KR102531515B1 - Composition for preventing, treating, or improving melanin deficiency disease comprising FAM86A inhibitor as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing, treating, or improving melanin deficiency diseases comprising a FAM86A inhibitor as an active ingredient, and a method for screening a therapeutic agent for melanin deficiency diseases using the FAM86A inhibitor.

Description

Composition for preventing, treating, or improving melanin deficiency disease comprising FAM86A inhibitor as an active ingredient}

The present invention relates to a composition for preventing, treating, or improving melanin deficiency diseases comprising a FAM86A inhibitor as an active ingredient, and a method for screening a therapeutic agent for melanin deficiency diseases using FAM86A.

Melanin pigment determines skin color and protects the skin by absorbing ultraviolet rays. Melanin pigment is composed of an amino acid called tyrosine, and tyrosine is activated by an enzyme called tyrosinae. Tyrosine is synthesized into two types of melanin, pheomelanin or eumelanin, according to the conversion process. can see. Melanocytes that produce melanin pigment are derived from melanoblasts. When melanoblasts are stimulated and differentiated into melanocytes, tyrosinase is activated to convert tyrosine contained in the cells into DOPA (3,4-dihydroxy-L-phenyl-alanine), which then converts DOPA to dopaoxidase ( By the action of an enzyme called dopaoxidase, it is converted into a substance called dopaquinone and then synthesized into melanin. After making melanin, melanocytes migrate to the epidermal tissue of the upper layer of the skin and deliver melanin to keratinocytes present in the epidermal tissue. In the process of cell migration, melanin pigment is stored and transported in melanosomes. At the beginning of generation, there is no color, but as it gradually moves to the upper layer, it is filled with black pigment in 4-5 steps, finally becoming fully pigmented mature melanin granules.

Vitiligo is an acquired depigmentation disease in which white spots of various sizes and shapes appear on the skin due to death or necrosis of melanocytes. It is a relatively common disease that occurs in about 1% of the population worldwide, and there is no difference according to race or region. The most common age of onset is between the ages of 10 and 30, and in 95% of cases, the onset is before the age of 40, and 30% of patients have a family history. As for the clinical features of vitiligo, round or irregularly shaped white spots of various sizes appear, the degree of depigmentation is not clear at first, but it often becomes clear over time, and the boundary with normal skin may not be clear, but normal skin color It can be seen more clearly and distinctly. In rare cases, it may feel itchy. If white spots appear in hairy areas, especially in the hair and eyebrows, white hair may grow. Vitiligo can occur anywhere on the skin, but it often occurs in areas where bones protrude, such as fingers, toes, knees, and elbows, around the mouth, around the nose, around the eyes, armpits, and the inside of the wrist. It can also come to mucous membranes such as the lips or genitals, and it occurs especially well in areas that are frequently injured. The distribution of vitiligo may be bilaterally symmetrical or may show distribution along nerves. In addition to the simple appearance of white spots on the skin, vitiligo can be accompanied by pigment abnormalities in the iris and retina, diabetes, pernicious anemia, hypothyroidism or hyperactivity, Down syndrome, biliary cirrhosis, stomach cancer, Addison's disease, and alopecia areata. , can coexist with autoimmune diseases such as lupus erythematosus. Although the exact cause of vitiligo has not yet been clarified, several theories have been proposed, including autoimmune theory, stress, virus hypothesis, neurohumoral theory, and self-destruction theory of melanocytes. In addition, various factors such as inherent cellular defect, genetic factors, apoptosis, and abnormal calcium metabolism have been suggested.

Vitiligo requires continuous treatment using steroids or ultraviolet light because the lesion worsens in most patients if untreated. However, there are many cases in which appropriate treatment is not performed with conventional treatment methods, so a more effective treatment method is urgently required.

In addition to this, contrary to the general people's desire to have white and fair skin, the trend of preferring beautifully tanned skin is increasing day by day. In the world of black people, the darker the skin, the more beautiful it is accepted, and in Europe and the East, healthy dark brown skin is accepted as a symbol of leisure to play sports, and is recently used in fashion.

Accordingly, in the prior art, suntanning was performed using suntan oil containing a sunscreen, but there were disadvantages such as poor skin roughness or fine wrinkles. In addition, by using dihydroxyacetone (dihydroxyacetone) to cause a chemical bond on the skin surface to artificially make the skin black. However, dihydroxyacetone has disadvantages in that it roughens the skin and causes irritation, and it is difficult to apply evenly, causing stains even when used, and particularly damaging clothes when contaminated.

However, the relationship with FMA86A in the use of melanin deficiency-related diseases such as vitiligo and darkening of the skin is unclear. Therefore, in the present invention, it is intended to confirm the efficacy of FAM86A inhibitors in improving vitiligo or treating albinism and the effect of FAM86A inhibitors in darkening the skin.

Republic of Korea Patent Publication No. 10-2013-0017871

The technical problem to be achieved by the present invention is to provide a composition for treating and improving melanin deficiency diseases including vitiligo and white hair, wherein the composition inhibits the FAM86 family to treat and improve melanin deficiency diseases such as vitiligo. It was confirmed that it can be completed by including FAM86A inhibitors that can be expressed.

Accordingly, an object of the present invention is to provide a composition for preventing, treating or improving melanin deficiency diseases comprising a FAM86A inhibitor as an active ingredient.

In addition, an object of the present invention is to provide a screening method for melanin deficiency disease prevention or treatment comprising the following steps.

(a) treating cells expressing FAM86A protein or its mRNA with a test substance;

(b) measuring the expression level of the FAM86A protein or its mRNA in cells treated with and without a test substance; and

(c) selecting a substance that reduces the expression level of the FAM86A protein or its mRNA compared to control cells as a preventive or therapeutic agent for melanin deficiency disease.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

In order to solve the above problems, the present inventors confirmed that the amount of secretion and formation of melanin was significantly increased in the FAM86A knockdown group in melanocyte cell lines, thereby providing a composition for preventing, treating or improving melanin deficiency diseases comprising a FAM86A inhibitor as an active ingredient to provide.

As one embodiment of the present invention, the composition may be provided in the form of a pharmaceutical composition, a food composition, or a cosmetic composition, but is not limited thereto.

As another embodiment of the present invention, the food composition may be a health functional food composition, but is not limited thereto.

In another embodiment of the present invention, the melanin deficiency disease is leukoderma, vitiligo, quadchrome vitiligo, vitiligo ponctue, and syndromic albinism [eg, Alezzandrini syndrome, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome (Elejalde syndrome, Griscelli syndrome type 2 and Griscelli syndrome type 3, Waardenburg syndrome, Tietz syndrome, CrossMuKusick-Brin syndrome Breen syndrome), ABCD syndrome, albinism-deafness syndrome and Vogt-Koyanagi-Harada syndrome], oculocutaneous albinism, gray hair Canities, hypomelanosis (idiopathic guttate hypomelanosis, phylloid hypomelanosis, progressive macular hypomelanosis), piebaldism, nevus depigmentosus, postinflammatory hypopigmentation, pityriasis alba, Vagabond's leukomelanoderma, Yemenite deaf-blind hypopigmentation syndrome, It may be one or more selected from the group consisting of Wende-Bauckus syndrome, Woronoff's ring, melanism, Leucism, and skin depigmentation-related diseases, preferably It may be vitiligo or white hair, but is not limited thereto.

As another embodiment of the present invention, the composition may promote the synthesis or secretion of melanin.

As another embodiment of the present invention, the inhibitor may be a FAM86A activity inhibitor or expression inhibitor.

As another embodiment of the present invention, the activity inhibitor may be one or more selected from the group consisting of compounds, peptides, peptidomimetics, substrate analogs, aptamers, and antibodies that specifically bind to the FAM86A protein.

As another embodiment of the present invention, the expression inhibitor may be one or more selected from the group consisting of antisense nucleotides, RNAi, siRNA, miRNA, shRNA, and ribozymes that complementarily bind to mRNA of the FAM86A gene.

As another embodiment of the present invention, the shRNA may be represented by one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 11 to SEQ ID NO: 20.

As another embodiment of the present invention, the shRNA may target one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 21 to SEQ ID NO: 30.

As another embodiment of the present invention, the miRNA may be represented by one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 40 to SEQ ID NO: 45.

In addition, the present invention provides a method for preventing or treating melanin deficiency diseases by administering to a subject a composition comprising a FAM86A inhibitor as an active ingredient.

In addition, the present invention provides the use of a FAM86A inhibitor for preparing a medicament for the prevention or treatment of melanin deficiency diseases.

In addition, the present invention provides a preventive or therapeutic use of a melanin deficiency disease of a composition comprising a FAM86A inhibitor as an active ingredient.

In addition, the present invention provides a screening method for melanin deficiency disease prevention or treatment comprising the following steps.

(a) treating cells expressing FAM86A protein or its mRNA with a test substance;

(b) measuring the expression level of the FAM86A protein or its mRNA in cells treated with and without a test substance; and

(c) selecting a substance that reduces the expression level of the FAM86A protein or its mRNA compared to control cells as a preventive or therapeutic agent for melanin deficiency disease.

As another embodiment of the present invention, measuring the expression level of the mRNA is RT-PCR, quantitative or semi-quantitative RT-PCR (Quentitative or semi-Quentitative RT-PCR), quantitative or semi-quantitative real-time RT-PCR (Quentitative or semi-quantitative RT-PCR) It may be measured using one or more methods selected from the group consisting of semi-Quentitative real-timeRT-PCR), Northern blot, and DNA or RNA chip.

As another embodiment of the present invention, the protein expression level measurement is Western blot, ELISA, radioimmunoassay, radioimmunodiffusion method, Ouchterlony immunodiffusion method, rocket immunoelectrophoresis, immunohistochemical staining, immunoprecipitation analysis , complement fixation assay, it may be measured using one or more methods selected from the group consisting of FACS and protein chip.

As another embodiment of the present invention, the cell expressing the protein of FAM86A or its mRNA in step (a) may be a cell that produces excessive melanin, but is not limited thereto.

In addition, the present invention provides a composition for promoting black hair induction comprising a FAM86A inhibitor as an active ingredient.

In addition, the present invention provides a method for preventing gray hair or promoting black hair by administering a composition containing a FAM86A inhibitor as an active ingredient to a subject.

In addition, the present invention provides the use of a FAM86A inhibitor for preparing an agent for preventing gray hair or an accelerator for inducing black hair.

In addition, the present invention provides a use of a composition containing a FAM86A inhibitor as an active ingredient to prevent white hair or promote black hair.

In addition, the present invention provides a composition for color control of a subject comprising a FAM86A inhibitor as an active ingredient.

In addition, the present invention provides a method for controlling the color of a subject by administering to the subject a composition containing a FAM86A inhibitor as an active ingredient.

The present invention also provides the use of a FAM86A inhibitor for the manufacture of a color modulating agent in a subject.

In addition, the present invention provides a color control use of a subject comprising a FAM86A inhibitor as an active ingredient.

The composition containing the FAM86A inhibitor of the present invention as an active ingredient is related to melanin deficiency diseases, promotes melanin formation and secretion, and increases the expression of melanin formation-related genes to prevent, treat, or improve melanin deficiency diseases such as vitiligo. possible.

Therefore, using the FAM86A inhibitor of the present invention as a leading material, it can be used in various fields such as pharmaceuticals, external drugs, food additives, and cosmetic materials for the prevention and treatment of melanin deficiency diseases including vitiligo and hair loss. It is expected.

1 shows the result of confirming the amount of melanin produced through melanin contents assay by knocking down FAM86A in mouse melanoma cells using shRNA and then treating them with α-MSH that promotes melanin formation.
Figure 2 is a result of confirming the amount of melanin secretion through melanin secretion assay by knocking down FAM86A using shRNA in mouse melanoma cells and then processing α-MSH that promotes melanin formation.
Figure 3 is a result of confirming the amount of melanin production through melanin contents assay after knocking down FAM86A using shRNA in mouse melanoma cells.
Figure 4 is a result of confirming the amount of melanin secretion through melanin secretion assay after knocking down FAM86A using shRNA in mouse melanoma cells.
5 is a MAPK & MC1R signaling pathway protein related to FAM86A K / D level and melanin formation through western blotting analysis after knockdown of FAM86A using shRNA in mouse melanoma cells, ERK, JNK, p38, PKA, CREB, This is the result of confirming the expression level of MITF and Tyrosinase.
Figure 6 is a result of knocking down FAM86A using shRNA in mouse melanoma cells and then staining melanin through Fontana Masson staining to confirm the degree of melanin presence through a microscope.
Figure 7 is a result of measuring the expression level of genes (Tyrosinase, TYRP-1, TYRP-2, MITF) pivotal to melanin formation using real-time PCR after knockdown of FAM86A using shRNA in mouse melanoma cells am.
8 is a result of measuring the expression of cAMP, an important protein for melanin formation, using ELISA after FAM86A was knocked down using shRNA in mouse melanoma cells.
9 shows the results of confirming proteins binding to the MC1R protein, which is pivotal for melanin formation, in mouse melanoma cells by knockdown of FAM86A using shRNA and proceeding with immunoprecipitation-MC1R.

The present inventors have studied new therapeutic targets related to melanin to treat melanin deficiency diseases. Accordingly, FAM86A was explored and discovered among the FAM86 family, and the present invention was completed by confirming that FAM86A inhibitors have therapeutic and ameliorative effects on melanin deficiency diseases including albinism and vitiligo.

Specifically, the present inventors confirmed through the examples that the amount of melanin formation and secretion significantly increased in the FAM86A knockdown group compared to the α-MSH (melanocyte stimulating hormone) treated group and the control group in which FAM86A was not knocked down, FAM86A It was confirmed that the melanin deficiency disease treatment effect was excellent by inhibiting (see Examples of the present invention).

Accordingly, in order to solve the above problems, the present invention provides a composition for preventing, treating or improving melanin deficiency diseases comprising a FAM86A inhibitor as an active ingredient.

In addition, the present invention provides a composition for skin blackening comprising a FAM86A inhibitor as an active ingredient. When the FAM86A inhibitor of the present invention was applied to mouse melanoma cells, it showed a very strong melanin production promoting effect, confirming that it can be used as a skin darkening agent or suntanning agent.

Therefore, the FAM86A inhibitor of the present invention can be used as a composition for promoting melanin production, and can control the skin color or fur color of animals, including humans, by promoting melanin production, and can specifically exhibit an effect of darkening fur color.

As used herein, the term "protein" is used interchangeably with 'polypeptide' or 'peptide' and refers to a polymer of amino acid residues, eg as commonly found in proteins in nature.

As used herein, "polynucleotide" or "nucleic acid" refers to deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) in single or double stranded form. Unless otherwise limited, known analogs of natural nucleotides that hybridize to nucleic acids in a manner similar to naturally occurring nucleotides are also included. In general, DNA is composed of four bases: adenine (A), guanine (G), cytosine (C), and thymine (T), and RNA uses uracil (U) instead of thymine. has In a nucleic acid duplex, A forms a hydrogen bond with T or U, and C with G base, and the relationship between these bases is called 'complementary'.

On the other hand, 'mRNA (messenger RNA or messenger RNA)' is RNA that serves as a blueprint for polypeptide synthesis (protein translation) by transferring the genetic information of the nucleotide sequence of a specific gene to ribosome during protein synthesis. Using a gene as a template, single-stranded mRNA is synthesized through a transcription process.

In the present specification, "FAM86" is a protein belonging to the protein MTase family, and most mammalian genomes contain a single FAM86 gene, and primate FAM86 is contained within the replication region of a tumor-prone region and is located in several genomic locations. It is known to be widespread (Identification and Characterization of a Novel Evolutionarily Conserved Lysine-specific Methyltransferase Targeting Eukaryotic Translation Elongation Factor 2 (eEF2), JOURNAL OF BIOLOGICAL CHEMISTRY, VOLUME 289, NUMBER 44, OCTOBER 31, 2014).

In this specification, the FAM86 may be FAM86A, but is not limited thereto.

In the present specification, the FAM86A protein may be of mammalian origin, preferably of human origin. Most preferably, the FAM86A protein in the present invention is characterized by comprising the amino acid sequence of human FAM86A (NP_958802.1) represented by SEQ ID NO: 1 (NCBI Genbank accession number in parentheses).

The FAM86 mRNA preferably includes the nucleotide sequence of human FAM86A mRNA (NM_201400.4) represented by SEQ ID NO: 6 (NCBI Genbank accession number in parentheses). Characteristics such as the coding region (exon) of the above-mentioned human FAM86A mRNA transcript variants are confirmed in the sequence information obtained by searching the NCBI database with the Genbank accession number indicated in parentheses.

In the present specification, the inhibitor may be a FAM86A activity inhibitor or expression inhibitor, but is not limited thereto.

In the present specification, the activity inhibitor may be one or more selected from the group consisting of compounds, peptides, peptidomimetics, substrate analogs, aptamers, and antibodies that specifically bind to the FAM86A protein, but is not limited thereto.

In the present specification, the expression inhibitor may be one or more selected from the group consisting of antisense nucleotides, RNAi, siRNA, miRNA, shRNA, and ribozymes that complementarily bind to mRNA of the FAM86A gene, but are not limited thereto.

As used herein, the term "siRNA" refers to a sequence in which the sense strand (eg, a sequence corresponding to the FAM86A gene mRNA sequence) and the antisense strand (eg, a sequence complementary to the FAM86A gene mRNA sequence) are located opposite each other Thus, it may have a structure forming a double chain. In addition, siRNA molecules that can be used in the present invention may have a single-stranded structure having self-complementary sense and antisense strands. siRNA is not limited to complete pairing of double-stranded RNA parts that pair with each other, but is not paired by mismatch (corresponding bases are not complementary), bulge (no base corresponding to one chain), etc. parts may be included. Specifically, the total length is 10 to 100 bases, more specifically 15 to 80 bases, and even more specifically 20 to 70 bases. In the present invention, the siRNA may specifically target one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 31 to SEQ ID NO: 39.

As used herein, the term "shRNA (small hairpin RNA or short hairpin RNA)" refers to a sequence of RNA that makes a robust hairpin turn, which can be used to silence gene expression through RNA interference. The shRNA can be introduced into cells using any promoter that can function in eukaryotic cells, but the pLKO.1 vector was used in the present invention. These vectors are always passed on to the daughter cells so that the gene silencing can be inherited. The shRNA hairpin structure is degraded into siRNA, which is an intracellular mechanism, and is bound to the RNA-induced silencing complex. The complex described above binds to and degrades mRNA matched to the siRNA bound thereto. shRNAs are transcribed by RNA polymerase III, and shRNA production in mammalian cells may trigger an interferon response, as cells recognize the shRNA as a viral attack and seek defense. In the present invention, the shRNA may specifically include one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 11 to SEQ ID NO: 20, preferably one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 11 to SEQ ID NO: 20 may be made up of In the present invention, the shRNA may specifically target one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 21 to SEQ ID NO: 30.

In this specification, the term "miRNA (microRNA, microRNA)" refers to a single-stranded RNA molecule of 21-25 nucleotides that binds to the 3'-UTR of mRNA (messengerRNA) to control gene expression in eukaryotes ( BartelDP, et al., Cell, 23; 116(2): 281-297 (2004)). MiRNA is produced as a stem-loop precursor miRNA (pre-miRNA) by Drosha (RNaseIII type enzyme), moves to the cytoplasm, and is cleaved by Dicer to produce mature miRNA. In the present invention, the miRNA may specifically include one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 40 to SEQ ID NO: 45, preferably one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 40 to SEQ ID NO: 45 may be made up of

As used herein, the term "antisense oligonucleotide" refers to DNA or RNA or derivatives thereof containing a nucleic acid sequence complementary to a specific mRNA sequence, and binds to a complementary sequence in mRNA to translate the mRNA into a protein. has an inhibitory effect. For example, the antisense sequence of the present invention refers to a DNA or RNA sequence that is complementary to FAM86A and capable of binding to FAM86A mRNA, and is responsible for translation of FAM86A mRNA, translocation into the cytoplasm, maturation, or all other overall functions. May interfere with essential activities for biological functions. The length of the antisense nucleic acid is 6 to 100 bases, specifically 8 to 60 bases, more specifically 10 to 40 bases.

In the present specification, the term "ribozyme" is a type of RNA that has a function such as an enzyme that recognizes a specific RNA base sequence and cuts it itself. A ribozyme is composed of a region that binds with specificity to a complementary nucleotide sequence of a target messenger RNA strand and a region that cleaves the target RNA. As used herein, the term "aptamer" refers to an oligonucleotide (generally, an RNA molecule) that binds to a specific target. Specifically, "aptamer" in the present specification refers to an oligonucleotide aptamer ( For example, RNA aptamer).

In the present specification, siRNA or shRNA may be one in which various modifications are applied to improve in vivo stability of oligonucleotides, impart resistance to nucleases, and reduce non-specific immune responses. The modification of the oligonucleotide is that the OH group at the 2' carbon position of the sugar structure in one or more nucleotides is -CH ₃ (methyl), -OCH ₃ (methoxy), -NH ₂ , -F, -O-2-methoxyethyl, -O-propyl, -O-2-methylthioethyl, -O-3-aminopropyl, -O-3-dimethylaminopropyl, -ON-methylacetamido or -O-dimethylami modification by substitution with dooxyethyl; a modification in which an oxygen in a sugar structure in a nucleotide is replaced by a sulfur; Alternatively, one or more modifications selected from modifications of nucleotide bonds to phosphorothioate, boranophosphate, or methyl phosphonate bonds may be used in combination, and PNA (peptide nucleic acid), Modification in the form of locked nucleic acid (LNA) or unlocked nucleic acid (UNA) can also be used.

As used herein, the term "complementary" means that a targeting moiety in a nucleic acid molecule is selectively directed to a target (e.g., the FAM86A gene) under predetermined hybridization or annealing conditions, specifically physiological conditions (intracellular). It means something complementary enough to hybridize, which can have one or more mismatch base sequences, and has a meaning encompassing both substantially complementary and perfectly complementary things. , more specifically means fully complementary.

In the present specification, the melanin deficiency diseases to which the composition of the present invention can be applied include leukoderma, vitiligo, quadchrome vitiligo, vitiligo ponctue, and syndromic albinism. [e.g., Alezzandrini syndrome, Hermansky-Pudlak syndrome, ChediakHigashi syndrome, Griscelli syndrome (Elejalde syndrome) , Griscelli syndrome type 2 and Griscelli syndrome type 3, Waardenburg syndrome, Tietz syndrome, CrossMuKusick -Breen syndrome), ABCD syndrome, albinism-deafness syndrome and Vogt-Koyanagi-Harada syndrome], oculocutaneous albinism, canities, melanosis (idiopathic guttate hypomelanosis, phylloid hypomelanosis, progressive macular hypomelanosis), piebaldism , nevus depigmentosus, postinflammatory hypopigmentation, pityriasis alba, Vagabond's leukomelanoderma, Yemenite deaf-blind hypopigmentation syndrome , Wende-Bauckus syndrome, Woronoff's ring, amelanism, Leucism, and skin depigmentation-related diseases.

"Vitiligo", which is the object of improvement, treatment or prevention of the present invention, is a pigment deficiency characterized by localized depigmented spots as a result of loss of melanin and functional melanocytes from the skin epidermis. In addition, "canities (hair graying)" is a symptom called "graying or graying of hair", which means that the color tone of individual hair gradually weakens, and hair of various shades from normal to white hair is mixed. do. It is known that the gray hair is caused by a decrease in tyrosinase activity in hair bulbar melanocytes due to toxic oxidative damage of melanocytes, which are melanin biosynthetic cells.

The composition of the present invention may be provided in the form of a pharmaceutical composition, food composition, or cosmetic composition, but is not limited thereto.

In addition, the present invention provides a method for preventing or treating melanin deficiency diseases by administering to a subject a composition comprising a FAM86A inhibitor as an active ingredient.

In addition, the present invention provides the use of a FAM86A inhibitor for preparing a medicament for the prevention or treatment of melanin deficiency diseases.

In addition, the present invention provides a composition for preventing hair loss comprising a FAM86A inhibitor as an active ingredient.

In addition, the present invention provides a method for treating albinism by administering to a subject a composition containing a FAM86A inhibitor as an active ingredient.

In addition, the present invention provides the use of a FAM86A inhibitor for the preparation of a medicament for the prevention or treatment of albinism.

In the present specification, the composition may be to promote the synthesis or secretion of melanin, but is not limited thereto.

In addition, the present invention provides a composition for promoting black hair induction comprising a FAM86A inhibitor as an active ingredient. In addition, the present invention provides a method for promoting black hair induction by administering a composition containing a FAM86A inhibitor as an active ingredient to a subject and a use of the FAM86A inhibitor for promoting black hair induction.

In addition, the present invention provides a composition for adjusting the color of an individual comprising a FAM86A inhibitor as an active ingredient, and specifically, it may be a composition for adjusting the color of a companion animal's fur or skin color. In addition, the present invention provides a method for adjusting the color of a subject by administering a composition containing the FAM86A inhibitor as an active ingredient to the subject and a use of the FAM86A inhibitor for color control in the subject.

Since the FAM86A inhibitor of the present invention has an effect of promoting melanin production, the inclusion of the FAM86A inhibitor can prevent gray hair and promote the induction and production of black hair.

The present invention may also include a pharmaceutically acceptable salt of a FAM86A inhibitor as an active ingredient. As used herein, the term "pharmaceutically acceptable salt" includes salts derived from pharmaceutically acceptable inorganic acids, organic acids, or bases. In the present invention, the term "acceptable salt in food science" includes salts derived from organic acids, inorganic acids, or bases acceptable in food science. As used herein, the term "veterinarily acceptable salt" includes a salt derived from a veterinarily acceptable inorganic acid, organic acid, or base.

Examples of suitable acids are hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid , benzoic acid, malonic acid, gluconic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid and the like. Acid addition salts can be prepared by conventional methods, for example, by dissolving a compound in an aqueous solution of excess acid and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. It can also be prepared by heating equimolar amounts of the compound and an acid or alcohol in water and then evaporating the mixture to dryness, or suction filtering the precipitated salt.

Salts derived from suitable bases may include, but are not limited to, alkali metals such as sodium and potassium, alkaline earth metals such as magnesium, and ammonium. An alkali metal or alkaline earth metal salt can be obtained, for example, by dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable for pharmaceutical purposes to prepare a sodium, potassium or calcium salt, and the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

The content of the FAM86A inhibitor in the composition of the present invention can be appropriately adjusted according to the symptoms of the disease, the progress of the symptoms, the condition of the patient, etc., for example, 0.0001 to 99.9% by weight, or 0.001 to 50% by weight based on the total weight of the composition. It may be, but is not limited thereto. The content ratio is a value based on the dry amount after removing the solvent.

The pharmaceutical composition according to the present invention may further include suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions. The excipient may be, for example, one or more selected from the group consisting of a diluent, a binder, a disintegrant, a lubricant, an adsorbent, a moisturizer, a film-coating material, and a controlled release additive.

The pharmaceutical compositions according to the present invention are powders, granules, sustained-release granules, enteric granules, solutions, eye drops, elsilic agents, emulsions, suspensions, spirits, troches, perfumes, and limonadese, respectively, according to conventional methods. , tablets, sustained-release tablets, enteric tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, perfusate, It can be formulated and used in the form of external preparations such as warning agents, lotions, pasta agents, sprays, inhalants, patches, sterile injection solutions, or aerosols, and the external agents are creams, gels, patches, sprays, ointments, and warning agents. , lotion, liniment, pasta, or cataplasma may have formulations such as the like.

Carriers, excipients and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Corn starch, potato starch, wheat starch, lactose, sucrose, glucose, fructose, di-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, phosphoric acid as additives for tablets, powders, granules, capsules, pills, and troches according to the present invention Calcium monohydrogen, calcium sulfate, sodium chloride, sodium bicarbonate, purified lanolin, microcrystalline cellulose, dextrin, sodium alginate, methylcellulose, sodium carboxymethylcellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropylmethyl excipients such as cellulose, HPMC 1928, HPMC 2208, HPMC 2906, HPMC 2910, propylene glycol, casein, calcium lactate, and Primogel; Gelatin, gum arabic, ethanol, agar powder, cellulose phthalate acetate, carboxymethyl cellulose, calcium carboxymethyl cellulose, glucose, purified water, sodium caseinate, glycerin, stearic acid, sodium carboxymethyl cellulose, sodium methyl cellulose, methyl cellulose, microcrystalline cellulose, dextrin Binders such as hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, purified shellac, starch arc, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, and polyvinylpyrrolidone may be used, Hydroxypropyl Methyl Cellulose, Corn Starch, Agar Powder, Methyl Cellulose, Bentonite, Hydroxypropyl Starch, Sodium Carboxymethyl Cellulose, Sodium Alginate, Calcium Carboxymethyl Cellulose, Calcium Citrate, Sodium Lauryl Sulfate, Silicic Anhydride, 1-Hydroxy Propyl cellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, sodium bicarbonate, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, disintegrants such as amylopectin, pectin, sodium polyphosphate, ethyl cellulose, white sugar, magnesium aluminum silicate, di-sorbitol solution, and light anhydrous silicic acid; Calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopod, kaolin, petrolatum, sodium stearate, cacao butter, sodium salicylate, magnesium salicylate, polyethylene glycol 4000, 6000, liquid paraffin, hydrogenated soybean oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, macrogol, synthetic aluminum silicate, silicic anhydride, higher fatty acid, higher alcohol, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, starch, sodium chloride, A lubricant such as sodium acetate, sodium oleate, dl-leucine, light anhydrous silicic acid; may be used.

Additives for the liquid formulation according to the present invention include water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, sucrose monostearate, polyoxyethylene sorbitol fatty acid esters (tween esters), polyoxyethylene monoalkyl ethers, lanolin ethers, Lanolin esters, acetic acid, hydrochloric acid, aqueous ammonia, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethyl cellulose, sodium carboxymethyl cellulose, and the like may be used.

In the syrup according to the present invention, a solution of white sugar, other sugars, or a sweetener may be used, and aromatics, coloring agents, preservatives, stabilizers, suspending agents, emulsifiers, thickeners, etc. may be used as necessary.

Purified water may be used in the emulsion according to the present invention, and emulsifiers, preservatives, stabilizers, fragrances, etc. may be used as needed.

Suspension agents according to the present invention include acacia, tragacantha, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose (HPMC), HPMC 1828, HPMC 2906, HPMC 2910, etc. Agents may be used, and surfactants, preservatives, stabilizers, colorants, and fragrances may be used as needed.

Injections according to the present invention include distilled water for injection, 0.9% sodium chloride injection, IV injection, dextrose injection, dextrose + sodium chloride injection, PEG, lactated IV injection, ethanol, propylene glycol, non-volatile oil-sesame oil , solvents such as cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristate, and benzene benzoate; solubilizing agents such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, twins, nijuntinamide, hexamine, and dimethylacetamide; buffers such as weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, albumins, peptones, and gums; tonicity agents such as sodium chloride; Stabilizers such as sodium bisulfite (NaHSO ₃ ) carbon dioxide gas, sodium metabisulfite (Na ₂ S ₂ O ₃ ), sodium sulfite (Na ₂ SO ₃ ), nitrogen gas (N ₂ ), and ethylenediaminetetraacetic acid; Sulfating agents such as sodium bisulfide 0.1%, sodium formaldehyde sulfoxylate, thiourea, ethylenediamine disodium tetraacetate, acetone sodium bisulfite; analgesics such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; Suspending agents such as Siemesis sodium, sodium alginate, Tween 80, aluminum monostearate may be included.

The suppository according to the present invention includes cacao butter, lanolin, witapsol, polyethylene glycol, glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture of stearic acid and oleic acid, subanal, cottonseed oil, peanut oil, palm oil, cacao butter + Cholesterol, Lecithin, Lannet Wax, Glycerol Monostearate, Tween or Span, Imhausen, Monolen (Propylene Glycol Monostearate), Glycerin, Adeps Solidus, Buytyrum Tego-G -G), Cebes Pharma 16, Hexalide Base 95, Cotomar, Hydroxycote SP, S-70-XXA, S-70-XX75 (S-70-XX95), Hyde Hydrokote 25, Hydrokote 711, Idropostal, Massa estrarium (A, AS, B, C, D, E, I, T), Massa-MF, Masupol, Masupol-15, Neosupostal-N, Paramound-B, Suposiro (OSI, OSIX, A, B, C, D, H, L), suppository type IV (AB, B, A, BC, BBG, E, BGF, C, D, 299), Supostal (N, Es), Wecobi (W, R, S, M, Fs), testosterone triglyceride base (TG-95, MA, 57) and The same mechanism can be used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations contain at least one excipient, for example, starch, calcium carbonate, sucrose, etc. ) or by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.

The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type of patient's disease, severity, activity of the drug, It may be determined according to factors including sensitivity to the drug, administration time, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field.

The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by a person skilled in the art to which the present invention belongs.

The pharmaceutical composition of the present invention can be administered to a subject by various routes. All modes of administration can be envisaged, eg oral administration, subcutaneous injection, intraperitoneal administration, intravenous injection, intramuscular injection, paraspinal space (intrathecal) injection, sublingual administration, buccal administration, intrarectal insertion, vaginal It can be administered by intraoral insertion, ocular administration, otic administration, nasal administration, inhalation, spraying through the mouth or nose, dermal administration, transdermal administration, and the like.

The pharmaceutical composition of the present invention is determined according to the type of drug as an active ingredient together with various related factors such as the disease to be treated, the route of administration, the age, sex, weight and severity of the disease of the patient.

In the present invention, "subject" means a subject in need of treatment of a disease, and is not limited as long as it is a vertebrate, but specifically, humans, mice, rats, guinea pigs, rabbits, monkeys, pigs, horses, cows, It can be applied to sheep, antelopes, dogs, cats, fish and reptiles, preferably mammals with fur, and more preferably humans.

In the present invention, "administration" means providing a given composition of the present invention to a subject by any suitable method.

In the present invention, “prevention” refers to any action that suppresses or delays the onset of a desired disease, and “treatment” means that the desired disease and its resulting metabolic abnormality are improved or improved by administration of the pharmaceutical composition according to the present invention. All actions that are advantageously altered are meant, and "improvement" means any action that reduces a parameter related to a target disease, for example, the severity of a symptom, by administration of the composition according to the present invention.

In addition, the present invention provides a food composition comprising a FAM86A inhibitor as an active ingredient.

In addition, FAM86A inhibitors can be added to food for the purpose of improving melanin deficiency diseases.

In the present invention, food includes functional food and health functional food.

Preferably, the health functional food has the advantage of having a more excellent effect by ingesting it in the form of inner beauty food. The inner beauty refers to food referred to as 'eating cosmetics or beauty food', which absorbs various ingredients good for the skin into the body and changes the skin constitution to a healthy one. You can choose and consume the inner beauty food that suits your individual skin condition and lifestyle. More preferably, when the cosmetics containing the cosmetic composition and the inner beauty food containing the FAM86A inhibitor are mixed, the effect of treating or improving melanin deficiency diseases including vitiligo and white hair is significantly better than using only cosmetics or drugs. It has the advantage of being able to see a more effective melanin-related skin disease treatment or improvement effect.

When the FAM86A inhibitor of the present invention is used as a food additive, the FAM86A inhibitor may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In general, when producing food or beverage, the FAM86A inhibitor of the present invention is added in an amount of 15% by weight or less, preferably 10% by weight or less, based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

There is no particular limitation on the type of food. Examples of foods to which the above substances can be added include meat, sausages, bread, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice creams, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and includes all health functional foods in a conventional sense.

The health beverage composition according to the present invention may contain various flavoring agents or natural carbohydrates as additional components, like conventional beverages. The aforementioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrins and cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used. The proportion of the natural carbohydrate is generally about 0.01-0.20 g, preferably about 0.04-0.10 g per 100 mL of the composition of the present invention.

In addition to the above, the composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, A carbonation agent used in carbonated beverages and the like may be contained. In addition, the composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The ratio of these additives is not critical, but is generally selected in the range of 0.01-0.20 parts by weight per 100 parts by weight of the composition of the present invention.

The FAM86A inhibitor may be provided in the form of a cosmetic composition.

The formulation of the cosmetic composition according to the present invention is skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, moisture cream, hand cream, foundation, essence, nutrient essence, It may be in the form of a pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion or body cleanser.

The cosmetic composition of the present invention may further include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, and sphingolipids.

Any water-soluble vitamin can be used as long as it can be formulated into cosmetics, but preferably vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H, etc. salts (thiamin hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbic acid-2-phosphate, magnesium salt of ascorbic acid-2-phosphate, etc.) included Water-soluble vitamins can be obtained by conventional methods such as a microbial transformation method, a purification method from a microbial culture, an enzymatic method, or a chemical synthesis method.

Any useful vitamin may be used as long as it can be formulated into cosmetics, but preferably vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), etc. are mentioned. , their derivatives (ascorbine palmitate, ascorbine stearate, ascorbine dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol nicotinate, vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenylethyl ether, etc.) and the like are also included in the useful vitamins used in the present invention. The useful vitamins can be obtained by conventional methods such as microbial transformation, purification from microbial culture, enzymatic or chemical synthesis.

Any polymeric peptide may be used as long as it can be formulated into cosmetics, but preferably collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin and the like are mentioned. Polymer peptides can be purified and obtained by conventional methods such as a purification method from a culture medium of microorganisms, an enzyme method, or a chemical synthesis method, or can be used after being purified from natural products such as pig or cow dermis or silkworm silk fibers.

Any polymeric polysaccharide may be used as long as it can be incorporated into cosmetics, but hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or a salt thereof (sodium salt or the like) is preferable. For example, chondroitin sulfate or a salt thereof can be used after being purified from mammals or fish.

Any sphingolipid can be used as long as it can be incorporated into cosmetics, but ceramide, phytosphingosine, sphingoglycolipid and the like are preferred. Sphingolipids can be purified from mammals, fish, shellfish, yeast or plants by conventional methods or obtained by chemical synthesis.

In the cosmetic composition of the present invention, in addition to the above essential ingredients, other ingredients normally formulated in cosmetics may be blended as necessary.

Other ingredients that may be added include fats and oils, humectants, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, A blood circulation accelerator, a cooling agent, an antiperspirant, purified water, etc. are mentioned.

Examples of the oil and fat component include ester oils, hydrocarbon oils, silicone oils, fluorine oils, animal fats and vegetable oils.

Examples of ester oils include glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, and stearic acid. Butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine Diisopropyl acid, isoalkyl neopentanoate, tri(capryl, capric acid) glyceryl, trimethylolpropane tri2-ethylhexanoate, trimethylolpropane triisostearate, pentaelislitol tetra2-ethylhexanoate , Cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinooleate, isostea laurate Lil, isotridecyl myristate, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, 2-ethylhexanoate Aryl, 2-ethylstearyl hexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, di(caprylic, capric acid) propylene glycol, propylene glycol dicaprylate, dicap Neopentyl glycol prinate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate , Octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleate, polyglycerin isostearate, Triisocetyl citrate, triisoalkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyltriethyl citrate, acetyltributyl citrate, trioctyl citrate, dimalate Isostearyl, 2-ethylhexyl hydroxystearate, di2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, Cholesteryl Hydroxystearate, Cholesteryl Oleate, Dihydrocholesteryl Oleate, Physteryl Isostearate, Physteryl Oleate, Isocetyl 12-stealoylhydroxystearate, 12-stealoyylhydro and esters such as stearyl oxystearate and isostearyl 12-stealoylhydroxystearate.

Examples of hydrocarbon-based fats and oils include hydrocarbon-based fats and oils such as squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybuden, microcrystalline wax, and vaseline.

Examples of silicone oils include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane/methylcetyloxysiloxane copolymer, dimethylsiloxane/methylstealoxysiloxane copolymer, alkyl Modified silicone oil, amino modified silicone oil, etc. are mentioned.

Examples of fluorine-based fats and oils include perfluoropolyether and the like.

Animal or vegetable oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, birdflower oil, soybean oil, corn oil, rapeseed oil, algae oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil , cottonseed oil, palm oil, kukui nut oil, wheat germ oil, rice germ oil, shea butter, moonshine colostrum, marker damian nut oil, meadowsweet oil, egg yolk oil, beef tallow, horse oil, mink oil, orange raffia oil, jojoba oil , animal or plant fats and oils such as candelilla wax, carnaba wax, liquid lanolin, and hydrogenated castor oil.

Examples of the moisturizer include water-soluble low-molecular moisturizers, fat-soluble molecular moisturizers, water-soluble polymers, and oil-soluble polymers.

Examples of water-soluble low-molecular moisturizers include serine, glutamine, sorbitol, mannitol, pyrrolidone-sodium carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (polymerization degree n = 2 or more), polypropylene Glycol (polymerization degree n = 2 or more), polyglycerol B (polymerization degree n = 2 or more), lactic acid, lactate, etc. are mentioned.

Cholesterol, cholesterol ester, etc. are mentioned as a fat-soluble low-molecular moisturizer.

Examples of water-soluble polymers include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, water-soluble chitin, chitosan, dextrin, and the like. can

Examples of the fat-soluble polymer include polyvinylpyrrolidone/eicosene copolymer, polyvinylpyrrolidone/hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and high molecular silicone.

Examples of the emollient agent include long-chain acyl glutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, lanolin fatty acid cholesteryl ester, and the like.

Examples of the surfactant include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.

Nonionic surfactants include self-emulsifying glycerin monostearate, propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, POE (polyoxyethylene) sorbitan fatty acid esters, POE sorbitan fatty acid esters, POE Glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POE·POP (polyoxyethylene·polyoxypropylene) copolymer, POE·POP alkyl ether, polyether modified silicone, lauric acid alkanolamides, alkylamine oxides, hydrogenated soybean phospholipids, and the like.

Anionic surfactants include fatty acid soaps, alpha-acyl sulfonates, alkyl sulfonates, alkyl allyl sulfonates, alkyl naphthalene sulfonates, alkyl sulfates, POE alkyl ether sulfates, alkyl amide sulfates, alkyl phosphates, POE alkyl phosphates, and alkyl amide phosphates. , alkyloylalkyl taurine salts, N-acylamino acid salts, POE alkyl ether carboxylate salts, alkyl sulfosuccinate salts, sodium alkyl sulfoacetate, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, and the like. .

As the cationic surfactant, alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, chloride Benzalkonium, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salt, etc. are mentioned.

Amphoteric surfactants include carboxybetaine type, amidebetaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amideamine type, etc. An amphoteric surfactant etc. are mentioned.

As organic and inorganic pigments, silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium-coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, aluminum oxide inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine and complexes thereof; Polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenolic resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene/styrene copolymer, organic pigments such as silk powder, cellulose, CI pigment yellow and CI pigment orange, and composite pigments of these inorganic pigments and organic pigments.

Examples of the organic powder include metal soaps such as calcium stearate; Alkyl phosphate metal salts, such as zinc sodium cetylrate, zinc laurylate, and calcium laurylate; polyvalent metal salts of acyl amino acids such as N-lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc, and N-lauroyl glycine calcium; polyvalent metal salts of amide sulfonic acids such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoylizine, N-alpha-paritoylolnithine, N-alpha-lauroylarginine, N-alpha-hardened beef fatty acid acylarginine, etc. -acyl basic amino acids; N-acyl polypeptides such as N-lauroyl glycyl glycine; alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid; polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzene/styrene copolymer, tetrafluoroethylene, and the like.

Examples of UV absorbers include para-aminobenzoic acid, ethyl para-aminobenzoate, amyl para-aminobenzoate, octyl para-aminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, and benzyl cinnamate. , paramethoxycinnamic acid-2-ethoxyethyl, paramethoxycinnamic acid octyl, diparamethoxycinnamic acid mono-2-ethylhexane glyceryl, paramethoxycinnamic acid isopropyl, diisopropyl-diisopropylcinnamic acid ester mixture, uro Cannic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenonesulfonic acid and its salts, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone , tetrahydroxybenzophenone, 4-tert-butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1 ,3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, etc. are mentioned.

Bactericides include hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zincophylthione, benzalkonium chloride, photosensitizer So No. 301, mononitroguacol sodium, undecyrenic acid, etc. are mentioned.

Examples of antioxidants include butylhydroxyanisole, propyl gallic acid, and elisorbic acid.

Examples of the pH adjuster include citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumalate, succinic acid, sodium succinate, sodium hydroxide, and sodium monohydrogenphosphate.

Examples of alcohol include higher alcohols such as cetyl alcohol.

In addition, the blending components that may be added are not limited to these, and any of the above components can be blended within a range not impairing the objects and effects of the present invention, but preferably 0.01 to 5% by weight relative to the total weight, More preferably, it is formulated at 0.01-3% by weight percentage.

When the formulation of the present invention is a lotion, paste, cream or gel, animal fiber, vegetable fiber, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide as a carrier component can be used

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane / May contain a propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyl glycol oil, fatty acid esters of glycerol, polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or tracanth and the like may be used.

When the formulation of the present invention is surfactant-containing cleansing, as carrier components, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives, or ethoxylated glycerol fatty acid esters may be used.

In the present specification, the composition may be at least one formulation selected from the group consisting of shampoo, conditioner, hair tonic, hair nutrient lotion, hair essence, hair serum scalp treatment, hair treatment, hair conditioner, hair shampoo and hair lotion, , but is not limited thereto.

The composition according to the present invention may further contain appropriate components according to the formulation, and will be described in detail as follows.

In the present specification, it further contains any one or more selected from the group consisting of surfactants, preservatives and viscosity modifiers, pH modifiers, fragrances, dyes, hair conditioning agents, and water.

In the present specification, the surfactant is any one or more selected from anionic surfactants, amphoteric surfactants, and nonionic surfactants.

In the present specification, the anionic surfactant may be an alkyl sulfate or an alkyl ether sulfate, and specific examples thereof include sodium lauryl sulfate, ammonium lauryl sulfate, triethanolamine lauryl sulfate, polyoxyethylene sodium lauryl sulfate, and polyoxyethylene lauryl sulfate. Uryl ammonium sulfate etc. are mentioned.

In the present specification, the amphoteric surfactant may be an alkyl betaine or an alkyl amidopropyl betaine, and specific examples thereof include cocodimethyl carboxymethyl betaine, lauryldimethyl carboxymethyl betaine, lauryldimethyl alpha-carboxyethyl beta Phosphorus, cetyldimethyl carboxymethyl betaine, cocamido propyl betaine, etc. are mentioned.

In the present specification, the nonionic surfactant may be an alkanol amide or an amine oxide, and specific examples thereof include lauryl diethyl amine oxide, coconut oil alkyldimethyl amine oxide, lauric acid diethanolamide, coconut oil fatty acid diethanolamide, Coconut oil fatty acid monoethanolamide etc. are mentioned.

In the present specification, the preservative is at least one selected from the group consisting of methyl parahydroxybenzoate, propyl paraoxybenzoate, sodium benzoate, methylchloroisothiazolinone, methylisothiazolinone, and sodium benzoate.

In the present specification, the viscosity modifier is at least one of cocamide MEA (CME), cocamide DEA (CDE) and sodium chloride.

In the present specification, the pH adjusting agent is any one or more of sodium phosphate, disodium phosphate, citric acid and sodium citrate.

In the present specification, the hair conditioning agent is a dimethicone base, a cationic polymer, or a combination thereof.

In the present specification, the hair conditioning agent may further include any one or more of a tertiary amidoamine, a quaternary ammonium compound, a high melting point compound, and a silicone compound.

Specific examples of the tertiary amidoamine include cocaamidopropyl dimethylamine, stearamidopropyl dimethylamine, beheniramidopropyl dimethylamine, oleamidopropyl dimethylamine, isostearamidopropyl dimethylamine, and the like. can

Specific examples of the quaternary ammonium compound include alkyl (C 14 to 22) trimethyl ammonium chloride, dialkyl (C 14 to 22) dimethyl ammonium chloride, hydrogenated tallow alkyl trimethyl ammonium chloride, and ditallow alkyl dimethyl ammonium chloride. there is.

Specific examples of the high melting point compound include fatty alcohols, fatty acids, fatty alcohol derivatives, and hydrocarbons, and more specifically, cetyl alcohol, stearyl alcohol, and cetostearyl alcohol.

Specific examples of the silicone compound include polyalkylsiloxanes, polyarylsiloxanes, polyalkylarylsiloxanes, and polyethersiloxane copolymers.

In addition, the present invention provides a screening method for melanin deficiency disease prevention or treatment comprising the following steps.

(a) treating cells expressing FAM86A protein or its mRNA with a test substance;

(b) measuring the expression level of the FAM86A protein or its mRNA in cells treated with and without a test substance; and

(c) selecting a substance that reduces the expression level of the FAM86A protein or its mRNA compared to cells not treated with the test substance as a preventive or therapeutic agent for melanin deficiency disease.

In the present specification, the cell expressing the FAM86A protein or its mRNA includes cells in which the FAM86A protein or its mRNA is endogenously expressed or transiently highly expressed, or a nucleic acid encoding FAM86A is inserted into the cell. It can be used by introducing and transforming to overexpress, but is not particularly limited thereto.

In the present specification, the cell expressing the FAM86A protein or its mRNA may be one that produces excessive melanin, but is not particularly limited thereto.

As used herein, "expression" means the production of a protein or nucleic acid in a cell. The FAM86A-expressing cell may be a cell endogenously expressing FAM86A or a cell transformed with a recombinant expression vector containing a polynucleotide encoding FAM86A to overexpress FAM86A. Preferably, cells expressing the FAM86A gene may be cells derived from melanocytes. The present inventors have used the B6F10 cell line as a cell endogenously expressing FAM86A.

The term "test substance" used while referring to the screening method of the present invention refers to an unknown substance used in screening to examine whether or not it affects the expression of FAM86A of the present invention. The test substance is siRNA (small interference RNA), shRNA (short hairpin RNA), miRNA (microRNA), ribozyme, DNAzyme, PNA (peptide nucleic acids), antisense oligonucleotide, antibody, aptamer, natural extract or Including, but not limited to, chemicals.

In addition, the cells used in step (a) may be provided in the form of laboratory animals. In this case, the screening method of the present invention further comprises inducing a melanin deficiency disease in the laboratory animals, and the test substance and Contact includes parenteral or oral administration, stereotaxic injection, but is not limited thereto, and those skilled in the art will be able to select an appropriate method for testing a test substance on an animal.

Treating the test substance means adding the test substance to the cell or tissue culture medium and then incubating the cells for a certain period of time. When the cells are provided in the form of an experimental animal, contact with the test substance is not limited to parenteral or oral administration, including stereotaxic injection, and those skilled in the art can select an appropriate method to test the test substance on animals. will be.

In step (b) of the present invention, mRNA expression level measurement is performed by RT-PCR, quantitative or semi-quantitative RT-PCR (Quentitative or semi-Quentitative RT-PCR), and quantitative or semi-quantitative real-time RT-PCR (Quentitative or semi-quantitative RT-PCR). It may be measured using one or more methods selected from the group consisting of -Quentitative real-time RT-PCR), Northern blot, and DNA or RNA chip, but is not limited thereto.

In the step (b) of the present invention, the protein expression level measurement is Western blot, ELISA, radioimmunoassay, radioimmunoassay, Ouchterlony immunodiffusion method, rocket immunoelectrophoresis, immunohistochemical staining, immunoprecipitation analysis , complement fixation assay, it may be measured using one or more methods selected from the group consisting of FACS and protein chip, but is not limited thereto.

The step (c) is a step of selecting a substance that reduces the expression level of the FAM86A protein or its mRNA compared to the control cells as a preventive or therapeutic agent for melanin deficiency disease.

The control cells may be cells not treated with a test substance, but are not limited thereto.

Since the present invention can apply various transformations and have various embodiments, specific embodiments will be illustrated in the drawings and described in detail in the detailed description. However, this is not intended to limit the present invention to specific embodiments, and should be understood to include all conversions, equivalents, or substitutes included in the spirit and scope of the present invention. In describing the present invention, if it is determined that a detailed description of related known technologies may obscure the gist of the present invention, the detailed description will be omitted.

Hereinafter, a preferred embodiment is presented to aid understanding of the present invention. However, the following examples are provided to more easily understand the present invention, and the content of the present invention is not limited by the following examples.

[Example]

Example 1. Cell culture

B16F10 cells, a murine melanoma cell, and cells were cultured in DMEM (Dulbecco's modified Eagle's medium) containing 10% fetal bovine serum (FBS) and penicillin-streptomycin at 37°C and 5% carbon dioxide (CO2). ₂ ) was cultured in a cell culture medium.

Example 2. Confirmation of increase in melanin formation in α-MSH induced melanocytes

In order to induce melanin formation in a melanocyte cell line, α-MSH (melanocyte stimulating hormone), a melanin synthesis promoting hormone, was used.

The B16F10 cells cultured in Example 1 were dispensed in a 6-well plate to form 5×10 ⁴ cells per well, cultured for 24 hours, and then the FAM86A gene was synthesized using FAM86A shRNA represented by SEQ ID NO: 17 in Table 1. after knocking down. α-MSH was treated to be 100 nM. The treated cells were cultured for 48 hours in a cell incubator at 37°C and 5% carbon dioxide (CO ₂ ), then the cell culture medium was removed, and 200 μl of cell lysis buffer was applied to each well to lyse the cells, and then the cells were lysed. After centrifugation at 12,000 rpm for 5 minutes at ℃, the supernatant was removed. 100 μl of 10% sodium dodecyl sulfate-1M NaOH solution was dispensed into the obtained precipitate and heated at 60° C. for 30 minutes. Thereafter, the heated solution was left at room temperature, cooled to 25° C., and absorbance was measured at 405 nm, and the results are shown in FIG. 1 . At this time, the amount of melanin was calculated based on the amount of melanin formed in the cells not treated with α-MSH as 100%.

As shown in Figure 1, it was confirmed that the amount of melanin increased in the FAM86A knockdown group by treatment with α-MSH, a melanin synthesis promoting enzyme. Through this, it was found that melanin formation can be increased through FAM86A inhibition.

FAM86A shRNA ( Homo sapiens, Mus musculus ) sequence and target sequence sequence (shRNA sequences used in the examples are shown in bold ) Species shRNA No. Gene NCBI accession no. shRNA sequences Target sequence Vector Mean Knockdown level Homo sapiens One FAM86A NM_201400.4 CCGGGCAGAAACTGTTTCCCTACGACTCGAGTCGTAGGGAAACAGTTTCTGCTTTTTG GCAGAAACTGTTTCCCTACGA pLKO.1 0.93 2 FAM86A NM_201400.4 CCGGCGAGGGAATGTCCTTCTCAATCTCGAGATTGAGAAGGACATTCCCTCGTTTTTG CGAGGGAATGTCCTTCTCAAT pLKO.1 0.84 3 FAM86A NM_201400.4 CCGGGATGTTGTCATTGCAGCAGATCTCGAGATCTGCTGCAATGACAACATCTTTTTG GATGTTGTCATTGCAGCAGAT pLKO.1 0.79 4 FAM86A NM_201400.4 CCGGGCCAGCAGTTCTGGTTCTTAACTCGAGTTAAGAAACCAGAACTGCTGGCTTTTTG GCCAGCAGTTCTGGTTCTTAA pLKO.1 0.77 5 FAM86A NM_201400.4 CCGGGCAGACATCACTGCCAAGTTACTCGAGTAACTTGGCAGTGATGTCTGCTTTTTG GCAGACATCACTGCCAAGTTA pLKO.1 0.6 Mus musculus One FAM86 NM_027446.2 CCGGGAGCATTCAGCCATCGTAATCCTCGAGGATTACGATGGCTGAATGCTCTTTTTG GAGCATTCAGCCATCGTAATC pLKO.1 0.56 2 FAM86 NM_027446.2 CCGGGTCTATGTAGCCTATACTATCCTCGAGGATAGTATAGGCTACATAGACTTTTTG GTCTATGTAGCCTATACTATC pLKO.1 0.87 3 FAM86 NM_027446.2 CCGGGCCTTACAGGCCTGGCAATTTCTCGAGAAATTGCCAGGCCTGTAAGGCTTTTTG GCCTTACAGGCCTGGCAATTT pLKO.1 unverified 4 FAM86 NM_027446.2 CCGGACGGACCTTCTGTGAAGTATGCTCGAGCATACTTCACAGAAGGTCCGTTTTTG ACGGACCTTCTGTGAAGTATG pLKO.1 unverified 5 FAM86 NM_027446.2 CCGGGTTGTCATTGCAGCAGATGTACTCGAGTACATCTGCTGCAATGACAACTTTTTG GTTGTGATTGCAGCAGAGATGTA pLKO.1 unverified

siRNA ( Homo sapiens) Target sequence sequence of FAM86A Species siRNA No. Gene NCBI accession no. siRNA target sequence Homo sapiens One FAM86A NM_201400.4 aactcttgctgcagagttt 2 FAM86A NM_201400.4 cttagaagcaaagttaaga 3 FAM86A NM_201400.4 ttaagagactcatcagatt 4 FAM86A NM_201400.4 tctcaatggcctctcatta 5 FAM86A NM_201400.4 gaatgtttggagaatgtta Species siRNA No. Gene NCBI accession no. siRNA target sequence Mus musculus One FAM86A NM_027446 AAGAGCATTCAGCCATCGTAA 2 FAM86A NM_027446 AAGATGCTCGAGGACTGCCAG 3 FAM86A NM_027446 AACTCAGTTACACTCTCTGAG 4 FAM86A NM_027446 AAAACTCAGTTACACTCTCTGA

FAM86A miRNA ( Homo sapiens, Mus musculus ) sequence and target sequence Species miRNAs miRNA target gene miRNA target region miRNA sequences miRNA target sequences Reference Homo sapiens miR-145 FAM86A 397-404 of 3' UTR caccttgtcctcacggtccagttttcccaggaatcccttagatgctaagatggggattcctggaaatactgttcttgaggtcatggtttggaaatactgttcttgagg tcatggtt
aggaatc Integrated MicroRNA-mRNA profiling identifies oncostatin M as a marker of mesenchymal-like ER-negative/HER2-negative breast cancer, Target scan human_prediction of microRNA targets miR-204 FAM86A 767-773 of 3' UTR ggctacagtctttcttcatgtgactcgtggacttccctttgtcatcctatgcctgagaatatatgaaggaggctgggaaggcaaagggacgttcaattgtcatcactggc aaaggga Target scan human_prediction of microRNA targets miR-211 FAM86A 767-773 of 3' UTR tcacctggccatgtgacttgtgggcttccctttgtcatccttcgcctagggctctgagcagggcagggacagcaaaggggtgctcagttgtcacttcccacagcacggag aaaggga Target scan human_prediction of microRNA targets Mus musculus miR-370 FAM86 796-802 of 3' UTR agacggagagaccaggtcacgtctctgcagttacacagctcatgagtgcctgctggggtggaacctggtttgtctgtct cagcagg Target scan mouse_prediction of microRNA targets miR-290 FAM86 813-819 of 3' UTR ctcatcttgcggtactcaaactatgggggcacttttttttttctttaaaaagtgccgcctagttttaagccccgccggttgag tttgaga Target scan mouse_prediction of microRNA targets miR-292 FAM86 813-819 of 3' UTR cagcctgtgatactcaaactgggggctcttttggattttcatcggaagaaaagtgccgccaggttttgagtgtcaccggttg tttgaga Target scan mouse_prediction of microRNA targets

Sequence ( Homo sapiens, Mus musculus ) sequence of the FAM86 family Species Gene NCBI accession no. Sequence Homo sapiens FAM86A NM_201400.4 atggcgcccgaggagaacgcggggaccgaactcttgctgcagagtttcgagcgccgcttcctggcggcacgcacactgcgctccttcccctggcagagcttagaagcaaagttaagagactcatcagattctgagctgctgcgggatattttgcacaagactgtgaagcatcctgtgtgtgtgaagcacccgccgtccgtcaaatatgc ccggtgctttctctcagaactcatcaaaaagcacgaggctgtccacacagagcctttggacgagctgtatgaagcgctggcggagaccctgatggccaaggagtccacccagggccaccggagctatttgctgccctcgggaggctcggtcacactctccgagagcacggccatcatctcctacggtaccacaggcctggtcacatgggacgccgccctct accttgcagaatgggccatcgagaacccggcagtcttcactaacaggactgtcctagagcttggcagtggtgctggcctcacaggcctggccatctgcaagatgtgccgcccccgggcatacatcttcagcgactgtcacagccgggtccttgagcagctccgagggaatgtccttctcaatggcctctcattagaggcagacatcactgccaagttagacagcc ccagggtgacagtggcccagctggactgggacgtcgcgacggtccatcagctctctgccttccagccagatgttgtcattgcagcagatgtgctgtattgcccagaagccatcatgtcgctggtcggcgtcctgcggaggctggctgcctgccgggagcaccagcgggctcctgaggtctacgtggcctttaccgtccgcaacccagagacgt gccagctgttcaccaccgagctaggccgggccgggatcagatgggaagtggaacctcgtcatgagcagaaactgtttccctacgaagagcacttggagatggcaatgctgaatctcaccctgtag FAM86B1 NM_001083537.2 atggcgcccgaggagaacgcggggaccgaactcttgctgcagggttttgagcgccgcttcctggcggtgcgcacactgcgctccttcccctggcagagcttagaggcaaagttaagagactcatcagattctgagctgctgcgggatattttgcagaagactgtgaggcatcctgtgtgtgtgaagcacccgccgtcagtcaagtatg cctggtgctttctctcagaactcatcaaaaagtcctcaggaggctcagtcacactctccaagagcacagccatcatctcccacggtaccacaggcctggtcacatgggatgccgccctctaccttgcagaatgggccatcgagaacccggcagccttcattaacaggactgtcctagagcttggcagtggtgccggcctcacaggccttgccatctgcaaga tgtgccgccccccgggcatacatcttcagcgaccctcacagccgggtcctcgagcagctccgagggaatgtccttctcaatggcctctcattagaggcagacatcactggcaacttagacagccccagggtgacagtggcccagctggactgggacgtagcaatggtccatcagctctctgccttccagccagatgttgtcattgcagcagacgtgctgtattgcc cagaagccatcgtgtcgctggtcggggtcctgcagaggctggctgcctgccgggagcacaagcgggctcctgaggtctacgtggcctttaccgtccgcaacccagagacgtgccagctgttcaccaccgagctaggccgggatgggatcagatgggaagcggaagctcatcatgaccagaaactgtttccctatggagagcacttggagatggcaatg ctgaacctcacactgtag FAM86B2 NM_001137610.2 atggcgcccgaggagaacgcggggaccgaactcttgctgcagggttttgagcgccgcttcctggcggtgcgcacactgcgctccttcccctggcagagcttagaggcaaagttaagagactcatcagattctgagctgctgcgggatattttgcagaagactgtgaggcatcctgtgtgtgtgaagcacccgccgtcagtcaagtatg cctggtgctttctctcagaactcatcaaaaagcacgaggctgtccacacggagcctttggacaaactgtacgaggtgctcgcggagactctgatggccaaggagtccacccagggccaccggagctatttgctgtcctcaggaggctcagtcacactctccaagagcacagccatcatctcccacggtaccacaggcctggtcacatgggatgccgccctct accttgcagaatgggccatcgagaacccggcagccttcattaacaggactgtcctagagcttggcagtggtgccggcctcacaggccttgccatctgcaagatgtgccgcccccgggcatacatcttcagcgaccctcacagccggatcctcgagcagctccgagggaatgtccttctcaatggcctctcattagaggcagacatcactggcaacttagacagcccc agggtgacagtggcccagctggactgggacgtagcaatggtccatcagctctctgccttccagccagatgttgtcattgcagcagacgtgctgtattgcccagaagccatcgtgtcgctggtcggggtcctgcagaggctggctgcctgccgggagcacaagcgggctcctgaggtctacgtggcctttaccgtccgcaacccagagacatgccagct gttcaccaccgagctaggccgggatgggatcagatgggaagcggaagctcatcatgaccagaaactgtttccctatggagagcacttggagatggcaatgctgaacctcacactgtag FAM86C1 NM_018172.3 atggcgcccgaggagaacgcggggagcgaactcttgctgcagagttttcaagcgccgcttcctggcagcgcgcgccctgcgctccttccgctggcagagcttagaagcaaagttaagagactcatcagattctgagctgctgcgggatattttgcagaagcacgaggctgtccacacagagcctttggatgagctgtacgaggtg ctggtggagaccctgatggccaaggagtccacccagggccaccggagctatttgctgacgtgctgtattgcccagaagccatcgtgtcgctggtcggggtcctgcggaggctggctgcctgccgggagcaccagcgggctcctcaattctacatggcccttaccgtctgcaacccagagatgtgccagctgttcaccaccgagctatgctggactggga tcagatgggaagcggaagctcatcatgaccagaaactgtttccctacagagagcacttggagatggcaaagctga Mus musculus FAM86 NM_027446.2 atggcgcctgaggaccacgagggggccacgtctctgctgcagagtttcgagcgccgcttcctggcggctcgcgcgctgccctcctttccctggcagagcctagaagaaaaactaaaggacccctcgggttctgagctgttgctggctattctgcagaggactgtgaagcaccctgtgtgtgtgcagcacggaccttctgtgaag tatgcccgctgctttctctcaaagctcatcaaaaagcatgaggctgtacccacggagcctttggatgcactgtatgaggcgttggcagaggttctgatgacccaagagtccacccagtgccaccggagctatttgctgccttcaggaaactcagttacactctctgagagcactgccatcgtgtcccatggcaccacaggcttggttacatgggacgct gctctctacctggcagaatgggccattgagaacccagcagccttcactgacaggactatcctggagctaggcagtggagctggccttacaggcctggcaatttgcaaggcatgctgccccagagcatacatcttcagcgactgtcatgcccaagtgcttgagcagctccgtggaaacgttctcctcaacggcttctccttagagccgcacacccccattgacgca ggcagctcgaaggtgacagtggctcagctggactgggacgaggtgacagcctctcagctctctgccttccaggcagatgttgtcattgcagcagatgtactgtactgctgggagatgacactgtcactggtcagggtcctgaagatgctcgaggactgccagaggaagagcgctcctgatgtctatgtagcctatactatccgcagccaggacacaggca agctgttcatcgaagagctggaccgtgctggaatctactgggaagaggtgccccctcacactggcaaactgttcccttacgaagagcattcagccatcgtaatcctgaagctggtgctgaccagtcgccatggtgtttga

Amino Acid Sequence FAM86A (NP_958802.1) mapeenagtelllqsferrflaartlrsfpwqsleaklrdssdsellrdilhktvkhpvcvkhppsvkyarcflselikkheavhtepldelyealaetlmakestqghrsyllpsggsvtlsestaiisygttglvtwdaalylaewaienpavftnrtvlelgsgagltglaickmcrprayifsdchsrvleqlrgnvllnglsleaditakld sprvtvaqldwdvatvhqlsafqpdvviaadvlycpeaimslvgvlrrlaacrehqrapevyvaftvrnpetcqlfttelgragirweveprheqklfpyeehlemamlnltl FAM86B1 (NP_001077006.1) mapeenagtelllqgferrflavrtlrsfpwqsleaklrdssdsellrdilqktvrhpvcvkhppsvkyawcflselikkssggsvtlskstaiishgttglvtwdaalylaewaienpaafinrtvlelgsgagltgla ickmcrprayifsdphsrvleqlrgnvllnglsleaditgnldsprvtvaqldwdvamvhqlsafqp dvviaadvlycpeaivslvgvlq rlaacrehkrapevyvaftvrnpetcqlfttelgrdgirweaeahhdqklfpygehlemamlnltl FAM86B2 (NP_001131082.1) mapeenagtelllqgferrflavrtlrsfpwqsleaklrdssdsellrdilqktvrhpvcvkhppsvkyawcflselikkheavhtepldklyevlaetlmakestqghrsyllssggsvtlskstaiishgttglvtwdaalylaewaienpaafinrtvlelgsgagltglaickmcrprayifsdphsrileqlrgnvllnglsleaditgnldspr vtvaqldwdvamvhqlsafqpdvviaadvlycpeaivslvgvlqrlaacrehkrapevyvaftvrnpetcqlfttelgrdgirweaeahhdqklfpygehlemamlnltl FAM86C1 (NP_060642.2) mapeenagselllqsfkrrflaaralrsfrwqsleaklrdssdsellrdilqkheavhtepldelyevlvetlmakestqghrsylltcciaqkpscrwsgscggwlpagstsgllnstwplpsatqrcascsppsyaglgsdgkrklimtrncfptestwrwqs FAM86 (NP_081722.1) mapedhegatsllqsferrflaaralpsfpwqsleeklkdpsgselllailqrtvkhpvcvqhgpsvkyarcflsklikkheavptepldalyealaevlmtqestqchrsyllpsgnsvtlsestaivshgttglvtwdaalylaewaienpaaftdrtilelgsgagltglaickaccprayifsdchaqvleqlrgnvllngfslephtpid agsskvtvaqldwdevtasqlsafqadvviaadvlycwemtlslvrvlkmledcqrksapdvyvaytirsqdtgklfieeldragiyweevpphtgklfpyeehsaivilklvltsrhgv

Example 3. Confirmation of increase in melanin secretion in α-MSH induced melanocytes

In order to induce melanin formation in a melanocyte cell line, α-MSH (melanocyte stimulating hormone), a melanin synthesis promoting hormone, was used.

B16F10 cells cultured in Example 1 were divided into 5×10 ⁴ cells per well in a 6-well plate and cultured for 24 hours. FAM86A (family with sequence similarity 86, member A) represented by SEQ ID NO: 17 After knocking down the FAM86A gene using shRNA, α-MSH was treated to 100 nM. The treated cells were cultured for 48 hours in a cell incubator at 37°C and 5% carbon dioxide (CO ₂ ), and then 800 μl of the cell culture was transferred to a new tube and centrifuged at 4°C at 12,000 rpm for 5 minutes to obtain a supernatant. 100 μl of the obtained supernatant was dispensed into a 96-well plate and absorbance was measured at 475 nm, and the results are shown in FIG. 2 . At this time, the amount of melanin was calculated based on the amount of melanin secretion in the cell culture medium not treated with α-MSH as 100%.

As shown in Figure 2, it was confirmed that the secretion of melanin, the formation of which was increased by the treatment of α-MSH, a melanin synthesis promoting enzyme, was increased in the FAM86A knockdown group. Through this, it was found that the effect of increasing melanin secretion by FAM86A inhibition was found.

Example 4. Confirmation of increase in melanin formation according to the presence or absence of FAM86A knockout

B16F10 cells cultured in Example 1 were divided into 5×10 ⁴ cells per well in a 6-well plate, cultured for 24 hours, and then FAM86A gene knockdown was induced using FAM86A shRNA represented by SEQ ID NO: 17 did Cells were incubated for 48 hours in a cell incubator at 37℃ and 5% carbon dioxide (CO ₂ ), then the cell culture medium was removed, and 200 μl of cell lysis buffer was applied to each well to lyse the cells. After centrifugation for 5 minutes, the supernatant was removed. 100 μl of 10% sodium dodecyl sulfate-1M NaOH solution was dispensed into the obtained precipitate and heated at 60° C. for 30 minutes. Thereafter, the heated solution was left at room temperature, cooled to 25° C., and absorbance was measured at 405 nm, and the results are shown in FIG. 3 . At this time, the amount of melanin was calculated based on 100% of the amount of melanin in cells in which the FAM86A gene was not knocked out.

As shown in Figure 3, it was confirmed that the amount of melanin was increased in the FAM86A knockdown group. Through this, it was found that the effect of increasing melanin formation by FAM86A inhibition was found.

Example 5. Confirmation of increase in melanin secretion according to the presence or absence of FAM86A knockout

The B16F10 cells cultured in Example 1 were divided into 5×10 ⁴ cells per well in a 6-well plate, cultured for 24 hours, and then FAM86A gene knockdown was induced using FAM86A shRNA represented by SEQ ID NO: 17 did The cells were cultured for 48 hours in a cell incubator at 37°C and 5% carbon dioxide (CO ₂ ), and then 800 μl of the cell culture medium was transferred to a new tube, and the supernatant was obtained by centrifugation at 4°C and 12,000 rpm for 5 minutes. 100 μl of the obtained supernatant was dispensed into a 96-well plate and absorbance was measured at 475 nm, and the results are shown in FIG. 4 . At this time, based on the amount of melanin in the cells in which the FAM86A gene was not knocked out as 100%, the amount of melanin secretion was calculated.

As shown in Figure 4, it was confirmed that the melanin secretion increased in the FAM86A knockdown group. Through this, it was found that the effect of increasing melanin secretion by FAM86A inhibition was found.

Example 6. Western blotting for confirming melanin formation signaling pathway protein expression (Western blotting)

B16F10 cells cultured in Example 1 were divided into 5×10 ⁴ cells per well in a 6-well plate, cultured for 24 hours, and then FAM86A gene knockdown was induced using FAM86A shRNA represented by SEQ ID NO: 17 did The cells were cultured for 48 hours in a cell incubator at 37°C and 5% carbon dioxide (CO ₂ ) conditions. After that, it was washed twice with PBS. Then, after completely removing the PBS, 200 μl of RIPA buffer, which is a cell lysis and staining reagent, was put into each dish and scraped using a scraper. Then, after quantifying the protein by BCA assay, electrophoresis was performed using 10% SDS-PAGE. After transferring proteins from the electrophoresed SDS-PAGE gel to a PVDF membrane, the PVDF membrane on which protein transfer was completed was incubated with TBS-T (in 100 mM NaCl, 10 mM Tris, 0.1% (v/v) Tween-20, pH 7.4 ( PBST) containing 3% BSA). Then, after washing with TBS-T three times for 10 minutes, primary antibody was treated in TBS-T dissolved in 3% BSA for 1 hour, and TBS-T was sufficient. Washed. Then, the secondary antibody was treated for 1 hour and washed three times with PBS-T for 10 minutes each. Then, the amount and location of specific proteins were confirmed using the ECL detection system. The results are shown in FIG. 5 . Correction of the amount of protein was confirmed to be the same amount by confirming the amount of actin protein by recycling the PVDF membrane (stripping). Each antibody was purchased from Cell Signaling and Santacruz.

As shown in Figure 5, the expression level of MAPK & MC1R signaling pathway proteins related to melanin formation was confirmed. In the FAM86A knockdown group, p-JNK and p-p38, which are related to melanin formation, were increased, p-ERK was decreased, and the expression levels of p-PKA, p-CREB, and MITF proteins, which are proteins of the MC1R signaling pathway, were significantly increased. confirmed to increase. Through these results, it was confirmed that as the expression of FAM86A was lowered, the activity of MC1R, a melanin formation signaling pathway, increased, and when FAM86A was decreased, melanin formation was increased. Through this, it was found that the effect of increasing melanin secretion by suppressing FAM86A is shown.

Example 7. Fontana-Masson staining method for confirming the presence of melanin in cells (Fontana-Masson staining)

B16F10 cells cultured in Example 1 were divided into 5×10 ⁴ cells per well in a 6-well plate, cultured for 24 hours, and then FAM86A gene knockdown was induced using FAM86A shRNA represented by SEQ ID NO: 17 did Cells were cultured for 48 hours in a cell incubator at 37℃ and 5% carbon dioxide (CO ₂ ), washed twice with PBS, treated with 1ml of 1% amonical silver nitrate solution in each well, and dried in a 60℃ dryer for 1 hour. heated through. Then, after washing three times in running water, 0.2% gold chloride solution was treated for 30 seconds at 1ml each. Then, after washing twice in running water, 1 ml of 5% sodium thiosulfate solution was treated, and after washing twice in running water, 1 ml of neutral red 0.5% solution was treated for 2 minutes, and then washed in running water. After that, the result was confirmed through a microscope.

As shown in FIG. 6, it was confirmed that more melanin was present in the FAM86A knockdown group. Through this, it was found that the inhibition of FAM86A indicates that intracellular and extracellular melanin is increased.

Example 8. Confirmation of the expression level of genes related to melanin formation (realtime PCR)

B16F10 cells cultured in Example 1 were divided into 5×10 ⁴ cells per well in a 6-well plate, cultured for 24 hours, and then FAM86A gene knockdown was induced using FAM86A shRNA represented by SEQ ID NO: 17 did The cells were cultured for 48 hours in a cell incubator at 37°C and 5% carbon dioxide (CO ₂ ) conditions. After 48 hours, the cell culture medium was removed, the cells were lysed with TRI-Zol, and neutralized with BCP. After separating the supernatant from the neutralized liquid, mRNA was precipitated using isopropanol. Subsequently, only the precipitated mRNA was collected using a centrifuge and used for the experiment. Intracellular mRNA was synthesized into cDNA using a cDNA kit, and expression levels of Tyrosinase, TYRP-1, TYRP-2, and MITF genes, which are important genes for melanin formation, were confirmed through PCR, and are shown in FIG. 7 .

As shown in FIG. 7, it was confirmed that the expression levels of Tyrosinase, TYRP-1, TYRP-2, and MITF genes, which are important genes for melanin formation, were significantly increased in the FAM86A knockdown group. Through this, it was found that FAM86A exhibits an effect of increasing melanin formation.

Example 9. Confirmation of cAMP expression level (ELISA)

B16F10 cells cultured in Example 1 were divided into 5×10 ⁴ cells per well in a 6-well plate, cultured for 24 hours, and then FAM86A gene knockdown was induced using FAM86A shRNA represented by SEQ ID NO: 17 did After that, it was washed twice with PBS. Then, after completely removing the PBS, 200 μl of RIPA buffer, which is a cell lysis and staining reagent, was put into each dish and scraped using a scraper. Then, the protein was quantified by BCA assay, and cAMP protein expression was measured using cAMP ELISA KIT (ab65355).

As shown in Figure 8, it was confirmed that cAMP expression increased in the FAM86A knockdown group.

Example 10. Identification of proteins binding to MC1R protein (immunoprecipitation method)

The B16F10 cells cultured in Example 1 were divided into 5×10 ⁴ cells per well in a 6-well plate, cultured for 24 hours, and then FAM86A gene knockdown was induced using FAM86A shRNA represented by SEQ ID NO: 17 did After that, it was washed twice with PBS. Then, after completely removing the PBS, 200 μl of RIPA buffer, which is a cell lysis and staining reagent, was put into each dish and scraped using a scraper. Then, in order to perform immunoprecipitation analysis after protein quantification by BCA assay, the cell lysate was treated with anti-MC1R antibody (3 μg) and reacted in PBS for 1 hour, and then protein A/G-agarose Beads (protein A/G-agarose beads) were added and reacted for 24 hours at 4°C. The beads were washed three times with PBS containing 1 mM DTT and incubated with 2X protein loading dye (25% SDS, 62.5mM Tris-HCl (pH 6.8), 25% Gylcerol, and 0.01% Bromophenol Blue) for 5 minutes. It was heated to a temperature of 95°C. The samples were subjected to electrophoresis using SDS-PAGE to identify proteins binding to the MC1R protein, which is pivotal for melanin formation in knockdown cells.

As shown in Figure 9, it was confirmed that MC1R acts on melanin formation by binding to FAM86A.

In summary of the above examples, the present inventors have confirmed that melanin formation and secretion are increased through FAM86A inhibition, thereby preventing and treating melanin deficiency diseases. It can be seen that it can be used for pharmaceuticals, health functional foods, and cosmetic compositions for the prevention, treatment, or improvement of, and lead materials for their development.

The above description of the present invention is for illustrative purposes, and those skilled in the art can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting.

<110> Research & Business Foundation SUNGKYUNKWAN UNIVERSITY <120> Composition for preventing, treating, or improving melanin deficiency disease comprising FAM86 inhibitor a an active ingredients <130> MP19-208P1 <150> KR 10-2019-0100308 <151> 2019- 08-16 <160> 45 <170> KoPatentIn 3.0 <210> 1 <211> 330 <212> PRT <213> Artificial Sequence <220> <223> FAM86A(NP_958802.1) <400> 1 Met Ala Pro Glu Glu Asn Ala Gly Thr Glu Leu Leu Leu Leu Gln Ser Phe 1 5 10 15 Glu Arg Arg Phe Leu Ala Ala Arg Thr Leu Arg Ser Phe Pro Trp Gln 20 25 30 Ser Leu Glu Ala Lys Leu Arg Asp Ser Ser Asp Ser Glu Leu Leu Arg 35 40 45 Asp Ile Leu His Lys Thr Val Lys His Pro Val Cys Val Lys His Pro 50 55 60 Pro Ser Val Lys Tyr Ala Arg Cys Phe Leu Ser Glu Leu Ile Lys Lys 65 70 75 80 His Glu Ala Val His Thr Glu Pro Leu Asp Glu Leu Tyr Glu Ala Leu 85 90 95 Ala Glu Thr Leu Met Ala Lys Glu Ser Thr Gln Gly His Arg Ser Tyr 100 105 110 Leu Leu Pro Ser Gly Gly Ser Val Thr Leu Ser Glu Ser Thr Ala Ile 115 120 125 Ile Ser Tyr Gly Thr Thr Gly Leu Val Thr Trp Asp Ala Ala Leu Tyr 130 135 140 Leu Ala Glu Trp Ala Ile Glu Asn Pro Ala Val Phe Thr Asn Arg Thr 145 150 155 160 Val Leu Glu Leu Gly Ser Gly Ala Gly Leu Thr Gly Leu Ala Ile Cys 165 170 175 Lys Met Cys Arg Pro Arg Ala Tyr Ile Phe Ser Asp Cys His Ser Arg 180 185 190 Val Leu Glu Gln Leu Arg Gly Asn Val Leu Leu Asn Gly Leu Ser Leu 195 200 205 Glu Ala Asp Ile Thr Ala Lys Leu Asp Ser Pro Arg Val Thr Val Ala 210 215 220 Gln Leu Asp Trp Asp Val Ala Thr Val His Gln Leu Ser Ala Phe Gln 225 230 235 240 Pro Asp Val Val Ile Ala Ala Asp Val Leu Tyr Cys Pro Glu Ala Ile 245 250 255 Met Ser Leu Val Gly Val Leu Arg Arg Leu Ala Ala Cys Arg Glu His 260 265 270 Gln Arg Ala Pro Glu Val Tyr Val Ala Phe Thr Val Arg Asn Pro Glu 275 280 285 Thr Cys Gln Leu Phe Thr Thr Glu Leu Gly Arg Ala Gly Ile Arg Trp 290 295 300 Glu Val Glu Pro Arg His Glu Gln Lys Leu Phe Pro Tyr Glu Glu Glu His 305 310 315 320 Leu Glu Met Ala Met Leu Asn Leu Thr Leu 325 330 <210> 2 <211> 296 <212> PRT <213> Artificial Sequence <220> <223> FAM86B1 (NP_001077006.1) <400> 2 Met Ala Pro Glu Glu Asn Ala Gly Thr Glu Leu Leu Leu Leu Gln Gly Phe 1 5 10 15 Glu Arg Arg Arg Phe Leu Ala Val Arg Thr Leu Arg Ser Phe Pro Trp Gln 20 25 30 Ser Leu Glu Ala Lys Leu Arg Asp Ser Ser Asp Ser Glu Leu Leu Arg 35 40 45 Asp Ile Leu Gln Lys Thr Val Arg His Pro Val Cys Val Lys His Pro 50 55 60 Pro Ser Val Lys Tyr Ala Trp Cys Phe Leu Ser Glu Leu Ile Lys Lys 65 70 75 80 Ser Ser Gly Gly Ser Val Thr Leu Ser Lys Ser Thr Ala Ile Ile Ser 85 90 95 His Gly Thr Thr Gly Leu Val Thr Trp Asp Ala Ala Leu Tyr Leu Ala 100 105 110 Glu Trp Ala Ile Glu Asn Pro Ala Ala Phe Ile Asn Arg Thr Val Leu 115 120 125 Glu Leu Gly Ser Gly Ala Gly Leu Thr Gly Leu Ala Ile Cys Lys Met 130 135 140 Cys Arg Pro Arg Ala Tyr Ile Phe Ser Asp Pro His Ser Arg Val Leu 145 150 155 160 Glu Gln Leu Arg Gly Asn Val Leu Leu Asn Gly Leu Ser Leu Glu Ala 165 170 175 Asp Ile Thr Gly Asn Leu Asp Ser Pro Arg Val Thr Val Ala Gln Leu 180 185 190 Asp Trp Asp Val Ala Met Val His Gln Leu Ser Ala Phe Gln Pro Asp 195 200 205 Val Val Ile Ala Ala Asp Val Leu Tyr Cys Pro Glu Ala Ile Val Ser 210 215 220 Leu Val Gly Val Leu Gln Arg Leu Ala Ala Cys Arg Glu His Lys Arg 225 230 235 240 Ala Pro Glu Val Tyr Val Ala Phe Thr Val Arg Asn Pro Glu Thr Cys 245 250 255 Gln Leu Phe Thr Glu Leu Gly Arg Asp Gly Ile Arg Trp Glu Ala 260 265 270 Glu Ala His His Asp Gln Lys Leu Phe Pro Tyr Gly Glu His Leu Glu 275 280 285 Met Ala Met Leu Asn Leu Thr Leu 290 295 <210> 3 <211> 330 <212> PRT <213> Artificial Sequence <220 > <223> FAM86B2 (NP_NP_001131082.1) <400> 3 Met Ala Pro Glu Glu Asn Ala Gly Thr Glu Leu Leu Leu Leu Gln Gly Phe 1 5 10 15 Glu Arg Arg Phe Leu Ala Val Arg Thr Leu Arg Ser Phe Pro Trp Gln 20 25 30 Ser Leu Glu Ala Lys Leu Arg Asp Ser Ser Asp Ser Glu Leu Leu Arg 35 40 45 Asp Ile Leu Gln Lys Thr Val Arg His Pro Val Cys Val Lys His Pro 50 55 60 Pro Ser Val Lys Tyr Ala Trp Cys Phe Leu Ser Glu Leu Ile Lys Lys 65 70 75 80 His Glu Ala Val His Thr Glu Pro Leu Asp Lys Leu Tyr Glu Val Leu 85 90 95 Ala Glu Thr Leu Met Ala Lys Glu Ser Thr Gln Gly His Arg Ser Tyr 100 105 110 Leu Leu Ser Ser Gly Gly Ser Val Thr Leu Ser Lys Ser Thr Ala Ile 115 120 125 Ile Ser His Gly Thr Thr Gly Leu Val Thr Trp Asp Ala Ala Leu Tyr 130 135 140 Leu Ala Glu Trp Ala Ile Glu Asn Pro Ala Ala Phe Ile Asn Arg Thr 145 150 155 160 Val Leu Glu Leu Gly Ser Gly Ala Gly Leu Thr Gly Leu Ala Ile Cys 165 170 175 Lys Met Cys Arg Pro Arg Ala Tyr Ile Phe Ser Asp Pro His Ser Arg 180 185 190 Ile Leu Glu Gln Leu Arg Gly Asn Val Leu Leu Asn Gly Leu Ser Leu 195 200 205 Glu Ala Asp Ile Thr Gly Asn Leu Asp Ser Pro Arg Val Thr Val Ala 210 215 220 Gln Leu Asp Trp Asp Val Ala Met Val His Gln Leu Ser Ala Phe Gln 225 230 235 240 Pro Asp Val Val Ile Ala Ala Asp Val Leu Tyr Cys Pro Glu Ala Ile 245 250 255 Val Ser Leu Val Gly Val Leu Gln Arg Leu Ala Ala Cys Arg Glu His 260 265 270 Lys Arg Ala Pro Glu Val Tyr Val Ala Phe Thr Val Arg Asn Pro Glu 275 280 285 Thr Cys Gln Leu Phe Thr Thr Glu Leu Gly Arg Asp Gly Ile Arg Trp 290 295 300 Glu Ala Glu Ala His His Asp Gln Lys Leu Phe Pro Tyr Gly Glu His 305 310 315 320 Leu Glu Met Ala Met Leu Asn Leu Thr Leu 325 330 <210> 4 <211> 165 <212> PRT <213> Artificial Sequence <220> <223> FAM86C1(NP_NP_060642.2) <400> 4 Met Ala Pro Glu Glu Asn Ala Gly Ser Glu Leu Leu Leu Gln Ser Phe 1 5 10 15 Lys Arg Arg Phe Leu Ala Ala Arg Ala Leu Arg Ser Phe Arg Trp Gln 20 25 30 Ser Leu Glu Ala Lys Leu Arg Asp Ser Ser Asp Ser Glu Leu Leu Arg 35 40 45 Asp Ile Leu Gln Lys His Glu Ala Val His Thr Glu Pro Leu Asp Glu 50 55 60 Leu Tyr Glu Val Leu Val Glu Thr Leu Met Ala Lys Glu Ser Thr Gln 65 70 75 80 Gly His Arg Ser Tyr Leu Leu Thr Cys Cys Ile Ala Gln Lys Pro Ser 85 90 95 Cys Arg Trp Ser Gly Ser Cys Gly Gly Trp Leu Pro Ala Gly Ser Thr 100 105 110 Ser Gly Leu Leu Leu Asn Ser Thr Trp Pro Leu Pro Ser Ala Thr Gln Arg 115 120 125 Cys Ala Ser Cys Ser Pro Pro Ser Tyr Ala Gly Leu Gly Ser Asp Gly 130 135 140 Lys Arg Lys Leu Ile Met Thr Arg Asn Cys Phe Pro Thr Glu Ser Thr 145 150 155 160 Trp Arg Trp Gln Ser 165 <210> 5 <211> 335 <212> PRT <213> Artificial Sequence <220> <223> FAM86 (NP_081722.1) <400> 5 Met Ala Pro Glu Asp His Glu Gly Ala Thr Ser Leu Leu Gln Ser Phe 1 5 10 15 Glu Arg Arg Phe Leu Ala Ala Arg Ala Leu Pro Ser Phe Pro Trp Gln 20 25 30 Ser Leu Glu Glu Lys Leu Lys Asp Pro Ser Gly Ser Glu Leu Leu Leu 35 40 45 Ala Ile Leu Gln Arg Thr Val Lys His Pro Val Cys Val Gln His Gly 50 55 60 Pro Ser Val Lys Tyr Ala Arg Cys Phe Leu Ser Lys Leu Ile Lys Lys 65 70 75 80 His Glu Ala Val Pro Thr Glu Pro Leu Asp Ala Leu Tyr Glu Ala Leu 85 90 95 Ala Glu Val Leu Met Thr Gln Glu Ser Thr Gln Cys His Arg Ser Tyr 100 105 110 Leu Leu Pro Ser Gly Asn Ser Val Thr Leu Ser Glu Ser Thr Ala Ile 115 120 125 Val Ser His Gly Thr Thr Gly Leu Val Thr Trp Asp Ala Ala Leu Tyr 130 135 140 Leu Ala Glu Trp Ala Ile Glu Asn Pro Ala Ala Phe Thr Asp Arg Thr 145 150 155 160 Ile Leu Glu Leu Gly Ser Gly Ala Gly Leu Thr Gly Leu Ala Ile Cys 165 170 175 Lys Ala Cys Cys Pro Arg Ala Tyr Ile Phe Ser Asp Cys His Ala Gln 180 185 190 Val Leu Glu Gln Leu Arg Gly Asn Val Leu Asn Gly Phe Ser Leu 195 200 205 Glu Pro His Thr Pro Ile Asp Ala Gly Ser Ser Lys Val Thr Val Ala 210 215 220 Gln Leu Asp Trp Asp Glu Val Thr Ala Ser Gln Leu Ser Ala Phe Gln 225 230 235 240 Ala Asp Val Val Ile Ala Ala Asp Val Leu Tyr Cys Trp Glu Met Thr 245 250 255 Leu Ser Leu Val Arg Val Leu Lys Met Leu Glu Asp Cys Gln Arg Lys 260 265 270 Ser Ala Pro Asp Val Tyr Val Ala Tyr Thr Ile Arg Ser Gln Asp Thr 275 280 285 Gly Lys Leu Phe Ile Glu Glu Leu Asp Arg Ala Gly Ile Tyr Trp Glu 290 295 300 Glu Val Pro Pro His Thr Gly Lys Leu Phe Pro Tyr Glu Glu His Ser 305 310 315 320 Ala Ile Val Ile Leu Lys Leu Val Leu Thr Ser Arg His Gly Val 325 330 335 <210> 6 <211> 993 <212> DNA <213> Artificial Sequence <220> < 223> FAM86A mRNA (NM_201400.4) <400> 6 atggcgcccg aggagaacgc ggggaccgaa ctcttgctgc agagtttcga gcgccgcttc 60 ctggcggcac gcacactgcg ctccttcccc tggcagagct tagaagcaaa gttaagagac 120 tcatca gatt ctgagctgct gcgggatatt ttgcacaaga ctgtgaagca tcctgtgtgt 180 gtgaagcacc cgccgtccgt caaatatgcc cggtgctttc tctcagaact catcaaaaag 240 cacgaggctg tccacacaga gcctttggac gagctgtatg aagcgctggc ggagaccctg 30 0 atggccaagg agtccaccca gggccaccgg agctatttgc tgccctcggg aggctcggtc 360 acactctccg agagcacggc catcatctcc tacggtacca caggcctggt cacatgggac 420 gccgccctct accttgcaga atgggccatc gagaacccgg cagtcttcac taacaggact 480 gtcctagagc ttggcagtgg tgctggcctc acaggcctgg ccatctgcaa gatgtgccgc 540 ccccgggcat acatcttcag cgactgtcac agccgggtcc ttgagcagct ccgagggaat 600 gtccttctca atggcctctc attagaggca gacatcactg ccaagttaga cagccccagg 660 gtgacagtgg cccagctg ga ctgggacgtc gcgacggtcc atcagctctc tgccttccag 720 ccagatgttg tcattgcagc agatgtgctg tattgcccag aagccatcat gtcgctggtc 780 ggcgtcctgc ggaggctggc tgcctgccgg gagcaccagc gggctcctga ggtctacgtg 840 gcctttaccg tccgcaaccc agagacgtgc cagctgttca ccaccgagct aggccgggcc 900 gggatcagat gggaagt gga acctcgtcat gagcagaaac tgtttcccta cgaagagcac 960 ttggagatgg caatgctgaa tctcaccctg tag 993 <210> 7 <211> 891 <212> DNA <213> Artificial Sequence <220> <223> FAM86B1 mRNA (NM_001083537.2) <400> 7 atggcgcccg aggagaacgc ggggaccgaa ctcttgctgc agggttttga gcgccgcttc 60 ctggcggtgc gcacactgcg ctccttcccc tggcagagct tagaggcaaa gttaagagac 12 cggtacc aca 300 ggcctggtca catgggatgc cgccctctac cttgcagaat gggccatcga gaacccggca 360 gccttcatta acaggactgt cctagagctt ggcagtggtg ccggcctcac aggccttgcc 420 atctgcaaga tgtgccgccc ccgggcatac atcttcagcg accctcacag ccgggtcctc 480 gagca gctcc gagggaatgt ccttctcaat ggcctctcat tagaggcaga catcactggc 540 aacttagaca gccccagggt gacagtggcc cagctggact gggacgtagc aatggtccat 600 cagctctctg ccttccagcc agatgttgtc attgcagcag acgtgctgta ttgcccagaa 660 gccatcgtgt cg ctggtcgg ggtcctgcag aggctggctg cctgccggga gcacaagcgg 720 gctcctgagg tctacgtggc ctttaccgtc cgcaacccag agacgtgcca gctgttcacc 780 accgagctag gccgggatgg gatcagatgg gaagcggaag ctcatcatga ccagaaactg 840 tttccctatg gagagcactt ggagatggca atgctgaacc tcacactgta g 891 <210> 8 <211> 993 <212> DNA <213> Artificial Sequence <220> <223> FAM86B2 mRNA (NM_001137610.2) < 400 > 8 atggcgcccg aggagaacgc ggggaccgaa ctcttgctgc agggttttga gcgccgcttc 60 ctggcggtgc gcacactgcg ctccttcccc tggcagagct tagaggcaaa gttaagagac 120 tcatcagatt ctgagctgct gcgggatatt ttgcagaaga ctgtgaggca tcctgtgtgt 180 gtgaagcacc cgccgtcagt caagtatgcc tggtgctttc tctcagaact catcaaaaag 240 cacgaggctg tccacacgga gcctttggac aaactgtacg aggtgctcgc ggagactctg 300 atggccaagg agtccaccca gggccacccgg agctatttgc tgtcctcagg aggctcagtc 360 acactctcca agagcacagc catcatctcc cacggtacca caggcctggt cacatgggat 420 gccgccctct accttgcaga atgggccatc gagaacccgg cagccttcat taacaggact 480 gtcctagagc ttggcagtgg tgccggcctc acaggccttg ccatctgcaa gatgtgccgc 540 ccccgggcat acatcttcag cgaccctcac agccggatcc tcgagca gct ccgagggaat 600 gtccttctca atggcctctc attagaggca gacatcactg gcaacttaga cagccccagg 660 gtgacagtgg cccagctgga ctgggacgta gcaatggtcc atcagctctc tgccttccag 720 ccagatgttg tcattgcagc agacgtgctg tattgcccag aagccatcgt gtcgctggtc 780 ggggtcctgc agaggctggc tgcctgccgg gagcacaagc gggctcctga ggtctacgtg 840 gcctttaccg tccgcaaccc agagacatgc cagctgttca ccaccgagct aggccgggat 900 gggatcagat gggaagcgga agctcatcat gaccagaaac tgtttcccta tggagagcac 960 ttggagatgg caatgctgaa cctcacactg tag 993 <210> 9 <2 11> 498 <212> DNA <213> Artificial Sequence <220> <223> FAM86C1 mRNA (NM_018172.3) <400> 9 atggcgcccg aggagaacgc ggggagcgaa ctcttgctgc agagtttcaa gcgccgcttc 60 ctggcagcgc gcgccctgcg ctccttccgc tggcagagct tagaagcaaa gttaagagac 120 tcatcagatt ctgagctgct gcgggatatt ttg cagaagc acgaggctgt ccacacagag 180 cctttggatg agctgtacga ggtgctggtg gagaccctga tggccaagga gtccacccag 240 ggccaccgga gctatttgct gacgtgctgt attgcccaga agccatcgtg tcgctggtcg 300 gggtcctgcg gaggctggct gcc tgccggg agcaccagcg ggctcctcaa ttctacatgg 360 cccttaccgt ctgcaaccca gagatgtgcc agctgttcac caccgagcta tgctggactg 420 ggatcagatg ggaagcggaa gctcatcatg accagaaact gtttccctac agagagcact 480 tggagatggc aaagctga 498 <210> 10 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> FAM86 mRNA (NM_027446.2) <400> 10 atggcgcctg aggaccacga gggggccacg tctctgctgc agagtttcga gcgccgcttc 60 ctggcggctc gcgcgctgcc ctcctttccc tggcagagcc tagaagaaaa actaaaggac 120 ccctcgggtt ctgagctgtt gctggctatt ctgcagagga ctgtgaagca ccctgtgtgt 180 gtgcagcacg gaccttctgt gaagtatgcc cgctgctttc tctcaaagct catcaaaaag 240 catgaggctg tacccacgga gcctttggat gcactgtatg aggcgttggc agaggttctg 300 atgacccaag agtccaccca gtgccaccgg agctatttgc tgccttcagg aaactcagtt 360 acactctctg agagcactgc catcgtgtcc catggcacca caggcttggt tacatgggac 420 gctgctctct acctggcaga atgggccatt gagaacccag cagccttcac tgacaggact 480 atcctggagc taggcagtgg agctggcctt acaggcctgg caatttgcaa ggcatgctgc 540 cccagagcat acatcttcag cgactgtcat gcccaagtgc ttgagcagct ccgtggaaac 600 gttctcctca acggcttctc cttagagccg caca ccccca ttgacgcagg cagctcgaag 660 gtgacagtgg ctcagctgga ctgggacgag gtgacagcct ctcagctctc tgccttccag 720 gcagatgttg tcattgcagc agatgtactg tactgctggg agatgacact gtcactggtc 780 agggtcctga agatgct cga ggactgccag aggaagagcg ctcctgatgt ctatgtagcc 840 tatactatcc gcagccagga cacaggcaag ctgttcatcg aagagctgga ccgtgctgga 900 atctactggg aagaggtgcc ccctcacact ggcaaactgt tcccttacga agagcattca 960 gccatcgtaa tcctgaagct ggtgctgacc agtcgccatg gtgtttga 1008 <210> 11 <211> 58 <212> RNA <213> Artificial Sequence < 220> <223> Homo sapiens FAM86A shRNA <400> 11 ccgggcagaa actgtttccc tacgactcga gtcgtaggga aacagtttct gctttttg 58 <210> 12 <211> 58 <212> RNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A shRNA <400> 12 ccggcgaggg aatgtccttc tcaatctcga gattgagaag gacattccct cgtttttg 58 <210 > 13 <211> 58 < 212> RNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A shRNA <400> 13 ccgggatgtt gtcattgcag cagatctcga gatctgctgc aatgacaaca tctttttg 58 <210> 14 <211> 58 <212> RNA <213> Artificial Sequence <22 0> < 223> Homo sapiens FAM86A shRNA <400> 14 ccgggccagc agttctggtt cttaactcga gttaagaacc agaactgctg gctttttg 58 <210> 15 <211> 58 <212> RNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A shRNA <400> 15 ccgggcagac atcactgcca agttactcga gtaacttggc agtgatgtct gctttttg 58 <210> 16 <211> 58 <212> RNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA <400> 16 ccgggagcat tcagccatc g taatcctcga ggattacgat ggctgaatgc tctttttg 58 < 210> 17 <211> 58 <212> RNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA <400> 17 ccgggtctat gtagcctata ctatcctcga ggatagtata ggctacatag actttttg 58 <210> 18 <211> 58 <212> RNA < 213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA <400> 18 ccgggcctta caggcctggc aatttctcga gaaattgcca ggcctgtaag gctttttg 58 <210> 19 <211> 57 <212> RNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA <400> 19 ccggacggac cttctgtgaa gtatgctcga gcatacttca cagaaggtcc gtttttg 57 <210> 20 <211> 58 <212> RNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA <400> 20 ccgggttgtc at tgcagcag atgtactcga gtacatctgc tgcaatgaca actttttg 58 <210> 21 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A shRNA Target sequence <400> 21 gcagaaactg tttccctacg a 21 <210> 22 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A shRNA Target sequence <400> 22 cgagggaatg tccttctcaa t 21 <210> 23 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A shRNA Target sequence <400> 23 gatgttgtca ttgcagcaga t 21 <210> 24 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A shRNA Target sequence <400> 24 gccagcagtt ctggttctta a 21 < 210> 25 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A shRNA Target sequence <400> 25 gcagacatca ctgccaagtt a 21 <210> 26 <211> 21 <212> DNA <213 > Artificial Sequence <220> <223> Mus musculus FAM86 shRNA Target sequence <400> 26 gagcattcag ccatcgtaat c 21 <210> 27 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA Target sequence <400> 27 gtctatgtag ccctatactat c 21 <210> 28 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA Target sequence <400> 28 gccttacagg cctggcaatt t 21 <210> 29 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA Target sequence <400> 29 acggaccttc tgtgaagtat g 21 <210> 30 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 shRNA Target sequence <400> 30 gttgtcattg cagcagatgt a 21 <210> 31 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A siRNA Target sequence <400> 31 aactcttgct gcagagttt 19 <210> 32 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A siRNA Target sequence <400> 32 cttagaagca aagttaaga 19 <210> 33 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A siRNA Target sequence <400> 33 ttaagagact catcagatt 19 <210> 34 <211> 19 <212> DNA <213> Artificial Sequence <220> < 223> Homo sapiens FAM86A siRNA Target sequence <400> 34 tctcaatggc ctctcatta 19 <210> 35 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A siRNA Target sequence <400> 35 gaatgtttgg agaatgtta 19 <210> 36 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 siRNA Target sequence <400> 36 aagagcattc agccatcgta a 21 <210> 37 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Mus musculus FAM86A siRNA Target sequence <400> 37 aagatgctcg aggactgcca g 21 <210> 38 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Mus musculus FAM86A siRNA Target sequence <400> 38 aactcagtta cactctctga g 21 <210> 39 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Mus musculus FAM86A siRNA Target sequence <400> 39 aaactcagtt acactctctg a 21 < 210> 40 <211> 116 <212> RNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A miR-145 <400> 40 caccttgtcc tcacggtcca gttttcccag gaatccctta gatgctaaga tggggattcc 60 tggaaatact gttcttga gg tcatggtttg gaaatactgt tcttgaggtc atggtt 116 <210> 41 <211> 110 <212> RNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A miR-204 <400> 41 ggctacagtc tttcttcatg tgactcgtgg acttcccttt gtcatcctat gcctgagaat 60 atatgaagga ggctgggaag gcaaagggac gttcaatt gt catcactggc 110 <210> 42 <211> 110 <212> RNA <213> Artificial Sequence <220> <223> Homo sapiens FAM86A miR-211 <400> 42 tcacctggcc atgtgacttg tgggcttccc tttgtcatcc ttcgcctagg gctctgagca 60 gggcagggac agcaaagggg tgctcagttg tcacttccca cagcacggag 110 <210> 43 <211> 79 <212> RNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 miR-370 <400> 43 agacggagag accaggtcac gtctctgcag ttacacagct catgagtgcc tgctggggtg 60 gaacctggtt tgtctgtct 79 <210> 44 <211> 83 <212> RNA <2 13> Artificial Sequence <220 > <223> Mus musculus FAM86 miR-290 <400> 44 ctcatcttgc ggtactcaaa ctatgggggc actttttttt ttctttaaaa agtgccgcct 60 agttttaagc cccgccggtt gag 83 <210> 45 <211> 82 <212> RNA <213> Artificial Sequence <220> <223> Mus musculus FAM86 miR-292 <400> 45 cagcctgtga tactcaaact gggggctctt ttggattttc atcggaagaa aagtgccgcc 60aggttttgag tgtcaccggt tg 82

Claims (21)

In the pharmaceutical composition for preventing or treating melanin deficiency diseases,
The composition contains a FAM86A inhibitor as an active ingredient,
The inhibitor is characterized in that shRNA,
The melanin deficiency disease is a pharmaceutical composition for preventing or treating melanin deficiency disease, characterized in that vitiligo or albinism.
delete delete delete delete According to claim 1,
The composition is a pharmaceutical composition for preventing or treating melanin deficiency diseases, characterized in that promotes the synthesis or secretion of melanin.
delete delete delete The pharmaceutical composition for preventing or treating melanin deficiency diseases according to claim 1, wherein the shRNA is represented by one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 11 to SEQ ID NO: 20.
The pharmaceutical composition for preventing or treating melanin deficiency diseases according to claim 1, wherein the shRNA targets one or more nucleotide sequences selected from the group consisting of SEQ ID NO: 21 to SEQ ID NO: 30.
delete A method for screening for a preventive or therapeutic agent for a melanin deficiency disease comprising the following steps:
(a) treating cells expressing FAM86A protein or its mRNA with a test substance;
(b) measuring the expression level of the FAM86A protein or its mRNA in cells treated with and without a test substance; and
(c) selecting a substance that reduces the expression level of the FAM86A protein or its mRNA compared to control cells as a preventive or therapeutic agent for melanin deficiency disease;
The melanin deficiency disease is characterized by vitiligo or white hair.
delete delete The method of claim 13, wherein the cell expressing the FAM86A protein or its mRNA in step (a) is a cell that produces excessive melanin.
In the composition for promoting black hair induction,
The composition contains a FAM86A inhibitor as an active ingredient,
The inhibitor is a composition for promoting black hair, characterized in that shRNA.
delete In the food composition for preventing or improving melanin deficiency disease,
The composition contains a FAM86A inhibitor as an active ingredient,
The inhibitor is characterized in that shRNA,
The melanin deficiency disease is a food composition for preventing or improving melanin deficiency disease, characterized in that vitiligo or albinism.
According to claim 19,
The food composition is a food composition for preventing or improving melanin deficiency disease, characterized in that the health functional food composition.
In the cosmetic composition for preventing or improving melanin deficiency disease,
The composition contains a FAM86A inhibitor as an active ingredient,
The inhibitor is characterized in that shRNA,
The melanin deficiency disease is a cosmetic composition for preventing or improving melanin deficiency disease, characterized in that vitiligo or albinism.

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