JPH10175842A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use capable of keeping an antimicrobial activities for a long period without using an antimicrobial agent or a preservative providing a fear of causing injury to human body by including an extract of a specific plant as an antimicrobial component. SOLUTION: The objective skin preparation for external use is obtained by including an extract of Melissa officinalis, especially the extract by a polar solvent (e.g. water and ethanol) as an antimicrobial component. Especially effective antimicrobial activities are obtained when the polar solvent such as ethanol, 1,3-butylene glycol and an aqueous solution thereof are used. A surfactant can be added for enhancing the extraction efficiency. The formulating amount of the extract of the Melissa officinalis in the preparation for the external use such as a drug, a guasi-drug, cosmetics, etc., as an active ingredient is preferably within a concentration range of 0.001-20wt.% from the points of the effect, and the perfume and color when being added.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The present invention relates to Melissa
officinalis ) as an antibacterial component.

[0002]

2. Description of the Related Art At present, in various fields, contamination or deterioration of products caused by microorganisms is prevented.
Various bactericides and preservatives have been used to ensure the storage stability of products. Of these, directly applied to the living body,
Or, in the field of products ingested by living organisms, especially in the fields of cosmetics, pharmaceuticals, and foods, the types and amount of fungicides and preservatives that can be used may be determined to ensure the safety of living organisms. Many.

Specifically, in the cosmetics field, there are raw materials for which the upper limit of the blending concentration is specified by the Ministry of Health and Welfare notification, benzoic acid is 0.2% by weight, benzoates are 1.0% by weight, and salicylic acid is 0.2% by weight, salicylates 1.0% by weight, sorbic acid and its salts 0.5% by weight, dehydroacetic acid and its salts 0.5% by weight, paraoxybenzoates 1.0% by weight And 0.1% by weight of hexachlorophene is exemplified. These are also display designation components, and it is necessary to indicate that they are blended.

In the field of pharmaceuticals, benzoic acid, sodium benzoate, benzalkonium chloride, benzethonium chloride, cresol, chlorobutanol, thymol, methyl paraoxybenzoate, propyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, phenol and benzyl Alcohol and the like are described in the Japanese Pharmacopoeia as preservatives. However, even if the type and the amount of use are limited in this way, some of them give an unpleasant sensation during use and have skin irritation.

[0005] Therefore, attempts have been made to impart antibacterial activity without using such a bactericide or preservative, and for example, a method of blending alcohol, a method of blending phenoxyethanol, and a method of using an antibacterial polyol. Method,
Methods using antibacterial components and extracts derived from animals and plants are known.

[0006] However, in the method of blending alcohol, phenoxyethanol, antibacterial polyol, antibacterial extract and the like, sufficient antibacterial activity cannot be obtained, and at room temperature, rot or mold grows during use. For this reason, compositions manufactured using these methods can be stored in containers in which microorganisms are unlikely to be mixed during production or in disposable small containers, or can be refrigerated after opening or used for a short period of time for antimicrobial treatment. Responding to lack of power.

[0007]

Accordingly, in the present invention, there is provided a bactericide which is toxic or irritating or may be harmful to living organisms, particularly to humans, and may be an allergen causing allergy. Without using preservatives,
It is an object of the present invention to provide a skin external preparation capable of maintaining a long-term antibacterial activity equal to or higher than the case of using these disinfectants and preservatives.

[0008]

In order to solve the above problems, a preservative and fungicide system having high stability and low allergenicity, irritation and toxicity has been studied. As a result, Melissa offi
cinalis ) extract has high antibacterial activity, and it has been confirmed that the skin external preparations containing it, such as pharmaceuticals and cosmetics, have antibacterial activity without causing irritation or discomfort to the human body, especially the skin. The present invention has been completed and the present invention has been completed.

[0009]

DETAILED DESCRIPTION OF THE INVENTION Melissa officinalis
Is a perennial plant of the Labiatae family, and has long been used as an herb because it has a scent like citrus lemon. This melissa was found to have a tyrosinase activity inhibitory action, and a whitening cosmetic containing the tyrosinase activity was disclosed (JP-A-6-199647). Recently, it has been known that this extract has a hyaluronidase activity inhibitory action. However, it is not yet known that Melissa extract has antibacterial activity.

[0010] The Melissa extract used in the present invention is a whole plant of Melissa or any of leaves, stems, roots, seeds and flowers thereof, or a combination of two or more. Further, it can be extracted as is or in a dry state.

Although the extraction solvent is not particularly limited,
Examples include water, ethanol, methanol, 1,3-butylene glycol, alcohols such as glycerin, diglycerin, polyglycerin, and isopropyl alcohol, and organic solvents such as acetone, ether, and tetrahydrofuran. These may be used alone or in combination of two or more. Can be used in combination. Further, a surfactant may be added to enhance the extraction efficiency. Among these extraction solvents, particularly effective antibacterial activity is obtained when a polar solvent such as ethanol, 1,3-butylene glycol and an aqueous solution thereof is used. The ratio of Melissa to solvent at the time of extraction is not particularly limited, but is preferably 2 to 1000 times by weight of Melissa 1 and more preferably 5 to 100 times by weight in terms of extraction operation and efficiency.

Further, as an extraction method, a method of extracting by impregnation at room temperature, cooled or heated, a method of extraction using a distillation method such as steam distillation, and a method of squeezing raw Melissa to obtain an extract Examples of the method include squeezing and the like, and these methods are used alone or in combination of two or more.

The melissa extract thus obtained can be used as such as the extract, and should be blended after deodorizing, purifying, etc., as long as the preservative and fungicidal action is not lost. Alternatively, a fraction may be obtained by column chromatography or the like. Further, these extracts, deodorized, purified, and fractionated products can be dried by removing the solvent therefrom, and further provided in the form of a solution solubilized in a solvent such as alcohol or in the form of an emulsion. can do.

The melissa extract obtained above is blended as an antibacterial active ingredient in skin preparations such as pharmaceuticals, quasi-drugs and cosmetics.

The external preparation for skin can be in any form such as cream, ointment, lotion, emulsion, solid, powder and the like. In particular, as cosmetics, basic cosmetics such as lotion, milky lotion, serum, moisturizing cream, sun care products such as sun cream, sun lotion, sun oil, carmine lotion, foundation, eyeliner, mascara, eye color, Makeup cosmetics such as teak color and lipstick, facial cleansers, body shampoos, hair shampoos and other cleaning agents, rinses, treatments, hair creams, hair oils, hair cosmetics and other hair cosmetics, perfumes, deodorants and antiperspirants Can be used for applications. At this time, various components generally used in cosmetics such as avocado oil, palm oil, peanut oil, rice bran oil, jojoba oil, and the like, as long as the effects of the present invention are not impaired.
Oil components such as orange roughy oil, macadamia nut oil, squalane, evening primrose oil, sesame oil, sunflower oil, safflower oil, carola oil, carnauba wax, paraffin wax, lanolin, diisostearyl malate, isostearyl alcohol, and liquid paraffin Humectants such as glycerin, diglycerin, polyglycerin, sorbit, polyethylene glycol, 1,3-butylene glycol, collagen, hyaluronic acid, vitamin A such as vitamin A oil, retinol, retinol acetate, riboflavin, riboflavin butyrate, etc. vitamin B _2, vitamin B ₆ such as pyridoxine hydrochloride, L- ascorbic acid, magnesium L- ascorbyl phosphate, L- vitamin C such as sodium ascorbate, etc., calcium pantothenate, D- pantothenyl alcohol, Pas Pantothenic acids such as nonthenyl ethyl ether and acetyl pantothenyl ethyl ether;
Vitamin D such as ergocalciferol and cholecalciferol, nicotinic acid such as nicotinic acid, nicotinamide, and benzyl nicotinate; vitamin Es such as α-tocopherol and tocopherol acetate; vitamins such as vitamin P and biotin; Benzophenone derivatives such as 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, para-aminobenzoic acid, ethyl para-aminobenzoate, Derivatives such as para-aminobenzoic acid derivatives such as octyl para-dimethylaminobenzoate, methoxycinnamic acid derivatives such as glyceryl 2-methoxyhexanoate and mono-2-ethylhexanoate, and salicyls such as octyl salicylate and myristyl salicylate. Derivatives, urocanic acid, 4-te
UV absorbers such as rt-butyl-4'-methoxydibenzoylmethane, 2- (2'-hydroxy-5'-methylphenyl) benzotriazole, guar gum, locust bean gum, carrageenan, quince seed, pectin, mannan, etc. Plant natural polysaccharides, microbial natural polysaccharides such as xanthan gum, dextran, curdlan, hyaluronic acid, animal polymers such as gelatin, casein, albumin, collagen, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose And other semi-synthetic polymers such as cellulose, soluble starch, carboxymethyl starch, and methyl starch; semi-synthetic polymers such as propylene glycol alginate and alginates; Synthetic polymers such as benzyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium polyacrylate, and polyethylene oxide; water-soluble polymers such as bentonite, laponite, and colloidal alumina; and dibutylhydroxytoluene, butylhydroxyanisole, Antioxidants such as gallic acid ester, higher fatty acid soap, alkyl sulfate ester salt, polyoxyethylene alkyl ether sulfate salt, acyl methyl taurine salt, alkyl ether phosphate ester salt, acyl amino acid salt and other anionic surfactants, alkyl chloride Cationic surfactants such as trimethylammonium, dialkyldimethylammonium chloride, and benzalkonium chloride; betaine alkyldimethylaminoacetate; Down, 2
Amphoteric surfactants such as alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, surfactants such as polyoxyethylene nonionic surfactant, alcohol ester nonionic surfactant, etc., sodium ethylenediaminetetraacetate, Sequestering agents such as sodium polyphosphate, citric acid, sodium metaphosphate, succinic acid, gluconic acid, placenta extract, soybean arbor extract, glutathione, kojic acid and derivatives thereof, hydroquinones such as hydroquinone glycosides and derivatives thereof Whitening agents such as glycyrrhizic acid, glycyrrhetinic acid, anti-inflammatory agents such as allantoin, azulene, hydrocortisone, ε-aminocaproic acid, astringents such as zinc oxide, allantoin hydroxyaluminum, aluminum chloride, tannic acid, citric acid, and lactic acid; Cooling agents such as benzoyl and camphor; antihistamines such as diphenhydramine hydrochloride and chlorpheniramine maleate; sebum suppressants such as estradiol, estrone and ethinyl estradiol; exfoliating / dissolving agents such as salicylic acid and resorcinol; Can be blended.

The amount of Melissa extract as an antibacterial active ingredient in skin preparations such as medicines, quasi-drugs, and cosmetics is determined in consideration of its effect, flavor and color tone when added. It is desirable that the concentration range is 0.001 to 20% by weight.

[0017]

[Action]

[Preparation method of Melissa extract]
After immersing in twice the volume of ethanol for one week, the mixture is filtered to obtain a plant extract. This was freeze-dried, and a 0.2 mg / ml aqueous solution was further prepared as a Melissa extract.

Using the above Melissa extract, safety tests and antibacterial activity tests of primary irritation, cumulative skin irritation and acute toxicity were performed. The primary skin irritation, cumulative skin irritation test, and antibacterial activity test were performed using a 10% by weight aqueous solution.

"Primary skin irritation test" A 10% by weight aqueous solution of Melissa extract was applied to rabbits whose backs were depilated (3 per group).
Of the animals). The judgment is 24, 48, 7 after pasting
Two hours later, evaluation was performed according to the criteria shown in Table 1, and the average value of the skin irritation index relating to the occurrence of erythema and edema was determined. Table 2 shows the evaluation results.

[0020]

[Table 1]

[0021]

[Table 2]

As shown in the results of the primary skin irritation test shown in Table 2, erythema and edema were not observed in most animals, and only slight transient erythema was observed after only 48 hours. Was. This indicated that the Melissa extract according to the present invention did not have primary skin irritation.

"Skin Cumulative Irritation Test" A test was carried out on the skin of a Hartley guinea pig (female, 5 per group) with hair removed from the flank.
Once a day, 5 times a week, 0.5 ml / 8 cm ² of a 10% by weight aqueous solution of Melissa extract was applied. Application was performed over 4 weeks and hair removal was performed on the last application day of each week. Judgment was evaluated on the day following the last day of each week according to the criteria shown in Table 1, and the average value of the skin irritation index relating to the occurrence of erythema and edema was determined. Table 3 shows the evaluation results.

[0024]

[Table 3]

As shown in the results of the cumulative skin irritation test shown in Table 3, erythema and edema were not observed in most animals. Some erythema was observed at some 3 weeks, but it was temporary erythema, and no erythema was observed on the next determination day. The occurrence of slight erythema was considered to be due to physical stimulation by hair clippers during hair removal. This indicated that the Melissa extract of the present invention had no skin cumulative irritation.

"Acute toxicity test" Melissa extract (2 g / kg) was orally administered to mice (5 mice per group) which had been fasted for 4 hours before the test, and the appearance and degree of toxicity symptoms were observed over time.
As a result, in all the mice, no abnormality was observed for 14 days, and the dissection result showed no abnormality.

"Antibacterial activity test" An antibacterial activity test against various bacteria and fungi was carried out using a 10% by weight aqueous solution of the Melissa extract. Escherichia col as a bacterium
i ), Staphylococcus aureus , Pseudomonas aeruginosa , and Candida ( C ) as fungi
andida albicans ) and black mold ( Aspergillus niger ) were inoculated with 10 ⁶ bacteria and 10 ⁵ fungi per gram of the sample, and cultured at 37 ° C. and 25 ° C., respectively. It was measured. In addition, the antibacterial activity is 2 weeks later, when the bacteria are killed, the number of viable bacteria is 1 for fungi.
It was determined that the test was successful when the value became / 1000 or less.
The results of the antibacterial test are shown in Table 4 as "O" for those that passed and "X" for those that failed.

[0028]

[Table 4]

As shown in Table 4, the Melissa extract was
Excellent antibacterial action against all bacteria and fungi.

[0030]

EXAMPLES Further, the features of the present invention will be described in detail with reference to examples.

Example 1 Lotion (1) Ethanol 7.0 (% by weight) (2) 1,3-butylene glycol 6.0 (3) Glycerin 2.0 (4) Polyoxyethylene hydrogenated castor oil 0 .6 (5) Melissa 50% ethanol extract 1.0 (6) Fragrance 0.06 (7) Purified water 83.34 Production method: Each component of (1) to (6) is sequentially added to (7), Mix evenly.

Example 2 Emulsion (1) Squalane 4.0 (% by weight) (2) Glyceryl tri-2-ethylhexanoate 2.0 (3) Cetyl 2-ethylhexanoate 3.0 (4) Cetanol 0.6 (5) Stearyl alcohol 0.4 (6) Sorbitan monostearate 1.2 (7) 1,3-butylene glycol 6.0 (8) Glycerin 4.0 (9) Polyoxyethylene (20EO) Sorbitan 0.8 monostearic acid ester (10) Purified water 72.9 (11) Melissa 50% 1,3-butylene glycol extract 5.0 (12) Fragrance 0.1 Production method: First, (1) to (6) ) Is mixed, heated and melted, and kept at 75 ° C. On the other hand, the aqueous phases (7) to (10) are mixed and dissolved by heating to 75 ° C., and the oil phase is added thereto with stirring to emulsify. After cooling, add (11) and (12) at 40 ° C and mix.

Example 3 Cream (1) Stearyl alcohol 6.0 (% by weight) (2) Stearic acid 2.0 (3) Hydrogenated lanolin 4.0 (4) Squalane 9.0 (5) Octyldodeca Knol 10.0 (6) Polyoxyethylene (25EO) cetyl alcohol ether 3.0 (7) Glyceryl monostearate 2.0 (8) 1,3-butylene glycol 6.0 (9) Purified water 56.4 (10) Melissa 98% ethanol extract 1.5 (11) Fragrance 0.1 Production method: Mix and heat the oil phase components of (1) to (7) to 75 ° C. On the other hand, the aqueous phase components (8) and (9) were mixed and heated to 7
The temperature was adjusted to 5 ° C., and the oil phase was added to the mixture and emulsified.
At 0 ° C., add (10) and (11).

[Example 4] Oil-based cleansing cream (1) Celesin 8.0 (% by weight) (2) Microcrystalline wax 5.0 (3) White petrolatum 35.0 (4) Squalane 49.5 (5) Melissa 1,3-butylene glycol extract 0.5 (6) Magnesium stearate 2.0 Manufacturing method: The components (1) to (6) are mixed and heated to gel,
Cooling.

[Example 5] Emulsion foundation (1) Stearic acid 2.4 (wt%) (2) Propylene glycol monostearate 2.0 (3) Cetostearyl alcohol 0.2 (4) Liquid lanolin 0 (5) Liquid paraffin 3.0 (6) Isopropyl myristate 8.5 (7) Sodium carboxymethylcellulose 0.2 (8) Bentonite 0.5 (9) Propylene glycol 4.0 (10) Triethanolamine 1. 1 (11) Purified water 55.5 (12) Melissa 50% ethanol extract 2.5 (13) Fragrance 0.1 (14) Titanium oxide 8.0 (15) Talc 4.0 (16) Bengala 3.0 (17) Yellow iron oxide 2.5 (18) Black iron oxide 0.5 Manufacturing method: After mixing the pigments of (14) to (18), the mixture is pulverized by a pulverizer. (11) is heated to 70 ° C., and (8) is added to swell well. To this is added (7) previously dispersed in (9), and then (10) is added and dissolved. The oil phases (1) to (6) are mixed, heated and melted to 80 ° C. The pigment is added to the aqueous phase with stirring, the mixture is heated to 75 ° C. through a colloid mill, and the oil phase is added with stirring to emulsify.
Add (12) and (13) at ° C.

[Example 6] Aqueous suspension type mascara (1) 50% by weight vinyl acetate emulsion 30.0 (% by weight) (2) Sodium carboxymethylcellulose 1.0 (3) 1,3-butylene glycol 3.0 (4) Melissa 50% 1,3-butylene glycol extract 1.0 (5) Titanium oxide 8.0 (6) Carbon black 1.6 (7) Bengala 0.4 (8) Purified water 55.0 Production method; (8) to (2) to (4) are added and dissolved, and then
(5) to (7) are added and dispersed through a colloid mill. Add (1) to this and disperse uniformly.

Example 7 Shampoo (1) Sodium alkyl ether sulfate 18.0 (% by weight) (2) Coconut oil fatty acid diethanolamide 2.0 (3) Melissa 98% ethanol extract 5.0 (4) Yellow No. 4 1% by weight aqueous solution 0.1 (5) Fragrance 0.1 (6) Purified water 74.8 Production method; (1) to (5) are sequentially added to (6) and uniformly mixed and dissolved.

Example 8 Hair Rinse (1) Cetanol 3.0 (% by weight) (2) Stearyltrimethylammonium chloride 0.7 (3) Glycerin 3.0 (4) Green No. 3 1% by weight aqueous solution 0.2 (5) Melissa 50% ethanol extract 5.0 (6) Fragrance 0.1 (7) Purified water 88.0 Production method; (3) and (4) added to (7), heated to 70 ° C, and aqueous phase And On the other hand, (1) and (2) are mixed and dissolved, and heated to 70 ° C. to form an oil phase. The oil phase is gradually added to the aqueous phase with stirring to pre-emulsify. After emulsifying with a homomixer, cool,
Then, (5) and (6) are added.

Example 9 Hair Cream (1) Polyoxyethylene (10EO) behenyl ether 5.0 (% by weight) (2) Hexyldecanol 5.0 (3) Liquid paraffin 35.0 (4) Purified lanolin 2 0.0 (5) Cetanol 2.0 (6) Glycerin 5.0 (7) Melissa 50% 1,3-butylene glycol extract 0.5 (8) Purified water 45.4 (9) Fragrance 0.1 The oil phase components (1) to (5) are mixed and heated to 75 ° C. On the other hand, the aqueous phase components (6) to (8)
The temperature was adjusted to 5 ° C., and the oil phase was added to the mixture and emulsified.
At 0 ° C. add (9).

Example 10 Hair Treatment (1) Polyoxyethylene (30EO) behenyl ether 4.0 (% by weight) (2) Self-emulsifying glyceryl monostearate 6.0 (3) Isopropyl myristate 0 (4) hexyldecanol 5.0 (5) squalane 3.0 (6) purified lanolin 3.0 (7) stearic acid 5.0 (8) lauryl dimethylaminoacetate betaine 5.0 (9) glycerin 5.0 ( 10) Purified water 54.8 (11) Fragrance 0.2 (12) Melissa 50% ethanol extract 4.0 Production method: Mix and heat oil phase components (1) to (7) to 80 ° C. On the other hand, the aqueous phase components (8) to (10) were mixed and heated to 8
The temperature was adjusted to 5 ° C., and the oil phase was added to the mixture and emulsified.
Add (11) and (12) at 0 ° C.

Example 11 Face Wash (1) Stearic acid 10.0 (wt%) (2) Palmitic acid 10.0 (3) Myristic acid 12.0 (4) Lauric acid 4.0 (5) Oleyl Alcohol 1.5 (6) Lanolin alcohol 1.0 (7) Potassium hydroxide 6.0 (8) Purified water 52.9 (9) Fragrance 0.1 (10) Melissa 50% 1,3-butylene glycol extract 2.5 Production method: The oil phase of (1) to (6) and the aqueous phase of (7) and (8) are mixed and dissolved at 75 ° C. respectively, and then the aqueous phase is added to the oil phase for saponification. After cooling, (9) and (10) are added and mixed at 40 ° C.

Example 12 Body Shampoo (1) Lauric acid 5.0 (% by weight) (2) Myristic acid 7.5 (3) Lauroyl diethanolamide 5.0 (4) Glycerin 20.0 (5) Water Potassium oxide (10% by weight aqueous solution) 3.0 (6) Purified water 57.2 (7) Melissa water extract 2.0 (8) Fragrance 0.3 Production method: Oil phase of (1) to (3) and ( After mixing and dissolving each of the aqueous phases 4) to 6) at 75 ° C., the aqueous phase is added to the oil phase for saponification. After cooling, (7) and (8) are added and mixed at 40 ° C.

Example 13 Toothpaste (1) Calcium pyrophosphate 42.0 (% by weight) (2) Sodium lauryl sulfate 1.2 (3) Glycerin 10.0 (4) Carrageenan 1.1 (5) Sucrose Fatty acid ester 2.0 (6) Melissa 75% 1,3-butylene glycol extract 0.7 (7) Purified water 42.8 (8) Fragrance 0.2 Production method: Kneading components (1) to (8) , Make uniform.

Example 14 Mouthwash (1) Ethanol 40.0 (% by weight) (2) Glycerin 15.0 (3) Polyoxyethylene (50EO) hydrogenated castor oil 2.0 (4) Saccharin sodium 0.5 (5) Melissa 98% ethanol extract 0.5 (6) Purified water 41.5 (7) Fragrance 0.5 Production method: The components (1) to (7) are sequentially added, mixed and homogenized.

Next, the above Examples 1 to 14 were tested for antibacterial activity against various bacteria and fungi in accordance with the above method. Simultaneously, those without the Melissa extract in the formulation of each example were also prepared, and each was used as a comparative example. Table 5 shows the results.

[0046]

[Table 5]

As shown in Table 5, Examples 1 to 1
4 showed antibacterial activity against all bacteria and fungi. However, in Comparative Examples 1 to 14 in which the melissa extract was not blended, none of the bacterial species passed.

[0048]

EFFECTS OF THE INVENTION As described in detail above, an external preparation for skin containing Melissa extract as an antibacterial active ingredient has extremely high safety and various kinds of bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas, Candida, Black mold) ), An excellent antibacterial action was obtained.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/06 A61K 7/06 7/16 7/16 7/50 7/50

Claims (2)

[Claims] 1. An external preparation for skin containing an extract of Melissa officinalis as an antibacterial component. 2. The external preparation for skin according to claim 1, which comprises a polar solvent extract of Melissa as an antibacterial component.