JP6753602B2 - Proton pump function accelerator - Google Patents

Description

The present invention comprises a proton pump function promoter, which comprises an extract of one or more plants selected from the group consisting of Phellodendron amur, Phellodendron amur, and marjoram, and a pharmaceutical product containing the proton pump function promoter. It relates to various compositions such as quasi-drugs, cosmetics and foods and drinks.

The pH of a healthy skin surface usually maintains a weak acidity of 4.5 to 6.0, and this pH environment plays a role of inhibiting the growth of pathogenic bacteria, viruses, fungi and the like. If the skin surface pH is alkalized for some reason, the risk of developing skin diseases due to the growth of pathogenic bacteria, viruses, fungi, etc. increases. For example, it has been reported that the skin surface pH of patients with atopic dermatitis is higher than that of healthy subjects, and the detection rate of Staphylococcus aureus, which is a major pathogenic bacterium, is also high (Non-Patent Document 1). .. In addition, Staphylococcus aureus is known to cause skin diseases such as infectious impetigo, purulent peri-spermitis and boil (Non-Patent Document 2).

Therefore, an acidic lotion used for the purpose of inhibiting the growth of bacteria by keeping the skin acidic has been developed (Non-Patent Document 3).

Further, as it has become clear that Staphylococcus aureus is involved in skin diseases as described above, agents having a bacteriostatic or bactericidal action against Staphylococcus aureus have been developed. As such agents, Mannentake fruiting body umbrella extract (Patent Document 1), Kujin extract (Patent Document 2), Chaga mushroom extract (Patent Document 3), chitosan derivative (Patent Document 4) and the like are disclosed.

It has been thought that the components contained in sweat and sebum affect the weak acidification of the skin surface pH, but in recent years, the proton pump present in the epidermal keratinocytes has played an important role, and sodium, which is a type of proton pump, has played an important role. It has been clarified that a decrease in the function of the / hydrogen ion exchange transporter (Na ⁺ / H ⁺ exchanger: NHE) leads to an increase in skin surface pH (Non-Patent Documents 4 and 5). An increase in skin surface pH due to a decrease in the function of the proton pump may lead to the growth of pathogenic bacteria, viruses, fungi and the like on the skin.

It is desired to develop a substance capable of maintaining the pH of the skin surface at a weak acidity and inhibiting the growth of pathogenic bacteria, viruses, fungi, etc. by promoting the function of the proton pump.

Rehmannia glutinosa Liboschitz var. Purpurea Makino, a plant of the genus Rehmannia of the family Rehmannia glutinosa, or a family plant thereof. It has been known that Zio has a moisturizing effect (Patent Document 5), a whitening effect (Patent Document 6), a skin metabolism promoting effect (Patent Document 7), and the like. However, nothing is known about the function promoting effect of the proton pump.

Oubaku is a plant Phellodendron amurense of the Rutaceae Phellodendron genus. It has been known that Phellodendron amur has an anti-androgen action (Patent Document 8), a Langerhans cell reduction inhibitory action (Patent Document 9), a hyaluronic acid production promoting action (Patent Document 10), and the like. However, nothing is known about the function promoting effect of the proton pump.

Marjoram is a plant belonging to the genus Oregano of the Labiatae family, and has been known to have a matrix metalloproteinase inhibitory action (Patent Document 11), a hydroxyl radical scavenging action (Patent Document 12), and the like. Has been done. However, nothing is known about the function promoting effect of the proton pump.

JP-A-6-116162 Japanese Patent Application Laid-Open No. 8-73364 JP-A-10-12589 JP-A-10-158305 Japanese Patent Application Laid-Open No. 2006-16337 JP-A-11-246384 JP 2009-13086 Japanese Patent Application Laid-Open No. 10-298055 JP 2000-239144 JP 2001-158728 JP 2001-192316 JP-A-10-36280

Kaoru Endo et al., Journal of the Japanese Dermatological Association, 110 (1), 19-25 (2000) Standard Dermatology, 6th Edition, supervised by Shigeo Ikeda, Igaku-Shoin, 368-372 (2001) Cosmetic Science, Takeo Tamura, Japan Hair Science Association, 256-259 (1987) Behne MJ et al, J. et al. Biol. Chem. , 277 (49), 47399-47406 (2002) Choi EH et al, J. et al. Invest. Dermatol. , 127 (6), 2847-2856 (2007)

As mentioned above, acidic lotions have been developed to keep the skin weakly acidic, but these effects are temporary and there is a problem in the sustainability of the effects.

In addition, agents having a bacteriostatic or bactericidal action against Staphylococcus aureus have been developed, and these are also used for indigenous bacteria on the skin such as Staphylococcus epidermidis and Micrococcus spec. Since it exerts a bacteriostatic or bactericidal action, it may change the indigenous flora, affect the homeostasis of the skin, and may cause an opportunistic infection.

Therefore, in the present invention, the proton pump function can be promoted to prevent the growth of pathogenic bacteria, viruses, fungi, etc. by maintaining the pH of the skin surface at a weak acidity by promoting the function of the proton pump. The challenge was to provide the agent.

As a result of diligent studies to solve the above problems, the present inventors have found that the extracts of Diou, Oubaku and Majorum have an excellent proton pump function promoting action, thereby maintaining the pH of the skin surface at a weak acidity. By doing so, it was found that the growth of pathogenic bacteria, viruses, fungi, etc. was blocked, and the present invention was completed.

That is, the present invention includes the following inventions.
(1) A proton pump function promoter containing an extract of one or more kinds of plants selected from the group consisting of Zio, Phellodendron amur, and Marjoram.
(2) The function promoter according to (1), wherein the proton pump is a sodium / hydrogen ion exchange transporter.
(3) An external composition for adjusting skin pH, which contains the agent according to (1) or (2).
(4) The composition for external use on the skin according to (3), wherein the composition for external use on the skin is a drug or a quasi-drug.
(5) The external composition for skin according to (3), wherein the external composition for skin is a cosmetic product.
(6) A food or drink for adjusting skin pH, which comprises the agent according to (1) or (2).
(7) The food or drink according to (6), wherein the food or drink is a health food, a functional food, a food for specified health use, or a dietary supplement.

The extracts of Phellodendron amur, Phellodendron amur, and Marjoram of the present invention were excellent in the effect of promoting the function of the proton pump. The proton pump function promoter containing these extracts inhibits the growth of pathogenic bacteria, viruses, fungi, etc. by maintaining the pH of the skin surface at a weak acidity. Further, since the proton pump function accelerator of the present invention contains a plant extract having a mild action as an active ingredient, it has no side effects and is highly safe. Therefore, it can be safely used for pharmaceuticals, quasi-drugs, cosmetics, and foods and drinks.

The geese referred to in the present invention are Rehmannia glutinosa Liboschitz var. Purpurea Makino, which is a plant of the family Scropulariaceae, and Rehmannia glutinosa. ..

The constituent parts of the extract of Jio used in the present invention as an extraction raw material are not particularly limited and can be appropriately selected according to the purpose. For example, leaves, stems, flowers, fruits and rhizomes of plants. A part or whole plant of the plant can be used. Of these, rhizomes are particularly preferred.

The Oubaku referred to in the present invention is a Phellodendron amurense, a plant of the Rutaceae family, and commercially available ones can be used.

The constituent parts of the extract of Phellodendron amur used in the present invention as an extraction raw material are not particularly limited and can be appropriately selected according to the purpose. For example, leaves, flowers, bark, fruits and rhizomes of plants. A part or a mixture of plants can be used. Of these, bark is particularly preferred.

The marjoram used in the present invention is a plant belonging to the genus Oregano of the Labiatae family, and its scientific name is Oregano majora, also known as mayorana. It is distributed along the Mediterranean coast, North Africa, West Asia, etc., and can be obtained from these regions. Moreover, a commercially available product can also be used.

The constituent parts of the marjoram extract used in the present invention as an extraction raw material are not particularly limited and can be appropriately selected according to the purpose. For example, leaves, stems, flowers, fruits and rhizomes of plants. A part or whole plant of the plant can be used. Of these, leaves are particularly preferred.

For the extraction of the above plant, the plant body may be used as it is, or may be subjected to treatments such as drying, crushing, and shredding. The method for extracting the plant is not particularly limited, and for example, it may be extracted by heating, or it may be extracted at room temperature or low temperature. Examples of the solvent to be extracted include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.) and liquid polyhydric alcohols (1,3-butylene glycol, propylene). Glycol, glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran, propyl, etc.) Ether, etc.). Polar solvents such as water, lower alcohols and liquid polyhydric alcohols are preferable, and water, ethanol, 1,3-butylene glycol and propylene glycol are particularly preferable. These solvents may be used alone or in admixture of two or more.

The above extract may be used as it is in the extracted solution, or may be used after being concentrated, diluted, filtered, decolorized with activated carbon or the like, deodorized, or the like, if necessary. Further, the extracted solution may be subjected to treatments such as concentrated drying, spray drying, freeze-drying and used as a dried product, or may be used after column purification and the like to concentrate or isolate the active ingredient. Is also good. Zio, Phellodendron amurensis and Marjoram used in the present invention are naturally derived plants, and the components extracted from them are a mixture in which a large number of compounds having various structures are present at the same time. Therefore, it is difficult to clarify all the structures or properties of the contained components, and it is preferable to treat them as an extract.

The pH adjustment as used in the present invention means maintaining the pH of the skin surface at a weak acidity of 4.0 to 6.5, preferably 4.5 to 6.0.

The proton pump referred to in the present invention is a protein that exists in the membrane of mammalian cells and actively transports intracellular hydrogen ions (H ⁺ ) to the outside of the cells. The sodium / hydrogen ion exchange transporter is an exchange transporter protein that exchanges and transports intracellular hydrogen ions (H ⁺ ) and extracellular sodium ions (Na ⁺ ) at a ratio of 1: 1 and is an intracellular ion. It plays an important role in adjusting the concentration and osmotic pressure.

The “promotion of proton pump function” in the present invention refers to promotion of expression of a proton pump gene in epidermal keratinocytes and promotion of protein synthesis thereof, but also includes promotion of subsequent H ⁺ transport from intracellular to extracellular.

In epidermal keratinocytes, when NHE, which is a kind of proton pump, functions normally, Na ⁺ is taken up into the cell and H ⁺ is transported to the outside of the cell. This extracellularly transported H ⁺ contributes to weak acidification of skin surface pH (Behne MJ et al, J. Biol. Chem., 277 (49), 47399-47406 (2002), Choi EH et al, J. Invest. Dermatol., 127 (6), 2847-2856 (2007)). The weakly acidic skin surface pH plays a role in inhibiting the growth of pathogenic bacteria, viruses, fungi, etc., and in the skin where the skin surface pH is elevated, the major pathogenic bacteria, yellow staphylococcus. The detection rate has increased, and this yellow staphylococcus is associated with skin diseases such as atopic dermatitis, infectious pyoderma, purulent peripertocular inflammation and rash (Kaoru Endo, Journal of the Japanese Society of Dermatology, 110 (1)). , 19-25 (2000), Standard Dermatology, 6th Edition, supervised by Shigeo Ikeda, Medical School, 368-372 (2001)). Therefore, the extracts of Dio, Oubaku and Marjoram used in the present invention can be used to prevent pathogenic bacteria, viruses, fungi, etc. by maintaining the pH of the skin surface at a weak acidity through the action of promoting the proton pump function. It can prevent growth. In addition, these extracts can be used for skin diseases caused by pathogenic microorganisms, such as atopic dermatitis, infectious impetigo, purulent periperforelitis, and boil through the growth inhibitory action of the pathogenic microorganism. It is useful for prevention and improvement of such diseases.

When the proton pump function promoter of the present invention is administered in vivo, it can be administered as it is, but it is provided by being contained in a skin external composition together with an appropriate additive as long as the effect of the present invention is not impaired. It is preferable to do so. The external composition for skin of the present invention includes pharmaceuticals, quasi-drugs, cosmetics and the like.

When the proton pump function promoter of the present invention is contained in a pharmaceutical product, it is mixed with a pharmacologically and pharmaceutically acceptable additive and formulated into various preparations in a preparation form suitable for application to an affected area. be able to. Pharmacologically and pharmacologically acceptable additives include excipients, thickeners, tonicity agents, pH regulators, stabilizers, preservatives, and preservatives, depending on the dosage form and application. , Dispersants, emulsifiers, gelling agents, pigments, fragrances and the like can be used. A suitable form for the pharmaceutical product of the present invention is an external preparation, and examples thereof include ointments, creams, gels, liquids, and patches. The ointment refers to a homogeneous semi-solid external preparation, and includes an oily ointment, an emulsion ointment, and a water-soluble ointment. A gel agent refers to an external preparation in which a water-holding compound, which is a water-insoluble component, is suspended in an aqueous solution. The liquid preparation refers to a liquid external preparation, and includes a lotion, a suspension, an emulsion, a liniment, and the like.

When the proton pump function accelerator of the present invention is contained in a non-pharmaceutical product or cosmetic, the dosage form is an aqueous solution system, a solubilization system, an emulsification system, a powder system, a powder dispersion system, an oil solution system, a gel system, It may be an ointment type, an aerosol type, a water-oil two-layer type, a water-oil-powder three-layer type, or the like. Further, in the quasi-drugs and cosmetics, various components, additives, bases and the like usually used in the external composition for skin are selected according to the type and appropriately contained together with the proton pump function accelerator. It can be produced according to a method known in the art. The form may be any of liquid, emulsion, cream, gel, paste, spray and the like. Examples of the contained components include fats and oils (olive oil, palm oil, evening primrose oil, jojoba oil, castor oil, hardened castor oil, etc.), waxes (lanolin, beeswax, carnauba wax, etc.), hydrocarbons (liquid paraffin, squalane, etc.). Squalane, Vaseline, etc.), fatty acids (lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, etc.), higher alcohols (myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, etc.), esters (myristin) Isopropyl acid, isopropyl palmitate, cetyl octanoate, glycerin trioctate, octyldodecyl myristate, octyl stearate, stearyl stearate, etc.), organic acids (citrate, lactic acid, α-hydroxyacetic acid, pyrrolidonecarboxylic acid, etc.), sugars (Martitol, sorbitol, xylobiose, N-acetyl-D-glucosamine, etc.), proteins and hydrolyzates of proteins, amino acids and their salts, vitamins, plant / animal extracts, various surfactants, moisturizers, Examples thereof include ultraviolet absorbers, antioxidants, stabilizers, preservatives, bactericides, and fragrances.

Types of non-pharmaceutical products and cosmetics include, for example, lotions, milky lotions, gels, beauty liquids, general creams, sunscreen creams, packs, masks, pigments, cosmetic soaps, foundations, whitewashes, bathing agents, body lotions, etc. Examples include body shampoos, hair shampoos, hair conditioners, scalp lotions, scalp creams, hair tonics, and hair restorers.

The content of the proton pump function promoter in the external composition for skin of the present invention is not particularly limited as long as it can exert the proton pump function promoting action in the epidermal keratinocytes, but the weight of the dry solid is 0.00001 to 10 weight. % Is preferable, and 0.0001 to 1% by weight is more preferable. Furthermore, the effect is remarkably enhanced by using the extracts of Phellodendron amur, Phellodendron amur and marjoram in combination, and it is more preferable to mix the extracts in a ratio of 1: 1: 1. The above amounts are merely examples, and may be appropriately set and adjusted in consideration of the type and form of the composition, general usage amount, efficacy / effect, cost, and the like.

Further, the proton pump function accelerator of the present invention can also be contained in foods and drinks. In the present invention, the food and drink is used to include health foods, functional foods, dietary supplements, and foods for specified health uses. The form of the food or drink may be any of edible forms such as solid, liquid, granular, granular, powdery, capsule-like, cream-like, and paste-like.

The types of foods and drinks include breads, noodles, confectionery, dairy products, processed marine and livestock foods, fats and oils, processed fats and oils, seasonings, and various beverages (soft drinks, sparkling drinks, beauty drinks, nutritional drinks, fruit drinks). , Milk beverages, etc.), concentrated stock solutions of the beverages, preparation powders, etc., but are not limited thereto.

The food or drink of the present invention may appropriately contain additives that are usually used depending on the type of food or drink. As the additive, any additive that is acceptable under the Food Sanitation Law can be used, and for example, sweeteners such as starch, sucrose, fructose, isomerized liquid sugar, aspartame, and stevia; citric acid and malic acid. , Acidulants such as citric acid; Excipients such as dextrin and starch; Binding agents, diluents, fragrances, coloring agents, buffers, thickeners, gelling agents, stabilizers, preservatives, emulsifiers, dispersants, suspensions Examples include turbidants and preservatives.

The content of the extracts of Phellodendron amurensis, Phellodendron amurensis, and marjoram in the food and drink of the present invention may be an amount capable of exerting the proton pump function promoting action in the epidermal keratinocytes, but the general intake of the target food and drink and the food and drink It may be appropriately set in consideration of form, efficacy / effect, taste, palatability, cost and the like.

Next, in order to explain the present invention in detail, specific examples will be given. These examples specifically explain the effect and do not limit the scope of the invention. The content in the examples is% by weight.

[Example 1]
(Production Example 1) Hot water extract of Gio Add 2 L of purified water to 100 g of dried rhizome of Akayazio, extract at 95-100 ° C for 2 hours, filter, concentrate the filtrate, freeze-dry and gio. 9.2 g of hot water extract was obtained.

(Production Example 2) 50% Ethanol Extraction of Rehmannia glutinosa Add 500 mL of purified water and 500 mL of ethanol to 100 g of dried rhizome of Rehmannia glutinosa, extract at room temperature for 7 days, filter, concentrate and dry the filtrate, and use Rehmannia glutinosa. 16.8 g of 50% ethanol extract of the above was obtained.

(Production Example 3) Extract of 50% 1,3-butylene glycol aqueous solution of Rehmannia glutinosa 200 mL of purified water and 200 mL of 1,3-butylene glycol were added to 20 g of dried rhizome of Rehmannia glutinosa, extracted at room temperature for 7 days, and then filtered. , A 50% 1,3-butylene glycol aqueous solution extract of Rehmannia glutinosa was obtained in an amount of 360 g.

(Production Example 4) Hot water extract of Phellodendron amur, 2 L of purified water is added to 100 g of dried bark of Phellodendron amurensis, extracted at 95-100 ° C. for 2 hours, filtered, the filtrate is concentrated, and freeze-dried. 5.0 g of the hot water extract of Phellodendron amur was obtained.

(Production Example 5) 50% ethanol extract of Phellodendron amur, 500 mL of purified water and 500 mL of ethanol are added to 100 g of dried bark of Phellodendron amurensis, extracted at room temperature for 7 days, filtered, and the filtrate is concentrated to dryness. 7.0 g of a 50% ethanol extract of Phellodendron amur was obtained.

(Production Example 6) Extract of 50% 1,3-butylene glycol aqueous solution of Phellodendron amur 200 mL of purified water and 200 mL of 1,3-butylene glycol were added to 20 g of dried bark of Phellodendron amurensis, extracted at room temperature for 7 days, and then filtered. , A 50% 1,3-butylene glycol aqueous solution extract of Phellodendron amur was obtained in an amount of 340 g.

(Production Example 7) Hot water extract of Majorum Add 2 L of purified water to 100 g of dried Majoram leaves, extract at 95-100 ° C for 2 hours, filter, concentrate the filtrate, freeze-dry and Majorum. 8.7 g of hot water extract was obtained.

(Production Example 8) 50% Ethanol Extract of Marjoram 500 mL of purified water and 500 mL of ethanol were added to 100 g of dried marjoram leaves, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness to make marjoram. To obtain 1.1 g of a 50% ethanol extract of.

(Production Example 9) 50% 1,3-butylene glycol aqueous solution extract of Majorum 200 mL of purified water and 200 mL of 1,3-butylene glycol are added to 20 g of dried Majoram leaves, extracted at room temperature for 7 days, and then filtered. , A 50% 1,3-butylene glycol aqueous solution extract of Majorum was obtained in an amount of 310 g.

[Example 2]
An experiment to evaluate the effect of the extracts of Phellodendron amur, Phellodendron amur, and Marjoram was conducted as follows.
(Test Example 1) Evaluation of Proton Pump Function Promoting Effect on Keratinocytes The effect of the extracts of Phellodendron amurensis, Phellodendron amurensis and Marjoram on the proton pump function was evaluated using the mRNA expression level of NHE1 as an index. The specific method will be described below.

HaCaT cells derived from keratinocytes were seeded in 1 × 10 ⁵ cells in a 60 mm dish and cultured in DMEM culture medium containing 10% FBS for 4 days under 37 ° C. and 5% CO ₂ conditions. Next, a DMEM culture solution in which each extract is added so as to have a final concentration of 10 μg / mL, or a DMEM culture solution in which all three types of extracts are added so that the final concentration of each extract is 3.3 μg / mL. After culturing for 24 hours in, total RNA was extracted. Extraction of total RNA from cells was performed using RNAiso Plus (TaKaRa), and the total amount of RNA was determined by absorbance at 260 nm using a spectrophotometer (NanoDrop). The mRNA expression level was measured by the real-time RT-PCR method based on the total RNA extracted from the cells. SYBR Select Master Mix (Life Technologies) was used for the real-time RT-PCR method. That is, after a reverse transcription reaction of 500 ng of total RNA, a PCR reaction (95 ° C: 15 seconds, 60 ° C: 30 seconds, 40 cycles) was performed. For other operations, the expression level of NHE1 mRNA was determined as a ratio to the expression level of β-actin mRNA, which is an internal standard, according to a predetermined method. The NHE1 expression level was calculated as the ratio of the expression level of NHE1 mRNA in the sample addition group to the expression level of NHE1 mRNA in the control. As the primers for NHE1 and β-actin, those shown below were used.

Primer set for NHE1 GCCCTGTTTAATCATCCGTC (SEQ ID NO: 1)
CACATGGAA ACCTATTCTCATGAG (SEQ ID NO: 2)
Primer set for β-actin CACTTTCCAGCCTTCCTTCC (SEQ ID NO: 3)
GTGTTGGGCGTACAGGTCTTG (SEQ ID NO: 4)

The results of these tests are shown in Table 1. As a result, a remarkable effect of promoting the function of the proton pump was observed in all the extracts of Phellodendron amur, Phellodendron amur, and Marjoram. Furthermore, by combining all three types, a remarkable proton pump function promoting effect was observed, which significantly exceeded the effect of the single type alone. Further, the same effect was observed in the extracts produced by different production methods.

[Example 3] Product formulation example The formulation example of a product containing extracts of Phellodendron amur, Phellodendron amur, and Marjoram is shown below.

(Prescription example 1) Lotion prescription content (% by weight)
1. Extract of Zio (Production Example 2 0.1
2. Extract of Phellodendron amur (Production Example 5) 0.1
3. Marjoram extract (Production Example 9) 0.1
4.1,3-butylene glycol 8.0
5. Glycerin 2.0
6. Xanthan gum 0.02
7. Citric acid 0.01
8. Sodium citrate 0.1
9. Ethanol 5.0
10. Methyl paraoxybenzoate 0.1
11. Polyoxyethylene hydrogenated castor oil (40EO) 0.1
12. Fragrance 0.1
13. Remaining amount of purified water [Manufacturing method] After components 1 to 8 and 13 and components 9 to 12 are uniformly dissolved, both are mixed and filtered to prepare a lotion.

(Prescription example 2) Cream prescription content (% by weight)
1. Extract of Zio (Production Example 1) 0.1
2. Extract of Phellodendron amur (Production Example 4) 0.1
3. Marjoram extract (Production Example 7) 0.1
4. Squalene 5.5
5. Olive oil 3.0
6. Stearic acid 2.0
7. Beeswax 2.0
8. Octyldodecyl myristate 3.5
9. Polyoxyethylene cetyl ether (20EO) 3.0
10. Behenyl alcohol 1.5
11. Glycerin monostearate 2.5
12. Fragrance 0.1
13. Methyl paraoxybenzoate 0.2
14. Ethyl paraoxybenzoate 0.05
15.1,3-butylene glycol 8.5
16. Remaining amount of purified water [Manufacturing method] Ingredients 4 to 11 are heated and dissolved and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 to 3 and 13 to 16 are heated and dissolved and mixed to prepare an aqueous phase at 75 ° C. Next, an aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring, component 12 is added at 45 ° C., and the mixture is further cooled to 30 ° C. to obtain a product.

(Prescription example 3) Emulsion prescription content (% by weight)
1. Extract of Zio (Production Example 3) 0.1
2. Extract of Phellodendron amur (Production Example 6) 0.1
3. Marjoram extract (Production Example 8) 0.1
4. Squalene 5.0
5. Olive oil 5.0
6. Jojoba oil 5.0
7. Cetanol 1.5
8. Glycerin monostearate 2.0
9. Polyoxyethylene cetyl ether (20EO) 3.0
10. Polyoxyethylene sorbitan monooleate (20EO) 2.0
11. Fragrance 0.1
12. Propylene glycol 1.0
13. Glycerin 2.0
14. Methyl paraoxybenzoate 0.2
15. Remaining amount of purified water [Manufacturing method] Components 4 to 10 are heated and dissolved and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 to 3 and 12 to 15 are heated and dissolved and mixed to prepare an aqueous phase at 75 ° C. An aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring, component 11 is added at 45 ° C., and the mixture is further cooled to 30 ° C. to obtain a product.

(Prescription example 4) Gel preparation Prescription content (% by weight)
1. Extract of Zio (Production Example 1) 0.1
2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4. Polyoxyethylene hydrogenated castor oil (60E.О.) 0.1
5. Appropriate amount of fragrance 6.1,3-butylene glycol 5.0
7. Glycerin 5.0
8. Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. Remaining amount of purified water [Manufacturing method] Components 2 to 5 and components 1 and 6 to 11 are uniformly dissolved, and both are mixed to obtain a product.

(Prescription example 5) Ointment prescription content (% by weight)
1. Extract of Zio (Production Example 2) 2.0
2. Polyoxyethylene cetyl ether (30EO) 2.0
3. Glycerin monostearate 10.0
4. Liquid paraffin 5.0
5. Cetanol 6.0
6. Methyl paraoxybenzoate 0.1
7. Propylene glycol 10.0
8. Remaining amount of purified water [Manufacturing method] Components 2 to 5 are heated and dissolved and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 and 6 to 8 are heated, dissolved and mixed, and kept at 75 ° C. to prepare an aqueous phase. An aqueous phase is added to the oil phase to emulsify, and the product is cooled to 30 ° C. with stirring.

(Prescription example 6) Pack prescription content (% by weight)
1. Extract of Zio (Production Example 3) 0.1
2. Polyvinyl alcohol 12.0
3. Ethanol 5.0
4.1,3-butylene glycol 8.0
5. Methyl paraoxybenzoate 0.2
6. Polyoxyethylene hydrogenated castor oil (20EO) 0.5
7. Citric acid 0.1
8. Sodium citrate 0.3
9. Appropriate amount of fragrance 10. Remaining amount of purified water [Manufacturing method] Dissolve components 1 to 10 uniformly to obtain a product.

(Prescription example 7) Foundation prescription content (% by weight)
1. Extract of Zio (Production Example 2) 1.0
2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20EO) 1.0
4. Polyoxyethylene cetyl ether (20EO) 2.0
5. Cetanol 1.0
6. Liquid lanolin 2.0
7. Liquid paraffin 3.0
8. Isopropyl myristate 6.5
9. Butyl paraoxybenzoate 0.1
10. Sodium Carboxymethyl Cellulose 0.1
11. Bentonite 0.5
12. Propylene glycol 4.0
13. Triethanolamine 1.1
14. Methyl paraoxybenzoate 0.2
15. Titanium dioxide 8.0
16. Talc 4.0
17. Bengala 1.0
18. Yellow iron oxide 2.0
19. Appropriate amount of fragrance 20. Remaining amount of purified water [Manufacturing method] Components 2 to 9 are heated and dissolved, and kept at 80 ° C. to prepare an oil phase. Ingredient 20 is well swollen with Ingredient 10, followed by Additions 1 and 11-14 and mixed uniformly. Ingredients 15 to 18 pulverized and mixed by a pulverizer are added thereto to prepare an aqueous phase. The temperature of the aqueous phase is raised to 80 ° C., and the aqueous phase is gradually added to the oil phase for emulsification. Then, the mixture is cooled with stirring, component 19 is added at 45 ° C., and the mixture is cooled to 30 ° C. to obtain a product.

(Prescription Example 8) Bar soap Prescription content (% by weight)
1. Extract of Phellodendron amur (Production Example 4) 0.1
2. Soap base (*) 80.0
3. Glycerin 10.0
4. Sorbitol 1.0
5. Edetonic acid 0.1
6. Titanium oxide 0.1
7. Appropriate amount of fragrance 8. Remaining amount of purified water (*) Sodium higher fatty acid mixture containing sodium laurate, sodium myristate, sodium palmitate, sodium stearate, sodium oleate [Manufacturing method] Mix all ingredients, knead with a mixer and roller, and knead. The product is obtained by stamping into a rod-shaped molding by compression with a prodder, and then cooling and drying the molding.

(Prescription example 9) Body cleaning agent Prescription content (% by weight)
1. Extract of Phellodendron amur (Production Example 5) 0.2
2. Stearic acid 10.0
3. Palmitic acid 8.0
4. Myristic acid 12.0
5. Lauric acid 4.0
6. Oleyl alcohol 1.5
7. Purified lanolin 1.0
8. Coconut oil fatty acid diethanolamide 1.0
9. Glycerin 10.0
10. Potassium hydroxide 6.0
11. Appropriate amount of fragrance 12. Preservatives Appropriate amount 13. Appropriate amount of sequestrant 14. Remaining amount of purified water [Manufacturing method] Components 2 to 5 are heated and dissolved and mixed, and kept at 70 ° C. to prepare an oil phase. Component 10 is dissolved in an appropriate amount of component 14 and added to the oil phase for saponification. Subsequently, components 6-9 are added to the saponified product, and components 1, 11 to 13 and the remaining components 14 are further added at room temperature.

(Prescription example 10) Hair lotion Prescription content (% by weight)
1. Extract of Phellodendron amur (Production Example 6) 0.2
2. Stearic acid 5.0
3. Cetyl alcohol 5.0
4. Liquid paraffin 2.0
5. Glycerin monostearate 1.3
6. Sorbitan Monooleate 1.5
7. Polyoxyethylene sorbitan monooleate (10EO) 0.8
8. Glycerin 6.0
9. Preservatives Appropriate amount 10. Remaining amount of purified water [Manufacturing method] Components 2 to 7 are heated and dissolved, mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 and 8 to 10 are heated, dissolved and mixed, and kept at 75 ° C. to prepare an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the product is cooled while stirring.

(Prescription example 11) Hair tonic prescription content (% by weight)
1. Marjoram extract (Production Example 7) 2.0
2.95% ethanol 60.0
3. Glycerin 2.0
4. Remaining amount of purified water [Manufacturing method] Dissolve component 1 in 2, add components 3 and 4, and mix well with stirring to obtain a product.

(Prescription example 12) Shampoo prescription content (% by weight)
1. Marjoram extract (Production Example 8) 0.1
2. Alkylation Triethanolamine 18.0
3. Lauric acid diethanolamide 3.0
4. Methyl cellulose 0.5
5. Appropriate amount of fragrance 6. Remaining amount of purified water [Manufacturing method] After component 4 is uniformly dissolved in component 6, components 1 and 2 are added, and after heating and dissolving at 70 to 75 ° C., component 3 is added, and component 5 is added during cooling 30. Cool to ℃ to make a product.

(Prescription Example 13) Bathing agent Prescription content (% by weight)
1. Marjoram extract (Production Example 9) 5.0
2. Sodium bicarbonate 50.0
3. Yellow No. 202 Appropriate amount 4. Appropriate amount of fragrance 5. Anhydrous sodium sulfate Remaining amount [Manufacturing method] Ingredients 1 to 5 are uniformly mixed to prepare a product.

(Prescription Example 14) Tablet Prescription content (% by weight)
1. Marjoram extract (Production Example 9) 1.0
2. Dried cornstarch 25.0
3. Carboxymethyl Cellulose Calcium 24.0
4. Microcrystalline Cellulose 40.0
5. Polyvinylpyrrolidone 7.0
6. Talc 3.0
[Manufacturing method] Ingredients 1 to 5 are mixed, then 10% water is added as a binder, and the mixture is extruded and granulated and then dried. Ingredient 6 is added to the molded granules, mixed and locked. One tablet weighs 0.52 g.

(Prescription Example 15) Beverage Prescription Content (% by weight)
1. Extract of Zio (Production Example 2) 0.1
2. Extract of Phellodendron amur (Production Example 5) 0.1
3. Marjoram extract (Production Example 9) 0.1
4. Stevia 0.05
5. Malic acid 5.0
6. Sodium ascorbate 1.0
7. Fragrance 0.1
8. Remaining amount of purified water [Manufacturing method] Components 1 to 7 are stirred and dissolved in a part of purified water of component 8. The remaining purified water of component 8 is then added, mixed, heated to 90 ° C. and filled in a 50 mL glass bottle.

The proton pump function promoter according to the present invention, which comprises extracts of Phellodendron amur, Phellodendron amur, and Marjoram, inhibits the growth of pathogenic microorganisms by maintaining the pH of the skin surface at a weakly acidic value. Therefore, pharmaceuticals, non-pharmaceutical products, cosmetics, etc. for the purpose of preventing or improving skin diseases caused by pathogenic microorganisms, such as atopic dermatitis, infectious impetigo, purulent peri-spermitis and boil. And can be used in the field of food and drink manufacturing.

Claims (3)

A proton pump function enhancer characterized by containing extracts of Phellodendron amur, Phellodendron amur and marjoram . The function promoter according to claim 1, wherein the proton pump is a sodium / hydrogen ion exchange transporter. An external composition for adjusting skin pH, which comprises the agent according to claim 1 or 2.