JP2009191043A - Elastase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an elastase inhibitor which, when used in an external preparation, can render the skin elastic and supple by inhibiting elastase and is useful also as a disease treating agent. <P>SOLUTION: The elastase inhibitor contains a solvent extract of Rhododendron simsii of Ericaceae Rhododendron. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an elastase inhibitor containing a plant-derived component as an active ingredient.

  Traditionally, the need for an anti-aging agent has been considered, but since the mechanism and definition of aging have not been clarified, in general, measurement of moisturizing state and skin elasticity are performed as moisture of the skin. It has been judged by visually observing the skin color. However, in recent years, research on aging has been promoted, and as a cause of skin aging, aging is an important factor when viewed macroscopically, and effects such as drying, oxidation, and sunlight (ultraviolet rays) are also directly related to skin aging. Has been cited as a major factor. Specific phenomena of skin aging are known such as a decrease in collagen and elastin in the skin dermis, a decrease in mucopolysaccharides including hyaluronic acid, and cell damage due to ultraviolet rays. Among them, elastin contributes to the elasticity of tissues by forming crosslinks with each other, but elastin is denatured and destroyed by overexpression of elastin, which is an elastin-degrading enzyme, by UV exposure and aging. However, it is thought to lead to a decrease in skin elasticity. Therefore, it is important to prevent the aging of the skin by suppressing the action of elastase and preventing the degeneration and destruction of elastin which gives elasticity and elasticity to the skin.

  In the case of cosmetics that are directly applied to the skin, naturally-derived components are preferred, but as such naturally-derived elastase inhibitors, for example, Tenjikubodaiji (Indobodaiji) extract (Patent Document 1), Yukinoshita Extracts (Patent Document 2), Asen drug extracts of Rubiaceae plants (Patent Document 3), and the like are known, and the topical skin preparation containing the extract is used in terms of wrinkles, fine wrinkles and skin firmness and tarmi. It is shown to show an improvement effect.

On the other hand, elastase inhibitors are also known to be useful as disease treatment agents in addition to topical skin preparations, for example, joint diseases such as rheumatoid arthritis and osteoarthritis, systemic inflammatory response syndrome, arteriosclerosis, It is reported to be effective for acute lung injury, acute respiratory distress syndrome, and the like.
Specifically, urinastatin for acute pancreatitis, acute circulatory failure (hemorrhagic shock), and the like, and cyberestat sodium, a selective neutrophil elastase inhibitor, effective in improving acute lung injury associated with systemic inflammatory response syndrome Such pharmaceuticals are known. As described above, the elastase inhibitor is used as a therapeutic agent for inflammatory diseases and the like. However, in consideration of safety and the like, in this case, a naturally derived component is preferable instead of a synthetic chemical.

JP 11-335230 A JP-A-11-246386 JP-A-10-182414

  An object of the present invention is to provide an elastase inhibitor that can be used as an external preparation to inhibit elastase to give elasticity and elasticity to the skin, and is also useful as a disease therapeutic agent.

  Therefore, the present inventors investigated elastase inhibitory activity for various plant extracts, and as a result, found that the solvent extract of Rhododendron simsii has excellent elastase inhibitory activity, and completed the present invention. .

  That is, the present invention is an elastase inhibitor characterized by comprising a solvent extract of Rhododendron simsii from the genus Rhododendron (Ericaceae). Here, as the solvent, alcohols or hydrous alcohols are preferable.

  Rhododendron simsii is an evergreen or semi- evergreen shrub distributed in the mainland of China from south of Amami Oshima, Taiwan. The Japanese names are Sinayama azalea and Taiwan azalea, and are also called azaleas and western azaleas. In China, flowers, fruits, leaves, roots, etc. are used medicinally and used for hemostasis of bleeding disorders, irregular menstruation and rheumatism. The flower part of rhododendron simushi is known by the name of a herbal medicine called silkworm.

  Further, a therapeutic agent for atopic dermatitis (JP-A-2003-231640), an agent for acne vulgaris / treatment prevention (JP-A-2004-43358), which is used as a raw material for extracting glycosphingolipids and contains the sphingolipid as an active ingredient. Nos.) And IgE antibody production inhibitors (Japanese Patent Application Laid-Open No. 2004-43359) are known. However, the relationship between rhododendron worms and elastase inhibitory activity has not been recognized at all.

  In the elastase inhibitor of the present invention, the solvent extract of Rhododendron simsii is preferably a solvent extract of its flower part.

According to the present invention, an excellent elastase inhibitor can be provided by including a Rhododendron simsii extract as an active ingredient. That is, a Rhododendron simsii extract exhibits elastase inhibitory activity, and can be used by blending it with an external preparation or various disease therapeutic agents.
For example, it can be applied to an external preparation to suppress the degeneration of elastin, which is an elastic fiber, to maintain elastic skin without wrinkles or sagging. It is also effective as a therapeutic agent for diseases such as rheumatoid arthritis, osteoarthritis and other joint diseases, systemic inflammatory response syndrome, arteriosclerosis, acute lung injury, acute respiratory distress syndrome and the like.

The best mode of the present invention will be described below.
Rhododendron simsii used for the elastase inhibitor of the present invention is an evergreen or semi- evergreen shrub, and is a plant distributed from the south of Amami Oshima, Taiwan to the mainland of China.

Examples of the solvent extract of Rhododendron simsii used in the elastase inhibitor of the present invention include, for example, an extract, a diluted solution of the extract, a dried product obtained by drying the extract, and the dried product. And the like obtained by dissolving in a solvent. These crudely purified products and purified products are also included.
The extraction solvent used in the present invention may be any solvent as long as it is usually used for extraction, and in particular, alcohols such as methanol, ethanol or 1,3-butylene glycol, hydrous alcohols, organic solvents such as acetone and ethyl acetate. Can be used alone or in combination. Of these, alcohols and hydrous alcohols are particularly preferred, and ethanol, 1,3-butylene glycol, hydrous ethanol, and hydrous 1,3-butylene glycol are particularly preferred. The solvent is preferably used at a temperature between room temperature and the boiling point of the solvent.
The plant part is preferably a flower part, but extracts from other parts can also be used.

  The elastase inhibitor of the present invention is preferably composed only of a solvent extract of Rhododendron simsii, but may contain other components.

  Since the solvent extract of Rhododendron simsii used in the present invention exhibits excellent elastase inhibitory activity on human skin, a skin external preparation containing the plant extract is It can prevent aging and maintain a youthful and healthy skin condition.

  When the elastase inhibitor of the present invention is blended in an external preparation, the amount of Rhododendron simsii solvent extract is 0.0005 to 20.0 mass%, preferably as a dry product in the total amount of the external preparation. Is 0.001-10.0 mass%. If it is less than 0.0005% by mass, the effect referred to in the present invention is not sufficiently exerted, and if it exceeds 20.0% by mass, it is difficult to make a preparation. Moreover, the improvement of the big effect is not seen even if 10.0 mass% or more is mix | blended.

  When the elastase inhibitor of the present invention is applied as an external preparation, it is usually used in skin external preparations such as cosmetics and pharmaceuticals, such as whitening agents, moisturizers, antioxidants, oily components, ultraviolet absorbers, interfaces. An activator, a thickener, an alcohol, a powder component, a coloring material, an aqueous component, water, various skin nutrients, and the like can be used in appropriate combination.

  Others, disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, sequestering agents such as gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extract, grabrizine , Hot water extract of fire thorn fruit, various herbal medicines, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid, etc. Whitening agents, sugars such as glucose, fructose, mannose, sucrose, trehalose and the like can be appropriately blended.

  The external preparation containing the elastase inhibitor of the present invention can be widely applied to cosmetics, quasi-drugs, and the like, particularly preferably cosmetics applied to the outer skin. A wide range of dosage forms such as a solubilizing system, an emulsifying system, a powder system, an oil liquid system, a gel system, an ointment system, an aerosol system, a water-oil two-layer system, and a water-oil-powder three-layer system can be adopted. That is, if it is a basic cosmetic, it can be widely applied in the above-mentioned various dosage forms in the form of face wash, lotion, milky lotion, cream, gel, essence (beauty liquid), pack, mask and the like. In addition, makeup cosmetics can be widely applied to foundations and the like, and toiletries such as body soaps and soaps. Furthermore, if it is a quasi-drug, it can be widely applied to various ointment forms. And the form which can take the external preparation containing the elastase inhibitor of this invention is not limited to these dosage forms and forms.

  Furthermore, the elastase inhibitor of the present invention can be applied as a therapeutic agent for diseases such as drugs for respiratory organs, drugs for acute lung injury and acute respiratory distress syndrome, and other drugs for organ damage.

  In order to formulate the elastase inhibitor of the present invention for such 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.

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. Unless otherwise specified, the amount is shown in mass%.
Prior to the examples, the test method and the results of the elastase inhibitory effect of the elastase inhibitor of the present invention will be described. All the plants used for extraction were from China.

1. Preparation of plant extract 60 g of Rhododendron simsii flowers were immersed in methanol at room temperature for 7 days, the extract was filtered, and the solvent of the filtrate was distilled off to obtain 13.7 g of methanol extract.
This extract was dissolved in 2% by mass in DMSO, and this solution was diluted to adjust the concentration and used for the following experiments.

2. Test Method for Elastase Inhibitory Activity and Results As a buffer for reaction, 0.1 M HEPES · Na and 0.5 M NaCl (pH 7.4) were used. Methoxy-succinyl-alanyl-alanyl-prolyl-valine-p-nitroanilide (BACHEM FEINCHEMIKAL IENAG) as an elastase substrate was dissolved in DMSO to 80 mM and diluted to 8 mM with a reaction buffer. Elastase derived from human leukocytes (ELASTIN PRODUCT CO., INC.) Was diluted to 5 μg / mL with reaction buffer.
To a 96-well plate, 25 μL of 8 mM elastase substrate was dispensed, and 50 μL of drug was added. Next, 25 μL of 5 μg / ml-elastase was added on ice and incubated at 37 ° C. for 20 minutes, and the absorbance was measured at 415 nm. The inhibition rate was determined by the following formula. The results are shown in Table 1.
Inhibition rate (%) = 100− (absorbance in the presence of inhibitor / absorbance without inhibitor) × 100

  Moreover, a hypericum extract already known to have an elastase inhibitory effect (see JP-A-11-315008) was prepared by the following method, and the elastase inhibition data measured by the above method was also used as a reference example. It is described in Table 1.

(Preparation of Hypericum extract)
Purified water 600 g and ethanol 600 g are added to 200 g of hypericum (scientific name: Hypericium erectum T.) and heated at 50 ° C. After cooling, it was filtered to obtain 25 g of hypericum extract.

  From the results of Table 1, a significant elastase inhibitory effect could be confirmed in the extract of Rhododendron simsii. The effect was greater than that of Hypericum extract.

  Below, the formulation example of the elastase inhibitor of this invention is given. Needless to say, the present invention is not limited by these formulation examples and is specified by the scope of claims.

Example 1 Cream (Prescription)
(1) Stearic acid 3.0 mass%
(2) Stearyl alcohol 5.0
(3) Isopropyl myristate 18.0
(4) Glycerol monostearate 3.0
(5) Propylene glycol 10.0
(6) Rhododendron simushi 50% ethanol water extract 0.01
(7) Caustic potash 0.2
(8) Sodium bisulfite 0.01
(9) Preservative appropriate amount (10) perfume appropriate amount (11) ion-exchanged water remaining

(Manufacturing method)
Propylene glycol, rhododendron simushi 50% ethanol water extract and caustic potash are added to ion-exchanged water, dissolved, heated and maintained at 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase is gradually added to the aqueous phase, and after the addition is complete, the temperature is maintained for a while to cause the reaction. Thereafter, the mixture is uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

Example 2 Cream (Prescription)
(1) Stearic acid 2.0% by mass
(2) Stearyl alcohol 7.0
(3) Hydrogenated lanolin 3.0
(4) Squalane 4.0
(5) 2-Octyldodecyl alcohol 6.0
(6) Polyoxyethylene (25 mol) cetyl alcohol ether 3.0
(7) Glycerin monostearate ester 2.0
(8) Propylene glycol 6.0
(9) Rhododendron simushi 70% ethanol water extract 0.05
(10) Sodium bisulfite 0.03
(11) Ethylparaben 0.3
(12) Appropriate amount of fragrance (13) Ion-exchanged water remaining

(Manufacturing 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). 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 (Prescription)
(1) Solid paraffin 5.0% by mass
(2) Beeswax 10.0
(3) Vaseline 15.0
(4) Liquid paraffin 41.0
(5) Glycerin monostearate ester 2.0
(6) Polyoxyethylene (20 mol) sorbitan monolaurate 2.0
(7) Soap powder 0.1
(8) Borax 0.2
(9) Rhododendron simushi ethanol extract 0.1
(10) Sodium bisulfite 0.03
(11) Ethylparaben 0.3
(12) Appropriate amount of fragrance (13) Ion-exchanged water remaining

(Manufacturing method)
Add soap powder and borax to ion-exchanged water, dissolve by heating and 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. After completion of the reaction, the mixture is uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well after emulsification.

Example 4 Latex (Prescription)
(1) Stearic acid 2.5% by mass
(2) Cetyl alcohol 1.5
(3) Vaseline 5.0
(4) Liquid paraffin 10.0
(5) Polyoxyethylene (10 mol) monooleate 2.0
(6) Polyethylene glycol 1500 3.0
(7) Triethanolamine 1.0
(8) Carboxyvinyl polymer 0.05
(9) Rhododendron simushi 50% 1,3-butylene glycol aqueous extract (solid content concentration 1.5%) 3.0
(10) Sodium bisulfite 0.01
(11) Ethylparaben 0.3
(12) Appropriate amount of fragrance (13) Ion-exchanged water remaining

(Manufacturing 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, dissolved by heating 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 (Prescription)
(1) Microcrystalline wax 1.0% by mass
(2) Beeswax 2.0
(3) Lanolin 20.0
(4) Liquid paraffin 10.0
(5) Squalane 5.0
(6) Sorbitan sesquioleate ester 4.0
(7) Polyoxyethylene (20 mol) sorbitan monooleate 1.0
(8) Propylene glycol 7.0
(9) Rhododendron simushi 70% 1,3-butylene glycol aqueous extract (solid content concentration 2.0%) 10.0
(10) Sodium bisulfite 0.01
(11) Ethylparaben 0.3
(12) Appropriate amount of fragrance (13) Ion-exchanged water remaining

(Manufacturing 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). While stirring the oil phase, the aqueous phase is gradually added thereto and uniformly emulsified with a homomixer. Cool to 30 ° C. while stirring well after emulsification.

Example 6 Jelly (Prescription)
(1) 95% ethyl alcohol 10.0% by mass
(2) Dipropylene glycol 15.0
(3) Polyoxyethylene (50 mol) oleyl alcohol ether 2.0
(4) Carboxyvinyl polymer 1.0
(5) Caustic soda 0.15
(6) L-arginine 0.1
(7) Rhododendron simushi 50% ethanol water extract 5.0
(8) Sodium 2-hydroxy-4-methoxybenzophenonesulfonate 0.05
(9) Ethylenediaminetetraacetate, 3 sodium, 2 water 0.05
(10) Methylparaben 0.2
(11) Perfume appropriate amount (12) Ion exchange water remaining

(Manufacturing method)
Carbopol 940 is uniformly dissolved in ion-exchanged water, while Rhododendron simushi 50% ethanol water 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 Cosmetic liquid (prescription)
(Phase A)
(1) Ethyl alcohol (95%) 10.0% by mass
(2) Polyoxyethylene (20 mol) octyldodecanol 1.0
(3) Pantotenyl ethyl ether 0.1
(4) Rhododendron simushi 50% 1,3-butylene glycol aqueous extract (solid concentration 1.5%) 1.5
(5) Methylparaben 0.15
(Phase B)
(6) Potassium hydroxide 0.1
(Phase C)
(7) Glycerin 5.0
(8) Dipropylene glycol 10.0
(9) Sodium bisulfite 0.03
(10) Carboxyvinyl polymer 0.2
(11) Purified water residue

(Manufacturing method)
A phase and C phase are uniformly dissolved, and A phase is added to C phase to solubilize. Next, filling is performed after adding phase B.

Example 8 Pack (Prescription)
(Phase A)
(1) Dipropylene glycol 5.0% by mass
(2) Polyoxyethylene (60 mol) hydrogenated castor oil 5.0
(Phase B)
(3) Rhododendron simushi 70% ethanol water extract 0.01
(4) Olive oil 5.0
(5) Tocopherol acetate 0.2
(6) Ethylparaben 0.2
(7) Fragrance 0.2
(Phase C)
(8) Sodium bisulfite 0.03
(9) Polyvinyl alcohol 13.0
(Saponification degree 90, polymerization degree 2,000)
(10) Ethanol 7.0
(11) Purified water residue

(Manufacturing method)
A phase, B phase, and C phase are uniformly dissolved, and B phase is added to A phase to solubilize. Next, this is added to phase C and then filled.

Example 9 Solid Foundation (Prescription)
(1) Talc 43.1% by mass
(2) Kaolin 15.0
(3) Sericite 10.0
(4) Zinc flower 7.0
(5) Titanium dioxide 3.8
(6) Yellow iron oxide 2.9
(7) Black iron oxide 0.2
(8) Squalane 8.0
(9) Isostearic acid 4.0
(10) POE sorbitan monooleate 3.0
(11) Isocetyl octanoate 2.0
(12) Rhododendron simushi ethanol extract 1.0
(13) Preservative appropriate amount (14) Perfume appropriate amount

(Manufacturing method)
Thoroughly blend the powder components of talc to black iron oxide with a blender, add the oily component of squalane to isocetyl octanoate, rhododendron simushi ethanol extract, preservative, and fragrance, knead well, and then fill and mold into a container .

Example 10 Emulsification Foundation (Cream Type)
(Prescription)
(Powder part)
(1) Titanium dioxide 10.3% by mass
(2) Sericite 5.4
(3) Kaolin 3.0
(4) Yellow iron oxide 0.8
(5) Bengala 0.3
(6) Black iron oxide 0.2
(Oil phase)
(7) Decamethylcyclopentasiloxane 11.5
(8) Liquid paraffin 4.5
(9) Polyoxyethylene-modified dimethylpolysiloxane 4.0
(Water phase)
(10) Purified water 46.5
(11) 1,3-butylene glycol 4.5
(12) Rhododendron simushi 30% 1,3-butylene glycol aqueous extract (solid content concentration 2.5%) 5.0
(13) Sorbitan sesquioleate 3.0
(14) Preservative appropriate amount (15) Fragrance appropriate amount

(Manufacturing method)
After the aqueous phase is heated and stirred, the powder part sufficiently mixed and pulverized is added and homomixed. Furthermore, after adding the heat-mixed oil phase and carrying out a homomixer process, a fragrance | flavor is added with stirring and it cools to room temperature.

Example 11 Latex (Prescription)
(1) Glycerin diisostearate 15.0% by mass
(2) Squalane 2.0
(3) Dimethicone 2.0
(4) Stearyl alcohol 3.0
(5) Rhododendron simushi 90% ethanol water extract 1.0
(6) Stearoyl methyl taurine sodium 1.0
(7) Polyoxyethylene (20) behenyl ether 0.5
(8) Glycerin 5.0
(9) 1,3-butylene glycol 5.0
(10) Carbomer 0.2
(11) Preservative appropriate amount (12) Purified water residue

(Manufacturing method)
A solution in which components (8) to (12) are uniformly dissolved is heated to 60 ° C., and a mixture of (1) to (7) at 70 ° C. is added with stirring to uniformly disperse and cooled to 30 ° C. To obtain an emulsion.

Example 12 Lotion (Prescription)
(1) Ethanol 5.0% by mass
(2) Glycerin 0.5
(3) Dipropylene glycol 2.0
(4) 1,3-butylene glycol 5.5
(5) Citric acid 0.02
(6) Sodium citrate 0.08
(7) Sodium hexametaphosphate 0.03
(8) Hydroxypropyl-β-cyclodextrin 0.1
(9) Rhododendron simushi 70% 1,3-butylene glycol aqueous extract (solid concentration 1.5%) 1.0
(10) Lavender oil 0.1
(11) Sodium alginate 0.001
(12) Purified water residue

(Manufacturing method)
(1) to (12) were mixed and dissolved according to a conventional method to obtain a skin lotion.

Example 13 Latex (Prescription)
(1) Dimethylpolysiloxane 3.0% by mass
(2) Decamethylcyclopentasiloxane 4.0
(3) Ethanol 5.0
(4) Glycerin 6.0
(5) 1,3-butylene glycol 5.0
(6) Polyoxyethylene methyl glucoside 3.0
(7) Squalane 2.0
(8) Potassium hydroxide 0.1
(9) Sodium hexametaphosphate 0.05
(10) Rhododendron simushi 70% ethanol water extract 0.5
(11) Xanthan gum 0.3
(12) Carboxyvinyl polymer 0.1
(13) Acrylic acid / alkyl methacrylate copolymer 0.1
(14) Methyl paraben appropriate amount (15) perfume appropriate amount (16) purified water residue

(Manufacturing method)
(9), (12) and (13) were added to (16) and dissolved, and further mixed with (10) and (4) to (6). Here, (14), (11) and (15) are added to and dissolved in (3) and mixed, and the mixture of (1), (2) and (7) is added to emulsify, It was neutralized and thickened by (8).

Example 14 Emulsion (Prescription)
(1) Vaseline 1.0% by mass
(2) Dimethylpolysiloxane 3.0
(3) Methylphenylpolysiloxane 3.0
(4) Stearyl alcohol 0.5
(5) Glycerin 7.0
(6) Dipropylene glycol 3.0
(7) 1,3-butylene glycol 7.0
(8) Squalane 1.0
(9) Isostearic acid 0.5
(10) Stearic acid 0.5
(11) Polystearic acid polyoxyethylene glycerol 1.0
(12) Glycerol monostearate 2.0
(13) Potassium hydroxide 0.05
(14) Rhododendron simushi ethanol extract 1.0
(15) EDTA.3 sodium 0.05
(16) Carboxyvinyl polymer 0.1
(17) Phenoxyethanol appropriate amount (18) perfume appropriate amount (19) purified water remainder

(Manufacturing method)
(6), (7), (13) was added to (19) and heated to maintain at 70 ° C. (aqueous phase). On the other hand, (1) to (4), (8) to (12) and (17) were mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is gradually added while stirring the aqueous phase, and (15), (16), (18), (5) and (14) are further added, and the mixture is uniformly emulsified with a homomixer. Cooled to 30 ° C.

Example 15 Syrup (Prescription)
(1) Rhododendron simushi 50% ethanol water extract 0.5% by mass
(2) Sucrose 60.0
(3) Ethyl paraoxybenzoate 0.02
(4) Propyl paraoxybenzoate 0.01
(5) Purified water residue

(Manufacturing method)
Each component was dissolved in purified water, stirred and homogenized to obtain a syrup.

Example 16 Lozenge (Prescription)
(1) Gum arabic 6.0% by mass
(2) Glucose 73.0
(3) Rhododendron simushi 70% ethanol water extract 0.05
(4) Potassium phosphate 0.2
(5) Monopotassium phosphate 0.1
(6) Lactose 17.0
(7) Fragrance 0.1
(8) Magnesium stearate residue

(Manufacturing method)
A troche was produced by a conventional method.

Example 17 Tablet (Prescription)
(1) Rhododendron simushi ethanol extract 2.0% by mass
(2) Crystalline cellulose 45.6
(3) Lactose 47.1
(4) carboxymethylcellulose calcium 3.5
(5) Talc 1.2
(6) Sodium stearate 0.6

(Manufacturing method)
The above ingredients were mixed uniformly and tableted to give 170 mg of 1 tablet according to a conventional method.

Example 18 Injection (Prescription)
(1) Rhododendron simushi 50% ethanol extract 0.5% by mass
(2) Sodium chloride 9.0
(3) Benzyl alcohol 9.0
(4) Distilled water residue (production method)
Rhododendron simushi 50% ethanol extract, sodium chloride and benzyl alcohol were dissolved in distilled water in the following amounts. The solution was filtered through a filter (pore size 0.2 μm) to produce an injection.

Example 19 Functional black tea A commercially available black tea leaf was pulverized, and a rhododendron simushi 50% ethanol extract was added to 0.5% by mass, mixed well, and packed in a tea pack. By putting this tea pack in hot water, it was possible to prepare functional black tea in which the extract was eluted into black tea.

Claims (2)

  An elastase inhibitor comprising a solvent extract of Rhododendron simsii from the genus Rhododendron (Ericaceae).   The elastase inhibitor according to claim 1, wherein the solvent extract is an alcohol extract or a hydrous alcohol extract.