JP2008019180A - Lipase inhibitor, horney plug formation inhibitor, pore conspicuousness inhibitor and pimple inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation for skins, which uses an ingredient found to have a lipase inhibiting activity and is effective against skin diseases and honey plug formation caused by bacterial lipases. <P>SOLUTION: A lipase inhibitor, a horney plug formation inhibitor, a pore conspicuousness inhibitor, and a pimple inhibitor each is characterized by comprising a solvent extract of Bergenia ciliata Sternb. An external preparation for skins, having both a pore conspicuousness inhibiting action and a pimple inhibiting action, is characterized by comprising a solvent extract of Bergenia ciliata Sternb. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a lipase inhibitor, a keratin plug formation inhibitor, a pore conspicuous inhibitor, an acne inhibitor, and a skin external preparation containing the same, and more particularly, microorganisms present in skin epidermis and hair follicle endothelial fat By inhibiting lipase, it prevents and prevents acne and other skin diseases caused by this lipase, and further suppresses hyperkeratinization by stimulating ingredients in sebum, thereby suppressing the formation of horn plugs. The present invention relates to a lipase inhibitor, a keratin plug formation inhibitor, a pore conspicuous inhibitor, an acne suppressant and an external preparation for skin containing the same, which have the effect of suppressing the conspicuous pores without spreading.

Bacterial lipases in the human body include lipases produced by microorganisms (Propionibacterium acnes, Pityrosporum ovale, Micrococcus sp., Etc.) resident on the skin surface. Breaks down triglycerides contained in sebum to produce free fatty acids. This free fatty acid is considered to cause an irritating inflammatory reaction to the skin and cause acne, dermatitis, dandruff and the like.
In particular, there is a correlation between the number of Propionibacterium acnes, the cause of acne, and the free fatty acids produced. The free fatty acids have a stimulating inflammatory reaction on the hair follicle wall and associated hyperkeratosis, comedones. It has been clarified that it causes the formation of horn plugs (see Non-Patent Document 1).

In contrast, the development of drugs that inhibit bacterial lipase to suppress or prevent diseases has not been advanced, and 2-Pyridylmethyl-2- (P- (2-methylpropyl) -phenyl) propionate (conventional) Nomenclature ibuprofen piconol) (see Non-Patent Document 2), tetracycline, metal salts (see Patent Document 1), and the like have only been reported.
The above-mentioned drugs that inhibit bacterial lipase, which have been used conventionally, cannot exhibit a lipase inhibitory effect due to the relationship with other compounding ingredients, and may not always be satisfactory in safety and effectiveness in topical application. It was not.
A drug that inhibits lipase also has an obesity-suppressing effect. Oils and fats are high-calorie food ingredients, and overdose is a direct cause of obesity. In the body, lipase plays a role of assisting in the digestion and absorption of food, so that the action of this digestive enzyme is inhibited, the absorption of lipids and the like in the body can be prevented, and obesity can be prevented.

  In addition, with regard to nasal heads and small nose horn plugs, it has been common to remove astringent lotion or horn plugs. However, the astringent lotion is intended to tighten the skin, and is due to the action of temporarily lowering the skin surface temperature with alcohol or coagulating proteins with organic acid or the like. Therefore, since the skin is temporarily tightened, the load on the skin is large, and it is not a fundamental solution for the formation of horn plugs, and the effect is not sufficient. In addition, the removal of horn plugs is a method of physically removing horn plugs clogged in pores. In this method, physical force may damage the skin, causing side effects on the skin. In addition, the effect is temporary, and the horn plug may be regenerated immediately, and the effect is not always sufficient.

JP 59-186919 A McGinley, K, J. et.al., J. Clin. Microbiol. 12: 672-675,1980 Western skin 47.5, 888-898, 899-908, 1985

  The problem to be solved by the present invention is to provide a component having a lipase inhibitory activity that can overcome such problems, and to prevent skin diseases and horn plug formation caused by bacterial lipase using the same. The object is to provide an effective topical skin preparation.

  In view of the current situation as described above, the present inventors have found that a medicinal component based on each occurrence mechanism, that is, a component having an inhibitory action on lipase, is effective in preventing and improving the occurrence of acne and horn plugs. As a result of investigating the presence or absence of such effects on a wide variety of substances, the solvent extract of Fuergegonia (Bergenia ciliata Sternb.) Has an excellent inhibitory action on lipase, and also on acne and horn plug formation It has been found that it has preventive and improving effects. In addition, as a result of suppressing the formation of horn plugs, the above plant extract has been found to have an effect of improving the conspicuousness of the pores (portion having horn plugs in the conduit portion) in the pores of the human nasal site. The present invention has been completed.

  The present invention is a lipase inhibitor comprising a solvent extract of Fuergegonia (Bergenia ciliata Sternb.).

  In addition, the present invention is a horn plug formation inhibitor, a pore conspicuousness inhibitor and an acne inhibitor characterized by comprising a solvent extract of Fuergegonia (Bergenia ciliata Sternb.).

  As far as the present inventors know, there has been no report on the lipase inhibitory action of the plant extract.

  In addition, the solvent extract of Fuergegonia (Bergenia ciliata Sternb.) Of the present invention has an excellent tyrosinase activity inhibitory action and is also useful as a tyrosinase activity inhibitor.

According to the lipase inhibitor of the present invention, it has preventive and ameliorating effects on various skin diseases, acne, keratin plug formation, pore conspicuousness, and obesity caused by lipase activity change, and is also excellent in safety. Is.
The horn plug formation inhibitor of the present invention is excellent in the effect of suppressing horn plug formation and excellent in safety.
The pore conspicuousness inhibitor of the present invention is excellent in the action of making pores inconspicuous and is excellent in safety.
The acne inhibitor of the present invention has preventive and ameliorating effects on the formation of acne and is excellent in safety.

The best mode of the present invention will be described below.
Fuebegonia (Bergenia ciliata Sternb.) Used in the present invention is an evergreen perennial belonging to the genus Bergenia, which is distributed in cashmere, Bhutan, Nepal, India, and the like.

  In the lipase inhibitor, keratin plug formation inhibitor, pore appearance inhibitor, and acne inhibitor of the present invention, any one of the leaves, stems, flowers, roots of the above plants, or a mixture thereof is immersed or heated together with an extraction solvent. After refluxing, it can be obtained by filtration and concentration. As the extraction solvent, any solvent can be used as long as it is usually used for extraction. For example, organic solvents such as alcohols such as methanol and ethanol, hydrous alcohols, acetone, ethyl acetate, 1,3-butylene glycol and the like. Can be used alone or in combination. In addition, an extract obtained by applying a treatment such as partitioning or adsorption chromatography to the extract using the above-mentioned solvent can be used.

  When using the agent of the present invention as a skin external preparation for inhibiting the formation of keratin plugs, a skin external preparation for suppressing the appearance of pores, a skin external preparation for suppressing acne, or a skin external preparation that simultaneously exhibits these effects. Contains 0.005 to 20.0 mass%, preferably 0.01 to 10.0 mass% of the above plant extract as a dry product in the total amount of the external preparation. If the amount is less than 0.005% by mass, the effect referred to in the present invention is not sufficiently exhibited, and if it exceeds 20.0% by mass, it is difficult to make a preparation. Moreover, even if it mix | blends 10.0 mass% or more, the improvement of the big effect is not seen.

  In addition to the above essential components, the external preparation for skin of the present invention is usually used for external preparations for skin such as cosmetics and pharmaceuticals, for example, humectants, antioxidants, oily components, ultraviolet absorbers, emulsifiers, surfactants. , Thickeners, alcohols, powder components, color materials, aqueous components, water, various skin nutrients, and the like can be appropriately blended as necessary.

  In addition, disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, sequestering agents such as gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, grabrizine, licorice, karin , Extracts of various herbal medicines such as yew, etc., drugs such as tocopherol acetate, glycyrrhetinic acid, glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid and other whitening agents, glucose , Sugars such as fructose, mannose, sucrose, trehalose, xylitol and the like can be appropriately blended.

  The external preparation for skin of the present invention can be applied in any form as long as it is conventionally used for external preparations for skin, such as ointments, creams, emulsions, lotions, packs, bath preparations and the like, and the dosage form is not particularly limited.

The lipase inhibitor of the present invention can be used as a drug for anti-obesity action, for example, an obesity preventive agent.
In order to formulate the lipase inhibitor of the present invention in such a use, it is made into a powder, granule, ampoule, injection solution, isotonic solution and the like by a usual method. That is, when preparing a solid preparation for oral use, excipients, if necessary, binders, wetting agents, disintegrants, surfactants, lubricants, dispersants, flavoring agents, flavoring agents, etc. were added. Then, it is made into tablets, coated tablets, granules, capsules, etc. by a conventional method.

  Examples of excipients used include lactose, glucose, sorbit, corn starch, and mannitol.Examples of binders include polyvinyl alcohol, polyvinyl ether, ethyl cellulose, gum arabic, gelatin, hydroxypropyl cellulose, and polyvinyl pyrrolidone. Disintegrants include calcium carbonate, calcium citrate, dextrin, starch, gelatin powder, lubricants include calcium carbonate, calcium citrate, talc, polyethylene glycol, etc. Colorants include cocoa powder, mint aroma Acid, mint oil and the like. These tablets and granules may be appropriately coated with sugar coating, gelatin coating, etc. if necessary. When formulating injections, add pH adjusters, buffers, surfactants, solubilizers, solvents, stabilizers, preservatives, etc. as necessary, and use subcutaneous, intramuscular, and intravenous methods in the usual way. Use injections.

EXAMPLES Next, an Example is given and this invention is demonstrated further in detail. Here, a compounding quantity is the mass%.
Prior to the examples, the test method regarding the lipase inhibitory action, the test method for inhibiting keratogenesis, the acne inhibitory effect, the pore conspicuous inhibitory effect and the evaluation criteria thereof will be described.

1. Lipase inhibition test
[Sample preparation]
50 g (wet weight) of dried rhizomes of Nepal's fugue begonia (Bergenia ciliata Sternb.) Were immersed in 5 times the amount of ethanol at room temperature for 1 week, and the extract was concentrated to dryness. This solid was dissolved in dimethyl sulfoxide (DMSO) to make a 10% solution. The following experiment was conducted using this.

[Measurement of lipase inhibitory action]
(1) Preparation of lipase The lipase was purified according to the method of Pablo et al. (J. Invest. Dermatol. 63, 213, 1974).
Specifically, a platinum ear of Propionibacterium acnes isolated from human skin was inoculated into a brain heart infusion broth medium, anaerobically cultured at 37 ° C for 7 days, and the culture was centrifuged at 4 ° C and 3000 rpm for 15 minutes. separated. 1L of 95% ethanol was added to 1L of the supernatant at -30 ° C, and the mixture was stirred with a stirrer at -10 ° C for 30 minutes, and then centrifuged at 4 ° C and 1000 rpm for 15 minutes. A lipase was used. 0.5 g of this was dissolved in 3 mL of 0.1 mol / L NaCl-0.02 mol / L acetate buffer (pH 5.2), and 0% was obtained using a Sephadex G-100 column (φ2.6 cm, length 45 cm). Gel filtration with 1 mol / L NaCl-0.02 mol / L acetate buffer gave 40 mL of the active fraction, which was used as the lipase solution.

(2) Preparation of comparative sample (a) 2-Pyridylmethyl-2- (P- (2-methylpropyl) -phenyl) propionate (common name ibuprofen piconol) currently used in skin external preparations as a lipase inhibitory drug ) (Western skin 47,5 888-898, 898-908, 1985), (b) Tetracycline (JP 59-186919 A) prepared by the following method was used as a comparative sample.

(A) 2-Pyridylmethyl-2- (P- (2-methylpropyl) -phenyl) propionate
2-Pyridylmethyl-2- (P- (2-methylpropyl) -phenyl) propionate was dissolved in DMSO so that the concentration when reacted in the enzyme solution was 0.1% and 0.01%.
(B) Tetracycline Tetracycline hydrochloride (manufactured by Sigma) was dissolved in DMSO so that the concentration when reacting in an enzyme solution was 0.1% and 0.01%.

(3) Measurement method of lipase activity and calculation of inhibition rate Each of the lipase solution obtained in (1) above was added with a test sample and a comparative sample, shaken at 37 ° C., and then each 1 mL was accurately dispensed ( Lipase solutions a to f).
On the other hand, 5 mL of olive oil emulsion and 4 mL of 0.1 mol / L phosphate buffer (pH 7.0) were accurately mixed in a 50 mL stoppered conical flask and preheated for 10 minutes using a 37 ° C. constant temperature water bath. Next, the lipase solutions a to f separated by 1 mL were added with stirring so that they were not concentrated in one place, and mixed well to carry out the enzyme reaction. After exactly 10 minutes, 20 mL of an acetone-ethanol mixture was poured, 5 drops of phenolphthalein reagent were added, and titrated with 0.05 mol / L sodium hydroxide solution.
Separately, 5 mL of olive oil emulsion and 4 mL of 0.1 mol / L phosphate buffer (pH 7.0) were accurately taken in a 50 mL conical flask with a stopper and heated at 37 ° C. for 30 minutes. -After pouring 20 mL of ethanol mixture, and then adding each 1 mL of lipase solution a to f, 5 drops of phenolphthalein reagent was added and titrated with 0.05 mol / L sodium hydroxide solution. The activity value was calculated by subtracting this from the titration amount in which the enzyme reaction was performed using the control solution.
Similarly, the activity value of the lipase solution to which no test sample or comparative sample was added was measured, and this value was expressed as an inhibition rate with an enzyme activity value of 100 (inhibition rate 0%). The results are shown in Table 1.

  As can be seen from Table 1, Fuergegonia (Bergenia ciliata Sternb.) Extract has an inhibitory effect on lipase, and its strength is superior to the lipase inhibitory action of ibuprofen piconol and tetracycline hydrochloride. Met.

2. Square plug formation inhibition test
[Sample preparation]
30% ethanol containing 3% extract obtained by immersing 50g rhizome (Bwetnia ciliata Sternb.) Rhizomes from Nepal at room temperature for 1 week in 5 times 50% ethanol. Was used to evaluate.

[Square plug formation inhibitory effect test method]
For 10 men aged 30 to 37 years old, 30% ethanol aqueous solution containing 3% fuebegonia extract and 30% ethanol as a control were applied to the right and left noses twice a day after morning and evening facial washing. Two weeks later, the left and right nose horn plugs were collected with a sheet pack for horn plug removal, and the sizes of all horn plugs (N = 543) were measured under a stereomicroscope to calculate the horn plug volume.

  From the results in Table 2, the volume of the horn plug decreased in the nostril on the side to which the 30% ethanol aqueous solution containing 3% fuebegonia extract was applied, and the effect of inhibiting horn plug formation was confirmed.

3. Acne suppression effect test and pore conspicuousness suppression effect test
[Test method]
For 40 men and women (20 people per group) suffering from acne from the age of 22 to 39 years old, thoroughly wash the face with cosmetic soap, then apply each skin external preparation shown in Table 3 on the face a day It was applied 2-3 times and observed after 4 weeks. The evaluation was made according to the following evaluation criteria, which were divided into two stages of (a) improved or unchanged or deteriorated (b) compared with the drug used before use.

<Acne suppression effect criteria>
(Effectiveness evaluation criteria)
(Double-circle): (a) is 15 or more in 20 people by general improvement degree.
○: The overall improvement degree is 10 to 14 in 20 (a).
(Triangle | delta): (a) is 5-9 persons in 20 in general improvement degree.
X: In general improvement degree, (a) is less than 4 in 20 people.

<Criteria for determining the effect of suppressing conspicuous pores in the nose>
(Effectiveness evaluation criteria)
(Double-circle): (a) is 15 or more in 20 people by general improvement degree.
○: The overall improvement degree is 10 to 14 in 20 (a).
(Triangle | delta): (a) is 5-9 persons in 20 in general improvement degree.
X: In general improvement degree, (a) is less than 4 in 20 people.

  As can be seen from Table 3, the skin external preparation (lotion) of the product of the present invention was found to have an acne suppressing effect and a pore conspicuous inhibitory effect that were superior to those of the comparative product.

4). Tyrosinase activity inhibitory effect test
[Test method]
The tyrosinase activity is carried out by using L-dopa as a substrate and measuring the amount of the reaction product, dopachrome, at an absorbance of 475 nm. That is, 0.5 ml of 0.05% L-dopa aqueous solution and 0.9 ml of 0.1 M phosphate buffer (pH 6.8) are taken, and 0.05 ml of an aqueous solution in which the sample is dissolved is added. To this, 0.05 ml of tyrosinase solution (SIGMA) is added and mixed, and reacted at room temperature for 90 seconds. The absorbance of the reaction solution is measured using a spectrophotometer. As a control, distilled water is added instead of the sample solution and the same reaction is performed. At the time of sample addition and control, the amount of change in absorbance was calculated, and the inhibition rate of tyrosinase activity was determined. The results are shown in Table 4.

  As a reference example, a test similar to the above was also performed on an extract (ethanol extraction) of a mussel (Schizonepeta tenuifolia) (Lamiaceae subfamily) that is already known to have an inhibitory action on tyrosinase activity. The results are also shown in Table 4.

  As can be seen from Table 4, the solvent extract of Fuergegonia (Bergenia ciliata Sternb.) Showed an excellent tyrosinase activity inhibitory action.

Next, prescription examples of the external preparation for skin having both pore conspicuous inhibitory action and acne inhibitory action according to the present invention are given in Examples 2-7.
Moreover, the formulation example of the external preparation for acne treatment, the external preparation for dermatitis treatment, and the external preparation for dandruff improvement which mix | blended the lipase inhibitor of this invention is given to Examples 8-10, respectively.

Example 2 Cream (Formulation) Mass%
Stearic acid 2.0
Stearyl alcohol 7.0
Hydrogenated Lanolin 2.0
Squalane 5.0
2-Octyldodecyl alcohol 6.0
Polyoxyethylene (25 mol)
Cetyl alcohol ether 3.0
Glycerin monostearate ester 2.0
Propylene glycol 5.0
Fuyu Begonia methanol extract 0.05
Tranexamic acid 0.2
Sodium bisulfite 0.03
Ethylparaben 0.3
Perfume Appropriate amount Ion exchange water Residue
Propylene glycol is added to ion-exchanged water and heated to 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted, and kept at 70 ° C. (oil phase). Preliminarily emulsify by adding an oil phase to the aqueous phase, uniformly emulsify with a homomixer, and then cool to 30 ° C. while stirring well.

Example 3 Cream (Formulation) Mass%
Solid paraffin 5.0
Beeswax 10.0
Vaseline 15.0
Liquid paraffin 41.0
Glycerin monostearate ester 2.0
Polyoxyethylene (20 mol)
Sorbitan monolaurate 2.0
Soap powder 0.1
Borax 0.2
Fuyu Begonia 70% methanol extract 0.1
Sodium bisulfite 0.03
Ethylparaben 0.3
Perfume Appropriate amount Ion exchange water Residue (Production method)
Add soap powder and borax to ion-exchanged water and heat to maintain at 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted, and kept at 70 ° C. (oil phase). The reaction is gradually added while stirring the oil phase in the aqueous phase. Thereafter, the mixture is uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

Example 4 Latex (Formulation) Mass%
Stearic acid 2.5
Cetyl alcohol 1.5
Vaseline 5.0
Liquid paraffin 10.0
Polyoxyethylene (10 mol)
Monooleate 2.0
Polyethylene glycol 1500 3.0
Triethanolamine 1.0
Carboxyvinyl polymer 0.05
(Product name: Carbopol 941, BF Goodrich Chemical company)
Fuyu Begonia ethyl acetate extract 0.02
Sodium bisulfite 0.01
Ethylparaben 0.3
Perfume Appropriate amount Ion exchange water Residue (Production method)
Dissolve the carboxyvinyl polymer in a small amount of ion-exchanged water (A phase). Polyethylene glycol 1500 and triethanolamine are added to the remaining ion-exchanged water, and the mixture is heated and dissolved and maintained at 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted, and kept at 70 ° C. (oil phase). Add the oil phase to the water phase, preliminarily emulsify, add the A phase, uniformly emulsify with a homomixer, and cool to 30 ° C. while stirring well after emulsification.

Example 5 Latex (Formulation) Mass%
Microcrystalline wax 1.0
Beeswax 2.0
Lanolin 20.0
Liquid paraffin 10.0
Squalane 5.0
Sorbitan sesquioleate ester 4.0
Polyoxyethylene (20 mol)
Sorbitan monooleate 1.0
Propylene glycol 7.0
Fuyu Begonia 30% butanol extract 2.0
Tranexamic acid 1.0
Sodium bisulfite 0.01
Ethylparaben 0.3
Perfume Appropriate amount Ion exchange water Residue (Production method)
Propylene glycol is added to ion-exchanged water and heated to 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted, and kept at 70 ° C. (oil phase). The water phase is gradually added while stirring the oil phase, and the mixture is uniformly emulsified with a homomixer, and then cooled to 30 ° C. while stirring well.

Example 6 Jelly (Prescription) Mass%
95% ethyl alcohol 10.0
Dipropylene glycol 15.0
Polyoxyethylene (50 mol)
Oleyl alcohol ether 2.0
Carboxyvinyl polymer 0.05
(Product name: Carbopol 940, BF Goodrich Chemical company)
Caustic soda 0.15
L-Arginine 0.1
Fuyu Begonia 30% ethanol extract 1.0
Sodium bisulfite 0.01
Ethylparaben 0.3
Perfume Appropriate amount Ion exchange water Residue
Carbopol 940 is uniformly dissolved in ion-exchanged water, while fuebegonia extract and polyoxyethylene (50 mol) oleyl alcohol ether are dissolved in 95% ethanol and added to the aqueous phase. Next, after adding other components, the mixture is neutralized and thickened with caustic soda and L-arginine.

Example 7 Pack (Prescription) Mass%
(Phase A)
Dipropylene glycol 5.0
Polyoxyethylene (60 mol)
Hardened castor oil 5.0
(Phase B)
Olive oil 5.0
Tocopherol acetate 0.2
Ethylparaben 0.2
Fragrance 0.2
(Phase C)
Sodium bisulfite 0.03
Polyvinyl alcohol 13.0
(Saponification degree 90, polymerization degree 2,000)
Ethyl alcohol 7.0
Fuyu Begonia 50% 1,3-BG extract 1.0
Purified water residue (production method)
A phase and B phase are uniformly dissolved, and B phase is added to A phase to solubilize. Next, the phase C in which the fuebegonia extract is dispersed is added thereto, followed by filling.

Example 8 Acne Treatment External Preparation (Prescription) Mass%
Pharmacopeia stearic acid 18.0
Pharmacopoeia Setanol 4.0
Phenoxyethanol 1.0
Triethanolamine 2.0
Pharmacopoeia Glycerin 5.0
Fuyu Begonia 40% 1,3-BG extract 1.0
Purified water residue (production method)
Stearic acid and cetanol are dissolved by heating. Phenoxyethanol, triethanolamine and fuebegonia 40% 1,3-BG extract are heated and mixed in glycerin and dissolved in purified water. The oil and water layers are mixed little by little.・ Emulsify and cool.

Example 9 External preparation for treatment of dermatitis (prescription)
Squalane 15.0
Pharmacopoeia White Petrolatum 7.0
Ceresin 2.0
Glycerol monooleate 2.0
Glyceryl distearate 2.0
Beeswax 1.0
Microcrystalline wax 2.0
Dipropylene glycol 1.0
Allantoin 2.0
Fuyu Begonia 50% 1,3-BG extract 1.0
Purified water residue (production method)
An oil-soluble component and a surfactant are heated and dissolved in the oil layer, and an aqueous layer in which the active component and water-soluble component are heated and dissolved is added, emulsified and cooled.

Example 10 External preparation for improving dandruff (prescription)
95% ethyl alcohol 60.0
β-glycyrrhizic acid 0.5
Fuyu Begonia 30% ethanol extract 1.0
Hydroxypropyl cellulose 2.0
Ion-exchanged water remaining (production method)
Hydroxypropyl cellulose is uniformly dissolved in ion-exchanged water (aqueous phase). On the other hand, the fuebegonia extract and β-glycyrrhizic acid are dissolved in 95% ethanol and added to the aqueous phase.

Example 11 External preparation for suppressing pore conspicuousness (prescription)
<A phase>
95% ethyl alcohol 10.0
POE (20) Octyldodecanol 1.0
Methylparaben 0.15
Pantothenyl ethyl ether 0.1
Fuyu Begonia 80% ethanol extract 1.0
<Phase B>
Potassium hydroxide 0.1
<Phase C>
Glycerin 5.0
Dipropylene glycol 10.0
Sodium bisulfite 0.03
Carboxyvinyl polymer 0.2
Ion-exchanged water remaining (production method)
A phase and C phase were uniformly dissolved, and A phase was added to C phase to solubilize. Then phase B was added and mixed.

Example 12 Granule (Formulation) Mass%
Fuyu Begonia 20% ethanol extract 50.0
Starch 10.0
Lactose 15.0
Ethylcellulose 20.0
Polyvinyl alcohol 5.0
Purified water residue (production method)
After mixing uniformly, crush and granulate and sieve to make granules.

Example 13 Tablet (Prescription) Mass%
Fuyu Begonia 50% 1,3BG extract 60.0
Polyvinyl alcohol 5.0
Purified water 30.0
(Manufacturing method)
After mixing uniformly, crush and granulate and sieve to make granules. 1/10 amount of crystalline cellulose is added to the obtained granules and compression-molded to obtain tablets with a diameter of 8 mm. Furthermore, an appropriate amount of syrup, gelatin, a mixed suspension of precipitated calcium carbonate and a coloring agent are used for this tablet to form a sugar-coated tablet.

Example 14 Injection (Formulation) Mass%
Fuyu Begonia 50% ethanol extract 0.5
Nonionic surfactant 2.5
Saline Residue (Production method)
After warming and mixing, sterilize to make an injection.

Example 15 Capsule The granules obtained in Example 12 are filled into a commercially available capsule container to form a capsule.

Claims (4)

  A lipase inhibitor comprising a solvent extract of Bergenia ciliata Sternb.   A horn plug formation inhibitor characterized by comprising a solvent extract of Fuergegonia (Bergenia ciliata Sternb.).   A pore conspicuousness inhibitor comprising a solvent extract of Fuergegonia (Bergenia ciliata Sternb.). An acne inhibitor comprising a solvent extract of Fuergegonia (Bergenia ciliata Sternb.).