KR0165938B1 - Hair growth stimulating composition containing extract of artemisia apiaceahance - Google Patents

Abstract

The present invention relates to a hair growth agent composition containing dichloromethane extract of Cheongho as an active ingredient. Cheongho dichloromethane extract according to the present invention shows an excellent hair growth effect with almost no side effects and can be used for hair growth promotion and hair loss prevention of alopecia, in particular male alopecia.

Description

Hair Loss Composition Containing Chungho Extract

The present invention relates to a novel hair restorer composition containing clarification extract. More specifically, the present invention relates to a hair restorer composition containing dichloromethane extract of Cheongho as an active ingredient.

The cause of hair loss is not known exactly, but according to the findings, it is divided into nutritional commentary, bacterial infection, autoimmune diseases, endocrine, and autonomic nervous system. This is considered to be the largest, and it is generally known that hair loss occurs due to a combination of various causes.

However, while the cause of hair loss has been studied relatively little, the treatment method has not yet been satisfactory. The main reason is that the cause of hair loss is not simple.

The methods currently used to prevent hair loss and hair growth include the application of a hair growth agent and physical stimulation to skin with hair roots. At present, hair growth agents for the prevention or treatment of alopecia include various preparations, for example, corticosteroids, female hormones, vitamins, amino acids, herbal extracts, various fungicides, keratin dissolvers, skin hyperstimulants and peripheral nerve stimulants such as menthol. It is used.

Such female hormone preparations may cause various cancers during long-term use, and herbal extracts contain extracts of butterbur or butterweed dandelion (Japanese Patent Publication No. 58-11923), Japanese cedar tree, Shiho And extracts containing leeches and the like (Japanese Patent Publication No. 58-40923) have been reported, but these are very difficult to obtain raw medicines, and the other methods described above also prevent and treat alopecia. Or the effect of mitigating was not satisfactory.

Meanwhile, it was confirmed that minoxidil, which was widely used as an antihypertensive agent in the 1980s, has a hair regrowth effect, and that the effect is thought to be a cause for increasing blood flow to the skin, unlike the conventional hair restorer, which is associated with the endocrine system. [Weiss, VC, et al., J. Am. Acad. Dermatol. 5, 224-226 (1981). However, when minoxidil is used as a hair restorer, there is a concern that minoxidil may cause side effects such as antihypertensive action, that is, deprivation caused by vasodilatation effect, hypotension, tachycardia, and the like, and thus it may not be a suitable drug for long-term use.

Accordingly, the present inventors conducted intensive research to develop a material that can exhibit excellent hair growth effects without the side effects of the conventional hair growth agents as mentioned above. As a result, it was confirmed that the dichloromethane extract of Cheongho, which is a natural plant, has excellent hair growth effect and shows little side effects, and completed the present invention.

Accordingly, the present invention relates to a hair restorer composition containing dichloromethane extract of Chungho as an active ingredient.

Cheongho is a dried outpost of Artemisia apiacea Hance, which has high quality, β-bulonene, palnesyl acetate, carliophylene, β-prmene, ε-cardinene, δ -Essential oils such as cardinene, α-pinene, β-pinene, canpene, limonene, 1,8-cineol, althemia ketone, α-yon, cobaene, γ-cardinene and abrotanin, vitamin A It has been found to contain antibacterial, antipyretic, hemostatic, and analgesic effects on skin fungi, and also has a dietary medicinal herb and anecdotal herbaceous medicinal herb (日 華 子 諸 家 本草). Cheongho is said to have the effect of helping hair grow or blackening hair.

Until now, Cheongho has been commonly used as a method of decoction with water or by drying powdered herbal medicine as it is in the private sector to maintain healthy hair. However, only this method could not actually achieve the effect described above for hair. In particular, when the water extract is applied as it is, it does not penetrate the scalp and remains as it is not able to achieve the desired effect, and sometimes has the disadvantage of causing redness and fungi. The present inventors verified the hair growth effect of the extract by using various organic solvents in order to obtain the extract showing the best hair growth effect from Cheongho, and as a result, the dichloromethane extract of Cheongho showed excellent hair growth effect and side effects and toxicity It was confirmed that there was almost no such purpose.

Cheongho's dichloromethane extract used as an active ingredient in the composition according to the present invention is obtained by extracting Cheongho with alcohol, suspending this alcohol extract in water and extracting with hexane, then separating the aqueous layer and extracting with dichloromethane.

In the extraction process of the present invention, the alcohol as the primary extraction solvent may preferably be a lower alcohol having 1 to 4 carbon atoms, such as methanol, ethanol, propanol, butanol, and the like. In particular, methanol is used. At this time, the amount of alcohol used varies slightly depending on the type of alcohol, but is generally used in a ratio of 10 to 20 liters, preferably 14 to 15 liters per kilogram of clarity. This extraction process is preferably carried out over 5 to 15 hours, preferably 9 to 10 hours using a reflux condenser under heating.

The alcohol extract thus obtained is suspended in water, preferably distilled water, and then extracted secondly with hexane. At this time, water is used in a ratio of 0.5 L to 1 L, preferably 0.7 to 0.8 L, with respect to 1 kg of chungho, which is a crude drug, and hexane is preferably used equally with water used.

After separation of the hexane extract, the remaining aqueous layer can be extracted with dichloromethane and the solvent is evaporated from the extract to obtain the dichloromethane extract of the clarity desired in the present invention in dried form. At this time, dichloromethane is used in a ratio of 1.5 to 3 L, preferably 2.1 to 2.4 L, based on 1 kg of chungho, which is a crude drug.

In the extraction process of the present invention, each extraction step may be performed once or several times as necessary, preferably 2 to 3 times.

The dichloromethane extract of Cheongho obtained according to the method of the present invention may be further fractionated as necessary to separate only the fraction which shows a better hair growth effect. Fractionation of the dichloromethane extract of Cheongho may be accomplished by column chromatography using a mixed solvent of chloroform and methanol as a eluent in a gradient of 20: 1 to 1: 1 to fractionate the eluate according to polarity. . In other words, by changing the mixing ratio of chloroform and methanol as eluents to 20: 1, 15: 1, 10: 1, 7: 1, 5: 1, 2: 1, respectively, fractions 1 to 6 were each eluted by evaporating the eluent. Can be obtained separately. Among the fractions thus obtained, fractions 1, 4 and 5 were found to exhibit particularly excellent hair growth effects. Therefore, these fractions of the dichloromethane extract of chungho can be particularly useful according to the present invention.

Cheongho dichloromethane extract obtained according to the method of the present invention as described above is believed to exhibit a hair growth effect by the following mechanism.

1. Promote hair growth by acting on peripheral blood vessels around follicles, causing local blood flow.

2. Locally inhibits male hormones on scalp tissue and normalizes physiological condition of hair follicles.

3. It acts directly on hair follicle epithelium, causing hair growth.

As mentioned above, the dichloromethane extract of Cheongho according to the present invention shows excellent hair growth effect with little side effects or toxicity, and thus is useful for promoting hair growth or preventing hair loss in alopecia, especially in humans and animals with androgenetic alopecia. Can be used.

Compositions containing the dichloromethane extract of Cheongho according to the present invention are conventional agents in the pharmaceutical field, such as tablets, capsules, troches, liquids, according to conventional pharmaceutical methods when used for hair growth promotion and hair loss prevention purposes. Oral preparations, ointments, creams, etc., in the form of oral preparations such as suspending agents, injectable solutions or suspensions, or ready-to-use dry powders which can be prepared by injection with distilled water for injection. It can be formulated into various formulations, such as topical formulations, such as a lotion, a liquid, and a spray.

Carriers that can be used for the formulation of the compositions of the invention are customary in the pharmaceutical art, for example in the case of oral preparations binders, suspending agents, disintegrating agents, excipients, solubilizers, dispersants, stabilizers, Pigments, flavoring agents, and the like. In the case of injections, preservatives, analgesics, solubilizers, stabilizers, and the like, and topical administration preparations include bases, excipients, lubricants, preservatives, and propellants. The pharmaceutical preparations thus prepared may be administered orally, parenterally, for example, by injection, such as intravenous, subcutaneous, intraperitoneal, or applied topically. The composition of the present invention is preferably formulated into topical formulations, such as ointments, lotions, sprays, and the like, and is directly applied to the hair loss site.

The composition of the present invention may also contain one or more additional herbal ingredients that may further enhance the hair growth effect of the dichloromethane extract of the present invention, as required. Herbal ingredients that can be included for this purpose may be used, for example, the raw, soybean yellow soybean, fragrant, sewage, baekbaekbyeon, lodging, tin, sulfur, and so on. When such additional herbal ingredients are included in the composition of the present invention, their content is preferably within 3% based on the total weight of the composition.

The application amount of the composition according to the present invention is appropriately selected depending on the type and severity of the alopecia, the patient's condition, etc., but in general, 3 to 60 mg of the chlorophyll dichloromethane extract or fraction thereof per kg body weight per day in adults (as dry matter) ), Preferably in an amount of 6 to 30 mg (as dry).

The present invention is explained in more detail by the following examples and experimental examples, but the present invention is not limited in any way by these.

Example 1 Preparation of Chlorinated Dichloromethane Extract

After drying 5 kg of clean water, the mixture was repeatedly heated three times for 6 hours with 20 L of methanol using a reflux condenser, and the extracts were combined and the solvent was removed under reduced pressure to obtain 254.5 g of methanol extract. The obtained methanol extract was suspended in 4 L of distilled water, and this suspension was extracted three times using an equal volume of hexane, and then the solvent was removed under reduced pressure to obtain 40.4 g of the hexane extract. After separating the hexane extract, the remaining aqueous layer was extracted three times with isotropic dichloromethane (CH ₂ Cl ₂ ) and the extracts were combined to remove the solvent under reduced pressure to give 38 g of the desired dichloromethane extract (as a dried product).

Example 2 Fractionation of Dichloromethane Extracts from Cheongho

29.8 g of dichloromethane extract of Chungho obtained in Example 1 was subjected to a gradient silica gel column chromatography using a mixture of chloroform (CHCl ₃ ) and methanol (MeOH) (20: 1 to 1: 1) as eluent to give chloroform. Eluent was evaporated from the six fractions in which methanol and methanol were eluted at a mixing ratio of 20: 1, 15: 1, 10: 1, 7: 1, 5: 1, 2: 1 to obtain each fraction as follows: 1: 3.07 g, Fraction 2: 4.85 g, Fraction 3: 2.06 g, Fraction 4: 4.38 g, Fraction 5: 8.11 g, Fraction 6: 3.4 g

Experimental Example 1 Search for Hair Growth Activity of Dichloromethane Extract of Cheongho

The dichloromethane extract of Cheongho obtained in Examples 1 and 2 and fractions 1 to 6, respectively, were charged with 2% Nicol (Nikkol HCO 60), 2% GMO (glyceryl monooleate) and Tween 80, followed by 30% Ethanol was added to prepare a test solution of 2 to 5% to search for hair growth activity according to the following hair growth test method.

As the animal for the hair growth test, a 23-28 g mouse (C57BL / 6) weighing 45-53 days of age was used, and as a test substance, the first test group (10 mice) received 3% test solution of dichloromethane extract, and the second 5% test solution of dichloromethane extract was applied to the test group (10 mice), and 2% test solution of each of fractions 1 to 6 was applied to the 3 to 7 test groups (10 mice per group), and to the control group (10 mice). A 5% test solution of Chungho's methanol extract was applied to the control group 2 (10 mice), and a 2% test solution of minoxidil, a known hair growth agent, was applied to the untreated group (10 mice). The specific experimental method is as follows.

The hair on the back of the mouse (C57BL / 6) weighing 45-53 days of age from 23 to 28 grams was depilated using a clipper (Oster # 40) and an electric razor. From the day after hair removal, each test substance was applied to the hair removal skin of each group of mice for 17 days in an amount of 2 ml per day, and simulated growth over time for 18 days from the day of initial treatment. The extent was searched by recording the hair growth score. The hair growth score was determined by the total hair loss state to 0, the hair follicles completely restored to 3, and subdivided into 0.5 units by measuring the length and area of hair follicles, depending on the degree of hair restoration and the restoration area.

In other words, as can be seen from the results shown in Table 1, when the minoxidil as a positive control group, the hair growth effect of the dichloromethane extract itself of Cheongho was slightly lower than that of minoxidil, but each fraction of the dichloromethane extract, particularly Fraction 4, was positive. The hair growth effect was about 3 times higher than that of the control group minoxidil. From these results, it was confirmed that the dichloromethane extract and its fractions of Cheongho according to the present invention are less toxic and have a hair growth effect several times greater than that of minoxidil.

Experimental Example 2: Acute Toxicity Test

In order to determine the acute toxicity of the dichloromethane extract of Cheongho according to the present invention was carried out the following experiment.

As the experimental animals, 5 male mice (average body weight 30g) 5 weeks old were used per group. As the test substance, the dichloromethane extract of Cheongho obtained in Examples 1 and 2 and each fraction thereof were orally administered to mice by suspending a dose of 1000 mg / kg of mouse in 1 ml of physiological saline, and each group survived 7 days after administration. The number of animals was observed. In the control group, only 1 ml of saline solution was orally administered. The measured results are shown in Table 2 below.

As can be seen from the results described in the table above, Chengho's dichloromethane extract and its respective fractions showed no toxicity to the experimental animals at the test maximum dose of 1000 mg / kg / day. Therefore, it is determined that the compound of the present invention is not toxic to humans or animals at the effective dose.

Experimental Example 3: Skin Stimulation Test

In order to determine the skin irritant toxicity of the dichloromethane extract of the cleaning according to the present invention was carried out the following experiment.

As test animals, 20 male mice (average body weight 30g), 5 weeks old, were used per group, and as test substance, the dichloromethane extract of Cheongho prepared in Example 1 was taken in an amount of 1000 mg per 1 kg of mouse. Add appropriate amounts of% Nicole HCO 60, 2% GMO (Glyceryl Monooleate) and Tween 80, prepare 5% test solution with 30% ethanol and apply it to the skin of mice for 30 days, and apply 30% ethanol only to the control in the same manner. The abnormality of the skin of the test animal was observed. The results are shown in Table 3 below.

As can be seen from the results shown in Table 3, the dichloromethane extract of Cheongho according to the present invention was observed for 30 days in the 1000 mg / kg application group, which is the maximum test dose, and the reddish shape judged to be merely incidental was extremely Although observed in some experimental animals, there was virtually no irritant toxicity to the skin of the test animals. Thus, the compounds of the present invention have been shown to have very low skin irritation and little irritation to human or animal skin.

[Configuration example]

In the following compositional examples, the active substance means that any of the dichloromethane extracts and the almost respective fractions of the chungho according to the present invention prepared in Examples 1 or 2 can be used. The following compositions may also contain an appropriate amount of auxiliary herbal ingredient in a range of 3% or less based on the total weight of the composition, if necessary.

[Composition Example 1: Ointment (1% and 3% ointment)]

The ointment was prepared according to the conventional method for preparing the ointment using the above components.

The ointment prepared by the above method is applied twice a day, 0.5 to 1 g at a time continuously for 3 to 6 months. The total daily weight should not exceed 2 g. After application to the affected area, it is preferable to massage gently to promote absorption.

[Composition Example 2: Roshon]

Using the above ingredients, the lotion was prepared according to the conventional method for preparing the lotion.

The lotion agent prepared in the same manner as described above is applied twice a day, 0.5 to 1 ml at a time continuously for 3 to 6 months. The total daily amount should not exceed 2 ml.

[Composition Example 3: Spray]

Using the above ingredients, a spray was prepared according to a conventional method for preparing a spray.

Spray the spray agent prepared by the above method 4 times or 8 times in one time (approximately 0.12ml injection), and when it is difficult to spray the chemical liquid because the remaining amount is small in the container, 21 to 42 times in the hair loss site with a brush Apply After application, it is preferable to massage gently to promote absorption.

Claims (13)

Hair restorer composition containing the dichloromethane extract of Cheongho or its fraction as an active ingredient. The hair restorer composition of Claim 1 whose fraction of the dichloromethane extract of Cheongho is any one of fractions 1-6 fractionated by the gradient elution of chloroform and methanol. The hair restorer composition according to claim 2, wherein the fractions 1 to 6 are the fractions eluted with the mixing ratio of chloroform and methanol at 20: 1, 15: 1, 10: 1, 7: 1, 5: 1 and 2: 1, respectively. The hair restorer composition of Claim 2 whose fraction of the dichloromethane extract of Chung-ho which is an active ingredient is fraction 1, 4, or 5. The hair restorer composition of Claim 1 containing the supplementary herbal component further selected from said raw, soybean rhubarb, fragrance | flavor, sewage, a white leaf, lodging, tint, and ripening sulfur. The hair restorer composition of claim 1 prepared in a pharmaceutical formulation using a pharmaceutically acceptable carrier. The hair restorer composition of claim 6 prepared as a topical formulation. The hair growth composition according to claim 7, wherein the topical formulation is an ointment, lotion or spray. Extracting the clarification with alcohol, suspending the alcoholic extract in water, extracting with hexane, and then extracting the larvae with dichloromethane to prepare the dichloromethane extract of clarification. The method of claim 9, wherein the alcohol is a lower alcohol having 1 to 4 carbon atoms. The method of claim 10, wherein the alcohol is methanol. 10. The method according to claim 9, wherein the dichloromethane extract obtained is subsequently fractionated by pre-dissolution using a mixed solvent of chloroform and methanol. 13. The process of claim 12, wherein the chloroform and methanol are gradient eluted in a ratio of 20: 1 to 1: 1.