KR101915386B1 - Composition for sensitive skin comprising peptide derived from adiponectin - Google Patents

Abstract

The present invention relates to a composition comprising a peptide fragment derived from adiponectin, and more particularly, to a composition comprising at least one of adiponectin-derived peptides selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 21 as an active ingredient Skin cosmetic compositions and pharmaceutical compositions. The adiponectin-derived peptide activates the downstream signal transduction pathway of the adiponectin receptor in the muscle cells involved in the major pathogenesis of the sensitive skin and inhibits the activity of the stimulating receptors induced by the sensitizing skin inducer, so that the adiponectin- Can be effectively used to inhibit or alleviate sensitive skin symptoms.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a composition for a skin comprising an adiponectin-derived peptide,

The present invention relates to a composition for sensitive skin comprising a peptide fragment (peptide fragment or small peptide) derived from adiponectin.

Sensitive skin refers to a skin that is more sensitive to external stimuli, allergenic substances, environmental changes or internal causes of the human body than normal skin, and thus causes irritation or dermatitis. Such sensitive skin holders are increasingly on the rise , And even more than half of all American women claim to be sensitive skin. Recently, interest in sensitive skin and dermatological importance are increasing, but there is not yet a method for relieving or treating sensitive skin symptoms.

It is well known that certain skin types are more sensitive than others. Although the symptoms and causes of sensitive skin are not clearly known, generally, sensitive skin caregivers easily exhibit adverse reactions due to external influences such as cosmetics, stress and air pollution. These adverse reactions range from non-inflammatory changes such as visible reactions such as erythema and skin dryness and skin roughness to subjective feelings such as stinging and itching. In contrast, dermatologists define sensitive skin as a skin that exhibits better contact stimuli or an allergic reaction than the average group. As an experiment for screening sensitive skin, there are cases in which sensitive skin is distinguished by treatment with lactic acid or DMSO, which is known to cause irritation.

The adverse reactions in sensitive skin may follow inflammatory pathways such as contact stimuli, and may follow the pathway of allergic reactions. Several inflammatory mediators (leukotrien, prostaglandin) and cytokines are involved in the reverse reaction, so that the reverse reaction can be mitigated or diluted by modulation of cytokines and inflammatory mediators.

It has also been argued that a healthy stratum corneum is the most important factor in protecting the skin from skin irritants. In fact, since skin irritation tendency and skin permeability are related to each other, skin barrier insufficiency is a cause of sensitive skin. Therefore, the strengthening of the skin barrier becomes one of the ways of normalizing the sensitive skin.

So far, cosmetic products for sensitive skin have been developed so as to remove active ingredients which are likely to cause irritation so that they do not cause contact dermatitis or allergic dermatitis. However, environmental and psychological factors require the use of active ingredients in the cosmetics of sensitive skin holders. Accordingly, there is a demand for the development of cosmetics having functions of alleviating the adverse reaction by controlling cytokines and inflammatory mediators, improving the skin barrier and improving and normalizing the sensitive skin through the skin protection function (Patent Document 1) .

On the other hand, adiponectin is a type of adipocine, a protein hormone secreted specifically in adipocytes. It promotes insulin function and induces insulin resistance, thereby regulating cardiovascular diseases such as hyperglycemia, hyperinsulinemia, obesity, and arteriosclerosis . Adiponectin also has the function of inhibiting the metastasis and inflammatory response of cancer cells. Adiponectin not only promotes the proliferation of keratinocytes but also promotes the expression of filaggrin, hyaluronic acid and extracellular matrix in the skin, thereby performing functions such as wound healing, fibrosis inhibition, skin wrinkle improvement, moisturizing Document 2). Recently, a microarray analysis on sensitive skin has been conducted, and it has been reported that control of neurotransmission processes such as CGRP due to decrease of adiponectin in muscle is important for sensitive skin disease (Non-Patent Document 1).

Adiponectin is composed of 244 amino acids and consists of a signal sequence, a collagen-like domain at the N-terminal and a globular domain at the C-terminal. A hexamer and a 400 kDa HMW complex are the major oligomers and the polymer complex is known to be more active than the LMW complex.

The development of peptides derived from adiponectin, which has been known to have various physiological activities, has been a target of many researchers and pharmaceutical companies at home and abroad, but the possibility of final success was relatively low due to the difficulty of forming a polymer in the body. Therefore, development of short peptides derived from adiponectin which can be applied to skin and has excellent physiological activity is required.

Korean Patent Publication No. 10-2005-0080480 Korean Patent Publication No. 10-2015-0032401

 Adiponectin Deficiency Contributes to Sensitivity in Human Skin. J Invest Dermatol. 2015 Sep; 135 (9): 2331-4.

A subject of the present invention is to provide a composition for sensitive skin containing an adiponectin-derived peptide.

In order to solve the above problems, the present invention provides a cosmetic composition or a pharmaceutical composition for sensitive skin comprising at least one of adiponectin-derived peptides selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 21 as an active ingredient.

According to one embodiment of the present invention, the composition of the present invention preferably contains at least one of adiponectin-derived peptides selected from the group consisting of SEQ ID NO: 16 and SEQ ID NO: 21 as an active ingredient, but is not limited thereto.

According to one embodiment of the present invention, the adiponectin-derived peptide may be contained in the cosmetic composition or the pharmaceutical composition at a concentration of 0.001 to 20 mM, but is not limited thereto.

According to another embodiment of the present invention, the cosmetic composition may be selected from cosmetics, essences, lotions, creams, packs, gels, ointments, patches or spray formulations, but is not limited thereto.

The present invention also relates to a method for the treatment or prevention of susceptible skin conditions comprising administering to a subject at least one of the adiponectin-derived peptides selected from the group consisting of the amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 21 in a pharmaceutically or cosmetically effective amount, Provide a mitigation method.

According to one embodiment of the present invention, the subject may be a human, but is not limited thereto.

The present invention relates to a composition comprising an adiponectin-derived peptide having a mitigating effect on sensitive skin, wherein the adiponectin-derived peptide activates the downstream signal transduction pathway of the adiponectin receptor in muscle cells involved in the main pathology of sensitive skin, The composition containing the adiponectin-derived peptide can be effectively used for suppressing or alleviating the sensitized skin symptom, since the activity of stimulating receptors induced by the sensitizing skin-inducing substance is suppressed.

1 is a photograph showing the skin permeability test result of the adiponectin-derived peptide of the present invention.
FIGS. 2A-2C show the effect of the adiponectin-derived peptides of the present invention on the increase of PPARR? And PPAR? Activity (FIGS. 2A and 2B) and phosphorylation of AMPK and ACC (FIG. 2C), which correspond to the lower signaling pathway of adiponectin receptor And electrophoresis images.
FIG. 3 is a graph showing the effect of the adiponectin-derived peptide of the present invention on the expression of ASIC3, TRPV1 and CGRP genes, which are skin sensitivity-related genes induced by lactic acid.
Figure 4 shows the crystal structure of the adiponectin peptide of the present invention in the structural position in which it is present in the adiponectin protein.
5 is a graph showing the sequence similarity between the P5 peptide of the present invention and other proteins present in the human body.

In order to achieve the above object, the present invention provides a cosmetic composition or a pharmaceutical composition for sensitive skin comprising at least one of adiponectin-derived peptides selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 21 as an active ingredient.

The adiponectin-derived peptide of the present invention is a 4-amino acid (4-mer) or 5-amino acid (5-mer) peptide fragment derived from adiponectin and has the amino acid sequence shown in Table 1 below.

Adiponectin
Peptides Amino acid sequence
(Molecular Weight) SEQ ID NO: Adiponectin
Peptides Amino acid sequence
(Molecular Weight) SEQ ID NO: P4-1 IPGL (398.5) One P1 KFHCNIPGLYYFAYHITV (2186.6) 22 P4-2 PGLY (448.52) 2 P2 IPGLYYFA (943) 23 P4-3 GLYY (514.58) 3 P3 IPGLY (561) 14 P4-4 LYYF (604.71) 4 P4 PGLYY (611) 15 P4-5 YYFA (562.63) 5 P5 GLYYF (662) 16 P4-6 YFAY (562.63) 6 P6 LYYFA (676) 17 P4-7 FAYH (536.59) 7 P7 CNIPG 503 18 P4-8 AYHI (502.57) 8 P8 KFHCN (647) 19 P4-9 YHIT (532.6) 9 P9 HCNIP (582) 20 P4-10 NIPG (399.44) 10 P10 NIPGL (512) 21 P4-11 CNIP (445.54) 11 P4-12 HCNI (485.56) 12 P4-13 Palmytoil-LYYF 13

According to one embodiment of the present invention, the adiponectin-derived peptide is contained preferably in a concentration of 0.001 to 20 mM in the cosmetic composition, more preferably in a concentration of 0.01 to 10 mM, but is not limited thereto. If the concentration of the peptide is less than 0.001 mM, it is difficult to obtain a mitigating effect on sensitive skin. If the concentration of the peptide is more than 20 mM, there is no significant increase in the effect due to the increase of the content.

The peptide of the present invention can be produced by general chemical synthesis, for example, solid-phase peptide synthesis, and culturing a microorganism transformed with a recombinant vector containing a nucleic acid encoding the peptide, Peptide, and then purified by a conventional method, but the present invention is not limited thereto.

The cosmetic composition according to the present invention may further contain, in addition to the above-mentioned peptides, other components which can give a synergistic effect to the effect of the peptide, within a range not impairing the objective effect of the present invention. For example, the cosmetic compositions of the present invention may be formulated with conventional excipients such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors as well as any other substances known to have a mitigating effect on sensitive skin, .

The cosmetic composition of the present invention is not particularly limited in its formulation and may be prepared into any of the formulations conventionally produced in the art, and examples thereof include solutions, suspensions, emulsions, pastes, gels, , Powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations and sprays. On the other hand, it is also possible to use other cosmetics such as scalp treatments, soaps, hair tonics, shampoos, rinses, hair packs, hair gels, lotions, conditioners, hair oils, mousses, creams, Emulsions, lotions, essences, patches or spray formulations.

When the formulation of the cosmetic composition is a paste, a cream or a gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide Talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as the carrier component in the case of a powder or a spray. In the case of a spray, in particular, a mixture of chlorofluorohydrocarbons, propane / Propane, such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, a solubilizing agent or an emulsifying agent may be used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, Propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid esters of sorbitan.

In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, In the case of cleansing containing a surfactant, alcohols such as aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, Imidazolinium derivatives, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative or ethoxylated glycerol fatty acid ester To be There.

According to a specific embodiment of the present invention, the adiponectin-derived peptide of the present invention has remarkably excellent permeability to the skin (see FIG. 1), and increases the activity of proteins in the lower signal transduction pathway through activation of adiponectin receptor in human- (See Figs. 2A to 2C).

In addition, according to another specific embodiment of the present invention, the adiponectin-derived peptide of the present invention can significantly suppress the expression of genes related to skin sensitivity caused by lactic acid in human-derived cells (see FIG. 3).

Therefore, the composition comprising the adiponectin-derived peptide of the present invention can be usefully used as an effective ingredient of a cosmetic composition for alleviating or suppressing sensitive skin symptoms.

Meanwhile, the administration route of the pharmaceutical composition for sensitive skin according to the present invention may include oral, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal administration, Or parenteral administration, but is not limited thereto. The term " parenteral " includes subcutaneous, intradermal, intravenous, intramuscular, intralesional injection or infusion techniques.

The pharmaceutical composition of the present invention may further contain one or more active ingredients showing the same or similar functions in addition to the adiponectin-derived peptide according to the present invention. The compositions may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, oral preparations, external preparations, suppositories and sterilized injection solutions according to a conventional method.

Solid form preparations for oral administration include powders, granules, tablets, capsules, soft capsules, and the like. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . As the agent for parenteral administration, the external preparation such as powders, granules, tablets, capsules, sterilized aqueous solutions, liquid preparations, non-aqueous solutions, suspensions, emulsions, syrups, suppositories and aerosols, The composition may be formulated in the form of a cream, a gel, a patch, a spray, an ointment, a warning agent, a lotion, a liniment, a pasta or a cataplasma, , But is not limited thereto. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

Such compositions may additionally contain preservatives, stabilizers, wettable or emulsifying accelerators, adjuvants such as salts and / or buffers for the control of osmotic pressure, and other therapeutically useful substances and may be prepared by conventional methods of mixing, It can be formulated according to the coating method.

The pharmaceutical composition of the present invention may be variously varied depending on various factors including the age, weight, general health, sex, administration time, route of administration, rate of excretion, drug combination and severity of a specific disease.

When the pharmaceutical composition containing the adiponectin-derived peptide of the present invention as an active ingredient is formulated in a unit dose form, it is preferable that the adiponectin-derived peptide is contained as an active ingredient in a unit dose of about 0.01 to 1,500 mg, The dosage required for treatment is usually, but not limited to, about 1 to 500 mg per day depending on the frequency and intensity of administration. For intramuscular or intravenous administration to an adult, a total dose of about 5 to 300 mg per day will suffice for a single dose, while for some patients a higher daily dose may be desirable. The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

The present invention also relates to a method for the treatment or prevention of susceptible skin conditions comprising administering to a subject at least one of the adiponectin-derived peptides selected from the group consisting of the amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 21 in a pharmaceutically or cosmetically effective amount, Provide a mitigation method.

The pharmacologically or cosmetically effective amount is 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg, but is not limited thereto. The treatment or dosage can be adjusted depending on the weight, age, sex, health condition, diet, administration period, administration method, elimination rate, severity of disease, etc. of the particular patient. The treatment or administration may be carried out once a day or divided into several times.

The subject is a vertebrate and preferably a mammal, more preferably a human or an experimental animal such as a mouse, a rabbit, a guinea pig, a hamster, a dog, a cat, and most preferably a human, but is not limited thereto .

The treatment or administration method may be applied by oral, parenteral or parenteral administration. In the case of parenteral administration, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine injection, intracerebral injection, May be administered by intramuscular injection.

Hereinafter, the present invention will be described in more detail by way of examples.

However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

Example 1. Preparation of peptides derived from adiponectin

Merrifield's SPPS (Solid Phase Peptide Synthesis) method (J. Am. Chem. Soc., 85 (14), 2149-2154) was used to synthesize the peptides of the present invention. First, synthesis was started using 2-chlorotrityl chloride (CTC) resin to synthesize the peptide of the present invention. The first step Fmoc (9-fluorenylmethoxy carbonyl) amino acid was N, N-diisopropylethylamine , N-diisopropylethylamine, DIEA) in dichloromethane (DCM) solvent. From the next step of Fmoc amino acid, HATU (N - [(dimethylamino-) -1H-1,2,3-triazolo [4,5- b] pyridin- 1 -yl- methylene] (1-hydroxy-7-azabenzotriazole (HOAt) or HBTU (N - [(1H-benzotriazol-1-yl) (dimethylamino) methylene] -N- (N, N-diisopropylethylamine) was used in combination with hydroxybenzotriazole (HOBt) to prolong the chain of the peptide. At this time, the Fmoc-amino acid was synthesized from the C-terminus to the N-terminus, and the Fmoc-amino acid was coupled to the amino terminus. Then, the Fmoc group was removed using a 20% piperidine solution (Solid-Phase Synthesis: A Practical Guide ), CRC Press.848) and washed several times with DMF (Dimethylforamide), followed by coupling. Finally, after the Fmoc-amino acid was coupled, the Fmoc group was removed with a 20% piperidine solution, and a solution of the carboxylic acid and N, N'-diisopropylcarbodiimide (DIC), 1-hydroxy- Triacetyl (HOAt) was used in combination to couple the acyl group and then washed several times with DMF and dried. A solution of TFA (triflu or o acetic acid) -H ₂ O-triisopropylsilane (95: 2.5: 2.5, vol. / Vol.) Was added and the reaction was carried out for 2 to 3 hours to remove the protective group and remove After the peptides were separated, each peptide having the amino acid sequence shown in Table 1 was synthesized by immersing the peptide in diethylether.

The crude peptide thus obtained was analyzed by RP-HPLC (2996 Detector, 515 Pump, Waters) in the gradient solvent composition of acetonitrile and water containing 0.1% TFA and the purity was confirmed As a result, 95% or less of peptides were separated and purified with Prep-LC to obtain 97% or more of peptides. As a result of elemental analysis with an element analyzer (EA1112, CE Instrument, Italy) in order to confirm the exact components of the peptide, it was confirmed that the content of the peptide was identical with the content of each element calculated from the amino acid sequence, Respectively.

Example 2. Measurement of skin permeability of adiponectin-derived peptide

Adiponectin is degraded into smaller units including globular domains, and subunits having a globular domain are more active than full length adiponectin. Such receptors for adiponectin are adiponectin receptor 1 (AdipoR1) and adiponectin Adiponectin receptor 2 (AdipoR2) (Crystal structures of the human adiponectin receptors, Nature, 2015 Apr 16, 520 (7547): 312-6, doi: 10.1038 / nature14301). Thus, the skin permeability of the adiponectin-derived peptide of the present invention prepared in Example 1 was verified by using pig skin which is most similar to human skin and generally used for permeability testing. The size of the pig skin was cut to 2 cm in length and 2 cm in length, and then the corresponding peptide stock (FITC fluorescently attached peptide stock (2-peptide of the 8-mer length of the control, 4-mer 4 peptide of the positive control) and DMSO Sheep. The light was blocked and placed in a 37 ° C incubator for 2 hours. Cryosection was performed after rapid freezing using LN2. After washing for 5 minutes with DAPI (nuclear staining), they were washed and observed with a confocal microscope.

As a result, it was confirmed that the adiponectin-derived peptide of the present invention was remarkably excellent in permeability to skin as compared with the peptide of 8 amino acid length used as a control (Fig. 1).

Example  3. Adiponectin  Derived peptide from human muscle cell lines Adiponectin  Effect on receptor activity

Adiponectin binds to adiponectin receptors and activates adiponectin receptors, which are known to increase phosphorylation of AMPK, a downstream signaling pathway, and PPARα / PPARγ activity (Adiponectin Receptor as a Key Player in Healthy Longevity and Obesity-Related Diseases Volume 17, Issue 2, 5 February 2013, Pages 185 196). The phosphorylation of AMPK (lower ACC phosphorylation) and the activity of PPARα / PPARγ were confirmed by using human cell line, RD cell line, which is reported to be involved in the main pathology of sensitive skin. The human muscle cell line, RD cells, were cultured and then replaced with serum-free cells at 90% level. After the adiponectin-derived peptide of the present invention prepared in Example 1 and the vehicle (normal control, CNT) were treated and harvested 24 hours later, proteins were separated, and their activity was measured using the corresponding assay kit and western blotting technique.

As a result, the adiponectin-derived peptides of the present invention induced an increase in the activity of PPAR [alpha] and PPAR [gamma] corresponding to proteins in the lower signal transduction pathway through activation of adiponectin receptor in human muscle cell lines (Figs. 2A and 2B) (Fig. 2C).

Example  4. Adiponectin  Effect of Derived Peptides on the Responses of Sensitive Skin Derivatives in Human Muscle Cell Lines

After the human muscle cell line RD cell line was cultured, the cells were changed to serum-free medium at 90% concentration. Then, 50 mM of lactic acid (LA) and 5 μg of the adiponectin peptide of the present invention prepared in Example 1 / Ml. After 4 hours, the cells were harvested and mRNA was extracted to observe the effect of ASIC3 and TRPV1 on stimulation receptors and CGRP, a neurotransmitter.

As a result, it was confirmed that the adiponectin-derived peptide of the present invention can remarkably inhibit the expression of genes related to skin sensitivity caused by lactic acid (FIG. 3).

Example  5. Adiponectin  Within the protein Adiponectin  Identification of peptide structure and possible action through in vivo polymer formation

The three-dimensional structure of adiponectin proteins present in humans was analyzed to analyze the structural positions of adiponectin peptides prepared in the present invention and the possibility of adiponectin receptor function in vivo.

As a result, in the case of adiponectin peptides, it was found that a total of 3 times was repeated in the form of a trimer in the spherical domain known as an action site of adiponectin protein. Especially, It is distributed on the outer periphery and is likely to act on the adiponectin receptor. In particular, in the case of the P5 peptide, it was confirmed that the peptide sequence repeating three times in the adiponectin protein forms a polymer when the three-dimensional protein structure is examined. The lipophilic amino acid inside the polymer and the hydrophilic amino acid outside the polymer (Fig. 4). As shown in Fig. 4, when a hydrophilic material was actually permeated through the human body, the polymer was again formed in the form of a polymer, and the possibility of acting on the adiponectin receptor was confirmed (Fig.

Example 6. Detection of duplication of sequence of adiponectin peptide with other protein

In the case of the adiponectin peptide prepared in the present invention, since it is a short amino acid sequence composed of 5-mer, there is a possibility that it actually overlaps with the amino acid sequence contained in other proteins present in the human body. In this case, it is difficult to identify the sequence specifically existing only in adiponectin, and thus there is a problem that the possibility of acting specifically on the adiponectin receptor is low. Using the UniProt database provided by the US NCBI, the sequence of the protein sequence in the human body overlapping with the adiponectin peptide sequence was searched.

As a result, in particular, the P5 peptide of the present invention was confirmed to exist only in the C1q complement protein superfamily to which the adiponectin protein belonged, and was identified as a peptide sequence highly specific to the adiponectin protein (FIG. 5).

Production Example 1. Preparation of cosmetic material

<1-1> Manufacture of flexible lotion

The softened lotion containing the adiponectin-derived peptide of the present invention as an active ingredient was prepared as shown in Table 2 below.

Raw material Content (parts by weight) The adiponectin-derived peptide of Example 1 10.00 1,3-butylene glycol 1.00 Disodium iodide 0.05 Allantoin 0.10 Dipotassium glycyrrhizate 0.05 Citric acid 0.01 Sodium citrate 0.02 Glycereth-26 1.00 Arbutin 2.00 Hydrogenated castor oil 1.00 ethanol 30.00 Preservative a very small amount coloring agent a very small amount Flavoring agent a very small amount Purified water Balance

<1-2> Preparation of nutritional cream

The nutritional cream containing the adiponectin-derived peptide of the present invention as an active ingredient was prepared in accordance with the composition shown in Table 3 below.

Raw material Content (parts by weight) The adiponectin-derived peptide of Example 1 10.0 1,3-butylene glycol 7.0 glycerin 1.0 D-Panthenol 0.1 Plant extract 3.2 Magnesium aluminum silicate 0.3 PEG-40 stearate 1.2 Stearic acid 2.0 Polysorbate 60 1.5 Chin type glyceryl stearate 2.0 Sorbitan sesquioleate 1.5 Cetearyl alcohol 3.0 Mineral oil 4.0 Squalane 3.8 Carlyric / capric triglyceride 2.8 vegetable oil 1.8 Dimethicone 0.4 Dipotassium glycyrrhizate a very small amount Allantoin a very small amount Sodium hyaruronate a very small amount Tocopheryl acetate Suitable amount Triethanolamine Suitable amount Preservative Suitable amount Flavoring agent Suitable amount Purified water Balance

<1-3> Production of Lotion

Lotions containing the adiponectin-derived peptide of the present invention as an active ingredient were prepared according to the composition shown in Table 4 below.

Raw material Content (parts by weight) The adiponectin-derived peptide of Example 1 3.5 Cetostearyl alcohol 1.6 Stearic acid 1.4 Pro-type glycerin monostearate 1.8 FAGE -100 stearate 2.6 Sorbic acid sesquioleate 0.6 Squalene 4.8 Macadia oil 2 Jojoba oil 2 Tocopheryl acetate 0.4 Methylpolysiloxane 0.2 Ethylparaben 0.1 Tocopheryl acetate 0.4 Methylpolysiloxane 0.2 Ethylparaben 0.1 Propylparaben 0.1 1,3-butylene glycol 4 Methylparaben 0.1 Xanthan gum 0.1 glycerin 4 d-Pandenol 0.15 Allantoin 0.1 Carbomer (2% aq. Sol) 4 Triethanolamine 0.15 ethanol 3 pt 41891 0.1 p-H20 48.3

Preparation Example 2. Preparation of pharmaceutical preparations

&Lt; 2-1 >

Adiponectin-derived peptide of the present invention ··········· 2 g

Lactose ························· 1 g

The above components were mixed and packed in airtight bags to prepare powders.

<2-2> Preparation of tablets

Adiponectin-derived peptides of the present invention:

Corn starch · · · · · · · · · · · · · · · · · · ·

· · · · · · · · · · · · · · · · · · · · 100 ㎎

Magnesium stearate ········· 2 mg

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

&Lt; 2-3 > Preparation of capsules

Adiponectin-derived peptides of the present invention:

Corn starch · · · · · · · · · · · · · · · · · · ·

Lactose · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

Magnesium stearate ········· 2 mg

After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.

&Lt; 2-4 >

Adiponectin-derived peptides of the present invention ...... 1 g

Lactose ····················· 1.5 g

Glycerin · · · · · · · · · · · · · 1 g

Xylitol ··········· 0.5 g

After mixing the above components, they were prepared so as to be 4 g per one ring according to a conventional method.

<2-5> Preparation of granules

Adiponectin-derived peptide of the present invention ········· 150 mg

Soybean extract ··································· 50 ㎎

Glucose ····················· 200 mg

Starch ······························· 600 ㎎

After mixing the above components, 100 mg of 30% ethanol was added and the mixture was dried at 60 캜 to form granules, which were then filled in a capsule.

<2-6> Preparation of Injection Solution

Adiponectin-derived peptides of the present invention · · · · · · · · · · · · · · · · · · · · · · 10 μg / ml

Dilute hydrochloric acid BP ···········································································································································································

Sodium chloride for injection BP ······················· 1 ml

The TRPV1 inhibitory peptide of the present invention was dissolved in an appropriate volume of injectable sodium chloride BP and the pH of the resulting solution was adjusted to pH 3.5 using diluted hydrochloric acid BP. The volume was adjusted using injectable sodium chloride BP and mixed thoroughly Respectively. The solution was filled in a 5 ml Type I ampoule made of clear glass and sealed under the upper lattice of the air by dissolving the glass and sterilized by autoclaving at 120 ° C for 15 minutes or longer to prepare an injection solution.

<110> SEOUL NATIONAL UNIVERSITY HOSPITAL <120> COMPOSITION FOR SENSITIVE SKIN COMPRISING PEPTIDE DERIVED FROM          ADIPONECTIN <130> 2017-DPA-1899 <160> 23 <170> KoPatentin 3.0 <210> 1 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-1 peptide from adiponectin (IPGL) <400> 1 Ile Pro Gly Leu   One <210> 2 <211> 4 <212> PRT <213> Artificial Sequence <220> &Lt; 223 > P4-2 peptide from adiponectin (PGLY) <400> 2 Pro Gly Leu Tyr   One <210> 3 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-3 peptide from adiponectin (GLYY) <400> 3 Gly Leu Tyr Tyr   One <210> 4 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-4 peptide from adiponectin (LYYF) <400> 4 Leu Tyr Tyr Phe   One <210> 5 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-5 peptide from adiponectin (YYFA) <400> 5 Tyr Tyr Phe Ala   One <210> 6 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-6 peptide from adiponectin (YFAY) <400> 6 Tyr Phe Ala Tyr   One <210> 7 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-7 peptide from adiponectin (FAYH) <400> 7 Phe Ala Tyr His   One <210> 8 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-8 peptide from adiponectin (AYHI) <400> 8 Ala Tyr His Ile   One <210> 9 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-9 peptide from adiponectin (YHIT) <400> 9 Tyr His Ile Thr   One <210> 10 <211> 4 <212> PRT <213> Artificial Sequence <220> &Lt; 223 > P4-10 peptide from adiponectin (NIPG) <400> 10 Asn Ile Pro Gly   One <210> 11 <211> 4 <212> PRT <213> Artificial Sequence <220> &Lt; 223 > P4-11 peptide from adiponectin (CNIP) <400> 11 Cys Asn Ile Pro   One <210> 12 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-12 peptide from adiponectin (HCNI) <400> 12 His Cys Asn Ile   One <210> 13 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P4-13 peptide from adiponectin (palmitoyl-LYYF) <400> 13 Leu Tyr Tyr Phe   One <210> 14 <211> 5 <212> PRT <213> Artificial Sequence <220> P3 peptide from adiponectin (IPGLY) <400> 14 Ile Pro Gly Leu Tyr   1 5 <210> 15 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> P4 peptide from adiponectin (PGLYY) <400> 15 Pro Gly Leu Tyr Tyr   1 5 <210> 16 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> P5 peptide from adiponectin (GLYYF) <400> 16 Gly Leu Tyr Tyr Phe   1 5 <210> 17 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> P6 peptide from adiponectin (LYYFA) <400> 17 Leu Tyr Tyr Phe Ala   1 5 <210> 18 <211> 5 <212> PRT <213> Artificial Sequence <220> &Lt; 223 > P7 peptide from adiponectin (CNIPG) <400> 18 Cys Asn Ile Pro Gly   1 5 <210> 19 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> P8 peptide from adiponectin (KFHCN) <400> 19 Lys Phe His Cys Asn   1 5 <210> 20 <211> 5 <212> PRT <213> Artificial Sequence <220> P9 peptide from adiponectin (HCNIP) <400> 20 His Cys Asn Ile Pro   1 5 <210> 21 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> P10 peptide from adiponectin (NIPGL) <400> 21 Asn Ile Pro Gly Leu   1 5 <210> 22 <211> 18 <212> PRT <213> Artificial Sequence <220> &Lt; 223 > P1 peptide from adiponectin (KFHCNIPGLYYFAYHITV) <400> 22 Lys Phe His Cys Asn Ile Pro Gly Leu Tyr Tyr Phe Ala Tyr His Ile   1 5 10 15 Thr Val         <210> 23 <211> 8 <212> PRT <213> Artificial Sequence <220> P2 peptide from adiponectin (IPGLYYFA) <400> 23 Ile Pro Gly Leu Tyr Tyr Phe Ala   1 5

Claims (9)

Derived peptide selected from the group consisting of amino acid sequences of SEQ ID NOS: 4, 6, 7, 10, 11 and 14-21 as an active ingredient. delete The method according to claim 1,
Wherein the adiponectin-derived peptide is contained at a concentration of 0.001 to 20 mM. The method according to claim 1,
Wherein the cosmetic composition has any one of formulations of lotion, essence, lotion, cream, pack, gel, ointment, patch or spray. Derived peptide selected from the group consisting of amino acid sequences of SEQ ID NOS: 4, 6, 7, 10, 11 and 14-21 as an active ingredient. delete The method of claim 5,
Wherein the adiponectin-derived peptide is contained at a concentration of 0.001 to 20 mM. delete delete

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