KR20120058866A - Cosmetic composition biomimetically designed from extracellular matrix for promoting the stemness of adipose-derived stem cell - Google Patents

Abstract

PURPOSE: A composition containing tripeptides, low molecular hyaluronic acid, mineral, and vitamin is provided to enhance stemness of adipose-derived stem cells. CONSTITUTION: A composition for enhancing stemness of adipose-derived stem cells contains 0.001-3 wt% of tripeptide of glycine-proline-hydroxyproline(Gly-Pro-Hyp), 0.01-50 wt% of low molecular hyaluronic acid, 0.001-3 wt% of mineral, and 0.001-3 wt% of vitamin as active ingredients. The composition is designed from ECM(extracellular matrix). The stem cell is human adipose derived stem cells(hADSCs).

Description

COSMETIC COMPOSITION BIOMIMETICALLY DESIGNED FROM EXTRACELLULAR MATRIX FOR PROMOTING THE STEMNESS OF ADIPOSE-DERIVED STEM CELL}

The present invention relates to a composition for enhancing stem cell function to maintain and enhance the characteristics of stem cells by simulating extracellular matrix.

The skin consists of the epidermis, the dermis and the subcutaneous tissue, and the dermal tissue has an extracellular matrix (ECM) containing three-dimensional scaffolds, aqueous solutions of inorganic salts, nutrients, and waste products and macromolecules. . It forms a network in the space surrounding the cells to maintain and support the morphology of the tissue, and plays an important role in regulating cell signaling and cell growth and differentiation.

Most of the ECM components simulated so far are derived from animals. However, animal-derived components are not used in cosmetics due to the safety issues such as pathogen infection.

Collagen, a major component of 70-80% of the total ECM, is one of the longest fibrous structural proteins that is known to be closely related to skin aging, such as decreased elasticity and wrinkle formation, as it regulates skin strength and elasticity. However, since most of the collagen currently being used is an animal-derived raw material and a polymer having a molecular weight of about 300,000 Da, absorption into collagen itself is limited in delivery through the skin.

Hyaluronic acid, one of the ECM components, binds cells of dermal tissues in the skin to each other and delivers nutrients, allowing the skin to maintain an appropriate amount of water. However, since hyaluronic acid has a molecular weight of several hundred thousand to millions of polymers, it has a high viscosity and is limited in the amount used when applied to cosmetics, and it is very difficult to penetrate the skin by applying directly to the skin.

The skin is the largest organ of the human body, occupying about 16% of our body volume, 1.8 m ² , 2 to 4 mm thick, and weighing about 3 kg. The epidermis, dermis and subcutaneous fat layer It consists of. The skin is in direct contact with the external environment and serves as an important protective film to protect the human body from various harmful factors such as human harmful microorganisms and external stimuli such as ultraviolet rays, while maintaining the biochemical functions necessary for metabolism of the whole body. It is an indispensable organ. In particular, the subcutaneous fat layer below the dermis is composed of the lobules of adipocytes, which act as a cushion to absorb the shock and protect the organs inside the skin against external heat, and the nutrients of triglyceride It is also stored in organelles called lipid droplets and used as an energy source when needed. However, with age, the skin is damaged by natural factors and various external stimuli. In particular, the activity and expression of collagen and elastic fiber (elastin), which are responsible for elasticity in the dermis, are reduced and elasticity is reduced. At the same time, fat production in the subcutaneous fat decreases, and eventually, each component of the entire cell is not functioning properly. Therefore, a widely used method is lipograft surgery, in which a syringe having a needle with a non-sharp tip of a tublip needle is used to collect its own fat and implant it in each part of the skin where elasticity is poor. to be. However, it has been reported that 40-60% of the graft volume is absorbed into the human body after liposuction, and liposuction in areas with thin skin and low subcutaneous fat causes problems such as cell masses being touched. In fact, the survival rate and survival time of transplanted fats are not as expected and re transplantation is needed.

There is an increasing demand for a composition that can sufficiently increase the subcutaneous fat layer while replacing liposuction with these problems. In addition, since the basic structure of the skin is maintained by the subcutaneous fat tissue, and the subcutaneous fat tissue plays a role in determining the volume and strength of the skin, it is more fat than the method of applying elasticity to the dermis or the epidermis of the outer skin layer. Increasing the volume of tissue can be a good solution for maintaining the volume of the skin.

Therefore, it is necessary to develop a composition capable of increasing the volume of adipose tissue in order to maintain and enhance the volume of the skin.

In order to solve the above problems, it is an object of the present invention to provide a composition that can increase the stem cell properties of adipose derived stem cells that can increase adipose tissue and increase the skin volume.

In order to achieve the above object, the present invention is a stem cell of fat-derived stem cells containing a tripeptide, low molecular weight hyaluronic acid, minerals and vitamins composed of glycine-proline-hydroxyproline (Gly-Pro-Hyp) as an active ingredient It provides a composition for enhancing sex.

In another aspect, the present invention provides a cosmetic or cosmetic composition for enhancing skin volume, comprising tripeptide, low molecular weight hyaluronic acid, minerals and vitamins composed of glycine-proline-hydroxyproline (Gly-Pro-Hyp) as an active ingredient. .

In another aspect, the present invention provides a skin external composition for enhancing skin volume, containing tripeptide, low molecular weight hyaluronic acid, minerals and vitamins composed of glycine-proline-hydroxyproline (Gly-Pro-Hyp).

The composition of the present invention is a tripeptides, low molecular weight hyaluronic acid, minerals and vitamins in the space surrounding the cells to form a network to maintain and maintain the shape of the tissue, by regulating the signaling between cells and the growth and differentiation of cells, It is useful for increasing adipose tissue for cosmetic or cosmetic purposes by enhancing stem cell properties of derived stem cells. Thus, the composition of the present invention promotes skin volume, promotes fat-derived stem cell regeneration and restores the function of damaged subcutaneous fat, so that it can be used as a cosmetic or cosmetic composition for enhancing skin volume, and used as an external skin composition. It is possible.

Figure 1 is treated with ECM mimetic composition of the present invention in human adipose derived stem cells (hADSCs) in a concentration of 0.0001 ~ 10% in order to determine the cytotoxicity of the composition and the degree of cytotoxicity CCK- The results confirmed using 8 kits are shown. Liquiderm means the composition of Example 1 of the present invention.
Figure 2 shows the change in the expression pattern of CD29, 44, 73, 90, 105 gene to measure the expression level of the adipose derived stem cell marker marker gene. Liquidum refers to the composition of Example 1 of the present invention.
Figure 3 shows the change in the number of cells expressing adipose derived stem cells through flow cytometry. Liquidum refers to the composition of Example 1 of the present invention.
Figure 4 shows the results of the growth factor array to determine the effect of the composition of the present invention on the growth factor expression of adipose derived stem cells. Liquidum refers to the composition of Example 1 of the present invention.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for enhancing stem cell growth of adipose derived stem cells containing a tripeptide consisting of glycine-proline-hydroxyproline (Gly-Pro-Hyp), low molecular weight hyaluronic acid, minerals and vitamins as an active ingredient. The stem cell (stemness) refers to a state in which stem cells have self-renewal ability and homeostasis and have stem cell activity, and stem cell enhancement means stem cell activity or increased stem cell activity.

In one embodiment of the present invention, the composition is an ECM simulation composition that is derived from a plant or made of synthetic materials, unlike an ECM derived from an animal, which simulates an extracellular matrix (ECM).

In one embodiment of the present invention, the Adipose derived stem cells (ADSC) are human adipose derived stem cells (hADSCs).

In one embodiment of the present invention, the composition increases adipose tissue to increase the volume on the skin. The composition promotes the differentiation of adipose derived stem cells into adipocytes to produce lipid droplets. So increasing the fat tissue to increase the volume of the skin of a certain area.

In one embodiment of the present invention, the composition is adipose derived stem cell markers differentiation cluster 29 (Cluster of Differentiation 29: hereinafter CD29), differentiation cluster 44 (Cluster of Differentiation 44: hereinafter CD44), differentiation cluster 73 (Cluster of Differentiation 73: CD73), the cluster of Differentiation 90 (CD90) or the differentiation cluster 105 (Cluster of Differentiation 105: CD105) may be increased. Increasing the expression level of CD29, CD44, CD73, CD90 or CD105 compared to the negative control means that the activity of adipose derived stem cells is increased. CD29 is another name for integrin beta 1 and is a marker of adipose derived stem cells, and CD44 increases the activity of adipose derived stem cells through Wnt signaling activity. CD73 is another name for 5'-nucleotidase, an enzyme that converts nucleotides to nucleosides and is a marker for adipose derived stem cells, and CD90 is another name for Thy1. It is a representative marker of stem cells, and CD105 is a marker of fat-derived stem cells as part of the receptor of TGFb under another name of endoglin.

In one embodiment of the present invention, the composition may increase the expression level of adipose derived stem cell growth factor, specifically, stem cell factor (hereinafter, SCF). Increasing the expression level of growth factor compared to the negative control means that the activity of adipose derived stem cells is increased.

In one embodiment of the present invention, the composition may contain 0.001 to 3% by weight of tripeptide, 0.01 to 50% by weight of low molecular weight hyaluronic acid, 0.001 to 3% by weight of minerals and 0.001 to 3% by weight of vitamins. have.

If the tripeptide of the present invention is less than 0.001% by weight relative to the total weight of the composition, its effect is insignificant, and if it exceeds 3% by weight, the effect increase is not large compared to the increase in content, and the price competitiveness is lost.

The tripeptide is composed of three amino acids, glycine-proline-hydroxyproline (Gly-Pro-Hyp), which promotes the production of collagen and has high skin permeability because of its low molecular weight. In addition, since the tripeptide is synthetically produced, the purity is high, and since there is no animal-derived component, there is no safety problem such as pathogen infection.

Hydrolysis of collagen with acids leads to various fragments that make it difficult to break them into tripeptides. Therefore, the present invention can obtain homogeneous tripeptides by using a method of synthesizing inversely based on amino acids. The tripeptides of the present invention can be prepared by amino acid synthesis methods customary in the art, and the method is not particularly limited.

Low molecular weight hyaluronic acid of the present invention may be used in 0.001 to 50% by weight, preferably 0.01 to 10% by weight relative to the total weight of the composition. The low molecular weight hyaluronic acid (hyaluronic acid) is easier to absorb the skin than the polymer hyaluronic acid and exhibits excellent skin moisturizing, wrinkle improvement, wound healing and anti-inflammatory effect. Low molecular weight hyaluronic acid of the present invention may have a molecular weight of 500 ~ 10,000 Daltons. This is because hyaluronic acid of 500 Daltons or less is not easy to manufacture and separate, and if it exceeds 10,000 Daltons, the skin permeability is difficult to show the effect and the viscosity is increased, resulting in poor formulation stability.

The low molecular weight hyaluronic acid may be prepared by a method conventional in the art, and the method is not particularly limited. Specific examples include high molecular weight hyaluronic acid using a method using high temperature heating and ultrasonic waves, a method using an acid or base catalyst, a method using a decomposition catalyst such as ammonium persulfate, or a method using a hyaluronidase enzyme. It can be made low molecular.

The mineral component of the present invention is contained in an amount of 0.001 to 3% by weight based on the total weight of the composition. If it is less than 0.001% by weight, the effect is insignificant, and if it exceeds 3% by weight, it is not preferable because it may impair the homeostasis of the skin.

The minerals are magnesium chloride, calcium chloride, potassium chloride, magnesium fluoride, manganese fluoride, manganese sulfate, zinc sulfate ), One or more selected from the group consisting of magnesium sulfate and copper sulfate, but is not limited thereto.

The magnesium chloride, calcium chloride and potassium chloride participate in epidermal differentiation, and mineral components such as magnesium fluoride, manganese fluoride, manganese sulfate, zinc sulfate, magnesium sulfate and copper sulfate are necessary for cell homeostasis and skin protection.

Vitamin of the present invention is contained in an amount of 0.001 to 3% by weight based on the total weight of the composition. If the amount is less than 0.001% by weight, the effect is insignificant, and if the amount is more than 3% by weight, discoloration, discoloration, etc. may occur, thereby inhibiting the stability of the composition.

The vitamin may be at least one selected from the group consisting of inositol, ascorbic acid, pantothenic acid, niacin, folic acid, thiamine, riboflavin, and derivatives thereof, but is not limited thereto.

One embodiment of the present invention is a cosmetic or cosmetic composition for enhancing skin volume, containing tripeptide, low molecular weight hyaluronic acid, minerals and vitamins composed of glycine-proline-hydroxyproline (Gly-Pro-Hyp) as an active ingredient. To provide.

The active ingredient may contain 0.0001 to 0.1% by weight, specifically 0.0001 to 0.001% by weight based on the total weight of the composition. If it is less than 0.0001% by weight, the effect is insignificant, and if it exceeds 0.1% by weight, there is a problem of showing cytotoxicity.

The composition may be used for non-limiting examples, such as breast augmentation through breast tissue formation, micro fat graft, auto fat graft, and the like to improve skin volume on the face and to remove nasolabial folds and fine lines and maintain elasticity.

The composition may be formulated in a unit dosage form suitable for administration in the body of a patient according to conventional methods in the pharmaceutical art. Formulations suitable for this purpose are preferably parenteral administration preparations for injection or topical administration. Injectable formulations are preferably aqueous isotonic solutions or suspensions. However, at this time, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. which are generally used may be used together.

The formulation of the present invention thus prepared may be administered parenterally, for example, directly to a specific site, according to conventional methods. At this time, the injection of the composition is made using a syringe. The daily dosage of the composition is 1 × 10 ⁵ to 1 × 10 ⁷ cells / kg body weight, preferably 5 × 10 ⁵ to 5 × 10 ⁶ cells / kg body weight, and can be administered once or in several doses. . However, it is to be understood that the actual dosage of the active ingredient should be determined in view of several related factors such as the amount of adipocytes to be differentiated and expanded, the route of administration, the weight of the patient, the age and gender of the patient, and thus the dosage should be It is not intended to limit the scope of the invention in any aspect.

An embodiment of the present invention provides a skin external composition for enhancing skin volume, containing tripeptide, low molecular weight hyaluronic acid, minerals and vitamins composed of glycine-proline-hydroxyproline (Gly-Pro-Hyp) as an active ingredient. do.

The active ingredient may contain 0.0001 to 0.1% by weight, specifically 0.0001 to 0.001% by weight based on the total weight of the composition. If it is less than 0.0001% by weight, the effect is insignificant, and if it exceeds 0.1% by weight, there is a problem of showing cytotoxicity.

The external preparation composition may be a cosmetic composition or a pharmaceutical composition.

The formulation of the cosmetic composition is not particularly limited and may be appropriately selected as desired. For example, it may be prepared in a formulation such as flexible lotion, nourishing lotion, massage cream, essence, nutrition cream, pack, but is not limited thereto.

The pharmaceutical composition may be, but is not limited to, transdermal dosage forms such as lotions, ointments, gels, creams, patches or sprays.

In the external composition for skin according to each formulation, other ingredients other than the composition of the present invention described above may be appropriately selected and blended by those skilled in the art according to the formulation or use purpose of the external skin preparation, and in this case, simultaneously applied with other raw materials. If you do, synergistic effects may occur.

In addition, when the composition according to the present invention is used as a pharmaceutical composition, it may further contain a pharmaceutical adjuvant and other therapeutically useful substances such as preservatives, stabilizers, hydrating or emulsifying accelerators, salts or buffers for osmotic control. And may be formulated in a variety of oral or parenteral dosage forms according to conventional methods.

It is to be understood that the actual dosage of the active ingredient should be determined in light of several relevant factors such as the severity of the symptom, the route of administration chosen, the age, sex, weight and health of the subject.

In general, the dosage of the active ingredient ranges from 0.001 mg / kg / day to approximately 2000 mg / kg / day. More preferred dosage is 0.5 mg / kg / day to 2.5 mg / kg / day.

The site of application of the composition for enhancing stem cell properties of adipose derived stem cells according to the present invention includes all of the adipose tissue of the body, but is not limited to a specific site, for example, may include a face area with less fat layer. . In addition, the effect of increasing the adipose tissue, but the effect of increasing the skin volume due to the increase in fat tissue for cosmetic or cosmetic purposes, but is not limited thereto.

Hereinafter, the present invention will be described in more detail with reference to the following examples and test examples, which are intended to illustrate the present invention, but the scope of the present invention is not limited thereto.

Example 1

To prepare a composition to simulate the extracellular matrix (ECM) in the composition of Table 1. Inositol and ascorbic acid were used as vitamins B and C, respectively, and niacinamide was used as a derivative of niacin, which is vitamin B3. Zinc sulfate, potassium chloride, calcium chloride, magnesium sulfate and copper sulfate were used as minerals. Oligo hyaluronic acid was purchased from Bioland Co., Ltd. and tripeptide from A & PEP Co., Ltd.

Ingredients Content (% by weight) Oligo hyaluronic acid
Weight average molecular weight 5,000 Daltons 0.6 Tripeptide 0.3 Polylysine 0.045 Glutamine 0.037 Arginine 0.015 Isoleucine 0.01 Oleic acid 0.002 Linoleic acid 0.002 Alanine 0.005 Inositol 0.002 Niacinamide 0.0002 Ascorbic acid 0.005 Zinc sulfate 0.043 Potassium chloride 0.03 Calcium chloride 0.012 Magnesium Sulfate 0.01 Copper sulfate 0.0002 Purified water Balance

Test Example 1 Identification of Cytotoxicity in Human Adipose-Derived Stem Cells

Adipose derived stem cells were passaged in 75 cm ² T-flask, and cultured in a CO ₂ incubator at 37 ° C and 5% CO ₂ . Typically, passage of the cells was performed at the second or third time.

Human adipose derived stem cells (hADSCs) were purchased from Lonza, Inc. Walkersville, MD, USA and cultured according to Lonza's instructions. In order to determine the cytotoxicity of the composition was treated at a concentration of 0.0001 ~ 10% and the degree of cytotoxicity was confirmed using a CCK-8 kit (Dojindo). Referring to the results of Figure 1, it was confirmed that the cell division promoting effect of about 10% without cytotoxicity when the concentration of 0.001% treatment.

Test Example 2 Measurement of Effect on Expression Level of Adipose-derived Stem Cell Marker Marker Gene

Oxidative stress of adipose derived stem cells was treated with hydrogen peroxide (H ₂ O ₂ ) at a concentration of 200 uM for 24 hours, and the composition was added to the medium at 0.001% to determine the stem cell enhancement effect of adipose derived stem cells. . Remove the cell culture of the adipose derived stem cells, wash the cells with 2 ml of Phosphate Buffered Saline (PBS), and then use Trizol reagent (Trizol reagent, Invitrogen, Carlsbad, CA, USA) RNA in the cells was isolated.

The isolated RNA was purified once more with KIAGEN's RNA kit (QIAGEN RNeasy kt, QIAGEN, Valencia, CA), and then Agilent's BioAnalyzer 2100 model instrument (Agilent 2100 BioAnalyzer, Agilent Technologies, Santa Clara, CA, USA). Was used to confirm the quality of RNA. CDNA was synthesized from the RNA using Invitrogen's Superscript Reverse Transcriptase (RT) kit, Invitrogen, Carlsbad, Calif., Which was then used for real time-reverse transcription polymerase chain reaction (Q). Quantitatively via -RT-PCR).

Changes in the expression patterns of CD29, 44, 73, 90, and 105 genes in adipose derived stem cells (TaqMangene expression assay kit, Applied Biosystems, Foster City, CA) (CD29 gene primer: Hs00559595_m1, CD44) Gene primer: Hs01075861_m1, CD73 gene primer: Hs01573922_m1, CD90 gene primer: Hs00174816_m1, CD105 gene primer: Hs00923996_m1) were evaluated, and the results are shown in FIG. The amount of expression of each gene was confirmed to increase by about 50% compared to the negative control. This increase was statistically significant, and the statistics were verified by the two-tailed Student's t test, indicating that there was a significant difference when the p value was less than 0.05.

Test Example 3 Measurement of Adipose-derived Stem Cells by Flow Cytometry

Human adipose derived stem cells were separated from a 75 cm ² Ti flask with 0.25% Trypsin -EDTA, allowed to settle for 5 minutes at 1500 rpm, and then the culture medium was removed and then 3 ml of blocking buffer: Blocking buffer, 2% Fetal calf serum (FCS) and 2% bovine serum albumin (Bovine Serum Albumin (BSA) KGM-2) were added to suspend the cells.

Cells (approximately 10 ⁶ cells) were applied at 4 ° C. for 15 minutes, followed by CD44 antibody (Cat No. 560977) (BD Pharmingen, CA, US) and PE-Cy (phycoerythrin) to which Fluorescein isothiocyanate (FITC) was attached. CD29 antibody (Cat No. 559882) (BD Pharmingen, CA, US) attached with -cyanine was added in 100: 1 each and reacted for 45 minutes at 4 ° C. On the other hand, cells used as a negative control FITC Rat IgG2a, k isotype (Cat No. 555742) and PE-Cy5 mouse IgG1 k isotype (Cat No. 555750) was also put in 100: l, 4 The reaction was carried out for 45 minutes at ° C.

After the reaction, the cells were washed twice with 3 ml of washing buffer (2% Bovine Serum Albumin (BSA) KGM-2) and the cells were suspended. Since FACSCalibur (BD Bioscience, San Jose, CA, U.S.) to observe the change in the number of cells expressing CD29, 44 in adipose derived stem cells, it is shown in Figure 3, Table 2.

Negative Control Composition treatment group Adipose derived stem cells expressing CD29 2558 4183 increase % 85% Adipose derived stem cells expressing CD44 3112 3747 increase % 52%

Referring to Figure 3 and Table 2, CD29 is 85% compared to the negative control. CD44 increased 42% .

Test Example 4 Expression of Growth Factors in Adipose-derived Stem Cells

In order to understand the effect of the composition of the present invention on the growth factor expression of adipose derived stem cells, a growth factor array (Growth factor array, Raybio) was performed.

A growth factor array was performed by harvesting a culture medium of adipose derived stem cells cultured for each condition. 2 ml of blocking buffer was treated at room temperature for 30 minutes, and then 1 ml of the culture solution was treated at room temperature for 2 hours. Thereafter, 5 minutes of washing with 2 ml of wash buffer and reaction was performed at room temperature with an anti-growth factor antibody bound to Biotin. In addition, it was washed 5 times with 2 ml of washing buffer for 5 minutes and treated with 2 ml of HRP-bound streptoavidin for 2 hours. After washing with washing buffer, it was reacted with detection buffer and developed with LAS-3000 (Fujifilm). It was.

As a result of analyzing a total of 41 growth factors according to Figure 4, the growth factor increased by more than 10% by oxidative stress and increased by more than 10% by treatment of the composition was analyzed Stem cell factor (SCF). This increase was statistically significant, and the statistics were verified by the two-tailed Student's t test, indicating that there was a significant difference when the p value was less than 0.05.

Formulation Example 1 Flexible Cosmetics

The flexible longevity formulation containing Example 1 was prepared according to a conventional manufacturing method with the composition shown in Table 3 below.

ingredient Content (% by weight) Betaine 3.0 Natto gum 3.0 Cellulose gum 0.005 ethanol 10.0 Polyoxyethylene Cured Castor Oil 0.2 Tocopherol Acetate 2.0 Example 1 10 antiseptic a very small amount Pigment a very small amount incense a very small amount Purified water Balance

Formulation Example 2 Nutritional Cosmetics

The nutrient cosmetic formulation containing Example 1 was prepared according to a conventional preparation method with the composition shown in Table 4 below.

ingredient Content (% by weight) Cetylethylenehexanoate 4.0 Cetostearyl alcohol 1.0 Lipophilic Monostearylic Acid Stearate 1.0 Squalane 0.5 Example 1 5.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 glycerin 5.0 Triethanolamine 0.5 Carboxyvinyl polymer 0.2 antiseptic a very small amount Pigment a very small amount incense a very small amount Purified water Balance

Formulation Example 3 Cream

A cream formulation containing Example 1 was prepared according to a conventional preparation method with the composition shown in Table 5 below.

ingredient Content (% by weight) Glyceryl Stearate 3.0 Polysorbate 60 1.0 Cetostearate 2.5 Beeswax 1.0 Squalane 2.0 Sorbitan sesquioleate 0.5 Cetylethylhexanoate 0.5 Liquid paraffin 5.0 Active ingredient mixture 5.0 glycerin 3.0 Propylene glycol 3.0 Example 1 5.0 antiseptic a very small amount Pigment a very small amount incense a very small amount Purified water Balance

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

Claims (15)

Glycine-proline-hydroxyproline (Gly-Pro-Hyp) consisting of tripeptides, low molecular weight hyaluronic acid, minerals and vitamins as an active ingredient for stem cell-enhanced composition for improving the stem cells. The method of claim 1,
The composition is a stem cell enhanced composition, characterized in that it mimics the extracellular matrix (hereinafter ECM). The method of claim 1,
The fat-derived stem cells are human adipose derived stem cells (hADSCs) characterized in that the composition for promoting stem cell, characterized in that. The method of claim 1,
The composition is a composition for enhancing stem cells, characterized in that to increase the adipose tissue to promote a sense of volume on the skin. The method of claim 1,
The composition is a stem cell marker for enhancing the composition, characterized in that for increasing the expression level of adipose derived stem cell markers CD29, CD44, CD73, CD90 or CD105. The method of claim 1,
The composition is a stem cell growth enhancing composition, characterized in that for increasing the expression level of fat-derived stem cell growth factor. The method of claim 6,
The growth factor composition for enhancing stem cell characterized in that the SCF The method of claim 1,
The composition is a stem cell enhancement, characterized in that it contains 0.001 to 3% by weight of the peptide, 0.01 to 50% by weight of low molecular weight hyaluronic acid, 0.001 to 3% by weight of minerals and 0.001 to 3% by weight of vitamins Composition. The method of claim 1,
Low molecular weight hyaluronic acid is a composition for enhancing stem cells, characterized in that having a molecular weight of 500 ~ 10,000 Daltons. The method of claim 1,
The minerals are magnesium chloride, calcium chloride, potassium chloride, magnesium fluoride, manganese fluoride, manganese sulfate, zinc sulfate ), Magnesium sulfate (magnesium sulfate) and copper sulfate (copper sulfate) composition for promoting stem cell, characterized in that at least one selected from the group consisting of. The method of claim 1,
The vitamin is inositol, ascorbic acid, pantothenic acid, niacin, folic acid, thiamine, riboflavin and derivatives for stem cell composition, characterized in that at least one selected from the group consisting of. Glycine-proline-hydroxyproline (Gly-Pro-Hyp) consisting of a tripeptide, low molecular weight hyaluronic acid, minerals and vitamins as an active ingredient for skin or cosmetic composition for enhancing the volume. The method of claim 12,
The active ingredient is a cosmetic or cosmetic composition for enhancing the volume of skin, characterized in that it contains 0.0001 to 10% by weight based on the total weight of the composition. A composition for external application of skin for enhancing the volume of skin containing a tripeptide composed of glycine-proline-hydroxyproline (Gly-Pro-Hyp), low molecular weight hyaluronic acid, minerals and vitamins as an active ingredient. The method of claim 14,
The active ingredient is an external composition for skin volume enhancement skin containing 0.0001 to 10% by weight based on the total weight of the composition.

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