JP3506627B2 - Chitosan derivative, external skin preparation containing the chitosan derivative and cosmetic - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a chitosan derivative, a skin external preparation containing the chitosan derivative, and a cosmetic.

[0002]

BACKGROUND OF THE INVENTION As is well known, chitosan is a deacetylated product of chitin obtained from crustaceans and filamentous fungi, has a moisturizing effect and an anticholesterol effect, and is excellent in safety. It has been put to practical use as a functional food material.

In the cosmetics field, derivatives having improved moisturizing properties of chitosan have been developed and put into practical use as moisturizing agents for cosmetics having moisturizing properties similar to hyaluronic acid (JP-A-2-107601). At present, it is limited to use as an agent.

In the development of emulsion type preparations (milky lotion, cream, etc.), it is necessary to coexist with a surfactant or an emulsifier (nonionic surfactant, anionic surfactant, cationic surfactant).

However, it is known that many conventional surfactants and emulsifiers show cytotoxicity due to destruction of cell membranes mainly composed of lipid bilayer membranes and protein denaturation.

[0006] Invasion of the horny layer and degeneration of keratin keratin also occur on the skin, so that skin irritation may be observed. In addition, keramide such as ceramide forming a lipid lamella structure membrane between horny layer cells. Intercellular lipids, amino acids, pyrrolidonecarboxylic acid, and other N. M. Since the F component (natural moisturizing factor) is eluted, there has been a problem that the stratum corneum moisturizing barrier function may be deteriorated.

[0007] Antibacterial agents and preservatives are used for the purpose of maintaining the quality by sterilizing effects of microorganisms and preventing contamination of preparations, but conventional antibacterial agents are often found to have cytotoxicity or allergenicity, and skin There was also a problem that irritation and the like may be recognized.

It is known that chitosan has an antibacterial property, but it has a weak antibacterial property against filamentous fungi and the like, and has a problem in the antibacterial spectrum. Therefore, it has an antiseptic effect for the purpose of preventing contamination. Inadequate (Yasushi Uchida: Chitin, Chitosan Handbook, p301, Gihodo Publishing, 1995).

It is known that there is a negative correlation between skin viscoelasticity and skin flexibility and aging, and improvement of skin viscoelasticity and skin flexibility is related to skin aging (small wrinkles, reduction in firmness, Rough skin)
It is said that it is useful for preventing skin irritation and improving skin surface morphology and for other beautiful skin effects.

% Of α-hydroxy acid such as glycolic acid
The formulation is said to have these improving effects, but there was a problem in terms of irritation.

The development of materials and skin cosmetics which are hypoallergenic and have an excellent effect of improving skin viscoelasticity and skin flexibility has not been sufficient.

Recently, derivatives having improved moisturizing properties of chitosan have been developed, and cosmetic moisturizing agents having moisturizing properties similar to hyaluronic acid have been developed, but the effect of improving skin moisturizing effect was not sufficient. .

[0013]

DISCLOSURE OF THE INVENTION The present invention has been made to solve such problems, and obtains a derivative having excellent amphipathicity and skin safety from chitosan having high biosafety. , Effective use makes it possible to reduce or remove conventional surfactants, antibacterial agents and antiseptics, and has a highly effective skin moisturizing effect, skin viscoelasticity improving effect, and skin softening effect. It is an object of the present invention to provide a skin external preparation having the following: mainly a mild skin external preparation.

[0014]

Means for Solving the Problems In order to solve such problems, the present inventors have found that the content of charged amino groups is 40 to 40%.
As a result of attempting to partially introduce an acyl group into 100% of chitosan salt, the introduction rate of higher acyl group having 7 to 20 carbon atoms was improved.
Partially higher acylated chitosan salt partially introduced with 0.1 to 30.0% has excellent functionality such as amphiphiles (antioxidants, moisturizers, skin softeners), high skin safety, and sensitive skin and The present invention was found to be safe for skin diseases such as skin (atopic dermatitis, contact dermatitis, etc.), and the present invention has been completed.

Further, the content of the charged amino group is 1.0 to 90.0.
%, And a partially higher acylated hydroxyalkyl chitosan having a hydroxyalkyl group having 2 to 6 carbon atoms or an acyl group partially introduced with a higher acyl group introduction rate of 7 to 20 carbon atoms of 0.1 to 30.0%. Salts and partially higher acylated acyl chitosan salts are also amphiphiles (antioxidants, humectants,
It has excellent functionality such as skin softener) and high skin safety.
It has been found that it is safe for sensitive skin and skin diseases such as atopic dermatitis and contact dermatitis.

This partially acylated chitosan salt is represented by the following formula (1).

[0017]

[Chemical 1]

In the formula (1), R _1, R _2, R _{3 and} R ₄ are a hydrogen atom, a higher acyl group having 7 to 20 carbon atoms, or 2 to 5 carbon atoms.
6 represents a hydroxyalkyl group or an acyl group, and R
₅ represents a hydrogen atom, a higher acyl group having 7 to 20 carbon atoms, an acetyl group, or a hydroxyalkyl group having 2 to 6 carbon atoms or an acyl group.

Here, the partial introduction ratio of the higher acyl group having 7 to 20 carbon atoms is 0.1 to 30.0%.

Further, a and b are integers of 1 or more, and 10
<A + b <2000. Further, the structural units marked with a and b may be randomly arranged.

By effectively utilizing the partially acylated chitosan salt of the present invention, it is possible to reduce or remove the surfactant, the antibacterial agent and the antiseptic agent, and improve the skin viscoelasticity and the skin flexibility and have high durability. It has become possible to provide a skin external preparation that exhibits improved skin moisturizing properties, mainly a mild skin external preparation.

The partial introduction rate of the higher acyl group described here indicates the introduction rate per residue of hexosamine, which is a constituent monosaccharide of chitosan. For example, the partially higher acylated chitosan glycolate having an introduction rate of the acyl group of 15.0%. Indicates that 15 acyl groups have been introduced into 100 residues of glucosamine glycolate, which is a constituent monosaccharide.

The site for introducing a higher acyl group is NH ₂ group or O.
It is important that the introduction rate of the acyl group, which is the H group or the NH ₂ group and the OH group and is the introduction rate per one residue of hexosamine, which is a constituent monosaccharide of chitosan, is in the range of 0.1 to 30.0%.

The partially higher acylated chitosan salt obtained by introducing 0.1 to 30.0% of the higher acyl group having 7 to 20 carbon atoms into the chitosan salt has excellent surface-active ability, and therefore, the conventional surfactant is remarkably reduced or eliminated. It can be widely used in emulsified cosmetics that can be added.

If the conventional surfactant is not blended in an amount of 2 to 5%, a good emulsion preparation (cream, emulsion, etc.) cannot be prepared, but the chitosan derivative of the present invention is 0.1 to 1.0%.
It is possible to prepare an emulsion-based preparation in a small amount.

The chitosan derivative of the present invention shows almost no cell membrane destruction or biotoxicity, is significantly superior in skin safety to conventional surfactants, and has a reduced skin barrier function (sensitive skin or skin diseased skin (atopic skin). Flame, contact dermatitis, etc.)
Is also safe against.

Cells such as ceramide that form a lipid lamella structure membrane between horny cells because they hardly cause the destruction of biological membranes (lipid bilayers) made of phospholipids and the like observed with conventional surfactants. Interstitial lipids, amino acids, etc. M. It does not elute the F component (natural moisturizing factor), and does not cause the deterioration of the stratum corneum moisturizing barrier function found in conventional surfactants.

By partially penetrating into the hydrophobic layer without destroying the lipid lamella structure membrane such as phospholipid or ceramide to enhance the stability of the lipid bilayer membrane, for example, by surface-disrupting the liposome. It is also possible to increase the safety of liposomes.

Regarding the emulsification mechanism, a higher acyl group is introduced into the surface of the oil droplet to form a stable emulsified form.

When it is desired to make the emulsified particle type as fine as 1 μm or less, it can be easily adjusted by high-pressure treatment with a microfluidizer or the like.

Since a hydrophobic substance is solubilized in the same manner as a conventional hydrophilic surfactant and the like, it can also be used for a lotion or the like in which a hydrophobic substance such as a fragrance is solubilized.

Hydrophobic active ingredients (oil-soluble vitamins, fragrances,
By encapsulating a UV absorber or the like), it becomes possible to use it in a formulation having improved sustained release and safety to the skin.

Since the chitosan derivative of the present invention having a higher acyl group introduction rate adjusted to 30.0% or less has water solubility, it has an advantage that it can be easily incorporated into a lotion or essence preparation which is a water-soluble base.

By partially introducing a higher acyl group having 7 to 20 carbon atoms into the chitosan salt in an amount of 0.1 to 30.0%, the action on the cell wall of the microorganism is improved and the assimilation by the microorganism is prevented, so that the chitosan salt is combined with the chitosan salt. In comparison, the improvement of the antibacterial spectrum and the improvement of the antibacterial property against filamentous fungi occur,
It has been found that the usefulness as an antibacterial agent is increased.

Since the antibacterial spectrum of chitosan is broadened, it is possible to reduce or remove antibacterial agents and preservatives.

By continuously applying the chitosan derivative of the present invention to human skin, excellent effects of improving skin moisturizing property, skin viscoelasticity, and skin flexibility are recognized.

Further, since the retention and affinity for the skin is enhanced, there is also an advantage that the effect of improving the skin function such as resistance to microorganisms on the skin and skin moisturizing property is good.

As examples of the higher acyl group having 7 to 20 carbon atoms,
Examples thereof include palmitoyl group, lauroyl group, myristoyl group, stearoyl group, salicyloyl group and the like.

The type of salt of the chitosan derivative of the present invention is not particularly limited, but pyrrolidone carboxylate,
Examples thereof include glycolate, salicylate and glutamate.

The molecular weight is not particularly limited either,
The average molecular weight is preferably about 5,000 to 2,000,000, and particularly preferably about 30,000 to 1,000,000.

The external preparation for skin according to the present invention can be applied to lotions, essences, emulsions, creams, hydrophilic ointments, gels, packs, emulsified foundations, etc.
The dosage form is not particularly limited.

The amount to be blended is not particularly limited either, but in the case of cream type, it is about 0.01 to 5.0%, in the case of emulsion or essence type, it is 0.1 to 3.0%, and in the case of lotion type.
0.01 to 2.0% is preferable.

The external preparation for skin of the present invention may be supplemented with other surfactants, emulsion stabilizers and thickeners.

Other components include oils and fats, higher alcohols, water-soluble polymers, polyhydric alcohols, fragrances, anti-inflammatory agents, steroid agents, antiallergic agents, cell activating agents, humectants, whitening agents, antibacterial agents. Ingredients generally used in skin external preparations such as preservatives can be added.

[0045]

EXAMPLES Examples of the present invention will be described below.

Example 1 The method for efficiently preparing the partially N-higher acylated chitosan salt of this example is shown below.

Chitosan (average molecular weight: about 100000, degree of deacetylation: 90.0%) and pyrrolidonecarboxylic acid (hereinafter P
(Abbreviated as CA) was added in an amount of 1 molar equivalent per one residue of the hexosamine salt of chitosan to dissolve it, and 1 volume of methanol was added to obtain a uniform solution.

To this solution was added myristic anhydride dissolved in methanol at 0.1 per 1 residue of chitosan hexosamine.
Partial acylation was performed by adding a molar equivalent and stirring overnight at room temperature, and a spongy partially N-myristoylated chitosan PCA salt was prepared by ultrafiltration, concentration, lyophilization, and washing with acetone.

The introduction ratio of the higher acyl group is determined by proton NMR.
(500 MHZ), from the peak derived from the N-acyl group,
As a result, the N-higher acyl group introduction rate was 9.5%.

The chitosan derivative obtained in this example is represented by the following formula (2).

[0051]

[Chemical 2]

In the formula (2), R ₆ represents PCA,
R ₇ represents a myristoyl group.

Further, a, b and c are integers of 1 or more, 40
0 <a + b + c <450.

The partial introduction rate of the myristoyl group per hexosamine residue is about 9.5%.

Further, the three kinds of structural units marked with a, b and c may be randomly arranged.

Example 2 The method for efficiently preparing the partial N, O-higher acylated chitosan salt of this example is shown below.

Lactic acid was added to chitosan (average molecular weight: about 100000, deacetylation degree: 90.0%) in an amount of 1 molar equivalent per one residue of the hexosamine salt of chitosan, and dissolved to obtain a uniform solution by adding 1 volume of ethanol. .

0.2 mol equivalent of lauric anhydride dissolved in ethanol was added to this solution per one residue of hexosamine of chitosan, and the mixture was stirred overnight at room temperature for partial acylation, followed by ultrafiltration, concentration and freezing. The sponge-like N, O-lauroylated chitosan lactate was prepared by drying and washing with acetone.

The introduction ratio of the higher acyl group is determined by proton NMR.
The peak was derived from N-acyl group and O-acyl group by (500MHZ), and as a result, the N, O-higher acyl group introduction rate was 19.2%.

The chitosan derivative obtained in this example is represented by the following formula (3).

[0061]

[Chemical 3]

In the formula (3), R ₈ represents lactic acid and R ₉
Represents a hydrogen atom or a lauroyl group, and R ₁₀ represents a lauroyl group.

Further, a, b and c are integers of 1 or more,
400 <a + b + c <450.

The partial introduction ratio of lauroyl group per hexosamine residue is about 19.2%.

Further, the three kinds of structural units marked with a, b and c may be randomly arranged.

Example 3 The method for efficiently preparing the partially O-higher acylated chitosan salt of this example is shown below.

Lactic acid was added to chitosan (average molecular weight: about 100,000, deacetylation degree: 90.0%) in an amount of 1 molar equivalent per one residue of the hexosamine salt of chitosan, and dissolved to form a Schiff base by adding 2.0% aqueous formaldehyde solution. It was

After protection with a Schiff base, 1-fold amount of ethanol was added, and 0.1 molar equivalent of myristic anhydride dissolved in ethanol was added to each hexosamine residue of chitosan, and the mixture was stirred at room temperature overnight.

After adding 1 molar equivalent of lactic acid per one residue of hexosamine salt to dissolve and remove the Schiff base, ultrafiltration, concentration, lyophilization, and washing with acetone were performed to form a sponge-like partially O-myristoylated chitosan. The lactate was adjusted.

The introduction ratio of the higher acyl group is determined by proton NMR.
The peak derived from O-acyl group was determined by (500MHZ), and the introduction rate of O-higher acyl group was 9.1%.

The chitosan derivative obtained in this example is represented by the following formula (4).

[0072]

[Chemical 4]

In the formula (4), R ₁₁ represents lactic acid, and R _11
12 represents a hydrogen atom or a myristoyl group.

Further, a and b are integers of 1 or more, and 600
<A + b <700.

The partial introduction rate of the myristoyl group per hexosamine residue is about 9.1%.

Further, the three kinds of structural units marked with a and b may be randomly arranged.

Example 4 A method for preparing the partially N-higher acylated N, O-hydroxybutyl chitosan PCA salt of this example is shown below.

N, O-Hydroxybutylated chitosan consisting of hydroxyalkyl group having 4 carbon atoms (average molecular weight: about
100000, degree of substitution of hydroxybutyl group: 0.71, amino group content: 51.5%) was added and dissolved in 0.5 mol equivalent of PCA per residue of hexosamine salt, and the charged amino group was 51.5%.
A solution of N, O-hydroxybutyl chitosan PCA salt was obtained.

To this solution, 1 volume of methanol was added to make a homogeneous solution, and 0.1 molar equivalent of myristic anhydride dissolved in methanol was added to each residue of hexosamine, and the mixture was stirred overnight at room temperature to carry out partial higher acylation. Then, the sponge-like partially N-myristoylated N, O-hydroxybutyl chitosan PCA salt was prepared by ultrafiltration, concentration, lyophilization, and washing with acetone.

The introduction rate of the myristoyl group was determined by H-NMR.
The peak derived from the N-myristoyl group was determined by (500MHZ) analysis, and as a result, the partial introduction rate was 8.9%.

The chitosan derivative obtained in this example is represented by the following formula (5).

[0082]

[Chemical 5]

In the formula (5), R ₁₃ represents PCA,
R ₁₄ represents a hydrogen atom or a hydroxybutyl group, R ₁₅ represents a hydroxybutyl group, and R ₁₆ represents a myristoyl group.

Further, a, b, c and d represent integers of 1 or more, and 300 <a + b + c + d <350.

The partial introduction rate of the myristoyl group per hexosamine residue is about 8.9%.

Further, the three kinds of structural units marked with a, b, c and d may be randomly arranged.

Example 5 A method for preparing the partially N-higher acylated N, O-succinylated chitosan lactate of this example is shown below.

N, O-succinylated chitosan consisting of an acyl group having 6 carbon atoms (average molecular weight: about 110,000, degree of substitution of succinyl group: 0.41, amino group content: 60.7%) and lactic acid per residue of hexosamine salt 0.65 molar equivalent was added and dissolved to obtain an N, O-succinylated chitosan glutamate solution having a charged amino group of 60.7%.

To this solution, 1 volume of methanol was added to form a uniform solution, and stearic anhydride 0.1 was dissolved in methanol.
Partial higher acylation was carried out by adding 05 molar equivalents and stirring overnight at room temperature, followed by ultrafiltration, concentration, lyophilization, and acetone washing to obtain a spongy partially N-stearoylated N, O-succinyl chitosan lactic acid. Adjusted the salt.

The introduction rate of the stearoyl group is as follows:
It was determined from the peak derived from the N-stearoyl group by R (500MHZ) analysis, and as a result, the partial introduction rate was 5.2%.

The chitosan derivative obtained in this example is represented by the following formula (6).

[0092]

[Chemical 6]

In the formula (6), R ₁₇ represents lactic acid, and R _17
18 represents a hydrogen atom or a succinyl group, R ₁₉ represents a succinyl group, and R ₂₀ represents a stearoyl group.

Further, a, b, c and d are integers of 1 or more, and 300 <a + b + c + d <350.

The partial introduction rate of the stearoyl group per hexosamine residue is about 5.2%.

Further, the three kinds of structural units marked with a, b, c and d may be randomly arranged.

Example 6 Mainly for each chitosan derivative obtained by the method of Examples 1 to 5
The volume of the 1.0% aqueous solution and squalane was adjusted to 1: 1 and the mixture was homomixer treated (7500 rpm, 1 minute) and sonicated to obtain a final emulsion.

Partially N-myristoylated chitosan PCA salts were also tested for those having a higher acyl group introduction ratio other than Example 1, and for partial N, O-lauroylated chitosan lactate, higher acyl groups other than those of Example 2 were tested. Tests were also conducted for those with a group introduction rate.

Accelerated test of stability of emulsion (centrifugation, 40
Evaluation was carried out by a cycle test).

As a positive control, a system utilizing a conventional nonionic surfactant was used.

The results are shown in Table 1.

[0102]

[Table 1]

As is clear from Table 1, the chitosan derivative of each Example has an excellent emulsifying ability, and the emulsion stability in the accelerated test is the same as that of the conventional nonionic surfactant. It was suggested that it is useful as an emulsifier because of its small degree.

On the other hand, when the introduction ratio of the higher acyl group exceeds 30%, an emulsion is formed, but the emulsion stability is not sufficient, and remarkable separation was observed in the accelerated test, which is not useful. Is.

For chitosan PCA salt and chitosan lactate,
Emulsion formation was insufficient.

Example 7 In this example, an antibacterial challenge test was conducted.

The chitosan derivative obtained by the method of Examples 3-5, and 0.2% of partially N-lauroylated chitosan PCA salt and partially N, O-myristoylated chitosan lactate.
Inoculate the aqueous solution with 1 × 10 ⁸ cells / ml of a microbial cell solution at a concentration of 1%, and
The mixture was allowed to stand at 0 ° C for 2 weeks, and the viable cell count was measured by the agar dilution method.

USP mixed bacteria, which is a mixture of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, was used as mixed bacteria, black mold, ganjita, and blue mold were mixed as mixed fungi, and domestic waste water filtrate was used as mixed waste bacteria. Using.

The results are shown in Table 2.

[0110]

[Table 2]

As is clear from Table 2, Examples 3 to 5
The chitosan derivative, and the partial N-lauroylated chitosan PCA salt and the partial N, O-myristoylated chitosan lactate are antibacterial against mixed fungi and drainage mixed bacteria, which were insufficient with chitosan PCA salt and chitosan lactate. Showed sex.

Since the antibacterial spectrum is broadened while maintaining a high antibacterial property, it is clear that the usefulness as an antibacterial agent and a preservative is enhanced.

When the introduction ratio of the higher acyl group exceeds 30%,
As shown in Table 2, the antibacterial property is lowered, which is clearly not preferable.

Example 8 This example describes a partially N-lauroylated chitosan PCA salt,
Effects of partial N-myristoylated chitosan glycolate, partial N, O-myristoylated chitosan PCA salt, partial N-lauroylated chitosan PCA salt, partial N-myristoylated hydroxybutyl chitosan PCA salt on skin viscoelasticity and skin moisturizing property It mainly considers the impact.

Lotion containing 0.4% (dry weight%) of chitosan derivative as the observation site, and lotion containing hyaluronic acid and chitosan salt of the same concentration as the control, with the outer part of the forearm of 15 healthy men and women (average age: 32.0 years) as the observation site. Was continuously applied for 4 weeks.

The skin viscoelasticity showing the flexibility and elasticity of the skin was measured with a Dermark torque meter (manufactured by DIA-STRON).
(Manufactured by S Co., Ltd.).

The measurement was performed after washing with hot water and resting at room temperature of 25 ° C. and humidity of 50% for 30 minutes.

The improvement effect was determined using the rate of change (%) of the measured value before and after the application as an index.

The results are shown in Table 3.

[0120]

[Table 3]

As is clear from Table 3, with respect to skin viscoelasticity, the chitosan derivative of this Example is superior in hyaluronic acid, chitosan PCA salt and chitosan glycolate in the significant improvement effect and its improvement level. It was suggested that

However, the skin viscoelasticity of the partially N-lauroylated chitosan PCA salt having an acyl group introduction rate exceeding 30% was similar to that of the chitosan PCA salt.

With respect to the skin moisturizing property as well, it was shown to be equal to or higher than that of hyaluronic acid which is a positive control. Clearly high.

However, the skin moisturizing property of the partially N-lauroylated chitosan PCA salt having an acyl group introduction rate of more than 30% was not better than those of the others.

[0125] Also, in the improvement of the skin surface morphology (improvement of unevenness and small wrinkles), a significant improvement effect was observed in image analysis by replica collection (3-D scanner, manufactured by Ichimaru Falcos Co., Ltd.) It was suggested that it is superior to acids and chitosan salts.

Prescription Example 1 This prescription example is a prescription example when used as a lotion.

[0127]     Ingredient ratio (wt%)   Trimethylglycine 2.0%   Glycerin 6.5%   Methylparaben 0.03%   Partially N-lauroylated chitosan lactate     (Higher acylation introduction rate: 9.8%) 0.1%   Ethanol 10.0%   pH adjusting agent   Tocopherol acetate 0.05%   Fragrance   Purified water Remaining amount

Prescription Example 2 This prescription example is a prescription example when used as an emulsion.

[0129]     Ingredient ratio (wt%)   Cetanol 2.5%   Liquid paraffin 10.5%   Vaseline 2.0%   Partial N, O-myristoylated chitosan pyrrolidone   Carboxylate (higher acylation rate; 13.5%) 0.3%   Glycerin 6.0%   1,3-butylene glycol 5.0%   Butylparaben 0.01%   Ceramide 0.1%   Natural vitamin E 0.02%   Fragrance   Purified water Remaining amount

Prescription Example 3 This prescription example is a prescription example when used as an essence.

[0131]     Ingredient ratio (wt%)   Hydroxymethyl cellulose 0.8%   Glycerin 10.0%   Polyethylene glycol 1000 3.0%   Paraben 0.3%   Partially O-octylated chitosan glycolate     (Higher acylation introduction rate: 5.5%) 0.2%   Ascorbic acid magnesium phosphate 1.0%   Vitamin A derivative (vitamin A palmitate) 0.02%   Fragrance   Purified water Remaining amount

Formulation Example 4 This formulation example is a formulation example when used as a cream or a hydrophilic ointment.

[0133]     Ingredient ratio (wt%)   Behenyl alcohol 5.0%   Vaseline 4.5%   Liquid paraffin 15.0%   Partially N-lauroylated chitosan pyrrolidone carboxylate   (Higher acylation introduction rate: 7.5%) 0.4%   Sorbitan palmitate 0.1%   Dipotassium glycyrrhizinate 0.1%   Indomethacin 0.1%   Purified water Remaining amount

Example 8 In this example, the effect of actually using the external preparation for skin was determined by conducting a monitor test and conducting a questionnaire evaluation.

In the monitor test, 35 women in their 20s to 50s (healthy skin: 20 people, sensitive skin: 15 people) who are worried about skin aging and skin troubles were used as monitors and passed the stability and antiseptic test. The two types of emulsions having the following compositions were applied on the half side 2-3 times / day for 2 months.

After the end of use, a questionnaire was evaluated for each item to determine its usefulness.

The composition of the emulsion used in this example is as follows.

[0138]     Ingredient ratio (wt%)   Cetanol 2.5%   Liquid paraffin 10.5%   Vaseline 2.0%   Partial N, O-myristoylated chitosan pyrrolidone   Carboxylate (acylation introduction rate; 13.5%) 0.5%   Sorbitan stearate (emulsifier) 0.1%   Glycerin 6.0%   1,3-butylene glycol 5.0%   Methylparaben (preservative) 0.02%   Fragrance 0.01%   Purified water Remaining amount

The composition of the emulsion of Comparative Example is as follows.

[0140]     Ingredient ratio (wt%)   Cetanol 2.5%   Liquid paraffin 10.5%   Vaseline 2.0%   POE (25) monostearyl sorbitan (emulsifier) 4.0%   Sorbitan stearate (emulsifier) 1.0%   Glycerin 6.0%   1,3-butylene glycol 5.0%   Methylparaben (preservative) 0.2%   Fragrance 0.01%   Purified water Remaining amount

The test results of usability are shown in Table 4 (results of this example) and Table 5 (results of use examples).

[0142]

[Table 4]

[0143]

[Table 5]

As is clear from Tables 4 and 5, the safety of the emulsion of this example in which the emulsifier and the preservative can be reduced is that the skin safety is improved as compared with the conventional emulsion. Was confirmed.

Regarding the items relating to the improvement of skin viscoelasticity and skin moisturizing property, which show the flexibility and elasticity of the skin,
It was confirmed that the excellent effect was exhibited.

[0146]

INDUSTRIAL APPLICABILITY As described above, the chitosan derivative of the present invention has excellent skin safety, emulsifying ability and antibacterial ability, and therefore, conventional emulsifiers, antibacterial agents and preservatives that cause irritation and the like. It has become possible to reduce or remove the addition of the above, and to provide a skin external preparation such as a cosmetic having a skin moisturizing effect, a skin viscoelasticity improving effect, and a skin softening effect.

Continuation of front page (51) Int.Cl. ⁷ Identification symbol FI A61K 31/722 A61K 31/722 A61P 17/00 A61P 17/00 (72) Inventor Jiro Yoshino, 1-3-1, Muroya, Nishi-ku, Kobe City Pierce Stocks Central Research Laboratory (72) Inventor Emi Akamatsu 1-3-1 Muroya, Nishi-ku, Kobe City Pierce Stocks Central Research Laboratory (56) Reference JP 63-12699 (JP, A) JP 10-158304 (JP) , A) Shinichi Hayakawa et al., Partially acylated chitosan as a polymer surfactant, Proceedings of the oil chemistry debate, 1998, 37, 42 Sakai et al., Chitin and chitosan research, 1997, Vol. 3, No. 2,228-229 Sino et al., Fragrance Journal, 2001, 2001-12, 77-82 (58) Fields investigated (Int.Cl. ⁷ , DB name) C08B 37/08 A61K 7/00-7 / 48 A61K 31/722 CAPLUS (STN) MEDLINE (STN) REGISTRY (STN) JISST file (JOIS)

Claims (28)

(57) [Claims] 1. The content of charged amino groups is 40 to 100%, and the introduction rate of higher acyl groups having 7 to 20 carbon atoms is 0.1 to 30.0.
% Or a partial N-higher acylated chitosan salt, a partial O-higher acylated chitosan salt, or a partial N, O-higher acylated chitosan salt, or a chitosan derivative.
A skin external preparation characterized by containing at least one species . 2. The charged amino group content is 40 to 100 %, and the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to 30.0.
% Partially der Ru moiety N- higher acyl chitosan salts, parts
Min O-higher acylated chitosan salt or partial N, O-higher
One or two chitosan derivatives that are acylated chitosan salts
A cosmetic comprising at least one species. 3. The charged amino group content is 40 to 100 %, and the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to 30.0.
% Partially der Ru moiety N- higher acyl chitosan salts, parts
Min O-higher acylated chitosan salt or partial N, O-higher
One or two chitosan derivatives that are acylated chitosan salts
An emulsifier containing at least one species. 4. The content of charged amino groups is 40 to 100 %.
The introduction rate of higher acyl groups having 7 to 20 carbon atoms is 0.1 to 30.0
% Partial N-Higher Acylated Chitosan Salts, Partial
Min O-higher acylated chitosan salt or partial N, O-higher
One or two chitosan derivatives that are acylated chitosan salts
An emulsion stabilizer containing at least one species. 5. The content of charged amino groups is 40 to 100 %.
The introduction rate of higher acyl groups having 7 to 20 carbon atoms is 0.1 to 30.0
% Partial N-Higher Acylated Chitosan Salts, Partial
Min O-higher acylated chitosan salt or partial N, O-higher
One or two chitosan derivatives that are acylated chitosan salts
An antibacterial agent containing at least one species. 6. The content of charged amino groups is 40 to 100 %.
The introduction rate of higher acyl groups having 7 to 20 carbon atoms is 0.1 to 30.0
% Partial N-Higher Acylated Chitosan Salts, Partial
Min O-higher acylated chitosan salt or partial N, O-higher
One or two chitosan derivatives that are acylated chitosan salts
A skin moisturizer containing at least one species. 7. The content of charged amino groups is 40 to 100 %.
The introduction rate of higher acyl groups having 7 to 20 carbon atoms is 0.1 to 30.0
% Partial N-Higher Acylated Chitosan Salts, Partial
Min O-higher acylated chitosan salt or partial N, O-higher
One or two chitosan derivatives that are acylated chitosan salts
A emollient containing at least one species. 8. The content of charged amino groups is 40 to 100 %.
The introduction rate of higher acyl groups having 7 to 20 carbon atoms is 0.1 to 30.0
% Partial N-Higher Acylated Chitosan Salts, Partial
Min O-higher acylated chitosan salt or partial N, O-higher
One or two chitosan derivatives that are acylated chitosan salts
An anti-aging agent containing at least one species. 9. The content of charged amino groups is 1.0 to 90.0 %.
Yes, the introduction rate of higher acyl groups having 7 to 20 carbon atoms is 0.1 to 3
Partial with 0.0 %, having an acyl group with 2 to 6 carbon atoms
Partial N-higher acylated acyl chitosan salt, partial O-high
Highly acylated acyl chitosan salt or partial N, O-higher acyl
One or more chitosan derivative which is a silylated acyl chitosan salt
Is an external preparation for skin characterized by containing two or more kinds. 10. The content of charged amino groups is 1.0 to 90.0 %.
And the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to
Partial with 30.0 % and has an acyl group with 2 to 6 carbon atoms
Partial N-higher acylated acyl chitosan salt, partial O-high
Highly acylated acyl chitosan salt or partial N, O-higher acyl
One or more chitosan derivative which is a silylated acyl chitosan salt
Is a cosmetics characterized by containing two or more kinds. 11. The charged amino group content is 1.0 to 90.0 %.
And the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to
Partial with 30.0 % and has an acyl group with 2 to 6 carbon atoms
Partial N-higher acylated acyl chitosan salt, partial O-high
Highly acylated acyl chitosan salt or partial N, O-higher acyl
One or more chitosan derivative which is a silylated acyl chitosan salt
Is an emulsifier containing two or more kinds. 12. The content of charged amino groups is 1.0 to 90.0 %.
And the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to
Partial with 30.0 % and has an acyl group with 2 to 6 carbon atoms
Partial N -higher acylated acyl chitosan salt, partial O-high
Highly acylated acyl chitosan salt or partial N, O-higher acyl
One or more chitosan derivative which is a silylated acyl chitosan salt
Is an emulsion stabilizer containing two or more kinds. 13. The content of charged amino groups is 1.0 to 90.0 %.
And the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to
Partial with 30.0 % and has an acyl group with 2 to 6 carbon atoms
Partial N-higher acylated acyl chitosan salt, partial O-high
Highly acylated acyl chitosan salt or partial N, O-higher acyl
One or more chitosan derivative which is a silylated acyl chitosan salt
Is an antibacterial agent characterized by containing two or more kinds. 14. The content of charged amino groups is 1.0 to 90.0 %.
And the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to
Partial with 30.0 % and has an acyl group with 2 to 6 carbon atoms
Partial N-higher acylated acyl chitosan salt, partial O-high
Highly acylated acyl chitosan salt or partial N, O-higher acyl
One or more chitosan derivative which is a silylated acyl chitosan salt
Is a skin moisturizer containing two or more kinds. 15. The content of charged amino groups is 1.0 to 90.0 %.
And the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to
Partial with 30.0 % and has an acyl group with 2 to 6 carbon atoms
Partial N-higher acylated acyl chitosan salt, partial O-high
Highly acylated acyl chitosan salt or partial N, O-higher acyl
One or more chitosan derivative which is a silylated acyl chitosan salt
Is a softening agent containing two or more kinds. 16. The content of charged amino groups is 1.0 to 90.0 %.
And the introduction rate of the higher acyl group having 7 to 20 carbon atoms is 0.1 to
Partial with 30.0 % and has an acyl group with 2 to 6 carbon atoms
Partial N-higher acylated acyl chitosan salt, partial O-high
Highly acylated acyl chitosan salt or partial N, O-higher acyl
One or more chitosan derivative which is a silylated acyl chitosan salt
Is an anti-aging agent containing two or more kinds. 17. A partial reed represented by the following formula (1) :
Chitosan induction characterized by consisting of chitosan salt
body. [Chemical 1] (In the formula (1), R ₁ , R ₂ , R ₃ and R ₄ are hydrogen atoms and carbon
A higher acyl group having a prime number of 7 to 20 or a hydroacyl group having a carbon number of 2 to 6
A xyalkyl group or an acyl group, R ₅ is hydrogen
Child, higher acyl group having 7 to 20 carbon atoms , acetyl group, or charcoal
A hydroxyalkyl group or acyl group having a prime number of 2 to 6
Show. Partial introduction rate of higher acyl groups with 7 to 20 carbon atoms is 0.1
~ 30.0 %. a and b represent an integer of 1 or more, and 10 <
a + b < 2000 . The structural units with a and b are run
It may be arranged in a dam. ) 18. A higher acyl group having 7 to 20 carbon atoms is
18. The chitosan derivative according to claim 17, which is a stoyl group . 19. A higher acyl group having 7 to 20 carbon atoms is represented by
Quito of claim 17 wherein the Royle group or stearoyl group
Sun derivative. 20. A portion N− represented by the following equation (2) :
Chito characterized by comprising a higher acylated chitosan salt
Sun derivative. [Chemical 2] (In the formula (2), R ₆ represents PCA and R ₇ represents millis
Indicates a toyl group. Part introduction rate of the myristoyl group from 0.1 to
It is 30.0 %. Also, a, b, c are integers of 1 or more,
400 <a + b + c < 450 . In addition, a, b, c
The three types of attached structural units are randomly arranged
May be ) Key of 21. according to any one of claims 17 to 20
Characterized in that it contains one or more tosan derivatives
External preparation for skin. 22. according to any one of claims 17 to 20 keys
Characterized in that it contains one or more tosan derivatives
Cosmetics to do. 23. according to any one of claims 17 to 20 keys
Characterized in that it contains one or more tosan derivatives
Emulsifier to do. 24. according to any one of claims 17 to 20 keys
Characterized in that it contains one or more tosan derivatives
An emulsion stabilizer. 25. A according to any one of claims 17 to 20 keys
Characterized in that it contains one or more tosan derivatives
Antibacterial agent. 26. The according to any one of claims 17 to 20 keys
Characterized in that it contains one or more tosan derivatives
Skin moisturizer. Key of 27. according to any one of claims 17 to 20
Characterized in that it contains one or more tosan derivatives
A skin softening agent. Key of 28. according to any one of claims 17 to 20
Characterized in that it contains one or more tosan derivatives
Anti-aging agent.