KR20210045125A - Composition for preventing hair loss or promoting hair growth comprising tocopheryl linoleate - Google Patents

Abstract

The present invention relates to a composition for preventing hair loss or promoting hair growth comprising tocopheryl linoleate, and according to the present invention, by including tocopheryl linoleate, an essential active component, it is possible to promote the expression of any one or more of keratinocyte growth factor, fibroblast growth factor, and vascular endothelial growth factor, thereby providing an excellent effect of preventing hair loss or promoting hair growth.

Description

Composition for preventing hair loss or promoting hair growth comprising tocopheryl linoleate}

The present invention relates to a composition for preventing hair loss or promoting hair growth comprising tocopheryl linoleate, and more specifically, by including tocopheryl linoleate, which is an essential active ingredient, keratinocyte growth factor, fibroblast growth factor, and It relates to a composition exhibiting excellent hair loss prevention or hair growth promoting effect by promoting the expression of any one or more of the vascular endothelial growth factors.

Human hair grows in hair follicles and hair follicles derived from epithelial cells. There are Dermal Papilla Cells that dominate the hair above the hair follicle, and there are Hair Mother Cells that make hair just above these dermal papilla cells, producing new hairs while continuing to divide and pushing them up.

Each hair of the human body works and progresses in an independent cycle, and as a specific cycle, it grows and falls through an anagen, a catagen, and a telogen. In general, the hair loss phenomenon can be classified into a general telogen hair loss phenomenon in which the hair falls out of the telogen state and a growth phase hair loss phenomenon, which is an abnormal hair loss phenomenon. In particular, the latter is referred to as alopecia.

The cause of hair loss has not yet been clearly identified, but the genetic cause is largely occupied, and it is known to be caused by poor blood circulation in the scalp, excessive action of male hormones, excess sebum secretion, aging, and stress. According to these various causes, various hair loss prevention and hair growth agents are being developed, and specifically, vasodilators such as capronium chloride, minoxidil and extracts of various plants to circulate sufficient blood to the scalp, and the action of male hormones to eliminate hair There are female hormones such as estrogen, estrazol, and progesterone, or male hormone activation inhibitors such as pentadecanoic acid and finasteride.

However, most of the hair loss agents show some effect in preventing hair loss, but the effect related to hair growth was not very satisfactory, and Korean Patent Publication No. 10-1467568 essentially contains minoxidil, an emollient, and a skin retention agent. Although the hair growth effect of the composition is described, there is a problem in that the prior art including the patent does not predict whether the above effect is exhibited due to which active ingredient, and still does not show a satisfactory effect.

Accordingly, there is a need to develop a composition that contains essential active ingredients and exhibits excellent hair loss prevention or hair growth promoting effect.

Korean Registered Patent Publication No. 10-1467568 (announced date 2014.12.02)

The present invention was conceived to solve the above problems, and the object of the present invention is to include tocopheryl linoleate, which is an essential active ingredient, so that any of keratinocyte growth factor, fibroblast growth factor, and vascular endothelial growth factor It is to provide a composition exhibiting an excellent hair loss prevention or hair growth promoting effect by promoting the expression of one or more.

In order to achieve the object of the present invention described above, the present invention provides a composition for preventing hair loss or promoting hair growth, comprising tocopheryl linoleate as an active ingredient.

According to the present invention, by including the essential active ingredient tocopheryl linoleate, by promoting the expression of any one or more of keratinocyte growth factor, fibroblast growth factor, and vascular endothelial growth factor, excellent hair loss prevention or hair growth promoting effect is achieved. to provide.

1 is a view evaluating the effect on the growth of human dermal papilla cells according to an embodiment of the present invention.
2 is a view evaluating the effect on the hair follicle length growth according to an embodiment of the present invention.
3 is a view confirming the increase in expression of keratinocyte growth factor according to an embodiment of the present invention.
Figure 4 is a view confirming the increase in the expression of vascular endothelial growth factor according to an embodiment of the present invention.

Hereinafter, the present invention will be described in detail with reference to examples and drawings.

The present invention provides a composition for preventing hair loss or promoting hair growth, comprising tocopheryl linoleate as an active ingredient.

The composition of the present invention may be a pharmaceutical composition or a cosmetic composition.

In addition, the present invention provides a use of the active ingredient contained in the composition of the present invention to prevent hair loss or promote hair growth.

In addition, the present invention provides a method for preventing hair loss or promoting hair growth, comprising administering to a mammal, including or not including humans, an active ingredient contained in the composition of the present invention.

In addition, the present invention provides the use of tocopheryl linoleate to produce a pharmaceutical formulation having a prophylactic or therapeutic effect of alopecia.

In addition, the present invention provides a pharmaceutical composition for preventing or treating alopecia, for preventing or promoting hair loss, comprising tocopheryl linoleate as an active ingredient.

The alopecia (or alopecia) is alopecia areata, hereditary androgen alopecia, telogen alopecia, traumatic alopecia, bald wall alopecia, pressure alopecia, growth stage alopecia, non-rigid alopecia, syphilitic alopecia, seborrhea, depending on the form, symptom, or cause It may be one or more selected from alopecia, symptomatic alopecia, non-scarring alopecia, scarring alopecia, and congenital alopecia.

Vitamin E is a type of fat-soluble vitamin, and refers to a compound containing both Tocopherol (TCP) and Tocotrienol, not a single component. Vitamin E is known as an antioxidant and is also known to improve blood circulation. On the other hand, Tocopheryl linoleate included as an active ingredient in the composition of the present invention is also known as an antioxidant as an ester of the tocopherol and linoleate. However, there is no study on the effect of improving blood circulation when using tocopheryl linoleate alone, not as a vitamin E compound, and the effect of preventing hair loss or promoting hair growth through this.

The present inventors added tocopheryl linoleate as the sole active ingredient, Keratinocyte Growth Factor (KGF), Fibroblast Growth Factor (FGF), and Vascular Endothelial Growth Factor (VEGF). The present invention was completed by discovering that it can be used as a composition for preventing hair loss or promoting hair growth through the effect of promoting the expression of any one or more of them.

The keratinocyte growth factor, fibroblast growth factor, and vascular endothelial growth factor are all factors related to the growth of dermal papilla cells, and the increase in expression of these growth factors is important for maintaining the growth of dermal papilla cells.

Keratinocyte growth factor is one of the fibroblast growth factors and is also named fibroblast growth factor-7 (FGF-7), and fibroblast growth factor promotes angiogenesis of skin cells to strengthen skin nutrition and elasticity, thereby enhancing hair and skin cells. Promotes the growth of and activates dermal papilla cells. In addition, it increases the synthesis of hyaluronic acid in keratinocytes, promotes the biosynthesis of collagen and elastin in the dermal layer, regulates the hair cycle, maintains the hair condition, and prevents hair loss.

Vascular endothelial growth factor promotes cell division and migration by increasing the plasma protein permeation of capillaries, promotes the formation of new blood vessels, is involved in blood vessel maintenance, and increases the size and distribution of capillaries in hair follicles, thereby improving the thickness and distribution of hair. Increases and promotes hair growth.

As described above, the composition of the present invention may be a pharmaceutical composition, and the pharmaceutical composition may include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers are lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like. In addition, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants are included.

The pharmaceutical composition may be formulated in the form of oral preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, parenteral preparations, injection preparations, and topical administration preparations according to a conventional method.

Among the oral formulations, solid formulations for oral use include tablets, pills, powders, granules, capsules, and the like, and such solid formulations include at least one excipient, such as starch, calcium carbonate, and sucrose. Alternatively, lactose, gelatin, and the like may be included, and lubricants such as magnesium stearate and talc may be included. Among the oral formulations, liquid formulations for oral use include suspensions, liquid solutions, emulsions, syrups, and the like, and may include diluents such as water and liquid paraffin, wetting agents, sweetening agents, fragrances, preservatives, and the like. Parenteral preparations include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, and freeze-dried preparations. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, ethylol And injectable esters such as rate.

In addition, the pharmaceutical composition may be administered to mammals, including or not including humans, by various routes, for example, by oral, intravenous, intramuscular, or subcutaneous injection.

The composition of the present invention can be administered topically. Topical administration refers to the direct application of the active ingredient or composition to the skin and/or hair, and includes a composition for external application for skin. The topical composition of the present invention may be in the form of a solution, lotion, ointment, cream, ointment, liposome, spray, gel, foam, roller stick, or any other formulation routinely used in dermatology. have.

In the composition, use, and method of the present invention, the dosage of the active ingredient varies depending on the condition and weight of the patient, the severity of the disease, the drug form, the route and duration of administration, but may be appropriately selected depending on the case. The administration may be administered once or several times a day.

As described above, the composition of the present invention may be a cosmetic composition, and the cosmetic composition may be prepared in various forms according to a conventional cosmetic preparation method including the tocopheryl linoleate as an active ingredient. Specifically, the cosmetic composition contains the tocopheryl linoleate as an active ingredient, hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder, gel, hair pack , Hair treatment, eyebrow hair growth agent, eyelash hair growth agent, eyelash nutritional supplement or general ointment may be prepared in a formulation such as.

In addition, the cosmetic composition may include conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments, and fragrances commonly used in the field of cosmetic compositions, and may include a carrier acceptable for cosmetics.

Acceptable carriers for cosmetics include, but are limited to, purified water, oils, waxes, fatty acids, fatty alcohols, fatty acid esters, surfactants, desiccants, thickeners, viscosity stabilizers, chelating agents, buffers, preservatives, lower alcohols, etc. It is not. If necessary, moisturizers, anti-inflammatory agents, antibacterial agents, antifungal agents, vitamins, sunscreen agents, antibiotics, perfumes, and dyes may be included.

{Example}

Hereinafter, the present invention will be described in detail by examples. However, the following examples are only examples to aid in an overall understanding of the present invention, and the contents of the present invention are not limited to the following examples.

<Example 1> Extraction of tocopheryl linoleate as the sole active ingredient

Tocopheryl linoleate for use in the test examples was subjected to esterification by loading free linoleic acid into a reactor, and then adding Tocopherol (TCP) to the reactor, followed by purification and filtration. Proceeded to. Next, after packing, labeling, and sampling were performed, Final Quality Control (FQC) was completed through issuance of a Certificate of Analysis (CoA).

<Test Example 1> Evaluation of the effect of tocopheryl linoleate on the growth of human dermal papilla cells

The effect of the tocopheryl linoleate according to the present invention on the growth of human dermal papilla cells was evaluated using human dermal papilla cells (Dankook University Dermatology Department).

Specifically, in DMEM (Dulbecco's Modified Eagle Media, HyClone GE Healthcare) medium containing 10% FBS (Fetal Bovine Serum, Cambrex), 1% antibiotics, and 0.1% fungizone, human dermal papilla cells Was inoculated into a 96-well plate so as to be 5 × 10 ³ cells/ml, and cultured _{for 72 hours at 37° C. and under 5% CO 2 moist conditions.} After 24 hours, it was washed twice with DPBS (Dulbecco's Phosphate Buffer Saline, Sigma Aldrich, USA), and then replaced with a medium from which FBS was removed.

Tocopheryl linoleate extracted in Example 1 was treated in the culture solution at a concentration of 5 and 10 ppm, respectively, and cultured for 72 hours, and then CCK-8 (Cell Counting Kit-8, CK04-11, Dojindo Molecular Technologies, Inc. , MA, USA) to confirm the cell viability. After incubation with CCK-8 for 2 hours, absorbance at 450 nm was measured using a microplate reader.

The same conditions as above, but the culture medium treated with 5% FBS instead of tocopheryl linoleate was used as a negative control, and the culture medium treated with 5 and 10 ppm vitamin E, respectively, instead of tocopheryl linoleate, was used as a positive control. I did. The test was repeated three times, and the obtained results are shown in FIG. 1.

As can be seen in Figure 1, compared to the sample untreated group (Control), the positive control group 5, 10 ppm vitamin E treatment group improved the growth of human dermal papilla cells by about 105 to 109% or more, 5, 10 ppm The tocopheryl linoleate-treated group of was improved the growth of human dermal papilla cells by about 127-130% or more.

From the results of FIG. 1, compared to vitamin E as a compound, tocopheryl linoleate, which is a single component included as an active ingredient in the composition of the present invention, exhibits more excellent dermal papilla cell growth promoting activity, and has excellent hair loss prevention or hair growth promoting effect. You can see that there is.

<Test Example 2> Evaluation of the effect of tocopheryl linoleate on hair follicle length growth

The effect of the tocopheryl linoleate according to the present invention on the growth of hair follicles was evaluated in an organ culture using a hair follicle provided by Dankook University's Dermatology Department.

Specifically, hair follicles were isolated from the human occipital scalp tissue provided by the Department of Dermatology at Dankook University using tweezers under microscope observation (hair follicle sample information: 57 years old, female).

For the hair follicles, 2mM L-glutamine, 10 ng/ml hydrocortisone, 1% antibiotics, and 0.1% fungizone were added to a medium based on Williams E culture medium. And cultured. After dispensing 500 µl of the medium into a 24-well plate, 6 samples (*2) per well were cultured.

The culture medium was treated with the tocopheryl linoleate extracted in Example 1 at a concentration of 5 ppm, and a culture medium treated with 5 ppm vitamin E instead of tocopheryl linoleate was used as a positive control. Twenty follicular units were used for each experimental group, and the medium was exchanged at intervals of 2 to 3 days during cultivation. After cutting according to the red line shown in Fig. 2, the hair follicle growth length was measured. A photograph of hair follicle length growth taken on day 7 taken using a stereomicroscope was taken as a representative image, and is shown in FIG. 2.

From the results of FIG. 2, it can be seen that compared to vitamin E as a compound, tocopheryl linoleate, which is a single component included as an active ingredient in the composition of the present invention, exhibits excellent hair follicle length growth promoting efficacy. Therefore, it was confirmed that tocopheryl linoleate has an excellent effect of promoting hair follicle length growth, preventing hair loss, promoting hair growth, and further promoting hair health.

<Test Example 3> Confirmation of increased expression of keratinocyte growth factor

1. Cell culture

In DMEM (Dulbecco's Modified Eagle Media, HyClone GE Healthcare) medium containing 10% FBS (Fetal Bovine Serum, Cambrex) and 1% antibiotics, 0.3 × Human Dermal Papilla Cells (Dankook University Dermatology Clinic) It was inoculated into a 6-well plate so as to be ^{10 5} cells/ml, and cultured _{for 24 hours under conditions of 37° C. and 5% CO 2 moistening.}

Tocopheryl linoleate extracted in Example 1 was treated with the culture solution at a concentration of 20 ppm and cultured for 24 hours.

2. Confirmation of relative growth factor expression level using real-time qPCR (RT-qPCR)

Expression of keratinocyte growth factor (fibroblast growth factor-7) was confirmed by testing in human dermal papilla cells (Control) without tocopheryl linoleate, and in human dermal papilla cells after treatment with tocopheryl linoleate. . GAPDH was used as a control gene.

MRNA was extracted from ^{10 5} to 10 ⁶ cells using TRIzol reagent (Invitroge). Using the extracted mRNA as a template, cDNA was synthesized by reverse transcription chain polymerization using Superscript (Invitrogen, Superscript III) reverse transcriptase. Thereafter, the cDNA sample was quantified by RT-qPCR.

The relative expression level of the target gene was leveled by the expression level of GAPDH, and then expressed as a relative %. All real-time analysis was performed using Applide Biosystems 7500 (Applied Biosystems).

3. Confirmation result of increase in expression of growth factor

As a result of examining the expression of keratinocyte growth factor, as shown in FIG. 3, when tocopheryl linoleate was treated as compared to the tocopheryl linoleate-free group, the expression of keratinocyte growth factor affecting the proliferation of hair follicle dermal papilla cells was observed. It was confirmed that it increased significantly.

<Test Example 4> Confirmation of increased expression of vascular endothelial growth factor

The effect of tocopheryl linoleate according to the present invention on the expression of Vascular Endothelial Growth Factor (VEGF) was evaluated using Human Dermal Papilla Cells (Dankook University Department of Dermatology).

Specifically, in DMEM (Dulbecco's Modified Eagle Media, HyClone GE Healthcare) medium containing 10% FBS (Fetal Bovine Serum, Cambrex) and 1% antibiotics, human dermal papilla cells are 3 × 10 ⁵ cells/ml. Inoculated into a 96-well plate, and cultured for 24 hours at 37° C. and 5% CO ₂ moist conditions.

The tocopheryl linoleate extracted in Example 1 was treated at a concentration of 20 ppm, and the expression level of the growth factor was confirmed after 48 hours using RT-qPCR. The experimental method was performed in the same manner as in Test Example 3, and the experimental results are shown in FIG.

From the results of FIG. 4, it was confirmed that the vascular endothelial growth factor was expressed at a level when tocopheryl linoleate was treated at a concentration of 20 ppm compared to the untreated control group (Control).

These results show that the tocopheryl linoleate of the present invention has the effect of expressing vascular endothelial cell growth factor, thereby increasing the plasma protein permeation of capillaries, promoting cell division and migration, promoting new blood vessel generation, and maintaining blood vessels. It means that it can increase the thickness and distribution of hair by increasing the size and distribution of capillaries in the hair follicle and promote hair growth.

Although the present invention has been described in connection with the above-mentioned preferred embodiments, it is possible to make various modifications or variations without departing from the spirit and scope of the invention. Accordingly, the appended claims will include such modifications or variations as long as they fall within the gist of the present invention.

Claims (9)

A pharmaceutical composition for preventing hair loss or promoting hair growth, comprising tocopheryl linoleate as an active ingredient. The method of claim 1,
The composition is for the prevention or treatment of alopecia, a pharmaceutical composition for preventing hair loss or promoting hair growth. The method of claim 2,
The alopecia is alopecia areata, hereditary androgen alopecia, telogen alopecia, traumatic alopecia, bald wall alopecia, pressure alopecia, growth stage alopecia, alopecia piriformis, syphilis alopecia, seborrheic alopecia, symptomatic alopecia, non-scarring alopecia, scarring alopecia , And at least one selected from congenital alopecia, a pharmaceutical composition for preventing hair loss or promoting hair growth. The method of claim 1,
The tocopheryl linoleate is a pharmaceutical composition for preventing hair loss or promoting hair growth, which promotes the expression of any one or more of keratinocyte growth factor, fibroblast growth factor, and vascular endothelial growth factor. The method according to any one of claims 1 to 4,
The composition is a composition for external application for skin, a pharmaceutical composition for preventing hair loss or promoting hair growth. Cosmetic composition for preventing hair loss or promoting hair growth, comprising tocopheryl linoleate as an active ingredient. The method of claim 6,
The tocopheryl linoleate is a cosmetic composition for preventing hair loss or promoting hair growth, which promotes the expression of any one or more of keratinocyte growth factor, fibroblast growth factor, and vascular endothelial growth factor. The method according to claim 6 or 7,
The composition is a composition for external application for skin, a cosmetic composition for preventing hair loss or promoting hair growth. The method of claim 8,
The formulation of the composition is hair tonic, hair cream, hair lotion, hair shampoo, hair conditioner, hair conditioner, hair spray, hair aerosol, pomade, powder, gel, hair pack, hair treatment, eyebrow hair growth agent, eyelash hair growth agent, eyelash nutrient, And selected from the group consisting of a general ointment, a cosmetic composition for preventing hair loss or promoting hair growth.

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