respect is extremely large. Example 1 Methoxyethylene maleic anhydride copolymer 75g
was heated and dissolved in 699.5 g of water, and after cooling, 18 g of sodium hydroxide was added to neutralize it, and 200 g of 1M lactic acid buffer (PH6.0) and 7.5 g of aluminum hydroxide were added
After adding g and mixing uniformly, let stand to crosslink.
1000g of synthetic polymer gel was obtained. The resulting gel was a transparent gel that was elastic and did not wet the hands when touched. Example 2 75g of sodium polyacrylate was dissolved in 897.5g of water, neutralized by adding 20g of lactic acid, 7.5g of aluminum hydroxide was added and mixed uniformly, and then left to stand for crosslinking to form a synthetic polymer gel. Obtained 1000g. The resulting gel was a transparent elastic gel that did not wet the hands when touched. The gels obtained in Examples 1 and 2 above were each put into a cell with a diameter of 6 cm and a height of 5 cm, and the upper surface of the cell was compressed by a distance of 5 mm with a disk of 20 mm in diameter at 25°C, and connected to the top of the disk. The stress applied to the disk by the compressed gel was detected using a differential transformer, and the elastic modulus of the gel (dyne/cm ² ) was measured. The elastic modulus of the gel in Example 1 was 4.67×10 ⁵ .
The elastic modulus of the gel of Example 2 was 1.10×10 ⁵ .
Next, in order to examine the thermal stability of the gels obtained in Examples 1 and 2, these gels were sealed in a plastic film and subjected to 2 weeks of abuse in a constant temperature bath at 50°C, and then returned to room temperature and the elastic modulus was determined again. The elastic modulus (dyne/cm ² ) after the above abuse was measured and observed for the presence or absence of syneresis (spitting out of water), which occurs when the water-holding ability is reduced due to the above abuse.
was 4.67×10 ⁵ for the gel of Example 1 and 1.10×10 ⁵ for the gel of Example 2, and no syneresis phenomenon was observed in any of the gels. Below are some Examples, the water content, elastic modulus and appearance properties of the gels obtained in these Examples, and the elastic modulus and presence or absence of syneresis after the same abuse as for the gels of Examples 1 and 2 above. are summarized in Table 1.

【table】

[Table] Furthermore, since the polymer gel obtained by the method of this invention has the characteristics as described above,
The method of the present invention can be applied to the production of polymer gels for specific uses, such as syrups and flavor preservatives. In that case, the above-mentioned gel may be produced by adding various components suitable for the specific use to the polymer gel obtained by the method of the present invention, but in the process of the method of the present invention, various components suitable for the specific use may be added By adding various components, it is also possible to produce gels for specific purposes, including the polymer gels obtained by the method of the present invention. Next, we will show examples of these applications. Application example 1 Suspend 35 g of sodium polyacrylate and 50 g of sodium carboxymethyl cellulose in 200 g of propylene glycol, and add 400 ml of water to this.
and 150 ml of IN hydrochloric acid were added and stirred. After obtaining a uniform gel-like liquid, add 5 g of aluminum hydroxide.
was suspended in 50 ml of water, and a homogeneous oily liquid prepared by pre-mixing 12 g of peppermint oil, 8 g of d1-camphor, 9 g of d1-menthol, 9 g of methyl salicylate, and 2 g of "Polysorbate 80" was stirred vigorously. A synthetic polymer gel was obtained by adding the mixture into the above gel-like liquid. Further to this gel
Add 50ml of 1M lactic acid buffer (PH5.0) and water to make a total volume of 1000g, spread the resulting gel-like liquid on flannel or nonwoven fabric, cut it, and seal it in an aluminum bag. I got a bottle of medicine. The viscosity of a 0.5% aqueous solution of sodium polyacrylate is
The average polymerization degree was 1,400 to 1,800 cps and 30,000 to 40,000. Application Example 2 50g of starch was placed in 500ml of water, heated to about 90°C and stirred to dissolve. After it became a translucent gel-like liquid, it was cooled to 60°C, 20g of gelatin was added and stirred to uniformly dissolve it, and after dissolution, it was further cooled to 35°C. Separately, 35 g of sodium polyacrylate was suspended in 200 g of glycerin and added to the above starch solution with stirring. After the sodium polyacrylate crystals are completely dissolved,
20ml of 3N sulfuric acid, 31g of tartaric acid, 8g of l-menthol, 30g of methyl salicylate prepared separately,
A mixed solution of 2 g of "Polysorbate 80" was added with vigorous stirring. Finally, 5% aluminum alum solution
An aluminum hydroxide suspension obtained by mixing 60 ml with 20 ml of 5% sodium hydroxide solution under vigorous stirring was added, water was added to make a total amount of 1000 g, and the mixture was stirred again to mix uniformly. The resulting gel-like liquid was spread on a cloth to a thickness of 2 mm, the surface was covered with polyethylene film, the pieces were cut to a size of 20 cm x 14 cm, and the sheets were sealed in an aluminum bag to contain the drug. Obtained. Application example 3 Add and dissolve 20 g of carboxyvinyl polymer in 500 ml of water, and mix 35 g of sodium polyacrylate with 60 g of propylene glycol, 29 g of delta gluconolactone, and
140 g of 70% sorbitol solution was added and stirred until it became a transparent gel-like liquid. Next, an aluminum hydroxide suspension obtained by adding 20 ml of 5% sodium hydroxide solution to 34 ml of 5% aluminum chloride solution and a mixture of 25 g of salicylic acid glycol ester, 5 g of methyl salicylate, and 2 g of "polysorbate 80" prepared in advance were added. The suspension was added and stirred vigorously until a homogeneous gel-like solution was obtained. Finally, water was added so that the total amount was 1000 g, and the mixture was stirred again until it became homogeneous. Using the obtained gel-like liquid, a drug with the same specifications as in Application Example 2 was obtained. The cooling effects and thermal stability of the syrups obtained in Application Examples 1 to 3 above are shown in Table 2 below in comparison with three commercially available syrups.

【table】

[Table] The cooling effect was evaluated using a sample with the film attached to the paste surface at 20°C.
Calculate the amount of evaporation per 1 g of the initial weight of the paste based on the value obtained by leaving the support fabric side up in a 60% RH room for 24 hours and measuring the amount of water evaporation from the support fabric surface as a change in weight during that time. and further 20℃
It was obtained by converting it into the latent heat of vaporization. However, the initial weight of the paste can be calculated from the initial weight of the sample by immersing it in water at 90°C and crushing it with a spatula to disperse the paste, then taking the support cloth, washing it with water, drying it, and measuring its weight. The weight of the film is subtracted. For volatile active ingredients such as methyl salicylate, thymol, and terpenoids, weight correction was performed assuming that 10% of the labeled amount evaporated with water in 24 hours. Thermal stability was determined by sealing the sample in an aluminum bag, heating it at 50°C for 2 weeks, leaving it at room temperature for 1 day, opening the bag, and observing changes in properties. As is clear from the above results, it is clear that the drug capsule containing the synthetic polymer gel produced by the method of the present invention is significantly superior in both cooling effect and thermal stability compared to commercially available products. It became. Application example 4 Methoxyethylene/maleic anhydride copolymer 50
Add 400 ml of water to the solution, heat, dissolve, and neutralize by adding 10% sodium hydroxide solution. This plus lactic acid 15
After adding and dissolving 50 g of "Macrogol #6000" and 3 g of propyl paraoxybenzoate, the liquid was cooled. To this solution, add an aluminum hydroxide suspension prepared by the method described below with vigorous stirring, and then add peppermint oil to saturated water.
Add 100ml. Add water to this so that the total amount is 1000g, then mix until homogeneous.
Within a few hours, pour the mixture to a thickness of 5 mm onto a smooth board with raised edges and leave it there. The next day, the agar-like solidified gel was cut into the required size to obtain a cold compress or skin cooling agent. The aluminum hydroxide suspension is 10% aluminum sulfate (Al ₂
It was prepared by adding 35 ml of 10% sodium hydroxide solution little by little to 107 ml of (SO ₄ ) ₃ ·18H ₂ O) solution with vigorous stirring. Application example 5 Methoxyethylene/maleic anhydride copolymer 50
g was added to 500 ml of water, and dissolved by heating and stirring. After dissolving, add 190ml of 2N sodium hydroxide solution and
Add 80ml of 2M lactic acid and 1g of dehydroacetic acid, mix and dissolve uniformly. Separately, 1 g of tocopherol acetate,
1 g of guaya azulene, 0.1 g of bergamot oil, 5 ml of nonyl phenyl ether surfactant, and 50 ml of water.
Prepare a liquid emulsified by stirring vigorously, and a liquid in which 5 g of aluminum hydroxide is suspended in 100 ml of water, add to the above liquid while stirring, and finally add water to make a total volume of 1000 g. Do this within 2 hours
It was poured to a thickness of 3 mm onto a smooth board with a raised edge on the periphery and left. The next day, the agar-like solidified gel was cut into the required size to obtain a pack. Application example 6 Methoxyethylene/maleic anhydride copolymer 50
Add 500 ml of water to the solution and dissolve by heating, and neutralize by adding 152 ml of 10% sodium hydroxide solution. Next, after cooling this solution, 22 g of malic acid was added thereto, and then a mixture of 50 g of rose-based mixed fragrance and 50 g of castor oil-based surfactant was added with vigorous stirring, and then succinic acid was added with continued stirring. Add a suspension of 3 g of aluminum, 3 g of dehydroacetic acid, and 1 g of propyl paraoxybenzoate in 100 ml of water, and add water to make a total volume of 1000 ml.
Mixed evenly. Pour this liquid into the specified mold,
After standing overnight, it was removed from the mold and inserted into a plastic container to obtain a gel fragrance.

Claims (1)

[Claims] 1. In the presence of an organic acid containing a hydroxyl group in the molecule or its salts in a 0.5 to 30% aqueous solution of a water-soluble polymer of an aliphatic carboxylic acid or its salts, a poorly soluble aluminum compound is converted into an aliphatic compound in terms of aluminum. 1. A method for producing a synthetic polymer gel, which comprises adding 0.15 to 15% by weight of a water-soluble polymer of carboxylic acid or its salts and reacting at a pH of 4.0 to 7.0.