WO2020050429A1 - Composition for sensitive skin comprising adiponectin-derived peptide - Google Patents

Abstract

The present invention relates to a composition comprising a peptide fragment derived from adiponectin and, more particularly, to a cosmetic composition and a pharmaceutical composition for sensitive skin comprising at least one adiponectin-derived peptide selected from the group consisting of the amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 21 as an active ingredient. Since the adiponectin-derived peptides activate downstream signaling pathways of adiponectin receptors in muscle cells involved in major pathogenesis of sensitive skin and also inhibit the activity of stimulatory receptors induced by sensitive skin-causing agents, the composition comprising an adiponectin-derived peptide can be effectively used for suppressing or alleviating symptoms of sensitive skin.

Description

Composition for sensitive skin comprising adiponectin derived peptide

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

Sensitive skin refers to skin that is more sensitive to external irritants, allergic substances, or environmental changes or internal causes of the body than normal skin, which causes irritation or dermatitis. These sensitive skin holders are on the increase. Some even claim that over half of all women in the United States are sensitive skin. Recently, interest in and skin science of sensitive skin has been increasing, but there is no method for alleviating 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, in general, sensitive skin holders easily react to adverse reactions due to external influences such as cosmetics, stress, and air pollution. These adverse reactions can vary not only from visible reactions such as erythema and non-inflammatory changes such as skin dryness or skin roughness, but also from subjective feelings such as itching and itching. In response, skin scientists define sensitive skin as skin that exhibits better contact stimuli or allergic reactions than the average population. As an experiment to screen sensitive skin, there is an example of distinguishing sensitive skin by treating lactic acid or DMSO known to cause irritation.

Adverse reactions on sensitive skin may follow inflammatory pathways such as contact irritation and allergic reactions. Since various inflammatory mediators (leukotrien, prostaglandin) and cytokines are involved in the reverse reaction, adverse reactions can be mitigated or diluted by the regulation of cytokines and inflammatory mediators.

In addition, it has been argued that a healthy stratum corneum is the most important factor in protecting skin from skin irritants. In fact, since the degree of skin irritation tendency and skin permeability are correlated, skin barrier failure is also a cause of sensitive skin. Therefore, strengthening the skin barrier is also one of the ways to normalize sensitive skin.

So far, cosmetic products for sensitive skin have been developed so that they do not cause contact dermatitis, allergic dermatitis, etc. by removing active ingredients that may cause irritation. However, due to environmental and psychological factors, the use of active ingredients is also required in cosmetics of sensitive skin holders. Accordingly, there is a need to develop a cosmetic product having a function of alleviating adverse reactions by regulating cytokines and inflammatory mediators, and improving and normalizing sensitive skin through a skin barrier strengthening function and a skin protection function (Republic of Korea Patent Publication) No. 10-2005-0080480).

On the other hand, adiponectin is a type of adipocaine, a protein hormone specifically secreted by fat cells. It improves insulin function and induces insulin resistance, thereby regulating cardiovascular diseases such as hyperglycemia, hyperinsulinemia, obesity, and atherosclerosis. Plays an important role in In addition, adiponectin has a function of suppressing metastasis and inflammatory reactions of cancer cells. Adiponectin not only promotes keratinocyte proliferation, but also promotes the expression of filarggrin, hyaluronic acid and extracellular matrix in the skin, thereby performing functions such as wound healing, suppressing fibrosis, improving skin wrinkles, and moisturizing (Korea) Published Patent Publication No. 10-2015-0032401). Recently, as a result of previous studies that performed microarray analysis on sensitive skin, abnormalities in the regulation of neurotransmission processes such as CGRP due to adiponectin reduction in muscles have been reported to be important for the pathogenesis of sensitive skin (Adiponectin Deficiency Contributes to Sensitivity in Human Skin.J Invest Dermatol. 2015 Sep; 135 (9): 2331-4).

Adiponectin consists of 244 amino acids and consists of a signal sequence, a collagen-like domain located at the N-terminal and a C1q-like globular domain located at the C-terminus. The hexamer and the 400 kDa polymer complex (HMW complex) are the major oligomers, and the polymer complex is known to have higher activity than the low molecular complex (LMW complex).

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

An object of the present invention is to provide a composition for sensitive skin containing adiponectin-derived peptide.

In order to solve the above problems, the present invention provides a cosmetic composition or pharmaceutical composition for sensitive skin containing at least one of adiponectin-derived peptides selected from the group consisting of the amino acid sequence 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, but is not limited thereto.

According to one embodiment of the present invention, the adiponectin-derived peptide may be contained in a cosmetic composition or pharmaceutical composition in 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, but is not limited to, a lotion, essence, lotion, cream, pack, gel, ointment, patch or spray formulation.

In addition, the present invention is a sensitized skin symptom comprising the step of treating or administering to a subject at least one of adiponectin derived peptides selected from the group consisting of a pharmaceutical or cosmetically effective amount of the amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 21. Provide mitigation methods.

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

The present invention relates to a composition comprising an adiponectin-derived peptide having a relaxing effect on sensitive skin, wherein the adiponectin-derived peptide activates a downstream signaling pathway of the adiponectin receptor in muscle cells involved in a major etiology of sensitive skin, and Since it inhibits the activity of stimulating receptors induced by sensitive skin-causing substances, the composition comprising the adiponectin-derived peptide can be effectively used to suppress or alleviate sensitive skin symptoms.

1 is a photograph showing the skin permeability test results of the peptide derived from adiponectin of the present invention.

2A to 2C show the effects of the adiponectin-derived peptides of the present invention on the increased activity of PPARRα and PPARγ corresponding to the sub-signaling pathway of the adiponectin receptor (FIGS. 2A and 2B) and phosphorylation of AMPK and ACC (FIG. 2C). It is a graph showing and electrophoresis pictures.

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, skin-sensitization-related genes induced by lactic acid.

Figure 4 shows the crystal structure for the structural position of the adiponectin peptide present in the adiponectin protein of the present invention.

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

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

Adiponectin peptide	Amino acid sequence (molecular weight)	Sequence number	Adiponectin peptide	Amino acid sequence (molecular weight)	Sequence number
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	Palmitoyl-LYYF	13

According to one embodiment of the invention, the adiponectin-derived peptide is preferably contained in a concentration of 0.001 to 20 mM in the cosmetic composition, more preferably contained in a concentration of 0.01 to 10 mM, but is not limited thereto. When the concentration of the peptide is less than 0.001 mM, it is difficult to obtain a relieving effect on sensitive skin, and when it exceeds 20 mM, there is no obvious increase in effect due to an increase in the content, resulting in poor production economics. Synthetic, for example, can be prepared by solid-phase peptide synthesis (solid-phase peptide synthesis), the microorganism is transformed with a recombinant vector containing a nucleic acid encoding the peptide to express the peptide by culturing the microorganism, and then It may be purified by the method of, but is not limited thereto.

The cosmetic composition according to the present invention may contain, in addition to the above peptides, other ingredients that can give a synergistic effect to the effects of the peptides, within a range that does not impair the desired effect of the present invention. For example, the cosmetic composition of the present invention can be used as a conventional adjuvant, such as antioxidant, stabilizer, solubilizer, vitamin, pigment, and fragrance, as well as any other substances that have a known emollient effect on sensitive skin, or carriers. It can contain.

The cosmetic composition of the present invention is not particularly limited in its formulation, and may be prepared in any formulation conventionally prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions , Powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray, and the like. On the other hand, scalp treatments, soaps, hair tonics, shampoos, conditioners, hair packs, hair gels, lotions, conditioners, hair oils, mousses, creams, solids, solutions, emulsions, dispersants, micelles, liposomes, ointments, It can also be prepared in the form of a lotion, essence, patch or spray.

When the formulation of the cosmetic composition is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier components. Can be used, and in the case of a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder can be used as a carrier component, especially in the case of a spray, additionally chlorofluorohydrocarbon, propane / And propellants such as butane or dimethyl ether.

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

When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, ethoxylated isostearyl alcohol, suspensions such as polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystals Cellulose, aluminum metahydroxide, bentonite, agar or trakant can be used, and in the case of surfactant-containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, Imidazolinium derivatives, methyltaurate, sarcosinate, fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters Become There.

According to a specific embodiment of the present invention, the adiponectin-derived peptide of the present invention has a remarkably excellent permeability to the skin (see FIG. 1), and increases the activity of proteins in the lower signaling pathway through activation of adiponectin receptors in human-derived cell lines. Can be induced (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 inhibit 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 active ingredient of a cosmetic composition for alleviating or suppressing sensitive skin symptoms.

On the other hand, the route of administration of the pharmaceutical composition for sensitive skin according to the present invention includes skin, oral cavity, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal, oral Or parenteral administration is preferred, but is not limited thereto. The '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 exhibiting the same or similar function to the adiponectin derived peptide according to the present invention. The composition may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, external preparations, suppositories, and sterile injectable solutions, respectively, according to a conventional method.

Solid preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills, and the like. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include external preparations and sterile injections such as powders, granules, tablets, capsules, sterilized aqueous solutions, liquids, non-aqueous solvents, suspensions, emulsions, syrups, suppositories, aerosols, etc. It can be used in the form of a formulation, preferably a cream, gel, patch, spray, ointment, warning agent, lotion agent, linen agent, pasta agent or cataplasma pharmaceutical composition for external use for the skin can be prepared and used. , But is not limited to this. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.

The composition may further contain preservatives, stabilizers, hydration or emulsification accelerators, adjuvants such as salts and / or buffers for osmotic pressure control, and other therapeutically useful substances, which are conventional methods of mixing, granulating or It can be formulated according to the coating method.

The pharmaceutical composition of the present invention can be variously changed according to various factors including the age, weight, general health, sex, administration time, administration route, discharge rate, drug combination, and severity of a specific disease.

When a 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 to contain the adiponectin-derived peptide in a unit dose of about 0.01 to 1,500 mg as an active ingredient, and for adults 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. When administered intramuscularly or intravenously to an adult, a single dose usually would be sufficient for a total dose of about 5 to 300 mg per day, but for some patients a higher daily dose may be desirable. The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormonal therapy, chemotherapy, and biological response modifiers.

In addition, the present invention is a sensitized skin symptom comprising the step of treating or administering to a subject at least one of adiponectin derived peptides selected from the group consisting of a pharmaceutical or cosmetically effective amount of the amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 21. Provide mitigation methods.

The pharmaceutically 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 may be adjusted according to the weight, age, sex, health status, diet, administration period, administration method, elimination rate, disease severity, etc. of a specific patient. Treatment or administration may be administered once a day, or may be carried out in several times.

The individual is a vertebrate, preferably a mammal, more preferably a human or a laboratory animal such as a rat, rabbit, guinea pig, hamster, dog, cat, and most preferably human, but is not limited thereto. .

The treatment or administration method may be applied, oral or parenteral administration, and when administered parenterally, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine epidural injection, cerebrovascular injection or chest It can be administered by my injection.

Hereinafter, the present invention will be described in more detail through examples.

However, the following examples are only for illustrating the present invention, and the contents of the present invention are not limited by the following examples.

Example 1. Preparation of adiponectin derived peptide

To synthesize the peptide of the present invention, Merrifield's SPPS (Solid PhasePeptide Synthesis) method (J. Am. Chem. Soc., 85 (14), 2149-2154) was used. First, for the synthesis of the peptide of the present invention, synthesis was started using 2-chlorotrityl chloride (CTC) resin, and the first step of Fmoc (9-fluorenylmethoxy carbonyl) amino acid was N, N-diisopropylethylamine (N , N-diisopropylethylamine, DIEA) was coupled under dichloromethane (DCM) solvent. HATU (N-[(dimethylamino-)-1H-1,2,3-triazolo [4,5-b] pyridin-1-yl-methylene] -N-methylmethaneamini from the next step Fmoc amino acid Um hexafluorophosphate N-oxide) and 1-hydroxy-7-azabenzotriazole (HOAt) or HBTU (N-[(1H-benzotriazol-1-yl) (dimethylamino) methylene] -N- The chain of peptides was extended by performing coupling using methylmethanealuminum hexafluorophosphate N-oxide) and DIEA (N, N-diisopropylethylamine) together with hydroxybenzotriazole (HOBt). At this time, synthesis from the C-terminal to the N-terminal direction, coupling the Fmoc-amino acid to the amino terminal, and then removing the Fmoc group with a 20% piperidine solution (Solid-Phase Synthesis: A Practical Guide (1 ed. ) .CRC Press.848), washed several times with DMF (Dimethylforamide), and then proceeded by coupling. Finally, after coupling the Fmoc-amino acid, the Fmoc group is removed with a 20% piperidine solution and carboxylic acid and N, N'-diisopropyl carbodiimide (DIC), 1-hydroxy-7-azabenzo Triacyl (HOAt) was used to couple the acyl group, followed by washing with DMF several times to dry. To this, TFA (Trifuloroacetic acid) -H ₂ O-triisopropylsilane (95: 2.5: 2.5, vol. / Vol.) Solution was added and reacted for 2 to 3 hours to remove the protecting group and remove it from the resin. After separating the peptides, each peptide having the amino acid sequence shown in Table 1 was synthesized by dipping the peptides with diethylether.

The crude peptide obtained by the above method was confirmed by using RP-HPLC (2996 Detector, 515 Pump, Waters) as a gradient solvent composition of acetonitrile and water containing 0.1% TFA, and confirming purity. As a result, less than 95% of the peptide was separated and purified by Prep-LC to obtain more than 97% of the peptide. As a result of elemental analysis with an elemental analyzer (EA1112, CE Instrument, Italy) to confirm the exact component of the peptide, it was confirmed that the content of each element of the peptide is identical to the content of each element obtained by calculating from the amino acid sequence. Did.

Example 2. Measurement of skin permeability of adiponectin derived peptide

Adiponectin is also broken down into smaller units containing a globular domain, and subunits having a globular domain have a higher activity than adiponectin having a full length, and these receptors for adiponectin include adiponectin receptor 1 (AdipoR1). Known as adiponectin receptor 2 (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 most similar to that of human skin and was verified using pig skin, which is generally used for the permeability test. After cut the size of pig skin into 2 cm in width and length, prepare FITC fluorescently attached peptide stock (positive control 8-mer length peptide 2, 4-mer peptide 4) and DMSO by concentration, and then fill the pig skin with sufficient The amount was applied. The light was blocked and placed in a 37 ° C incubator for 2 hours. After rapid freezing using LN2, cryosection was performed. After washing with DAPI (nuclear staining) for 5 minutes, it was 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 the skin as compared to a peptide having a length of 8 amino acids used as a control (FIG. 1).

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

Adiponectin acts by binding to adiponectin receptors, and when adiponectin receptors are activated, it is known to increase phosphorylation of AMPK, a lower signaling pathway, and activity of PPARα / PPARγ (Adiponectin Receptor as a Key Player in Healthy Longevity and Obesity-Related Diseases) Cell metabolism.Volume 17, Issue 2, 5 February 2013, Pages 185-196). Accordingly, the phosphorylation of AMPK (promoting sub-ACC phosphorylation) and the activity of PPARα / PPARγ were confirmed using the human muscle cell line RD cell line, which has been reported to be involved in the main etiology of sensitive skin. After culturing the human muscle cell line, RD cells, the cells were replaced with serum-free medium when the cells were 90% full. After treating the adiponectin-derived peptide and vehicle (normal control, CNT) of the present invention prepared in Example 1 and harvesting them after 24 hours, the proteins were separated, and the respective activity was measured using the corresponding assay kit and Western blot technique.

As a result, the adiponectin-derived peptide of the present invention induced an increase in the activity of PPARα and PPARγ corresponding to proteins of the lower signaling pathway through activation of the adiponectin receptor in human muscle cell lines (FIGS. 2A and 2B), and also AMPK and ACC. It was confirmed that phosphorylation was induced (FIG. 2C).

Example  4. Adiponectin  The effect of derived peptides on the action of sensitive skin-causing agents in human muscle cell lines

After culturing the human muscle cell line, the RD cell line, when the cells are 90% full, the cells are replaced with serum-free medium, and then the sensitive skin-inducing substance lactic acid (LA) 50 mM and the adiponectin peptide 5 μg of the present invention prepared in Example 1 / Ml, and after 4 hours, the cells were harvested and mRNA was extracted to observe the effect on the expression of the stimulatory receptors ASIC3 and TRPV1 and the neurotransmitter CGRP.

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

Example  5. Adiponectin  Within protein Adiponectin  Confirm the structure of peptides and the possibility of action through polymer formation in vivo

The three-dimensional structure of the adiponectin protein present in humans was analyzed to analyze the structural position of the adiponectin peptide prepared in the present invention and the possibility of adiponectin receptor action in vivo.

As a result, in the case of adiponectin peptide, it was found that a total of three times in the spherical domain known as the action site of the adiponectin protein were repeatedly present in the form of a trimer. Since it is distributed on the outer side, there is a high possibility that it can actually act on the adiponectin receptor. Particularly, in the case of the P5 peptide, it was confirmed that the peptide sequence repeated three times in the adiponectin protein formed a polymer when the three-dimensional protein structure was examined, and as a lipophilic amino acid inside the polymer and a hydrophilic amino acid outside the polymer. It can be confirmed that the possibility of acting on the adiponectin receptor by forming the polymer again when the hydrophilic substance is actually permeated into the human body (Fig. 4).

Example 6. Search for overlap of adiponectin peptide sequence with other proteins

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 overlaps with the amino acid sequence contained in other proteins actually present in the human body. In this case, it is difficult to see the sequence specifically present in adiponectin, and thus there is a problem that the likelihood of specifically acting on the adiponectin receptor decreases. Accordingly, a sequence overlapping with the adiponectin peptide sequence was searched among all protein sequences present in the human body using the UniProt database provided by NCBI.

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 belongs, and was confirmed to be a peptide sequence highly specific to the adiponectin protein.

Production Example 1. Preparation of cosmetic

<1-1> Preparation of flexible lotion

The flexible 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)
Adiponectin-derived peptide of Example 1	10.00
1,3-butylene glycol	1.00
Disodium LED	0.05
Allantoin	0.10
Dipotassium glyceride	0.05
Citric Acid	0.01
Sodium citrate	0.02
Glyceres-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
Flavor	a very small amount
Purified water	Balance

<1-2> Preparation of nutrition cream The nutrition cream containing the adiponectin-derived peptide of the present invention as an active ingredient was prepared as shown in Table 3 below.

Raw material	Content (parts by weight)
Adiponectin-derived peptide of Example 1	10.0
1,3-butylene glycol	7.0
glycerin	1.0
D-panthenol	0.1
Plant extracts	3.2
Magnesium aluminum silicate	0.3
PEG-40 stearate	1.2
Stearic Acid	2.0
Polysorbate 60	1.5
Lipophilic glyceryl stearate	2.0
Sorbitan sesquioleate	1.5
Cetearyl alcohol	3.0
Mineral oil	4.0
Squalane	3.8
Carlylic / Capric Triglyceride	2.8
vegetable oil	1.8
Dimethicone	0.4
Dipotassium glyceride	a very small amount
Allantoin	a very small amount
Sodium hyaluronate	a very small amount
Tocopheryl Acetate	Quantity
Triethanolamine	Quantity
Preservative	Quantity
Flavor	Quantity
Purified water	Balance

<1-3> Preparation of lotion A lotion containing the adiponectin-derived peptide of the present invention as an active ingredient was prepared as shown in Table 4 below.

Raw material	Content (parts by weight)
Adiponectin-derived peptide of Example 1	3.5
Cetostearyl alcohol	1.6
Stearic acid	1.4
Lipophilic monostearate glycerin	1.8
PAGE-100 Stearate	2.6
Sesquiolein acid sorbitan	0.6
Squalene	4.8
Macadamia oil	2
Jojoba oil	2
Tocopherol acetate	0.4
Methyl polysiloxane	0.2
Echile Paraben	0.1
Tocopherol acetate	0.4
Methyl polysiloxane	0.2
Echile Paraben	0.1
Propyl paraben	0.1
1,3-butylene glycol	4
Methyl paraben	0.1
Shotgun	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 preparation <2-1> Preparation of powder

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

Lactose ··········································································· 1 g

A powder was prepared by mixing the above components and filling the gas-tight fabric.

<2-2> Preparation of tablets

Adiponectin-derived peptide of the present invention ... 100 mg

Corn starch ··················· 100 mg

Lactose ······················ 100 mg

Magnesium stearate ················· 2 mg

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

<2-3> Preparation of capsules

Adiponectin-derived peptide of the present invention ... 100 mg

Corn starch ··················· 100 mg

Lactose ······················· 100 mg

Magnesium stearate ················· 2 mg

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

<2-4> Preparation of Ring

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

Lactose ························ 1.5 g

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

Xylitol · ····················· 0.5 g

After mixing the above components, it was prepared to be 4 g per ring according to a conventional method.

<2-5> Preparation of granules

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

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

Glucose ······················ 200 mg

Starch ·······················

After mixing the above components, 100 mg of 30% ethanol was added, dried at 60 ° C. to form granules, and then filled into the fabric.

<2-6> Preparation of injection solution

Adiponectin-derived peptide of the present invention: 10 μg / ml

Dilute hydrochloric acid BP ················ until pH 3.5

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

Dissolve the TRPV1 inhibitory peptide of the present invention in an appropriate volume of sodium chloride BP for injection, adjust the pH of the resulting solution to pH 3.5 using dilute hydrochloric acid BP, then adjust the volume using sodium chloride BP for injection and mix thoroughly Did. The solution was filled in a 5 ml Type I ampoule made of transparent glass, sealed under an upper grid of air by dissolving the glass, and autoclaved at 120 ° C. for 15 minutes or more to sterilize to prepare an injection solution.

Claims (9)

1. A cosmetic composition for sensitive skin containing at least one of adiponectin-derived peptides selected from the group consisting of amino acid sequences of SEQ ID NOs: 1 to 21.
2. The method according to claim 1,

   A cosmetic composition for sensitive skin containing at least one of adiponectin-derived peptides selected from the group consisting of SEQ ID NO: 16 and SEQ ID NO: 21.
3. The method according to claim 1,

   A cosmetic composition for sensitive skin containing the adiponectin-derived peptide at a concentration of 0.001 to 20 mM.
4. The method according to claim 1,

   The cosmetic composition is a cosmetic composition for sensitive skin having any one formulation selected from the group consisting of lotion, essence, lotion, cream, pack, gel, ointment, patch or spray formulation.
5. A pharmaceutical composition for sensitive skin containing at least one of adiponectin derived peptides selected from the group consisting of the amino acid sequences of SEQ ID NOs: 1 to 21.
6. The method according to claim 5,

   A pharmaceutical composition for sensitive skin containing at least one of adiponectin-derived peptides selected from the group consisting of SEQ ID NO: 16 and SEQ ID NO: 21.
7. The method according to claim 5,

   A pharmaceutical composition for sensitive skin containing the adiponectin-derived peptide at a concentration of 0.001 to 20 mM.
8. A method for alleviating sensitive skin symptoms comprising the step of treating or administering to a subject at least one of adiponectin derived peptides selected from the group consisting of a cosmetically effective amount of the amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 21.
9. The method according to claim 8,

   The subject is a method of alleviating human susceptible skin symptoms.

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