JPH09110634A - Skin protecting agent and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin protecting agent consisting of a neutral solution of a chitosan, good in feeling in use and high in safety, while holding a humidity maintaining property. SOLUTION: This skin protecting agent is obtained by dissolving a highly deacetylated chitosan, preferably a squid chitosan having >=75% deacetylation ratio, with 0.01-5wt.% organic acid buffer solution (e.g.; glutamic acid) and then neutralizing with the addition of an aqueous alkaline solution (e.g.; NaOH) to prepare a preparation fitted to pH4.5-6.5. It is prepared as a lotion, cream, etc. In contrast to the chitosan derived from a crab or a shrimp induces an allergy, the squid chitosan does not induce the allergy and is preferable in view of its safety. The chitosan as an inexpensive natural polymer is used as an industrial waste water treating agent, a growth promoter for agricultural products, a covering membrane for an injured skin, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a skin protective agent and a method for producing the same.

[0002]

2. Description of the Related Art Lotions, creams, ointments, and the like are widely used as cosmetic or topical pharmaceutical preparations, but various hygroscopic substances are provided for the purpose of imparting moisture retention to these products. High moisturizers are used as humectants. As described above, there are considerable types of substances having high moisture absorption ability, which are important physical properties that can be used as a humectant, including organic substances and inorganic substances. However, when these substances are actually used as humectants, they are excellent in safety, do not impair the form stability of products, have no restrictions on applications, etc., and have excellent usability. Is required.

[0003] Commonly used humectants include organic acid salts such as sodium lactate and sodium pyrrolidone carboxylate; polyhydric alcohols such as glycerin, sorbitol and propylene glycol; low molecular weight compounds such as urea; hyaluronic acid; And natural or synthetic water-soluble polymers such as elastin, polyethylene glycol and polyacrylic acid. These are used singly or in combination, but each has advantages and disadvantages in terms of effects on product stability, solubility, usability, and price.

[0004] As a moisturizer for medical use, a lotion or cream preparation containing 10 to 20% urea has been put on the market for the purpose of treating xerosis. These urea preparations, when applied to intact skin, exhibit high moisturizing properties and are very useful, but may cause itching as symptoms such as senile pruritus and atopic dermatitis. As a result, if there is damage to the skin, it causes significant pain at the application site. Despite the recent rapid increase in patients with these symptoms accompanied by pruritus, no suitable medical moisturizing skin protectant has been developed.

On the other hand, in the field of cosmetics, highly stimulating humectants such as urea are hardly used, and water-soluble natural high molecular compounds such as hyaluronic acid, collagen and elastin are used. These water-soluble natural polymer compounds have a suitable moisturizing property, but have a disadvantage that the raw material price is expensive and the film-forming property is poor, so that a sticky feeling remains for a long time.

In recent years, chitosan, which is an inexpensive natural polymer, is used as an industrial wastewater treatment agent by utilizing its cohesiveness, and is also used as an agricultural product growth promoter or by utilizing its good film-forming properties. Its application as an ethanol separation membrane has been considered. On the other hand, also in the medical field, a film produced from chitosan as a raw material has excellent skin adhesion and bacteriostatic action, and is therefore used as a coating film for damaged skin such as burns.

Although chitosan has excellent functions as described above, serious problems arise when it is used as a humectant. That is, chitosan is a water-insoluble basic polymer compound by nature, and is insoluble in pure water. Therefore, in order to obtain an aqueous solution of chitosan, a method of dissolving chitosan in an aqueous solution of an inorganic acid or an organic acid is usually employed.

In this case, a solution obtained by dissolving chitosan in diluted lactic acid, diluted acetic acid, etc. in a few percent gives an extremely good feeling of use when applied to healthy skin, but it has senile pruritus and atopic dermatitis. If the skin is damaged as in the case of the above, the acidity of the solution is high, resulting in strong irritation and pain.

[0009] It is an object of the present invention to provide a skin protective agent which uses chitosan and has a very good feeling in use and high safety while maintaining its characteristic moisturizing property.

[0010]

[Means for Solving the Problems] As a result of intensive studies to achieve the above object, (1) the deacetylation rate was 75.
% Highly deacetylated chitosan has excellent solubility,
The neutral solution has no irritation and is extremely comfortable to use.
(2) As for the highly deacetylated chitosan used, its biological origin is also important, whereas chitosan derived from crustaceans such as crab and shrimp causes allergies, whereas squid chitosan causes such allergies. The present invention has been completed by finding out that it is particularly preferable from the viewpoint of safety without doing so.

[0011] Therefore, the present invention provides a deacetylation rate of 75%.
The gist is a skin protectant characterized by comprising a neutral solution of squid chitosan as described above.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The skin protectant of the present invention comprises a neutral solution of chitosan, which satisfies the following requirements (1) and (2).

(1) Highly deacetylated chitosan having a deacetylation rate of 75% or more. (2) Squid chitosan whose biological origin is squid.

First, requirement (1) relating to the deacetylation rate will be described. Chitosan is produced by using chitin, which is completely insoluble in an aqueous solvent, as a raw material and deacetylating it. Therefore, chitosan is represented by the formula (a)

Embedded image And an N-acetylated D-glucosamine structural unit represented by the formula:

Embedded image And the D-glucosamine constitutional unit represented by are randomly distributed, the constitutional unit (a) is an acetylated unit, and the constitutional unit (b) is a deacetylated unit. Therefore, the ratio of the structural unit (b) in the structural units (a) and (b) is the deacetylation rate.

Various types of chitosan having a deacetylation rate of about 50 to 90% are supplied to the market depending on the degree of deacetylation. On the other hand, when trying to use an aqueous solution of chitosan as a medical moisturizing skin protective agent or moisturizing cosmetic, a formulation compatible with the pH of the skin (4.5 to 6.5) must be used in order not to cause irritation to the skin. There is a need to. It is known that chitosan having a deacetylation rate of about 50 to 90% is soluble in a dilute acid aqueous solution. However, the pH of these chitosans (4.5 to 6.
5) The solubility in the region was unknown. The present inventors examined the solubility of chitosan having a deacetylation ratio of 50 to 90% in various organic acid buffers (pH 5.75: average skin pH).

As a result, as shown in Experimental Example 1 below,
When chitosan having deacetylation rates of 53%, 62% and 69%, respectively, is added to each of the aqueous solutions of acetic acid, lactic acid, glutamic acid and glycolic acid, opacity or precipitation occurs, whereas the deacetylation rates are respectively increased. 80%, 91
% Chitosan is similar to acetic acid, lactic acid, glutamic acid,
It was revealed that chitosan was transparently dissolved in the organic acid buffer when added to each glycolic acid buffer.

The deacetylation rate is 80%, 91%
It has been clarified that the chitosan lactic acid, glutamic acid, and glycolic acid buffers have no irritating sensation when applied to the skin and are extremely comfortable to use.

This is the reason why the deacetylation rate of chitosan is limited to 75% or more in the present invention. The deacetylation rate of chitosan is preferably 75 to 98%, and 80 to 9%.
5% is particularly preferred.

Next, requirement (2) concerning the biological origin of chitosan will be described. Biological sources of chitin for industrially obtaining chitosan include crustaceans such as crab and shrimp and squid.

As shown in Experimental Example 2 below, the present inventors have obtained chitosan obtained by deacetylation of chitin derived from crustaceans such as crab and shrimp, and chitin derived from squid and obtained by deacetylation of chitin derived from squid. A patch test was performed using the obtained organic acid buffer of chitosan, and the occurrence of skin allergy was observed to evaluate the safety. The chitosan used was a crab-derived one having a deacetylation rate of 91%, a shrimp-derived one having a deacetylation rate of 85%, a squid-derived one having a deacetylation rate of 90%, and used as an organic acid buffer. Glutamate buffer was used.

As a result, in the case of chitosan derived from crab and shrimp, some subjects exhibited redness on the skin, whereas in the case of chitosan derived from squid, those exhibiting redness in the subject were observed. I couldn't. This is the reason for limiting the biological origin of chitosan to squid in the present invention.

The skin protectant of the present invention comprises a neutral solution of chitosan, and by using a chitosan which satisfies the above requirements (1) and (2), it has the moisturizing property originally possessed by chitosan. At the same time, when applied to the skin, there is no feeling of irritation, the feeling of use is extremely good, and there is a remarkable technical effect of not causing allergies.

The "neutral solution" in the neutral solution of chitosan constituting the skin protectant of the present invention is a solution having a pH of 4.5 to 6.5 which is the pH range of normal human skin. means.

The skin protective agent of the present invention is produced by, but not limited to, the following method.

(A) A method of dissolving squid chitosan having a deacetylation rate of 75% or more in an organic acid buffer solution of 0.01 to 5% by weight. A method of dissolving in an organic acid buffer solution of 01 to 5 wt% and adding an aqueous alkaline solution to neutralize the solution. (C) Dispersing squid chitosan having a deacetylation ratio of 75% or more in an aqueous alkaline solution, After hydration,
Method of adding and dissolving 0.01 to 5% by weight of an organic acid to form a neutral aqueous solution The organic acids used in the above methods (a), (b) and (c) include glycolic acid, lactic acid, malic acid and citric acid. Examples include hydroxyl group-containing carboxylic acids such as acid, tartaric acid, gluconic acid, glucuronic acid, and ascorbic acid; acidic amino acids such as glutamic acid and aspartic acid; and pyrrolidone carboxylic acids such as pyrologglutamic acid. As the organic acid, a salt thereof may be used.

A buffer using a lower fatty acid such as acetic acid or propionic acid is not preferred because it has an acidic odor even at pH 5-6. Intermediate and higher fatty acids cannot be used in terms of dissolution. Among amino acids, neutral amino acids and basic amino acids cannot be used because chitosan does not dissolve in the neutral region.

The alkali used in the methods (b) and (c) includes sodium hydroxide, potassium hydroxide, disodium hydrogen phosphate, sodium phosphate, potassium carbonate, sodium carbonate, sodium borate and the like.

The dissolving operation of squid chitosan in the above methods (a), (b) and (c) is not particularly limited, and any operation can be adopted. Of course, physical measures such as stirring and other mechanical means and warming may be taken to promote dissolution.

In the methods (a), (b) and (c), other additives can be added as long as the object of the present invention is not impaired.

[0030]

The present invention will be further described below with reference to experimental examples, examples and test examples.

Experimental Example 1 The relationship between the deacetylation rate of chitosan and the solubility in an organic acid buffer was examined.

Deacetylation rate is 53%, 62%, 69
%, 80%, 91% squid chitosan sample A,
Using B, C, D, and E, each chitosan sample was buffered with acetic acid, lactic acid, glutamic acid, and glycolic acid (pH =
5.75), the chitosan concentration was 1 wt%, and the solubility of each chitosan sample was tested. Table 1 shows the results. From Table 1, the deacetylation rate is 53%,
In the case of chitosan samples A, B and C having 62% and 69%, opacity and precipitation occur in all organic acid buffers, whereas chitosan sample D having deacetylation rates of 80% and 91%. , E dissolved transparently in all organic acid buffers.

[0033]

[Table 1]

It was also found that the chitosan samples D and E, which were excellent in solubility and had a deacetylation ratio of 80% and 91%, had no irritating sensation even when applied to the skin and had a very good usability.

Experimental Example 2 The relationship between the biological origin of chitosan and safety was examined.

A glutamate buffer solution (pH: 1%) containing 1% of crab-derived chitosan sample F (deacetylation rate: 89%)
= 5.75), and the safety was evaluated as follows.

An aqueous solution of canikytosan (1 g) was applied to the inside of the upper arm of 18 males and females aged 19 to 58, and the condition of the skin was observed 24 hours later. As a result, in the case of the aqueous solution of canikitosan, slightly strong redness was observed in female A at the age of 22 and mild redness at male B at the age of 53.

As a result of the interview, it was found that female A had a constitution that would cause allergies when eating crustaceans such as shrimp, crab, and mysid. Male B has shrimp as a subjective symptom,
There were no allergies to the crab.

Further, chitosan samble G derived from shrimp (deacetylation rate 85%), chitosan samble E derived from squid
A patch test was similarly performed on the female A and male B using a glutamate buffer (pH 5.75) containing 1% of each (deacetylation rate 91%). Table 2 shows the results
Shown in

As shown in Table 2, shrimp-derived chitosan sample G caused redness in both female A and male B, whereas squid-derived chitosan sample E exhibited a glutamic acid buffer sample H containing no chitosan. Similarly,
Both female A and male B were normal without redness.

From the above results, while chitosan derived from crustaceans such as crab and shrimp, which has been widely used, causes allergy at a considerable frequency, icaquitosan is the result of an additional patch test of 43 more persons. However, no abnormality was observed and it was revealed that the product was extremely excellent as a moisturizing skin protective agent and moisturizing cosmetic.

[0042]

[Table 2]

Example 1 (Lotion 1) 0.5 g of glutamic acid was dissolved in 100 ml of warm water, and 1 g of squid chitosan (91% deacetylation rate) was dissolved therein. A 1N aqueous sodium hydroxide solution was added to this solution while stirring to adjust the pH to 5.75, and a lotion (viscosity 250 CP, 20 ° C.) was produced.

Example 2 (Lotion 2) 0.3 g of sodium lactate was dissolved in 100 ml of water, and 1 g of squid chitosan (91% deacetylation rate) was dispersed therein. Lactic acid was added dropwise to the dispersion with stirring to adjust the pH to 5.
After adjusting to 75, the mixture was further stirred to dissolve the chitosan to produce a lotion (viscosity: 280 CP, 20 ° C.).

Example 3 (Lotion 3 ) 100 ml of 0.3 M glycolic acid buffer (pH 5.60)
1 g of squid chitosan (91% deacetylation rate) was added, stirred and dissolved to give a lotion (viscosity: 320 CP, 20 ° C.)
Was manufactured.

Example 4 (Cream) 39.5% aqueous solution of squid chitosan of Example 1 Liquid paraffin 33.0 Vaseline 6.0 Lanolin 5.0 Propylene glycol 5.0 Solid paraffin 3.0 Glycerin monostearate 2.5 Polyoxyethylene sorbitan monostearate 2.5 Stearyl alcohol 2.0 Perfume 0.5 Antioxidant and preservative A suitable amount was used to prepare a moisture cream by a conventional method.

Test Example 1 Lotion obtained in Example 3 and a lotion obtained by dissolving hyaluronic acid (1 wt%) in a glycolic acid buffer solution in the same manner as above. Skin horny layer moisture meter model SKICON-200 (made by IBS) When the heat-retaining property was examined by using, the difference between the two was hardly recognized. Next, lotion of Example 3 and lotion of hyaluronic acid
We asked women (20 to 46 years old) to try it out and conducted a questionnaire survey on their feeling of use. Table 3 shows the results.

[0048]

[Table 3]

Test Example 2 The cream obtained in Example 4 using the squid chitosan aqueous solution of Example 1 and 4 instead of the squid chitosan aqueous solution of Example 1 were used.
A urea cream prepared according to the same formulation as in Example 4 except that a 0% urea aqueous solution was used was applied to the affected part of a 38-year-old woman with red nails on both fingers for 1 week, and the feeling of use was heard. .

Results (i) The comparative urea cream suffered severe pain from the moment of application and was unbearable for use, so it was stopped once. (ii) The cream containing squid chitosan of Example 4 had no irritation at all, and no pain was felt even when the cream entered a large crack. After applying 4-6 times a day,
Fine cracks disappear in about three days, and after one week, large cracks are considerably smaller and have a healing effect. I got the answer.

[0051]

According to the present invention, there is provided a skin protective agent which is extremely safe to use and highly safe while maintaining the inherent moisturizing properties of chitosan, and a method for producing the same.

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[Procedure amendment]

[Submission date] October 25, 1995

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0047

[Correction method] Change

[Correction contents]

Test Example 1 The lotion obtained in Example 3 and a lotion in which hyaluronic acid (1 wt%) was similarly dissolved in a glycolic acid buffer solution were used. Skin horny layer moisture meter model SKICON-200 (manufactured by IBS) When the moisturizing property was examined using, there was hardly any difference between the two. Next, lotion of Example 3 and lotion of hyaluronic acid
We asked women (20 to 46 years old) to try it out and conducted a questionnaire survey on their feeling of use. Table 3 shows the results.

Claims (4)

[Claims] 1. A skin protective agent comprising a neutral solution of squid chitosan having a deacetylation rate of 75% or more. 2. The method for producing a skin protective agent according to claim 1, wherein squid chitosan having a deacetylation ratio of 75% or more is dissolved in a 0.01 to 5% by weight aqueous solution of an organic acid buffer. . 3. A method of dissolving squid chitosan having a deacetylation rate of 75% or more in a 0.01 to 5% by weight aqueous solution of an organic acid, and adding an alkaline aqueous solution to the solution to make it neutral. Item 10. A method for producing the skin protective agent according to item 1. 4. Ikachitosan having a deacetylation rate of 75% or more is dispersed in an alkaline aqueous solution, hydrated, and then dissolved by adding 0.01 to 5% by weight of an organic acid to form a neutral solution. The method for producing a skin protective agent according to claim 1, wherein