JPH07109214A - Sebum secretion promoter - Google Patents

Abstract

PURPOSE:To obtain a sebum secretion promoter having activating action on sebaceous gland function, improving effect on chapped skin by drying. CONSTITUTION:This sebum secretion promoter comprises 0.0001-10.0wt.%, preferably 0.001-3.0wt.% of bryonolic acid of the formula which is an acidic pentacyclic triterpenoid and is produced by culturing a cultured cell of cucurbitaceous plant in a medium containing auxin in a low concentration at a dark place. The dosage form of the promoter is powder, pill, tablet, injection, suppository or external preparation and the promoter is produced according to ordinary pharmaceutically manufacturing technology. A daily dose is 20-500mg, preferably 50-200mg and can be administered dividedly two to three times. The compound of the formula is obtained by inducing a callus of cucurbitaceous plant by a conventional method, preparing a cell of suspension culture, inoculating the cultured cell to a liquid medium containing 10<-6> to 10<-8>M2,4- dichlorophenoxybutyric acid, subjecting the cell to rotary shaking culture at a dark place for 1-3 weeks, drying the prepared cultured cell, extracting and concentrating to dryness.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an agent for promoting sebum secretion, which comprises bryonolic acid.

[0002]

2. Description of the Related Art A decrease in the amount of skin surface lipids causes rough skin, xerosis, etc., and atrophy of the sebaceous glands with age is considered to be one of the causes of aging of the skin. Therefore, cosmetics in the form of creams, emulsions, lotions and the like have been used for the purpose of replenishing oil to the skin having a decreased secretory function of sebum. Further, there is no application example of brynolic acid to a sebum secretagogue.

[0003]

In the conventional oil replenishment product, although it temporarily stays on the skin surface, it peels off due to external factors such as friction, so that the effect is not long-lasting. Therefore, there is a demand for a sebum secretion promoting agent that promotes the secretion of oil by blending a substance having a sebum secretion promoting action.

[0004]

Means for Solving the Problems This time, when the effectiveness of bryonolic acid was examined, the finding was found to activate the sebaceous gland function, and the present invention was completed. That is, the present invention is a sebum secretion promoter characterized by containing bryonolic acid. The term "brionolic acid" as used in the present invention is an acidic pentacyclic triterpenoid represented by the general formula (Formula 1), and is produced by culturing cultured cells of Cucurbitaceae plants in a dark medium containing a low concentration of auxin in the dark. (Plant Cell Physiol. 25 (8): 1571-1574 (1984),
JP-A-2-107194).

[Chemical 1]

For example, callus of a plant of the Cucurbitaceae (loofah, melon, etc.) is induced by a conventional method to prepare a suspension culture cell thereof. The cultured cells are inoculated into a liquid medium containing 10 ⁻⁶ to 10 ⁻⁸ M 2,4-dichlorophenoxyacetic acid (2,4-D), and cultured in the dark for 1 to 3 weeks with rotary shaking. The obtained cultured cells are dried, extracted with chloroform, and concentrated to dryness.
The obtained extract is chloroform / methanol (2: 1)
Needle-like crystals (bryonolic acid) are obtained by re-dissolving in and recrystallizing. Also, Cucurbitaceae plants, for example, melon,
Similarly, extract from roots such as pumpkins and crows,
After fractionation with a silica gel column, recrystallization can be performed to obtain bryonolic acid. The bryonolic acid referred to in the present invention does not necessarily have to be completely purified, and may be a crude product.

[0006] Brionolic acid is 0.0001 to 10.0% by weight, preferably 0.001 to 10% by weight in the total amount of the sebum secretagogue of the present invention.
It can be blended at 3.0% by weight. At a concentration of 0.0001% or less, a sufficient effect cannot be obtained, and at a concentration of 10.0% by weight or more, the effect is not enhanced and it is uneconomical. The sebum secretagogue of the present invention includes oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants and the like used in pharmaceuticals as long as the effect of bryonolic acid is not impaired. Raw materials can be blended. The dosage form of the sebum secretagogue of the present invention is a powder, a pill, a tablet, an injection, a suppository, an external preparation, etc., and is manufactured according to a usual formulation technique. The daily dose is 20 mg to 500 mg, preferably 50 mg
It is possible to administer it at a dose of up to 200 mg in 2 to 3 divided doses.

[0007]

EXAMPLES Next, examples will be given to explain the present invention in detail, but the present invention is not limited thereto. The parts of the compounding amounts shown in the examples are parts by weight. In addition, bryonolic acid was purified by the following method. 4.5 × 1 loofah cotyledon
The callus was placed on Murashige and Skoog agar medium containing 0 ^-6 M 2,4-D and 2.3 × 10 ^-6 M kinetin, and callus was induced by a conventional method. One month later, place the callus in the same liquid medium.
The cells were subjected to rotary shaking culture at 0 rpm to prepare the suspension-cultured cells. The cultured cells were inoculated into Murashige's and Skoog's liquid medium containing 10 ^-7 M 2,4-D and subjected to rotary shaking culture in the dark for 2 weeks. The obtained cultured cells were lyophilized, extracted with chloroform, and the extract was concentrated to dryness. The obtained extract was redissolved in chloroform / methanol (2: 1),
Subsequently, recrystallization was performed to obtain acicular crystals of bryonolic acid. The brionolic acid content was 1.2% based on the dry weight of the cells.

Example-1 Lotion formulation Formulation amount 1. Ethanol 5.0 parts 2. Methyl P-oxybenzoate 0.1 3. Polyoxyethylene (40) hydrogenated castor oil 0.1 4. Perfume proper amount 5. Purified water 10.0 6. Bryonol Acid 0.01 7.1,3-Butylene glycol 3.0 8. Glycerin 2.0 9. Xanthan gum 0.02 10. Purified water 79.5 Manufacturing method: Components 1 to 5 and components 6 to 10 are uniformly dissolved, mixed and filtered to obtain a product.

Example-2 Cream formulation Formulation amount 1. Liquid paraffin 6.5 parts 2. Vaseline 10.0 3. Stearic acid 4.0 4. Cetyl alcohol 3.0 5. Stearyl alcohol 1.0 6. Polyoxyethylene (25) monostearate 3.0 7 .Sorbitan monostearate 2.5 8.1,3-butylene glycol 5.0 9. Potassium hydroxide 0.1 10. Brionolic acid 1.0 11. Methyl P-oxybenzoate 0.2 12. Purified water 63.5 13. Perfume suitable amount Production method: oil phase component 1 ~ 7 and the water phase components 8 to 12 are heated and dissolved at 70 to 75 ° C, respectively, and then the oil phase components 1 to 7 are added to
Add 8 to 12 to emulsify, add component 13 during cooling, mix, and cool to 30 ° C to obtain a product.

Comparative Example-1 Conventional cream agent In Example-2, the conventional cream agent was prepared by replacing the brynolic acid with purified water.

Example-3 Emulsion Formulation Amount 1. Liquid paraffin 8.0 parts 2. Squalane 2.0 3. Stearyl alcohol 2.0 4. Sorbitan monooleate 2.5 5. Glycerin monostearate 2.3 6. Polyoxyethylene (10) sorbitan monooleate 0.8 7. Glycerin 6.0 8. Brionolic acid 0.1 9. Methyl P-oxybenzoate 0.2 10. Purified water 76.0 11. Perfume proper amount Production method: Oil phase components 1 to 6 and aqueous phase components 7 to 10 at 70 to 75 ° C, respectively. After heating and dissolving in oil phase components 1 to 6, water phase components
Add 7 to 10 to emulsify, add component 11 while cooling, mix, and cool to 30 ° C to obtain a product.

Example-4 Ointment Formulation Amount 1. Purified lanolin 5.0 parts 2. Salix beeswax 2.0 3. Brionolic acid 1.0 4. White petrolatum 92.0 Manufacturing method: Components 1 to 4 are heated and dissolved, mixed, and then cooled. And make it a product.

[0013]

INDUSTRIAL APPLICABILITY The bryonolic acid of the present invention has a sebum secretion promoting action, and the sebum secretion promoting agent containing bryonolic acid has an effect of improving dry skin roughness. next,
Experimental examples will be given to explain the effects of the present invention in detail. Experimental Example-1 Sebum Secretion Acceleration Test As test animals, 7-week-old female Syrian golden hamsters were used, each group consisting of 3 animals, 1% γ-oryzanol applied group, 1% bryonolic acid applied group and base (ethanol) applied. Three groups, each group consisting of 9 animals, were subjected to the test. γ−
Oryzanol was used as a sebaceous gland activator. 50 μl of each test substance was applied once a day to the inner parts of both ears of a hamster for 14 consecutive days. In the sebaceous gland area measurement method, the auricle skin was biopsied on the 15th day of the experiment, and the collected skin piece was left in physiological saline at 4 ° C for 18 hours. Peel the inner skin under a stereomicroscope,
After removing the cartilage from the skin pieces, 2 in 2N-NaBr at 37 ℃.
Soak for hours. Then, the epidermis was removed on a filter paper to obtain a dermis sheet in which a hair follicle sebum portion remained. This dermis sheet was stained with Sudan III, sealed with glycerin on a slide glass, and observed under an optical microscope. The sebaceous glands were observed as petaloid masses, and the area of this mass was photographed and then measured using a two-dimensional image analyzer, and displayed as the sebaceous gland area. The area of 10 sebaceous glands was measured for each dermal sheet, and the ratio of the test substance application group to the base application group was determined. The sebaceous gland-derived squalene content in skin surface lipids was measured by HPLC using the other auricle. The extraction method is as follows. A glass tube with a constant skin adhesion surface is adhered to the measurement site, and a mixture of chloroform and methanol (2: 1 V
/ V) was poured into a glass tube and extracted for 1 minute with shaking. The collected sample was dried by a rotary evaporator and dissolved in 1 ml of hexane. HPLC
The condition of is that Nova Pak C
₁₈ in the mobile phase acetonitrile / tetrahydrofuran /
Water (42: 50: 8), detection wavelength was UV = 210 nm.
As a result, by applying bryonolic acid, the sebaceous gland area was expanded and the activation rate was higher than that of known γ-oryzanol (Table 1). It also showed an increase in the squalene content in skin surface lipids, which is an index of the amount of sebum (Table 2).

[0014]

[Table 1] Table 1 Ear sebum area measurement results ─────────────────────────────── Test substance Test substance application group / Base application group ─────────────────────────────── 1% Brionolic acid 1.6 1% γ-Oryzanol 1.4 ───────────────────────────────

[0015]

[Table 2] Table 2 Results of quantitative analysis of squalene amount ──────────────────────────────── Test substance Squalene (μg / cm ² ) ─────────────────────────────── 1% Brionolic acid 27.6 ± 11.08 Base (ethanol) 10.4 ± 6.33 ── ─────────────────────────────

Experimental Example-2 Clinical Test Using the cream of Example-2 and the conventional cream of Comparative Example-1, 50 women (30) suffering from rough skin due to dryness.
(~ 50 years old). As a test method, twice a day, morning and night, an appropriate amount of the cream of Example-2 was used on the right frame and a conventional cream of Comparative Example-1 was used on the left frame for one month. After use, the amount of skin surface lipid was measured by the light transmission measurement method. As a result, Example-2 containing bryonolic acid
The cream of No. 1 had a larger amount of skin surface lipid than the conventional cream of Comparative Example 1 which was not blended. That is, the sebum secretagogue characterized by containing bryonolic acid,
It has an action of promoting sebum secretion and improved the symptoms of rough skin. Margin below

[0017]

[Table 3] Table 3 Skin surface lipid amount ─────────────────────────────── Test substance Skin surface lipid amount (μg / cm ² ) * ─────────────────────────────── 1% brionolic acid-containing cream 83.7 Conventional cream 69.5 ─────────────────────────────── *; Average

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 35/78 ADA S 8217-4C C07C 62/32 9356-4H

Claims (1)

[Claims] 1. A sebum secretagogue, which contains brionolic acid.