KR20160028806A - Composition for preventing hair loss or promoting hair growth comprising raddeanoside derivative and its pharmaceutically acceptable salt - Google Patents

Abstract

Provided is a composition for preventing hair loss or promoting hair growth, comprising a raddeanoside derivative and a pharmaceutically acceptable salt thereof as an active ingredient. More specifically, provided is a composition for preventing hair loss or promoting hair growth, comprising a compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. According to the present invention, the compound and the salt can be useful in the composition for preventing hair loss or promoting hair growth.

Description

[0001] The present invention relates to a composition for preventing hair loss or promoting hair growth, which comprises a ladanolide derivative and a pharmaceutically acceptable salt thereof,

The present invention relates to a composition for preventing hair loss or promoting hair growth, which comprises a ladanoide derivative and a pharmaceutically acceptable salt thereof as an active ingredient.

Corticotropin releasing hormone (CRH) is one of the major components of the hypothalamic-pituitary-adrenal axis (HPA axis) and is activated by mental stress. CRH is a peptide composed of 41 amino acids and is a major contributor to the HPA axis and plays an important role in the hormone and neurotransmitter cascade in vertebrates in response to stress.

Serious psycho-emotional stress significantly affects hair growth and also causes the development of alopecia areata. CRH inhibits hair shaft elongation and has been reported to promote apoptosis of hair matrix keratinocytes in vitro in human hair follicles (Ito N, et al., Human hair follicles display a functional equivalent of the hypothalamic-pituitary-adrenal (HPA) axis and synthesize cortisol, FASEB J. 19 (2005) 1332-4). In addition, it has been reported that CRH receptor antagonists induce hair growth in CRH over-expressing hairless mice (Lixin Wang, et al., CRH receptor antagonist astressin-B reverses and prevents alopecia in CRH over-expressing mice, Plos One. 6 (2011) e16377-e16385). It has also been reported that cultured human hair follicles respond to CRH stimulation and display the HPA axis, including regulatory feedback systems (Natsuho Ito, et al., Human hair follicles display a functional equivalent of the hypothalamic-pituitary-adrenal (HPA) axis and synthesize cortisol, Faseb J. 19 (2005) 1332-4).

Thus, CRH plays an important role in human hair growth, and a substance capable of regulating the expression of cytokines regulated by CRH is expected to be useful as a substance for preventing hair loss or promoting hair growth.

The present inventors evaluated the effect of CRH on human hair dermal papilla cells, which play an important role in hair formation, and found that CRH inhibits hair growth-related cytokines, namely KGF, TGFβ-2, Wnt5a And Nexin, and found that the hair cycle in the follicular culture system promotes the transition from growth phase to retrograde phase. In order to identify a substance capable of blocking the action of CRH including a receptor antagonist of CRH, the present inventors have isolated various compounds from various natural substances and their extracts, which have been proven to be safe, In order to find out more. As a result, it has been found that the specific ladanoide derivative significantly inhibits the transition of the growing hair to the regressor hair by CRH.

Accordingly, it is an object of the present invention to provide a composition for preventing hair loss or promoting hair growth comprising the ladanoide derivative or a salt thereof as an active ingredient.

According to one aspect of the present invention, there is provided a composition for promoting hair loss prevention or hair growth, which comprises, as an active ingredient, a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:

≪ Formula 1 >

In the composition according to the present invention, said hair loss may be stressful hair loss.

It has been found by the present invention that a specific ladanoide derivative having the chemical structure of Chemical Formula 1 significantly inhibits growth-regressor transition of hair, and this is due to the antagonistic action to the CRH receptor which is a stress hormone. Accordingly, the compound of formula (I) or a pharmaceutically acceptable salt thereof may be usefully used in compositions for preventing hair loss (particularly for preventing stress hair loss) or for promoting hair growth.

The present invention provides a composition for promoting hair loss prevention or hair growth, comprising a compound of the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

≪ Formula 1 >

The compound of Chemical Formula 1 is a known substance, and its chemical name is oleanolic acid-3-O- alpha -L-ramnopyranosyl- (1 → 2) - [β-D-glucopyranosyl- (1 → 4)] - L-arabinopyranoside (1 → 2) - [β-D-glucopyranosyl- (1 → 4)] - α-L-arabinopyranoside , The CAS number is 106577-39-3, and is also referred to as " Raddeanoside R13 " or Hederacolchiside A1. The compounds of formula (I) are known in the art, for example, Wei Li et al., Oleanane-type triterpenoid saponins from the roots of Pulsatilla koreana and their apoptosis-inducing effects on HL-60 human promyelocytic leukemia cells, Arch. Pharm . Res . (2013) 36, pp. 768-774, and the like. The salt of the compound of Formula 1 includes a conventional pharmaceutically acceptable salt, and may be in the form of, for example, an alkali metal salt such as a sodium salt or an alkaline earth metal salt such as calcium, but is not limited thereto.

The pharmaceutical composition of the present invention can be applied to prevent hair loss, and the hair loss includes alopecia such as alopecia areata and diffuse alopecia according to the form of hair loss, and alopecia such as stressful hair loss, . The pharmaceutical composition of the present invention can be particularly preferably applied to stress alopecia during hair loss for various causes.

The compositions of the present invention may be formulated in the form of pharmaceutical compositions and / or cosmetic compositions. For example, the composition of the present invention may be in the form of a pharmaceutical composition for preventing hair loss or promoting hair growth, which comprises the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. In addition, the composition of the present invention may be in the form of a composition for promoting hair loss prevention or hair growth, which comprises the compound of Formula 1 or a pharmaceutically acceptable salt thereof.

In the above pharmaceutical composition, the composition may contain a pharmaceutically acceptable carrier. The composition may be formulated into a parenteral formulation such as a liquid preparation, a suspension, an emulsion, a rosophage, an ointment or a lyophilizing agent according to a conventional method. Preferably, it can be formulated into a transdermal dosage form such as a solution for external use, an emulsion, and an ointment. The pharmaceutically acceptable carrier includes an aqueous diluent or solvent such as phosphate buffered saline, purified water, sterilized water, etc., and may be a non-aqueous diluent such as propylene glycol, polyethylene glycol, olive oil, . Further, if necessary, it may contain a wetting agent, a fragrance, a preservative, and the like. The dosage of the compound of the formula (1) or a pharmaceutically acceptable salt thereof contained in the pharmaceutical composition varies depending on the condition and body weight of the patient, the degree of disease, the drug form, the administration route and the period of time, . For example, the compound of Formula 1 or a pharmaceutically acceptable salt thereof may be administered at a dose of 0.01 to 1000 mg / kg, preferably 0.1 to 100 mg / kg per day, It may be administered once or several times.

In the cosmetic composition of the present invention, the composition may be in the form of a cosmetic composition containing the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. The cosmetic composition of the present invention can be prepared in various forms according to a conventional method for producing a cosmetic using the compound of the formula (1) or a pharmaceutically acceptable salt thereof. For example, the cosmetic composition of the present invention may be manufactured in the form of a perfume product, a shampoo, a hair lotion, a hair cream, a hair gel, a scalp essence, a tonic or the like containing the compound of the formula 1 or a pharmaceutically acceptable salt thereof Which can be diluted with a conventional cleansing liquid, a converging liquid and a humectant. The cosmetic composition may also contain conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments, and flavorings commonly used in the cosmetic composition arts. In the cosmetic composition of the present invention, the compound of Formula 1 or its pharmaceutically acceptable salt may be used in an amount effective to achieve hair loss prevention or hair growth promoting effect, for example, 0.001 to 50% by weight , And may be contained in an amount of preferably about 1 to 20% by weight.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrating the present invention, and the scope of the present invention is not limited to these examples.

Example . Evaluation of the effect of the compound of formula (1) on growth-regressor transfer in human hair culture test

Normal human scalp tissue (Bundang CHA) was washed with 70% ethanol for 2 minutes, phosphate buffered saline (PBS) for 2 minutes, then again with 5X Anti-anti (Gibco) for 2 minutes, PBS for 2 minutes The hair follicles corresponding to the growing period were selected and cultured for one day in William's medium (including insuline, hydrocortisone, HEPES, and anti-anti) (hereinafter referred to as "medium" The hair follicles were maintained in growth phase.

Growing period hair follicles were selected and one hair follicle was cultured with the above medium in one well in a 24-well cell culture container, and 20 hair follicles were used per group. The test was divided into three groups: a control group, a positive control group and a test group. The control group was cultured in the medium for 3 days and 6 days. The positive control group was further cultured for 6 days in a medium containing CRH 10 ^-6 M for 3 days. The test group was a compound of formula 1 0.5 uM for 2 hours, and cultured for 3 days and 6 days after addition of 10 ^-6 M of CRH. Each group was cultured for 3 days and 6 days, and the number of hairs in growth and retrogression was observed through a stereomicroscope. The test results are shown in Table 1 below.

Inhibition of Growth-Regressive Transition by the Compound of Formula (1) Control group Positive control group
(CRH) Test group
(1) 3 days 15% 60% 10% 6 days 60% 95% 10%

As can be seen from the results in Table 1, in the control group, 15% and 60% of the hair was transferred from the growing stage to the retrograde stage after culturing for 3 days and 6 days, respectively. In the positive control group, 60% and 95% of the hair cells were transferred to the regressors after 3 and 6 days of culture, respectively. In the test group, only 10% and 10% . From the above results, it can be seen that CRH promotes transition of the growing hair to the regressor hair, and the compound of the formula (1) effectively blocks the influence of CRH and keeps growing hair well.

Claims (2)

A composition for promoting hair loss prevention or hair growth, comprising a compound of the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
≪ Formula 1 >

The composition of claim 1, wherein said hair loss is stress hair loss.