JPH11199504A - Elastase inhibitor and preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a means for preventing the aging of skin by finding a substance inhibiting the action of elastase to decompose elastin and promote the aging of the skin from substances originated from natural resources. SOLUTION: An elastase-inhibiting substance extracted from a part of a plant of the genus Himalayan saxifrage such as Bergenia crassifolia and Bergenia perpurascens containing an elastase-inhibiting substance is used as an elastase inhibitor and a preparation for external use for skin.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an elastase inhibitor and an external preparation for skin which are effective in preventing aging of human skin.

[0002]

2. Description of the Related Art According to a recent study on skin aging, changes in the tissue level occurring in the skin with apparent aging include changes in collagen and elastin in the skin dermis and hyaluronic acid. These include decreased mucopolysaccharides and damage to epidermal cells.

As a cause of skin aging that progresses in parallel, aging is generally the most important.
Drying, oxidation, solar ultraviolet rays and the like are also mentioned as direct factors related to skin aging.

[0004] Among the above-mentioned skin aging phenomena, the reduction of elastin, which has a particularly remarkable result, is caused by ultraviolet rays or by aging. Elastin is a coiled hard protein that is entangled with fibrous collagen and has the property of returning to its original state after stretching like an elastic body, giving the skin firmness and elasticity in cooperation with collagen. Is what it is. Ultraviolet light activates the activity of elastase, a protease that specifically acts on this elastin, so that the skin exposed to a large amount of ultraviolet light promotes the decomposition of elastin, and as a result, the skin becomes firmer and more elastic. Lost (Fragrance Journal 1997-4). The action of elastase is activated by aging, with similar results.

[0005] Therefore, if the excessive action of elastase can be suppressed, the above mechanism can prevent skin aging. As a result of exploring substances having an elastase inhibitory action from such a viewpoint, it was confirmed that extracts such as jujube, eucalyptus, citrus, and the like were effective (Japanese Patent Application Laid-Open Nos. 9-95420, 9-87137, and 9-87137). 9-87136).

[0006]

SUMMARY OF THE INVENTION An object of the present invention is to find a substance having a strong elastase inhibitory activity and having properties suitable for use in an external preparation for skin from natural substances. Another object of the present invention is to provide a new means for preventing skin aging.

[0007]

SUMMARY OF THE INVENTION The present invention, which has successfully achieved the above object, has been extracted from Bergenia classifolia or Bergenia perprusens, for which the present inventors have confirmed for the first time that they contain an elastase inhibitor. An object of the present invention is to provide an elastase inhibitor containing an elastase inhibitor as an active ingredient, and an external preparation for skin obtained by adding the elastase inhibitor.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Bergenia crassifolia (Japanese name: Naganoyukinosita) and Bergenia purpurasc
(ens) is a plant belonging to the genus Saxifragaceae in the genus Himalayan Saxifragaceae. It is said to be effective against frail constitution, hemoptysis, hemoptysis, inflammatory swelling, etc., and uses whole plants. In addition, there are regions that use it as tea (Heibonsha, World Dictionary of Useful Plants). However,
This plant was not known to contain elastase inhibitors.

[0009] The elastase inhibitor is contained abundantly in the root portion of the plant of the genus Himalaya. Extraction of the active ingredient is desirably performed on a dried product, and fresh one has poor extraction efficiency. As the extraction solvent, water, a hydrophilic organic solvent or a mixture thereof can be used,
Preferred examples of the hydrophilic organic solvent include lower aliphatic alcohols such as methanol and ethanol, and ethyl acetate.

The extraction method is not limited, and the extraction can be carried out at room temperature or under reflux by using any apparatus. Briefly, an extraction raw material is charged into a treatment tank filled with an extraction solvent, and a soluble component is eluted with occasional stirring. When the obtained extract is concentrated and dried, an extract having an elastase inhibitory action is obtained.

Extracts having an elastase inhibitory activity can be obtained from other plants of the genus Himalayan Saxifrage such as Bergenia syriata, Bergenia cordifolia, Bergenia
Although it can be obtained from religators and the like, its importance as a raw material plant is low.

[0012] The extract or extract obtained as described above has a preferable aroma derived from the raw materials,
Although it can be used as an elastase inhibitor as it is, it is possible to improve elastase inhibitory activity and
The preparation may be subjected to purification for the purpose of deodorization or the like, or may be mixed with an optional auxiliary to prepare a formulation.

The elastase inhibitor of the present invention can be used to prevent aging of the skin by incorporating it into an external preparation for skin such as ointments, creams, emulsions, lotions, packs, baths and the like and absorbing it from the skin. The skin external preparation that can be blended is not limited to those in which only the elastase inhibitor of the present invention is the main agent. For example, avocado oil,
Oil components such as palm oil, peanut oil, beef tallow, rice bran oil, jojoba oil, carnauba wax, lanolin, liquid paraffin, squalane, oxystearic acid, isostearyl alcohol; glycerin, sorbitol, polyethylene glycol, collagen, hyaluronic acid and salts thereof, Moisturizing agents such as chondroitin sulfate and its salts; one or more ultraviolet absorbers such as amyl paradimethylaminobenzoate, urocanic acid, ethyl diisopropylcinnamate, etc., and further, sodium erythorbate, sage extract, parahydroxyanisole, etc. Surfactants such as sodium stearyl sulfate, diethanolamine cetyl sulfate, cetyl trimethyl ammonium chloride, polyethylene glycol isostearate, and glyceryl stearate; Preservatives such as tilparaben, butylparaben, etc .; extracts such as oak, spinach, siconium, peonies, assembly, birch, loquat; anti-inflammatory agents such as glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin; Extract, glutathione, saxifrage extract, arbitin, whitening agents such as ascorbic acid derivatives; carrots, aloe, mallow, iris, grape, yoquinin, luffa, lily, etc., royal jelly, photosensitizer, cholesterol derivatives, various amino acids Activator;
Saffron, Senkyu, Ginger, Hypericum,
Extracts such as ononis, rosemary and garlic; blood circulation promoters such as γ-oryzanol, dextran sodium sulfate; antiseborrheic agents such as sulfur and thiantole; thickeners such as fragrance, water, alcohol, carboxyvinyl polymer; titanium It can be appropriately blended with those containing yellow, carsamine, safflower red and any auxiliary.

The preferred compounding ratio of the elastase inhibitor of the present invention to the external preparation for skin is about 0.01 to 10% by weight in the case of a crude standard extract.

[0015]

The present invention will be described below in further detail with reference to examples.

Production Example 100 g of the dry powder of the root of the starting plant was extracted with an extraction solvent 500
2 hours, and heat-extract for 1 hour with a reflux extractor.
Do it twice. The obtained extracts are combined, concentrated under reduced pressure, and further dried to obtain an extract. Table 1 shows the results of the above extraction performed for Bergenia classifolia and Bergenia perprusens.

[0017]

[Table 1] Extract yield (based on the weight of the raw plant body ) Raw plant body water extraction 50% methanol extraction ethanol extraction B · classifolia 16.8 21.5 28.0 B · puraprance 17.0 20.8 27 .5

Among the obtained extracts, each extract of B. crushifolia was used in Examples 1 to 3 described below. Also,
The elastase inhibitory activity of the 50% methanol extract was tested by the following test method. Table 2 shows the test results.

Test method: A 96-well microplate is prepared, and a sample solution (solvent: DMSO + water) 50 per well is prepared.
μl, substrate solution (2 mM N-methoxysuccinyl-Ala-Ala-Pro
-Val-p-nitroanilide) and elastase solution (human neutrophil-derived elastase; 6 μg / ml). After reacting at 25 ° C. for 30 minutes, the reaction solution is collected and the absorbance at 415 nm is measured. The same enzymatic reaction and absorbance measurement as described above are carried out by adding only an equivalent amount of a solvent to the sample solution instead of the sample solution. Further, in each case, the same operation and measurement are performed without adding an elastase solution.

From the measurement results, the elastase inhibition rate is calculated by the following equation. Elastase inhibition rate (%) = [1- (AB) / (C-
D)] × 100 where A: Absorbance when sample solution is added and enzyme added B: Absorbance when sample solution is added and enzyme is not added C: Absorbance when sample is added and enzyme is added D: No sample is added and enzyme is not added Absorbance at the time The above-mentioned inhibition rate is measured by variously changing the concentration of the sample solution, and the concentration of the sample solution that inhibits the elastase activity by 50% is determined by interpolation.

[0021]

[Table 2]

Example 1 A lotion having the following composition was produced by a conventional method. B. classifolia water extract 0.15 g glycerin 4 g 1,3-butylene glycol 4 g ethanol 7 g POE / oleyl alcohol 0.5 g methyl paraben 0.05 g citric acid 0.01 g sodium citrate 0.1 g flavoring 0.05 g purified water balance (Total 100ml
And

Example 2 A cream having the following composition was produced by a conventional method. B. classifolia ethanol extract 0.5 g setosteryl alcohol 3.5 g squalane 40 g beeswax 3 g reduced lanolin 5 g ethyl paraben 0.3 g polyoxyethylene 2 g stearic acid monoglyceride 2 g 1,3-butylene glycol 5 g flavor 0.03 g glycerin 5 g Water balance (total amount 100ml
To)

Example 3 A pack having the following composition was produced by a conventional method. B. classifolia 50% methanol extract 0.5 g polyvinyl alcohol 15 g polyethylene glycol 3 g propylene glycol 7 g ethanol 10 g methyl paraben 0.05 g perfume 0.05 g purified water balance (total 100 ml)
To)

[0025]

As described above, according to the present invention, a novel elastase inhibitor and an external preparation for skin which are effective in preventing skin aging are provided. The active ingredient of the elastase inhibitor of the present invention is not only excellent in elastase inhibitory activity, but also excellent in safety because it is extracted from plants already used as crude drugs.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/48 A61K 7/48

Claims (3)

[Claims] [1] Bergenia classifolia (Bergen)
An elastase inhibitor comprising, as an active ingredient, an elastase inhibitor extracted from ia crassifolia) or Bergenia purpurascens. 2. The Bergenia classifolia (Bergen)
ia crassifolia) or Bergenia purpurascens containing elastase inhibitor containing water, methanol, ethanol, propanol,
An elastase inhibitor comprising, as an active ingredient, an extract obtained by an extraction treatment with 1,3-butylene glycol or a mixture thereof. 3. An external preparation for skin comprising the elastase inhibitor according to claim 1 or 2.