JP2003055191A - Skin care treatment external preparation for atopic dermatitis and various xeroderma and rough skin diseases - Google Patents

Abstract

PROBLEM TO BE SOLVED: To develop a preparation for preventing, reducing or treating atopic dermatitis and various xeroderma and rough skin diseases. SOLUTION: This external care preparation contains a stable ascorbic acid derivative as an active ingredient for the above-described symptoms in a higher concentration than those of conventional preparations.

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an "external preparation" containing ascorbic acid or an ascorbic acid derivative as an active ingredient at a high concentration and stably. More specifically, ascorbic acid, preferably an ascorbic acid derivative which is known to be resistant to oxidative degradation and has high stability over time, more preferably magnesium ascorbyl phosphate, can be produced at a high concentration and stably by a formulation technique. Ointments, creams and the like are prepared and applied to the skin of atopic dermatitis and various xeroderma and rough skin to improve or suppress those symptoms. These fields of application fall into the fields of dermatology and cosmetics. [0003] Atopic dermatitis is said to be a chronic dermatitis disease that repeatedly develops due to a genetic predisposition.
Not yet elucidated. It is known that various external stimuli easily cause inflammation and itching, and that sphingolipids (ceramides) in the stratum corneum of the upper layer of the skin are reduced. The function of the protective layer (barrier) is reduced, and dryness is exhibited. House dust, as an allergic substance causing atopic dermatitis,
Mites, certain foods and the like are known. As non-allergic causes, it is said that low humidity indoor environment due to air conditioning, ultraviolet rays, stress on social life, and the like also cause this disease. As described above, various causes are combined, and atopic dermatitis and various types of xeroderma and dermatitis corresponding thereto are increasing year by year. In other words, pediatric atopic dermatitis used to be large in the past, but recently it has been frequently observed in adults, and it is said that adult atopic dermatitis is increasing. As a result, it has become one of the major obstacles to social life. In addition, the number of patients with senile xeroderma, rough skin disease, especially rough hands (housewife eczema, progressive palmar keratosis, etc.) also increased due to indoor dryness, use of soap, detergent, etc. are doing. [0004] Many treatments have been conventionally performed in response to the above diseases, but steroid hormones have been frequently used as anti-inflammatory agents in the field of dermatology. Recently, certain immunosuppressants have also been used. However, these drugs are also known to cause side effects during long-term use, and aggravation of symptoms due to misuse is also a problem.
In particular, topical use of steroids has been used as an effective drug, but at the time of discontinuation of use, skin disorders due to rebound reactions may occur, making recovery difficult. On the other hand, various folk remedies using products other than steroids have also been frequently used, but their effectiveness is not always clear, and in some cases, the number of patients whose symptoms have worsened due to abuse has increased. In other words, atopic dermatitis is constitutional and difficult to completely cure. In addition to a doctor's careful search for the cause and treatment and guidance according to it, the patient is sedated and controlled by daily skin care of the patient himself. This is very important.
The treatment guidelines (1999) from the Ministry of Health and Welfare research group on atopic dermatitis also include the removal of causative factors, skin care to improve skin abnormal functions specific to this disease,
Three points of appropriate pharmacotherapy for suppressing inflammation are mentioned. Under such circumstances, there is a demand for the development of highly safe formulations that can be used not only in the treatment of inflammation but also in a wide range of applications, including skin care during periods when symptoms are alleviated. Also, with respect to various types of xerosis and rough skin disease, there is a high demand for an appropriate skin care preparation as in atopic dermatitis. However, none of the currently used external medicines and skin care products on the market sufficiently satisfy this purpose. In view of the above situation, the present inventors have considered these as problems that span the fields of skin care and treatment, and have proceeded with the development of the following formulations to solve these problems. [References] 1. Fragrance Journal, Volume 3, 7,
(1997) 2. Fragrance Journal, Volume 3, 20, (199
7) 3. Fragrance Journal, Volume 3, 29, (199
7) 4. Skin, Volume 42, Special Issue No. 22, (10) (200
0) 5. Allergy, Volume 49, 2/3, 137, (200
0) 6. Allergy, Volume 49, 2/3, 148, (200
0) 7. Allergy, Volume 49, 2/3, 154, (200
0) 8. Allergy, Volume 49, 2/3, 275, (200
0) 9. Vitamin, Vol. 41, No. 6, 387, (1970) 10. [0006] First, ascorbic acid was described as a candidate substance which is considered to be suitable for the above-mentioned object, and examined. This product has a long track record in the cosmetics field as a so-called whitening substance. However, since this product is easily oxidatively decomposed by heat or light, it has been difficult to maintain a constant concentration in the preparation for a long period of time. In recent years, various stable ascorbic acid derivatives have been developed and widely used in cosmetics and quasi-drugs. These derivatives have high resistance to oxidative degradation and can stably maintain an effective concentration in a preparation for a long period of time. By applying a formulation containing these components to the skin, it is possible to reach a high concentration of ascorbic acid into the skin cells, and various studies have been conducted on the effects of ascorbic acid on living organisms at high concentrations. Began to take place. These studies show that, in addition to the known effects of ascorbic acid (whitening, antioxidant, etc.), the inhibitory effect of barrier function decline, the promotion of collagen synthesis, the interaction with cytokines involved in photoaging, the inflammation Nerve growth factor (NGF), which is known to be closely related to
Interaction (anti-inflammatory action) and the like are presumed. still,
It is known that the ascorbic acid derivative used here easily releases ascorbic acid in the skin by a biodegrading enzyme. On the other hand, to reduce and control atopic skin inflammation caused by a combination of various factors, based on the hypothesis of ascorbic acid research described above, it is possible to stably mix much higher concentrations of ascorbic acid than before. Was considered appropriate. Therefore, a prescription was designed by blending a stable ascorbic acid derivative at a high concentration to prepare a preparation. First, these preparations were subjected to a closed patch test for healthy persons to confirm their safety. Next, a clinical test was performed on the effects of these preparations on patients with atopic dermatitis and various xerosis and rough skin patients. As a result, none of the subjects showed a positive reaction in the closed patch test of these preparations. The efficacy of these preparations against atopic dermatitis, various xerosis, and rough skin was confirmed. It was also effective against skin problems due to steroid rebound, and its inflammation was suppressed. As described above, it has been found that, compared to the conventional topical steroid preparation, it can be used in a wider range without side effects. That is, the present invention relates to an “external preparation” characterized by containing an effective concentration of a stable ascorbic acid derivative having resistance to oxidative degradation. [0008] Conventionally, most cosmetics and quasi-drugs containing ascorbic acid or derivatives thereof contain less than 3% by weight.
The formulation technology was also difficult. Then, considering that ascorbic acid reaches a sufficient concentration in the skin cells, a high concentration of 3% by weight or more was examined. For this purpose, a high concentration (5% or more) of an ascorbic acid derivative is blended in a pharmaceutical system to suppress the precipitation and growth of ascorbic acid crystals, and to increase the base oil component (particularly petrolatum),
In addition to preventing the evaporation of water from the dry skin surface, the distribution ratio of ascorbic acid (skin / formulation) between the skin surface and the coating film of the formulation is increased, and various factors are considered to facilitate the penetration of the active ingredient into the skin. As a result, the desired formulation was obtained. [0009] In a preparation containing an ascorbic acid derivative in an amount of 10% by weight or more, a small amount of crystal precipitation was observed during use, but the crystal state was fine and the skin was not irritating. Ascorbic acid used in the present invention may be a stable derivative having high resistance to oxidative degradation, and preferably, ascorbyl magnesium phosphate is suitable. The mixing ratio is 5 to 15% by weight, more preferably 7 to 15% by weight.
It is 12% by weight. Other active ingredients include vitamin E, anti-itch agents (such as crotamiton) and humectants (such as hyaluronic acid, ceramides, glycerin, and 1,3-butylene glycol). Further, the base component includes oils (white petrolatum, squalane, olive oil, etc.), higher alcohols (behenyl alcohol, etc.), higher fatty acids (stearic acid, palmitic acid, etc.), natural waxes (bee wax, carnauba wax, etc.), surfactants ( Components necessary for formulating a sucrose fatty acid ester, lecithin, sodium caseinate, etc.) and a thickening agent (methyl cellulose, etc.) can be added.
In addition, 20 to 95% by weight, preferably 3%
It is characterized by being added in an amount of 0 to 93% by weight. In addition, raw materials having the highest degree of purification were selected and used, except for components (cosmetic labeling-designated components), fragrances, pigments, and the like, which would cause allergies and irritants. [0010] Dosage forms applicable as the "external preparation" of the present invention include oily ointments, hydrophilic ointments, creams, gels and the like. Example 1, oily ointment type external preparation (weight%) Magnesium ascorbyl phosphate; 10 white petrolatum; 80 liquid paraffin; 8 99.5% ethanol; suitable amount (total amount is 100%) (production method) 100) Magnesium ascorbyl phosphate
No. 99.5% ethanol is added, and after pulverization, liquid paraffin is added and uniformly dispersed. After heating and melting, white petrolatum is added little by little to the mixture and kneaded. Example 2, Hydrophilic ointment type external preparation (Manufacturing method) A is dissolved at 80 ° C., B is dissolved at 60 ° C., C
Is dispersed at 40 ° C., and B is added to C with stirring to dissolve completely. A is added to this, and it stirs until it becomes 30 degreeC. [Example 3, cream type external preparation] (Manufacturing method) A is dissolved at 80 ° C., B is dissolved at 60 ° C., C
Is dispersed at 40 ° C., and B is added to C with stirring to dissolve completely. A is gradually added to this with stirring, emulsified, and then cooled to 30 ° C. [Safety Test] A closed patch test for 48 hours was conducted on 45 subjects using the normal closed patch test method in Japan, and the above-mentioned [Example 1] to [Example 3] The test was performed on three test samples.
As a result, no positive reaction was observed in any case, and it was confirmed that the reaction was basically safe. [Clinical test of patients with atopic dermatitis and various xerosis and dermatosis] (1) A total of 110 patients with atopic dermatitis and various xerosis and dermatosis were tested. A clinical test was conducted on the three test samples of Example 3 through the following test method. (Test method) For each test sample, apply to the skin of the trunk or fingers for a certain period (about 1 month) (1 day, 1 to 2
), And the skin condition of each sample after the start of the test and after the end of use was observed. In the comparative test, each sample was applied to the trunk or the left and right of the finger, and their effects were compared. (2) Comparison data of [Example 1] (hereinafter abbreviated as "A") and [Comparative Example 1] (hereinafter abbreviated as "B") for 56 subjects with atopic dermatitis described above It is shown below. [Comparative Example 1, steroid mixed type external preparation] White petrolatum; 80.0 B.I. Alcumetasone propionate ointment: 20.0 (Production method) Add A to B, and knead thoroughly. (3) In the comparison between the base (white petrolatum) and the test sample, all of the above samples (Example 1 to Example 3 and Comparative Example 1) were more evident than when the base was used alone. Demonstrated efficacy. From the above results, the "external preparation" of the present invention
Was confirmed to have excellent effects on atopic dermatitis, various xerosis, and rough skin disease. Ascorbic acid itself used in this drug has been a substance whose physiological action is well known, but a new effect qualitatively different by increasing the dose has been found. These external preparations have a milder action than conventional steroid ointments, but they have no side effects and are highly safe, so they can be widely used as daily skin care preparations. found.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 47/44 A61K 47/44 A61P 17/00 A61P 17/00 17/16 17/16 37/04 37 / 04 F-term (reference) 4C076 AA07 AA08 AA17 BB31 CC22 DD34A FF01 4C083 AA122 AC011 AC012 AC022 AC122 AC172 AC242 AC302 AC422 AC442 AC642 AD332 AD641 AD642 AD662 BB12 CC05 DD31 EE12 EE13 FF05 4C086 AA01 ZA89 ZA18Z

Claims (1)

Claims: 1. An ascorbic acid or ascorbic acid derivative, preferably 5 to 15% by weight, preferably 7 to 12% by weight of ascorbyl magnesium phosphate as an active ingredient.
Wt.
An external preparation for skin care and treatment for atopic dermatitis and various xerosis and rough skin (hereinafter abbreviated as "external preparation"), which is contained in an amount of 30 to 93% by weight.