JPH09151130A - Medicine for treating trichopoliosis and leukoplakia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject medicine containing a phenylpropanoid derivative having a tyrosinase-activating action, such as caffeic acid, and having excellent effects on trichopoliosis and leukoplakia for which substantially no therapeutic method has been found. SOLUTION: This medicine for treating trichopoliosis and leukoplakia contains at least one of caffeic acid, ferulic acid, chlorogenic acid and a compound of the formula [R' is CH2 OR" (R" is H, Me, Et, Pr, Bu, quinic acid, a monosaccharide), CHO, COOR"; R is H, Me, or R and R" together form CH2 , CMe2 ; (n) is 0-4] as an active ingredient. When the therapeutic medicine is prepared into a hair tonic, the caffeic acid, the chlorogenic acid, propylene glycol and a 50% ethanol/buffer solution are compounded, e.g. in amounts of 1g, 0.05g, 30g and a proper amount, respectively, per 100g of the whole amount. The therapeutic medicine can be prepared into a solution, an ointment, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to caffeic acid, ferulic acid, chlorogenic acid, and structural formulas. The present invention relates to a therapeutic agent for leukoplakia and leukoplakia containing at least one compound represented by the formula (1) as an active ingredient.

[0002]

BACKGROUND OF THE INVENTION Vitiligo is a type of primary eruption and refers to the spots caused by depigmentation. Congenital and generalized vitiligo are said to be albinism, and localized ones are classified as follows. 1) Vitiligo vulgaris: Commonly called white catfish. 2) Sutton efferent ecchymosis: An efferent expansion centering on pigmented nevus. 3) Localized congenital albinism: This is regarded as a kind of malformation, and some people call it depigmented nevus. 4) Syphilis or pseudosyphilis vitiligo. 5) Leprosy vitiligo. 6) In addition, white spots after bathing in the sea, white spots on the sun, and white spots after a rash that disappear over time. In particular, vitiligo vulgaris, which has the largest number of cases, is predisposed to systemic or local modulation of endocrine, autonomic dysfunction, internal organ disease, various skin diseases, etc.
It is caused by melanin pigment exudation with clear boundaries on a part of the skin. At present, there are almost no appropriate vitiligo treatments, and application of steroids or PUVA therapy, sunbathing, administration of tranquilizers, application of melanidine solution, etc. are only performed. Leukoplakia is a phenomenon in which white hair is formed in a localized island shape, and is mainly caused by a decrease in melanin formation due to a deficiency in enzymatic activity of tyrosinase of melanocytes in hair follicles. This localized leukoplakia may be genetic, familial, or acquired. It is also known that vitiligo vulgaris and white hair occur in the congenital albinism part. The only cure for albinism is to dye it exclusively. As the therapeutic agent, for example, JP-A-6-256144, 6-
256145, 6-172134, 6-100423, 5-117132, 5-78222,4-24
Hair cosmetics are described in 3808, 4-202115, 4-128214, but they have not been widely applied as a fundamental treatment method.

[0003]

It is believed that the melanogenic system in the skin or hair follicles is largely involved in pigmentation at the target site. Therefore, for tyrosinase which is a key enzyme of melanin production,
If the compound listed in 1 above has an activating effect, it is considered that the production of melanin at the target site is promoted to promote the improvement of leukoplakia and leukoplakia. The process from tyrosine to melanin production is described below.

[0004]

Means for Solving the Problems The present inventors have investigated the tyrosinase activating effect of the compound recited in claim 1,
We considered that these substances could enhance melanin production in the skin and could be excellent agents for vitiligo. At the same time, the effect of increasing the tyrosinase activity in hair melanocytes as a therapeutic agent for albinism was also examined.

[0005]

DETAILED DESCRIPTION OF THE INVENTION

Example 1 The results of measuring the tyrosinase activating effect of 6 kinds of substances from the compounds listed in claim 1 are shown. <Method> Tyrosine was used as a substrate. 900 μg of each test substance was made into a 50% ethanol solution and added to the reaction solution. As a control, 50% ethanol was added. 37
After preincubation at 10 ° C for 10 minutes, mushroom-derived tyrosinase was added, and after reacting at 37 ° C for a certain period of time, the tyrosinase activity was determined from the change in absorbance at 475 and 580 nm. <Results> ─────────────────────────────────── Sample tyrosinase activation A ₄₇₅ A ₅₈₀ ─── ──────────────────────────────── Reference 100 100 Caffeic acid 304 1133 Ferulic acid 127 604 Chlorogenic acid 141 622 Ferroy Luquinic acid 115 470 Coniferyl alcohol 121 556 Dihydroconiferyl alcohol 108 368 ──────────────────────────────────── <Summary> 900 μg of the above 6 samples into the reaction solution
When added, all had the effect of activating the activity of tyrosinase. Also, with respect to the other compounds recited in claim 1, the action of similarly activating the activity of tyrosinase was observed.

Example 2 An agent for treating albinism was prepared according to the following formulation. <Tonic> Caffeic acid 0.05-0.1g Carpronium chloride 3-5g 50% Ethanol / buffer * Suitable amount ──────────────────────── Total amount 100g * Sodium citrate / hydrochloric acid buffer (pH 4.8-5.0)

Example 3 An agent for treating albinism was prepared according to the following formulation. <Tonic> Caffeic acid 0.1 g Chlorogenic acid 0.05 g Propylene glycol 30 g 50% Ethanol / buffer * Proper amount ────────────────────── Total amount 100 g Sodium acid / hydrochloric acid buffer (pH 4.8 to 5.0)

Example 4 A therapeutic agent for vitiligo was prepared according to the following formulation. <Liquid formulation> Caffeic acid 0.05 -0.1 g Chlorogenic acid 0.05 g Carpronium chloride 3-5 g 1,3-Butylene glycol 40 g 20% Ethanol / buffer * Appropriate amount ────────────── ──────────────── Total amount 100g * Sodium citrate / hydrochloric acid buffer (pH 4.8 to 5.0)

Example 5 A drug for vitiligo disease was prepared according to the following formulation. <Liquid formulation> Caffeic acid 0.05-0.1 g Ferulic acid 0.05 g Carpronium chloride 3-5 g 1,3-Butylene glycol 40 g 20% Ethanol / buffer * Proper amount ────────────── ────────────── Total 100g * Sodium citrate / hydrochloric acid buffer (pH 4.8 to 5.0)

Example 6 A vitiligo therapeutic agent was prepared according to the following formulation. <Ointment> Caffeic acid 0.1 g Chlorogenic acid 0.1 g Carpronium chloride 3 g 1,3-Butylene glycol 10 g Hydrophilic poloid Suitable amount ───────────────────── Total amount 100 g

Example 7 The blackening effect of caffeic acid on hirsutism was examined. Five females and three males in their 30s with a part of their hair turned white and containing 0.05% caffeic acid 5
The 0% ethanol solution was applied to the hair twice a day for 4 months. Before application and 1 month, 2 months after the start of application, 4
Each month, 10 hairs were randomly removed and visually observed to judge the color tone. The score is white: 0 points, light gray:
1 point, gray: 2 points, black: 3 points. The highest score is 30
The point and the lowest point are 0 points.

Example 8 The blackening effect of caffeic acid was examined in 5 patients in their 50s who had completely whitened heads in the frontal region and the crown. A 50% ethanol solution containing 0.1% caffeic acid was applied to the hair twice a day for 8 months. Before application and 2 months, 4 months, and 8 months after the start of application,
Randomly stripped 10 hairs, Example 7. The color tone was judged in the same manner as in.

Example 9 Using various concentrations of caffeic acid, the blackening effect on albinism was examined. Five females in their 30s with a part of their hair turned white were selected from each group, and 50% ethanol solutions containing 0.01%, 0.05% and 0.1% of caffeic acid were applied to the hair for 2 months. Ten hairs were randomly extracted at the time of application disclosure and two months after the initiation of application, and Example 7.
The color tone was judged in the same manner as in.

Example 10. The therapeutic effect of caffeic acid on vitiligo vulgaris. Caffeic acid 0.0 on the white spots on the face and hands
20% ethanol solution containing 1% twice a day (morning and night), 4
It was applied for a month and its effect was examined. Patient is female (40
There are 5 people in their 50s and 50 men in their 50s to 60s. For the effect, the size of vitiligo nest and the color tone of vitiligo were visually judged. The degree of decrease in size was expressed as 1/3: +, 1/2: ++, and completely disappeared: +++. The color tone was judged to be red: +, red gray: ++, skin color (indistinguishable from surroundings): +++. The effects are summarized in the table below.

[Table 1] Gender 1 month 2 months 4 months Color tone Color tone Color tone Color tone Size ♂ + + ++ ++ +++ +++ ♂ − ＋＋ ＋ ++ ++ ♂ ＋ − ++ + ++ ++ ♂ ++ ++ ++ ++ +++ +++ ♂ + ++ ++ ++ +++ +++ ♀ − − ++ ++ ++ ++ ♀ ++ ++ ++ +++ +++ ♀ ＋ ++ ++ ++ +++ +++ ♀ ++ ＋ ++ ++ +++ +++ ♀ ＋ ++ ++ ++ +++ +++

Example 11 The effects of applying a 30% ethanol solution containing 0.1% each of caffeic acid, chlorogenic acid, and ferulic acid to vitiligo for one month were compared. Patient is female 5
Vitiligo on the name, face, hands, arms and legs. The average value of the effect is shown. The judgment criteria are in accordance with Example 10. The degree of its effect correlates with the activating effect of tyrosinase shown in Example 1.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI technical display location A61K 31/215 ADA A61K 31/215 ADA 31/36 31/36 31/70 31/70 // ( (A61K 31/19 31: 205) (A61K 31/215 31: 205) (72) Inventor Yuko Iikura 1-6-2 Yawatacho, Musashino City, Tokyo Metropolitan Institute for Pharmacology

Claims (1)

[Claims] 1. A therapeutic agent for leukoplakia and leukoplakia, which comprises caffeic acid, ferulic acid, chlorogenic acid, and at least one compound represented by the following structural formulas as an active ingredient.