WO2018044028A1 - 특정 siRNA을 포함하는 멜라닌 증진용 조성물 - Google Patents

특정 siRNA을 포함하는 멜라닌 증진용 조성물 Download PDF

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WO2018044028A1
WO2018044028A1 PCT/KR2017/009412 KR2017009412W WO2018044028A1 WO 2018044028 A1 WO2018044028 A1 WO 2018044028A1 KR 2017009412 W KR2017009412 W KR 2017009412W WO 2018044028 A1 WO2018044028 A1 WO 2018044028A1
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melanin
composition
sirna
hair
seq
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PCT/KR2017/009412
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English (en)
French (fr)
Korean (ko)
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최현정
배일홍
김형준
이영진
이태룡
조동형
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(주)아모레퍼시픽
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Priority to JP2019504926A priority Critical patent/JP7350652B2/ja
Priority to CN201780068933.6A priority patent/CN110167600A/zh
Publication of WO2018044028A1 publication Critical patent/WO2018044028A1/ko

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair

Definitions

  • the present specification relates to a composition for blackening hair, preventing melanin-lowering diseases, or improving melanin-lowering diseases comprising a specific siRNA.
  • Melanin is a biopolymer of phenols that is a complex of black pigment and protein. It is the browning that occurs when the cut surface of apples, potatoes, and bananas is exposed to the air, or the brown feathers, skin, hair, and eyes of animals. Is observed. When melanin is overproduced and deposited, blemishes, freckles, and the like are formed and directly linked to blackening of the hair, and melanin may promote skin or hair aging and cause skin cancer.
  • Melanocyte stimulating hormone is secreted by UV rays, inflammation, and hormones, and MSH reacts with receptors to enhance cAMP in melanocytes to synthesize melanin, and the synthesized melanin synthesizes melanin-forming cells. It is secreted to the outside to protect the skin or hair from ultraviolet rays. Synthesis of melanin is mainly regulated by ⁇ -MSH, and MITF, TYR, TRP1, TRP2 and the like are known as proteins involved in the synthesis of melanin.
  • Hair whitening which is recognized as a phenomenon of physiological aging, is caused by a decrease in the number of hair melanin forming cells and a decrease in melanin production due to deterioration of melanin forming cells.
  • dyeing is currently used as a solution for hair whitening, dyeing must be re-dyed by the growth of white hair in a temporary manner, and the components contained in the dyes of hair dyes become irritants, causing contact dermatitis or skin allergy. It is raised and is a problem.
  • siRNA small interfering RNA
  • RISC RNA-induced silencing complex
  • siRNA can inhibit gene expression in an amount of 4-10 times less than antisense oligonucleotide, so it has low cytotoxicity and excellent inhibition of selective expression of genes, so that genes that induce cancer or genetic diseases express proteins Inhibiting the use of the disease can eliminate the cause of the disease, which is receiving much attention as a new effective disease treatment.
  • the present invention comprises a siRNA consisting of a nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2 as an active ingredient for hair blackening, for preventing hair whitening, for preventing melanin-lowering diseases, for treating melanin-lowering diseases, Or to provide a composition for improving melanin-lowering disease, to promote the development of white hair care field and melanin-lowering disease related field, and to improve the welfare of consumers and patients concerned.
  • the present invention for the saponification of the hair comprising a siRNA consisting of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2 as an active ingredient, for prevention of hair whitening, prevention of melanin-lowering diseases, lowering melanin
  • compositions for the treatment of sexual disorders or for the improvement of melanin-lowering disorders are provided.
  • the present invention provides a method for hair blackening, a method for preventing hair whitening, a method for preventing melanin-lowering diseases, and a melanin, comprising administering to a subject a composition comprising a siRNA comprising a nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2
  • a method of treating hypothyroidism or a method for ameliorating melanin hypothyroidism is provided.
  • the present invention provides SEQ. ID. No. 1 as an active ingredient for use in blackening hair, preventing hair whitening, preventing melanin-lowering disease, treating melanin-lowering disease, or improving melanin-lowering disease.
  • SEQ. ID. No. 1 provides an active ingredient for use in blackening hair, preventing hair whitening, preventing melanin-lowering disease, treating melanin-lowering disease, or improving melanin-lowering disease.
  • siRNA consisting of the nucleotide sequence of SEQ ID NO: 2 and a composition comprising the same.
  • the present invention provides a base of SEQ ID NO: 1 or SEQ ID NO: 2 as an active ingredient for hair blackening, prevention of hair whitening, prevention of melanin-lowering diseases, treatment of melanin-lowering diseases, or improvement of melanin-lowering diseases.
  • the present invention provides a hair blackening composition, a composition for preventing hair whitening, a composition for preventing melanin-lowering disease, a composition for preventing melanin-lowering disease.
  • an siRNA consisting of a nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2 for use in the preparation of a therapeutic composition or a composition for improving melanin-lowering disease.
  • the composition may be a pharmaceutical composition or cosmetic composition.
  • composition comprising an siRNA consisting of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2 as an active ingredient, according to an aspect of the present invention, hair blackening, prevention of hair whitening, prevention of melanin-lowering diseases, or melanin-lowering The treatment and amelioration of a disease can be aimed at effectively.
  • Figure 1 shows that the melanin content is significantly increased by the siRNA consisting of the nucleotide sequence of SEQ ID NO: 1 or 2 in melan-a cells.
  • Figure 2 is a Western blot data showing that tyrosinase, TRP1 is significantly increased by siRNA consisting of the nucleotide sequence of SEQ ID NO: 1 or 2 in melan-a cells.
  • Figure 3 shows that the melanin content is significantly increased by the siRNA consisting of the nucleotide sequence of SEQ ID NO: 1 or 2 in B16F1 cells.
  • Figure 4 is a Western blot data showing that tyrosinase, TRP1 is significantly increased by siRNA consisting of the nucleotide sequence of SEQ ID NO: 1 or 2 in B16F1 cells.
  • hair refers to a hairy structure consisting of keratinized epithelial cells and emerging on the surface of the skin. Specifically, the term “hair” refers to the broadest concept including hair and body hair.
  • skin refers to a tissue covering the body surface of an animal, and is a broad concept including not only tissues covering the body surface such as the face or body, but also the scalp and hair.
  • blackening means that the colored pigment of the skin or hair is increased, and in particular, it may mean a phenomenon in which the amount of the melanin pigment is increased so that the skin or the hair shows a dark color.
  • blackening of the hair includes the phenomenon that the hair turns black, and it also includes preventing and preventing whitening or whitening of the hair.
  • whitening means a decrease in the color pigment of the skin or hair, and in particular, may mean a phenomenon in which the amount of the melanin pigment is reduced to make the skin or the hair pale.
  • Hair whitening or white hair for example, includes the phenomenon that the hair turns white.
  • the term "hair blackening efficacy substance” or “hair anti-whitening effect substance” may refer to a substance that darkens the brightness of hair or prevents whitening of hair from further progressing.
  • the color pigments in particular, may refer to a substance that acts to induce, improve and enhance the deposition of melanin, and may include a single compound, polymer, DNA, RNA, siRNA, miRNA, peptide, protein, etc. It is not limited.
  • Melanin-lowering disease in the present specification includes a disease in which melanin deposition is abnormally suppressed, melanin production is reduced, or a disease in which melanin is excessively removed due to abnormalities in the synthesis or degradation of melanin pigment.
  • leukoplakia Albinism
  • leukoderma partial leukemia, rash
  • vitiligo quadrichrome vitiligo
  • vitiligo ponctue idiopathic red hypopigmentation Syndrome
  • mumps leukemia syndromic Albinism
  • Alezzandrinisyndrome Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griselly Griscelli syndrome (Elejalde syndrome, Griscelli syndrome type 2 and Griscelli syndrome type 3), Waardenburg syndrome, Tischen syndrome (Tietz syndrome), Cross-MuKusick-Breen syndrome, ABCD syndrome, Albinism-deafness syndrome and Vogt-Goyanagi-Harada syndrome (Vo) gt-Koyanagi-Harada syndrome), oculocutaneous albinism, hypomelanosis (idiopathic guttate hypomelanosis, leafy hypomelanosis, progressive ectopic hypomelanosis) (progressive macular hypomelanosis), ecchymoses, pibaldism, nevus depigmentosus, post-inflammatory hypopigmentation, white pityriasis alba Vagabond's leukomelanoderma, Yemenite deaf
  • melanin-lowering disease prevention, amelioration and treatment efficacy substance a substance that prevents or inhibits a disease of melanin-lowering disease in advance, a substance that alleviates or alleviates the symptoms of the diseased melanin-lowering disease, melanin lowering It includes substances that relieve the cause of sexual disorders, substances that promote melanin synthesis, substances that inhibit the inhibition of melanin synthesis, substances that inhibit the breakdown of melanin, and include whole skin, whole hair, specific hair or specific skin areas.
  • Substances that act to darken the brightness or to induce, improve and enhance the deposition of melanin pigments may include a single compound, polymers, DNA, RNA, siRNA, miRNA, peptides, proteins, etc., but are not limited thereto. Do not.
  • the present invention comprises a siRNA consisting of a nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2 for hair blackening, for preventing hair whitening, for preventing melanin-lowering diseases, for treating melanin-lowering diseases, Or it provides a composition for improving melanin-lowering disease.
  • the siRNA comprising the nucleotide sequence of SEQ ID NO: 1 may be represented by "# 1"
  • the siRNA comprising the nucleotide sequence of SEQ ID NO: 2 may be represented by "# 2”
  • Each siRNA sequence may include the following nucleotide sequence.
  • the siRNA may include a nucleotide sequence having a homology of 80%, preferably 90%, more preferably 100% with the nucleotide sequence represented by SEQ ID NO: 1 or SEQ ID NO: 2.
  • the siRNA may be an independent single chain RNA strand comprising the sequence or a sequence having 80 to 100% homology with the sequence, or may be a double chain RNA strand.
  • the siRNA may comprise a sense RNA strand and an antisense RNA strand complementary thereto or may be a single RNA strand of stem-loop structure in which the senseRNA strand and the antisense RNA strand are connected by a loop.
  • the double chain or stem region may include a portion not paired by mismatch (corresponding base is not complementary), bulge (the base does not correspond to one chain) and the like.
  • the total length of the siRNA is 10 to 60 bases, preferably 15 to 40 bases, more preferably 18 to 30 bases.
  • siRNA terminal structures can be either blunt or cohesive.
  • the cohesive end structure can be both a 3 'end protruding structure and / or a 5' end protruding structure, and the number of protruding bases is not limited.
  • siRNA is a low-molecular RNA (for example, natural RNA molecules such as tRNA, rRNA, viral RNA or artificial RNA molecules such as tRNA, rRNA, viral RNA, etc.) in a range capable of maintaining the expression inhibitory effect of the target gene. ) May be included.
  • the siRNA terminal structure does not need to have a cleavage structure at both sides, and may be a structure in which one terminal portion of the siRNA is connected by a linker RNA.
  • the length of the linker is not particularly limited as long as it does not interfere with the pairing of the stem portions.
  • the RNA strand may include at least one chemical modification in its sugar moiety, nucleobase moiety, or internucleotide structure. Such modifications may make it possible to inhibit the destruction of siRNA by nucleases in vivo. All chemical modifications that can enhance the stability and biocompatibility of siRNA according to one aspect of the present invention in vivo are included in the scope of the present invention.
  • the position 2 'of the ribose such as 2'-deoxy, 2'-fluoro, 2'-amino, 2'-thio, or 2'-0-alkyl
  • the position 2 'of the ribose such as 2'-deoxy, 2'-fluoro, 2'-amino, 2'-thio, or 2'-0-alkyl
  • nucleobases 5-bromo-uridine, 5-iodo-uridine, N3-methyl-uridine, 2,6-diaminopurine (DAP, 5-methyl-2'-deoxycytidine Bound to cholesterol or a modified base such as 5- (1-propynyl) -2'-deoxy-uridine (pdU), 5- (1-propynyl) -2'-deoxycytidine (pdC)
  • bases Preferred modifications of the internucleotide backbone include the substitution of phosphodiester groups in the backbone by phosphorothioate, methylphosphonates, phosphorodiamidate groups, or peptides.
  • a backbone consisting of N- (2-aminoethyl) -glycine (PNA, peptide nucleic acid) linked by bonds
  • PNA peptide nucleic acid
  • a variety of modified bases, sugars, backbones are modified nucleic acids of the morpholino type. (Bases immobilized on morpholine rings and linked by phosphorodiamidate groups) or PNA (peptides) N- linked by a bond id (2-aminoethyl) may be coupled to the base fixed to the glycine units).
  • siRNA according to the present invention may be "isolated” or “bound” to other means of delivery and delivery, which means not in the natural state, but also include those obtainable in the natural state, Means that can be obtained by any means related to the intervention.
  • siRNAs according to the present invention can be prepared using chemical synthesis, enzymatic methods, polymerase chain reaction (PCR), amplification of specific nucleotide sequences, or by the synthesis of a variety of already existing nucleic acid structures or siRNA It can be obtained by purification.
  • the siRNA may be to promote melanin production or deposition.
  • the siRNA may be to enhance the expression of one or more of tyrosinase and Tyrosinase-Related Protein 1 (TRP1).
  • TRP1 Tyrosinase-Related Protein 1
  • the siRNA according to an aspect of the present invention promotes melanin production or deposition in melan-a cells and B16F1 cells, which are melanin forming cells, and enhances the expression of tyrosinase, an enzyme that produces melanin, and TRP1 protein involved in melanin formation. It was confirmed.
  • the treatment of the siRNA may increase the number of cells expressing tyrosinase or TRP1.
  • Tyrosinase is an enzyme involved in the formation of melanin and the like. When expression of tyrosinase is enhanced, melanin production or deposition is increased.
  • TRP1 is a protein involved in melanin synthesis.
  • TRP1 Like tyrosinase, enhanced expression of TRP1 increases melanin production or deposition.
  • Melanin in hair is an important factor in determining the color of hair.
  • Melanin produced in melanin-forming cells present in hair follicles is transferred to hair cortical keratinocytes, and then moves upwards with hair growth. Hair whitening is caused by a decrease in the number of hair melanin forming cells and a decrease in melanin production due to deterioration of melanin forming cells.
  • the siRNA may promote melanin production and enhance expression of enzymes and proteins involved therein, thereby making it possible to blacken skin and hair, and to prevent whitening of skin and hair.
  • the present invention in one aspect, it can be realized through the siRNA to promote the melanin production and to enhance the expression of the enzymes and proteins involved in it can be prevented, treated, and improved for melanin-lowering diseases and symptoms It is also.
  • the composition may further include any vehicle that enables the enhancement of the biocompatibility and delivery of the siRNA according to the present invention.
  • carriers that can be used with siRNA include liposomes, exosomes, peptides (eg, cell-penetrating peptides) and various nanoparticles.
  • a recombinant vector, plasmid, etc. containing the siRNA may be used as a delivery or transport means.
  • the delivery or delivery means may apply various techniques and methods known in the art, and may be modified, improved, etc. depending on the formulation.
  • the siRNA is preferably, but not limited to, operably linked to at least a promoter in order to be properly transcribed in the delivered cell.
  • the promoter may be any promoter capable of functioning in the cell.
  • the siRNA according to one aspect of the present invention may further include a regulatory sequence including a leader sequence, a polyadenylation sequence, a promoter, an enhancer, an upstream activation sequence, a signal peptide sequence, and a transcription terminator as necessary for efficient action. .
  • the content of siRNA in the composition may be from 0.000000001% to 20% by weight relative to the total weight of the composition.
  • the content is at least 0.000000001 wt%, at least 0.000000005 wt%, at least 0.00000001 wt%, at least 0.00000005 wt%, at least 0.0000001 wt%, at least 0.0000005 wt%, at least 0.000001 wt%, at least 0.000005 wt%, 0.00001, relative to the total weight of the composition.
  • 0.00005 or more, 0.0001 or more, 0.0005 or more, 0.001 or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.05 or more, 0.1 or more, 0.3 or more, 0.5 or more Can be at least 0.8%, at least 0.8%, at least 1%, at least 3%, at least 5%, at least 8%, at least 10%, at least 12%, at least 15%, or at least 18% by weight. have.
  • the content is 20 wt% or less, 18 wt% or less, 15 wt% or less, 12 wt% or less, 10 wt% or less, 8 wt% or less, 5 wt% or less, 3 wt% or less, based on the total weight of the composition, 1 wt% or less, 0.8 wt% or less, 0.5 wt% or less, 0.3 wt% or less, 0.1 wt% or less, 0.05 wt% or less, 0.01 wt% or less, 0.005 wt% or less, 0.001 wt% or less, 0.0005 wt% or less, 0.0001 wt% or less, 0.00005 wt% or less, 0.00001 wt% or less, 0.000005 wt% or less, 0.000001 wt% or less, 0.0000005 wt% or less, 0.0000001 wt% or less, 0.00000005 wt% or less,
  • the dosage of siRNA may be 0.000001mg / kg / day to 20mg / kg / day.
  • the dosage is 0.000001 mg / kg / day or more, 0.000005 mg / kg / day or more, 0.00001 mg / kg / day or more, 0.00005 mg / kg / day or more, 0.00001 mg / kg / day or more, 0.0005 mg / kg At least 0.0001 mg / kg / day, at least 0.0005 mg / kg / day, at least 0.001 mg / kg / day, at least 0.005 mg / kg / day, at least 0.01 mg / kg / day, 0.05 mg / kg / day At least 0.1 mg / kg / day, at least 0.5 mg / kg / day, at least 0.8 mg / kg / day, at least 1 mg / kg / day, at least 2 mg / kg / day, at least 3 mg / kg / day.
  • the dosage is 20 mg / kg / day or less, 18 mg / kg / day or less, 15 mg / kg / day or less, 12 mg / kg / day or less, 10 mg / kg / day or less, 8 mg / kg / Day or less, 5 mg / kg / day or less, 3 mg / kg / day or less, 2 mg / kg / day or less, 1 mg / kg / day or less, 0.8 mg / kg / day or less, 0.5 mg / kg / day 0.1 mg / kg / day or less, 0.05 mg / kg / day or less, 0.01 mg / kg / day or less, 0.005 mg / kg / day or less, 0.001 mg / kg / day or less, 0.0005 mg / kg / day or less, Up to 0.00001 mg / kg / day, up to 0.00005 mg / kg / day, up to 0.00001 mg / kg / day, or up
  • the present invention may be a composition for the prevention, treatment and improvement of melanin-lowering diseases comprising siRNA consisting of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2 as an active ingredient.
  • the melanin-lowering disease is selected from the group consisting of vitiligo, depigmentation nevus, white nasal ganglia, rash, post-inflammatory depigmentation, ecchymosis, partial leukemia, idiopathic hypopigmentation and pointy leukemia There may be more than one.
  • Melanin (melanin) is observed in the outer feathers, hair, skin, hair, eyes, etc. of the animal, melanin-lowering disease can be caused when the production of melanin is insufficient, inhibited deposition or excessive degradation.
  • the present invention enhances melanin production or deposition, and also promotes expression of tyrosinase and TRP1, and thus can be used for the prevention, improvement, and treatment of the melanin-lowering disease.
  • the composition may be a pharmaceutical composition.
  • the pharmaceutical composition may further contain carriers, excipients, preservatives, preservatives, stabilizers, emulsifiers or emulsifiers, pharmaceutical adjuvants such as salts and / or buffers for the control of osmotic pressure, and other therapeutically valuable substances, It may be formulated in various oral or parenteral dosage forms according to conventional methods.
  • the oral dosage forms include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, powders, powders, fine granules, granules, pellets, and the like, and these formulations include surfactants in addition to active ingredients. , Diluents (eg lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), glidants (eg silica, talc, stearic acid and its magnesium or calcium salts and polyethylene glycols). .
  • Diluents eg lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine
  • glidants eg silica, talc, stearic acid and its magnesium or calcium salts and polyethylene glycols.
  • Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt Pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, and sweeteners.
  • binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt
  • Pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, and sweeteners.
  • the tablets can be prepared by conventional mixing, granulating or coating methods.
  • parenteral dosage form may be a transdermal dosage form, for example, an injection, drop, ointment, lotion, gel, cream, spray, suspension, emulsion, suppository, patch, or the like. It may be, but is not limited thereto.
  • the pharmaceutical composition may be administered orally or parenterally, and parenteral administration may select external skin, intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intradermal, intrathoracic or cerebrovascular injection.
  • the pharmaceutical composition may be an external preparation for skin, and the external preparation for skin may be included herein as a generic term that may include anything applied outside the skin.
  • the composition may be a cosmetic composition for blackening hair, preventing hair whitening, preventing and improving melanin-lowering diseases.
  • the cosmetic composition may further include a functional additive and components included in the general cosmetic composition.
  • the functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids and seaweed extract.
  • oils and fats moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, blood circulation And accelerators, cooling agents, limiting agents, purified water, and the like.
  • the cosmetic composition is not particularly limited in formulation, and may be appropriately selected as desired.
  • skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisturizing cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing It may be prepared in any one or more formulations selected from the group consisting of foam, cleansing lotion, cleansing cream, body lotion and body cleanser, but is not limited thereto.
  • the carrier component is animal fiber, vegetable fiber, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. And the like can be used.
  • lactose talc
  • silica aluminum hydroxide
  • calcium silicate or polyamide powder may be used as the carrier component, in particular, in the case of a spray, additionally chlorofluoro Propellants such as hydrocarbon, propane / butane or dimethyl ether.
  • a solvent, solvating agent or emulsifying agent is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, Fatty acid esters of propylene glycol, 1,3-butylglycol oil, glycerol aliphatic esters, polyethylene glycols or sorbitan.
  • the carrier component is water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester.
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester.
  • Microcrystalline cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
  • the dosage form according to one aspect of the present invention is a surfactant-containing cleansing agent, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, methyltaurate, and sarcosy Nates, fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
  • the composition may be a food or health food composition.
  • the food or health food composition may be in a liquid or solid dosage form, for example, various foods, beverages, gums, teas, vitamin complexes, health functional foods, health supplements, and the like, powders, granules, tablets, It can be used in the form of a capsule or a beverage.
  • the food composition of each formulation may be appropriately selected and blended by those skilled in the art according to the formulation or purpose of use, in addition to the active ingredient, and synergistic effects may occur when applied simultaneously with other raw materials.
  • liquid component that can be contained in addition to the active ingredient disclosed herein, and may include various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates include conventional sugars such as disaccharides such as monosaccharides, glucose and fructose, polysaccharides such as maltose and sucrose, dextrins and cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol. Etc.
  • natural flavoring agents such as, tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (for example, saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of natural carbohydrates may generally be about 1-20 g, in one aspect about 5-12 g, per 100 ml of the composition disclosed herein.
  • the food composition may contain various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, flavoring agents such as coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and salts thereof.
  • it may include a pulp for the production of natural fruit juices and vegetable drinks.
  • the components can be used independently or in combination.
  • the ratio of the additive may vary, but is generally selected from 0.001 to about 20 parts by weight per 100 parts by weight of the composition disclosed herein.
  • Melan-A a melanocyte formed from C57BL / 6 J (black, a / a) mice, obtained from normal human epidermal melanocytes (NHEMs, Cascade Biologics, Portland, OR, USA) -A) Cell lines were obtained from Dr. Dorothy C. Bennett (St. George's Hospital Medical School, London, UK). B16F1 mouse melanoma cell line was obtained from ATCC (Manassas, VA, USA).
  • Human epidermal melanocyte forming cells were maintained under Human Melanocyte Growth Supplements (HMGS) (Cascade Biologics, Inc., Mansfield, UK) in M-254 medium.
  • Melan-A cells were maintained under 10% (v / v) fetal bovine serum, 1% (v / v) penicillin-streptomycin, and 0.2 ⁇ M phorbol 12-myristate 13-acetate in RPMI 1640 medium.
  • B16F1 mouse melanoma cell lines were cultured in DMEM with 10% (v / v) fetal bovine serum and 1% (v / v) penicillin-streptomycin.
  • siRNA # 1 (5'-CCAACCAGAACAAGCAGAACA-3 '), # 2 (5'-GAACACGAAGGCUGUAACAAA-3'), and negative control siRNA (scrambled control siRNA, siNC) (5'-CCUACGCCACCAAUUUCGU-3 ') (Genolution, Seoul, South Korea).
  • siRNA was transfected into Melan-a and B16F1 cells cultured in 60 mm dishes using Lipofectamine ® RNAi MAX (Invitrogen, Carlsbad, Calif., USA). After incubation with siRNA for 24 hours, cells were treated with each compound (reagent) and maintained for 48 hours.
  • Anti-actin antibody (MAB1501, 1: 10,000) was obtained from Millipore (Temecula, Calif., USA), and anti- ⁇ PEP7 (tyrosinase) antibody, 1 : 1000) and anti- ⁇ PEP1 (TRP1) antibody (anti- ⁇ PEP1 (TRP1) antibody, 1: 1000) were obtained from VJ Hearing (NIH, Bethesda, MD).
  • TRP1 anti- ⁇ PEP1 antibody, 1: 1000
  • the membrane was incubated with an HRP- conjugated secondary antibody gated signal was measured using a SuperSignal ® West Dura HRP Detection Kit ( Pierce Inc., Rockford, IL, USA).
  • SiNC, siRNA (# 1, # 2) were also transfected on B16F1 cells and treated with specific substance D (0.5 ⁇ M) or serum-free medium after 1 day to inhibit melanogenesis. Confirmed and analyzed by Western blot for tyrosinase, TRP1.
  • the present invention can be used for hair blackening and white hair care in one aspect.
  • this feature according to an aspect of the present invention can promote the production of melanin for a specific part of the skin or the entire skin, by using an aspect of the present invention to prevent, treat, or prevent melanin-lowering diseases or symptoms, And improvement can be aimed at.
  • 10 mg liposomes containing 2 mg of siRNA consisting of SEQ ID NO: 1 or SEQ ID NO: 2, 80-140 mg of L-carnitine, 180 mg of soybean oil, 2 mg of palm oil, 8 mg of vegetable hardened oil, 4 mg of lead, and 6 mg of lecithin are mixed in a conventional manner As a result, it was filled into one capsule to prepare a soft capsule.
  • Liposomal 10 mg, galactooligosaccharide 200 mg, lactose 60 mg and malt sugar 140 mg were mixed and granulated using a fluidized bed dryer, and then 6 mg of sugar ester was mixed with 10 mg of liposomes containing 2 mg of siRNA consisting of the nucleotide sequences of SEQ ID NO: 1 or SEQ ID NO: 2 Tablets were prepared by adding and tableting with a tablet press.
  • a liposome containing 2 mg of siRNA consisting of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2, 250 mg of anhydrous glucose, and 550 mg of starch were mixed, molded into granules using a fluidized bed granulator, and filled into sachets to prepare granules.
  • Injections were prepared in a conventional manner using a liposome 20 mg comprising siRNA 5 mg consisting of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2, a sterile distillate for injection, and a pH adjusting agent.
  • liposome containing 1.00% by weight of siRNA consisting of SEQ ID NO: 1 or SEQ ID NO: 2, 13.00% by weight polyvinyl alcohol, 1.00% by weight L-ascorbic acid-2-magnesium phosphate, lauroylhydride
  • the pack was prepared using 1.00% by weight of hydroxyproline, 2.00% by weight of water-soluble collagen (1% aqueous solution), 3.00% by weight of 1,3-butylene glycol, 5.00% by weight of ethanol and the balance of purified water.
  • Health food was prepared by conventional methods according to the compositions described in the table below.
  • composition ratio of the vitamin and inorganic mixture is a composition that is relatively suitable for health foods, for example, the composition ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method, and then the conventional method. According to the health food composition can be used.
  • the remaining amount of purified water was added to a total volume of 900 ml, and the above ingredients were mixed according to a conventional healthy beverage manufacturing method, and then stirred and heated at 85 ° C. for about 1 hour. Obtained in a sterilized 2 liter container, sterilized sealed, and then refrigerated to prepare a healthy beverage.

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