JP2009263262A - Igf-1 production promotor and hgf production promotor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an IGF-1 production promotor and an HGF production promotor having excellent actions and exhibiting high safety. <P>SOLUTION: The IGF-1 production promotor and the HGF production promotor contain swertiamarin as an active ingredient. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an IGF-1 production promoter and an HGF production promoter.

  Hair growth repeats growth and loss according to a periodic hair cycle (hair cycle) consisting of a growth period, a regression period, and a rest period. Of these hair cycles, the stage at which new hair follicles are formed from the rest period to the growth stage is considered to be most important for hair growth. And it is thought that hair papilla cells play an important role in the proliferation and differentiation of hair follicle epithelial cells at this stage. The dermal papilla cell is a cell located inside the hair follicle epithelial cell composed of outer root sheath cells and matrix cells in the vicinity of the hair root, and located in the root portion of the hair root wrapped in the basement membrane. It plays an important role in differentiation into hair, such as working on epithelial cells to promote their proliferation (see, for example, Non-Patent Document 1).

  Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a molecular weight of about 7,500 that has a structure and action very similar to insulin. IGF-1 is known to actively maintain cells in a healthy state, for example, by promoting cell differentiation and helping cell proliferation (see, for example, Non-Patent Documents 2 and 3) and preventing the progression of aging. (See, for example, Non-Patent Document 4).

  Further, it is shown that IGF-1 is expressed in the hair follicle dermal papilla cells (see, for example, Non-Patent Document 5), and it is clear that IGF-1 has a hair-growth effect through activation of hair roots. Became. Currently, hair growth agents containing IGF-1 as an active ingredient are already known (see, for example, Patent Document 1). However, since IGF-1 is an animal-derived component and has a large molecular weight, there are problems such as difficulty in percutaneous absorption by external application. Moreover, although the plant-derived extract which shows an IGF-1 production promotion effect has been discovered, the plant-derived substance which has the more excellent IGF-1 production promotion effect is calculated | required.

  Hepatocyte growth factor (HGF) was discovered in plasma of patients with fulminant hepatitis as a factor that promotes proliferation of hepatocytes. HGF is known to promote proliferation of not only the liver but also epithelial cells, endothelial cells, hematopoietic cells and the like derived from various organs. It has been reported that the blood concentration of HGF increases in various diseases such as liver disease, pneumonia, leukemia, cancer, myocardial infarction and the like. In addition, HGF has been recognized to suppress organ damage and fibrosis and promote regeneration. Patent Document 2 discloses a technique of using HGF as an active ingredient of a pulmonary fibrosis preventive agent.

In addition, HGF was shown to be expressed in the hair follicle cells of the hair follicle (see, for example, Non-Patent Document 6), and it was revealed that HGF has a hair-growth effect through hair root activation.
Until now, rice etc. are known as a plant extract which has an action of promoting HGF production (for example, refer to Patent Document 3).

As described above, the demand for each agent having IGF-1 production promoting action and HGF promoting action is extremely high.
However, conventionally, there has been a problem that a specific active ingredient having the above action has not been proposed yet. Moreover, the thing for which the specific active ingredient was proposed also had the problem that the said effect | action and effect were not enough even if it was not derived from a plant and was derived from a plant. In addition, since it is comparatively high in plant origin, there exists an advantage that it is easy to ingest or apply | coat daily.

On the other hand, the assembly is a plant of the Gentian family, the scientific name is “ Swertia japonica ”, and the herbal medicine name is “ Otsuka ”. The assembly contains swell thiamarin, which is a bitter glycoside, and is used as a bitter taste stomach medicine for gastrointestinal weakness, diarrhea, abdominal pain, and the like (for example, see Non-Patent Document 7).
Patent Document 4 discloses a technique in which the assembly extract is used by adding it to a hair-growth cosmetic. Patent Document 5 discloses a technique in which swell thiamarin contained in an assembly is blended with isoflavones and used as a dermatological agent.

  However, Patent Document 4 does not describe what kind of action Swellthiamarin exerts a hair-growth effect. Further, Patent Document 5 describes the effect exhibited by the mixture containing swell thiamarin, but does not describe what kind of action the swell thiamarin alone has.

  Therefore, to date, it is a natural product that is easy to obtain, inexpensive, and highly safe, and does not adversely affect the quality of the added object in terms of taste, smell, feeling of use, etc. IGF-1 production promoters and HGF production promoters that can be widely used as external preparations for skin, cosmetics, foods and drinks, pharmaceuticals and research reagents have not been provided yet, and there is a strong demand for their prompt provision This is the current situation.

Japanese Patent Publication No. 4-60567 JP 2006-131649 A JP 2004-99503 A JP 2006-124376 A JP 2007-246470 A “Trends Genet”, 1992, Vol. 8, p. 56-61 J. et al. Biol. Chem. 271, 28853-28860 (1996) Dermatology, 20, 325-329 (2002) Am. J. et al. Med. 115, 501-502 (2003) J. et al. Invest. Dermatol. 99, 343-349 (1992) Anti-aging series (1), actual hair, hair loss and hair growth, NTS, p. 1-18, 2005 “New Revised Primary Color Makino Wakuhan Encyclopedia”, Hokuryukan, p. 413

An object of the present invention is to solve the conventional problems and achieve the following objects.
That is, the first object of the present invention is to provide a natural IGF-1 production promoter that has an excellent IGF-1 production promoting action, has high safety, and is readily available as a raw material.
A second object of the present invention is to provide a natural HGF production promoter that has an excellent HGF production promoting action, has high safety, and is readily available as a raw material.

  In order to solve the above-mentioned problems, the present inventors have made extensive studies and as a result, obtained the following findings. That is, it was found that swell thiamarin has an excellent IGF-1 production promoting action and HGF production promoting action.

The present invention is based on the above findings by the present inventors, and means for solving the above problems are as follows. That is,
<1> An IGF-1 production promoter comprising swell thiamarin as an active ingredient.
<2> An HGF production promoter comprising swell thiamarin as an active ingredient.

According to the IGF-1 production promoter of the present invention, natural IGF- which can solve various problems in the past, has an excellent IGF-1 production promotion action, is highly safe, and is readily available as a raw material. 1 production promoter can be provided.
According to the HGF production promoter of the present invention, a natural HGF production promoter that can solve various problems in the past, has an excellent HGF production promoting action, is highly safe, and is readily available as a raw material. can do.

(IGF-1 production promoter and HGF production promoter)
The IGF-1 production promoter and HGF production promoter of the present invention contain swell thiamarin as an active ingredient, and further contain other ingredients as necessary.

<Swellcia Marine>
The swell thiamarin is a compound having a molecular formula of C ₁₆ H ₂₂ O ₁₀ and a molecular weight of 374.342, and is represented by the following structural formula (1).

  The swell thiamarin can be produced by isolation and purification from a plant extract containing the swell thiamarin, or can be produced by synthesis. In addition, when manufacturing by a synthesis | combination, the synthesis | combining method is not specifically limited, It can synthesize | combine by a well-known method.

  The plant extract containing the swell thiamarin can be obtained by an extraction method generally used for plant extraction. As a plant containing the said swell thiamarin, the plant of Gentianaceae is mentioned, for example.

  The swell thiamarin itself may be included as an active ingredient of the IGF-production promoter and the HGF production promoter, and a pharmacologically acceptable salt thereof may be included. Moreover, the hydrate or solvate of the said swell thiamarin or its pharmacologically acceptable salt may be contained. The swell thiamarin may be modified or substituted as long as the IGF-1 production promoting action and the HGF production promoting action are not impaired.

  The pharmacologically acceptable salt is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include hydrochloride, sulfate, hydrobromide, nitrate, hydrosulfate, and phosphoric acid. Salt, acetate, lactate, succinate, citrate, maleate, hydroxymaleate, tartrate, fumarate, methanesulfonate, p-toluenesulfonate, camphorsulfonate, sulfamine , Mandelate, propionate, glycolate, stearate, malate, ascorbate, pamonate, phenylacetate, glutamate, benzoate, salicylate, sulfanilate, 2 -Acetoxybenzoate, ethanedisulfonate, oxalate, isethionate, formate, trifluoroacetate, ethyl succinate, lactobionate, glucone Salt, glucoheptonate, 2-hydroxyethanesulfonate, benzenesulfonate, paratoluenesulfonate, lauryl sulfate, aspartate, adipate, hydroiodide, nicotinate, oxalate , Picrate, thiocyanate, undecanoate and the like.

The IGF-1 production promoter and HGF production promoter of the present invention may be the swell thiamarin itself, or may be composed only of a plant extract containing the swell thiamarin, or the swell thiamarin. Alternatively, a plant extract containing the swell thiamarin may be formulated.
There is no restriction | limiting in particular as content of the said swell thiamarin in the said IGF-1 production promoter and the said HGF production promoter, According to the objective, it can select suitably.

<Other ingredients>
The swell thiamarin is formulated into an arbitrary dosage form such as powder, granule, tablet, liquid, etc. according to a conventional method using a pharmaceutically acceptable carrier such as dextrin and cyclodextrin and any other auxiliary agent. In addition to being used in other compositions (for example, skin cosmetics), it can be used as an ointment, a liquid for external use, a patch, and the like. In this case, as an auxiliary agent, for example, an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring agent and the like can be used.

  In addition, the IGF-1 production promoter and the HGF production promoter of the present invention include other natural extracts having an IGF-1 production promoting action and an HGF promoting action as necessary, as well as plants containing the swell thiamarin. It can be used together with the extract as an active ingredient.

The IGF-1 production promoter exerts an IGF-1 production promoting action by the action of swell thiamarin contained as an active ingredient.
The HGF production promoter exerts an HGF production promoting action by the action of swell thiamarin contained as an active ingredient.

  According to the IGF-1 production promoter of the present invention, through excellent IGF-1 production promotion action, for example, differentiation / proliferation / growth of cells in general, suppression of aging progression, hypoglycemia, regulation of reproductive function, sulfate to cartilage Ion uptake can be promoted, and alopecia, skin aging, diabetes, hypopituitarism, pituitary dwarfism, etc. can be improved or treated. However, the IGF-1 production-promoting agent of the present invention can be used for all uses that are meaningful for exerting an IGF-1 production-promoting action in addition to these uses.

  According to the HGF production-promoting agent of the present invention, through excellent HGF production-promoting action, for example, the proliferation of epithelial cells, endothelial cells, hematopoietic cells and the like derived from each organ is promoted, and organ damage and fibrosis are suppressed. , Regeneration can be promoted, and alopecia, fibrosis, liver disease, obstructive arteriosclerosis, etc. can be improved or treated. However, the HGF production-promoting agent of the present invention can be used for all uses that are meaningful for exerting an HGF production-promoting action in addition to these uses.

The IGF-1 production promoter and the HGF production promoter of the present invention have an excellent action and are excellent in usability and safety when applied to the skin, and are therefore suitable for blending into an external preparation for skin. is there. Especially as said skin external preparation, a hair restorer and hair cosmetics are preferable. Examples of the hair cosmetics include hair tonics, hair liquids, shampoos, pomades, and rinses.
Moreover, since it has been confirmed that the IGF-1 production promoter and the HGF production promoter of the present invention have an excellent action and are not digested in the digestive tract, a cosmetic food or drink or pharmaceutical It is suitable for blending.
In addition, since the IGF-1 production promoter and the HGF production promoter of the present invention have an excellent action, they can be used for studying the functions of IGF-1 and HGF, and researching diseases related to IGF-1 and HGF. It can be suitably used as a reagent.

  The IGF-1 production promoter and HGF production promoter of the present invention are preferably applied to humans, but may be applied to animals other than humans as long as their respective effects are exhibited. You can also

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

<IGF-1 and HGF production promotion test>
Using Swellthiamarin (Wako Pure Chemical Industries, Ltd.) as a sample, the production promoting action of IGF-1 and HGF was tested by the following test method.

First, normal human hair hair papilla cells (TOYOBO, CA60205) were cultured using a hair papilla cell growth medium (TOYOBO, TPGM-250), and then cells were collected by trypsin treatment. The collected cells were diluted with 10% FBS-containing DMEM medium to a concentration of 2 × 10 ⁵ cells / mL, then seeded in 5 mL portions in a 60 mm diameter petri dish, and cultured overnight. The next day, after changing to serum-free DMEM medium with sample added and culturing for 4 hours, total RNA was extracted with ISOGEN (Nippon Gene, Cat. No. 311-02501), and the amount of each RNA was stored in a spectrophotometer. And total RNA was prepared to 200 μg / mL.
Using this total RNA as a template, the expression levels of IGF-1, HGF and GAPDH, which is an internal standard, were measured. Detection was performed by real-time 2 Step RT-PCR reaction using TaKaRa SYBR PrimeScript ^™ RT-PCT Kit (Perfect Real Time) (code No. RR063A) using a real-time PCR apparatus Smart Cycler (Cepheid). After correcting for the expression level of IGF-1 and HGF mRNA with the value of the expression level of GAPDH in the same sample, the mRNA expression promotion rate (%) of IGF-1 and HGF was calculated by the following formula (1). . The results are shown in Table 1.
IGF-1 and HGF mRNA expression promotion rate (%) = B / A × 100 (1)
[However, in the formula (1),
A: Correction value when no sample is added,
B: represents a correction value at the time of sample addition. ]

  From the result of Table 1, it was recognized that swell thiamarin has a high IGF-1 production promotion effect and a HGF production promotion effect.

  Since the IGF-1 production promoter and the HGF production promoter of the present invention have an excellent IGF-1 production promotion action and HGF production promotion action, they can be blended into skin external products such as hair restorers and hair cosmetics. It can be used in cosmetic cosmetics and pharmaceuticals, or as a research reagent.

Claims (2)

  An IGF-1 production promoter comprising swell thiamarin as an active ingredient.   An HGF production promoter comprising swell thiamarin as an active ingredient.