CN110638827A - Nadh及其盐在制备皮肤色素抑制剂中的应用 - Google Patents
Nadh及其盐在制备皮肤色素抑制剂中的应用 Download PDFInfo
- Publication number
- CN110638827A CN110638827A CN201910988662.7A CN201910988662A CN110638827A CN 110638827 A CN110638827 A CN 110638827A CN 201910988662 A CN201910988662 A CN 201910988662A CN 110638827 A CN110638827 A CN 110638827A
- Authority
- CN
- China
- Prior art keywords
- nadh
- parts
- extract
- skin
- nmn
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 title claims abstract description 46
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 title claims abstract description 45
- 150000003839 salts Chemical class 0.000 title claims abstract description 16
- 239000000049 pigment Substances 0.000 title claims abstract description 11
- 239000003112 inhibitor Substances 0.000 title claims abstract description 7
- 239000000203 mixture Substances 0.000 claims abstract description 27
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 15
- 239000002537 cosmetic Substances 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 208000012641 Pigmentation disease Diseases 0.000 claims description 14
- 238000002347 injection Methods 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 6
- 239000002417 nutraceutical Substances 0.000 claims description 6
- 235000021436 nutraceutical agent Nutrition 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- 241000132012 Atractylodes Species 0.000 claims description 3
- 240000006766 Cornus mas Species 0.000 claims description 3
- 235000004837 Polyporus umbellatus Nutrition 0.000 claims description 3
- 244000197580 Poria cocos Species 0.000 claims description 3
- 235000008599 Poria cocos Nutrition 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 241001061264 Astragalus Species 0.000 claims description 2
- 235000010110 Astragalus glycyphyllos Nutrition 0.000 claims description 2
- 230000005778 DNA damage Effects 0.000 claims description 2
- 231100000277 DNA damage Toxicity 0.000 claims description 2
- 235000002897 Grifola umbellata Nutrition 0.000 claims description 2
- 235000006533 astragalus Nutrition 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000000852 hydrogen donor Substances 0.000 claims description 2
- 229940069445 licorice extract Drugs 0.000 claims description 2
- 244000097863 Grifola umbellata Species 0.000 claims 1
- 230000019612 pigmentation Effects 0.000 abstract description 8
- 230000036541 health Effects 0.000 abstract description 5
- 231100000957 no side effect Toxicity 0.000 abstract description 2
- 208000017520 skin disease Diseases 0.000 abstract description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 26
- 210000003491 skin Anatomy 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 9
- 206010015150 Erythema Diseases 0.000 description 6
- 231100000321 erythema Toxicity 0.000 description 6
- 230000008099 melanin synthesis Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 208000003351 Melanosis Diseases 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 206010014970 Ephelides Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 229950006238 nadide Drugs 0.000 description 3
- 229960003966 nicotinamide Drugs 0.000 description 3
- 239000011570 nicotinamide Substances 0.000 description 3
- 210000004927 skin cell Anatomy 0.000 description 3
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 244000171085 Polyporus umbellatus Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000036564 melanin content Effects 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 230000004792 oxidative damage Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010008570 Chloasma Diseases 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 235000018142 Hedysarum alpinum var americanum Nutrition 0.000 description 1
- 240000006461 Hedysarum alpinum var. americanum Species 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 108020005196 Mitochondrial DNA Proteins 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
- 108091093105 Nuclear DNA Proteins 0.000 description 1
- 241000222640 Polyporus Species 0.000 description 1
- 241001619461 Poria <basidiomycete fungus> Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- FZAQROFXYZPAKI-UHFFFAOYSA-N anthracene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC3=CC(S(=O)(=O)Cl)=CC=C3C=C21 FZAQROFXYZPAKI-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- -1 but not limited to Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000007854 depigmenting agent Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 210000002780 melanosome Anatomy 0.000 description 1
- 229940037525 nasal preparations Drugs 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/13—Nucleic acids or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/076—Poria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/40—Cornaceae (Dogwood family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/18—Antioxidants, e.g. antiradicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Dermatology (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Food Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Birds (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明实施例公开了一种NADH及其盐在制备皮肤色素抑制剂中的应用。NADH和/或其药理学上可接受的盐可用于制备成抑制皮肤色素产生的药物组合物、保健品组合物及化妆品组合物。使用本发明的NADH组合物产品不会引起副作用，能有效抑制皮肤中的色素沉着，并且可用于预防或治疗与色素沉着相关的皮肤疾病。
Description
技术领域
本发明涉及药物、保健品或化妆品技术领域，尤其涉及NADH在制备皮肤色素抑制剂中的应用。
背景技术
当皮肤暴露于紫外线辐射时，产生黑色素，以保护皮肤细胞免受紫外线辐射。产生的黑色素吸收紫外线，从而防止紫外线深入皮肤。因此，黑色素是用于保护皮肤细胞的重要色素，但如果它过量产生，则会沉积在皮肤上并引起雀斑。从美容的观点来看，雀斑往往被排斥，消费者对皮肤美白剂非常感兴趣，并且还积极开发具有美白效果的成分以抑制黑色素在皮肤上的沉积。例如，据报道，烟酰胺可以通过抑制黑素小体从黑色素细胞向角质形成细胞转移，从而具有抑制由紫外线照射引起的色素沉积的作用，口服摄入烟酰胺可以防止色素沉着并抑制紫外线照射引起的雀斑、黄褐斑增加。
但并未有任何对NADH尤其是还原型NADH对皮肤色素影响的研究。
发明内容
鉴于上述问题，本发明的技术目的之一在于提供NADH及其盐在制备皮肤色素抑制剂中的应用。
在本发明中，所述NADH尤其指β-NADH，还原型烟酰胺腺嘌呤二核苷酸(Nicotinamide adenine dinucleotide)。
在本发明的其中一个实施例中，所述NADH及其盐为胃肠道给药或非胃肠道给药，胃肠道给药包括口服给药，非胃肠道给药包括注射给药。
在本发明的其中一个实施例中，口服给药时NADH的单次剂量为0.1～10mg/kg，优选为0.1～4mg/kg。日次数为1～3次，日用量为0.1～30mg/kg，优选是0.1～12mg/kg，更优选0.4～2mg/kg。注射给药时NADH的单次剂量为0.1～2mg/kg，优选是0.1～1mg/kg。其中kg为对象个体的体重单位。
在本发明的其中一个实施例中，使用NADH时将其与辅料混合制成不同的剂型，包括但不限于片剂、颗粒剂、粉剂、胶囊剂、液体剂、乳液剂、冻干制剂、注射剂、栓剂、软膏剂、凝胶剂、吸入剂、经鼻剂、肠内药和喷雾剂等。
本发明的技术目的之二在于提供一种抑制皮肤色素产生的药物组合物或保健品组合物，其以NADH和/或其药理学上可接受的盐为唯一活性成分。
在本发明的其中一个实施例中，上述药物组合物或保健品组合物还包括药学上或食品学上可接受的辅料。
在本发明的其中一个实施例中，上述药物组合物或保健品组合物是将NADH与常规的药用或食用辅料混合，以常规的方法制成各种剂型。
在本发明的其中一个实施例中，上述药物组合物或保健品组合物中还包含NMN(β-Nicotinamide Mononucleotide，β-烟酰胺单核苷酸)，作为辅助剂辅助或增强NADH的色素抑制作用。组合物中NADH或其盐与NMN的重量比为(1-10):(1-10)，优选为(1-3):(1-3)。
在本发明的其中一个具体实施例中，上述药物组合物还包括以下组分作为辅助活性成分：白术提取物、茯苓提取物、山茱萸提取物、猪苓提取物、沙苑蒺藜提取物和甘草提取物。
在本发明的其中一个更为具体的实施例中，上述药物组合物包括以下重量配比的组分：NADH 1～10份，NMN 1～10份，白术提取物1～10份，茯苓提取物1～10份，山茱萸提取物1～10份，猪苓提取物1～10份，沙苑蒺藜提取物1～10份，甘草提取物1～10份。
在本发明的其中一个实施例中，上述药物组合物的给药方式优选为口服给药、注射给药或经皮给药。
在本发明的其中一个实施例中，上述保健品组合物的给药方式为胃肠道给药或非胃肠道给药，胃肠道给药包括口服给药，非胃肠道给药包括注射给药。
本发明的技术目的之三在于提供一种抑制皮肤色素产生的化妆品组合物，所述化妆品组合物以NADH和/或其药理学上可接受的盐为唯一活性成分。
在本发明的其中一个实施例中，所述化妆品组合物还包括NMN作为辅助剂，NADH或其盐与NMN的重量比为(1-10):(1-10)。
在本发明的其中一个实施例中，上述化妆品组合物还包括化妆品中可接受的辅料。
在本发明的其中一个实施例中，上述化妆品组合物的给药方式为经皮给药。
实施本发明实施例，将具有如下有益效果：
紫外线是引起皮肤氧化损伤越来越主要的原因。紫外线B能直接与皮肤细胞的DNA发生作用，紫外线A则主要通过产生对人体有害的氧自由基而改变核DNA和线粒体DNA，因此，氧化损伤总是伴随着衰老，并引起皮肤各种各样的问题，如肤色变黄、暗沉、色素沉积。并且紫外线还会引起黑色素细胞增加，进一步增加皮肤色素沉积。本发明的技术方案中，烟酰胺腺嘌呤二核苷酸可以增加人体内NAD+的水平，从而达到抑制或预防由紫外(UV)光引起的皮肤DNA损伤。并且NADH作为人体内天然的氢供体，还可以进一步清除人体内有害的氧自由基。本发明将NADH作为活性成分应用在制备皮肤色素抑制的药物、保健品或化妆品中，其具体剂量可依据病情的严重程度、施药途径和相关因素决定。使用本发明的组合物产品不会引起副作用，能有效抑制皮肤中的色素沉着，并且可用于预防或治疗与色素沉着相关的皮肤疾病。
具体实施方式
下面将结合具体实施例对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1
NADH对细胞黑色素产生量影响的体外实验：
调整人黑素瘤细胞A375(购自深圳大学)浓度至1×105个/mL，接种于6孔板，每孔2mL。贴壁后细胞分组分别用25～200μmol·L-1的NADH处理(样品组)，对照组用200μmol·L-1天然人I型胶原蛋白处理，空白组用生理盐水处理，48h后用预冷的PBS洗涤3次刮下收集于无菌EP管中。黑色素含量的测定采用Tsuboi(1998)的方法：1500rpm离心5min弃上清，以0.5mL含10％DMSO的1mol·L-1NaOH溶液裂解细胞，超声波破碎30min，90℃水浴2h，使细胞团块完全裂解后，3000rpm离心15min，取上清至96孔板于酶标仪450nm处测A值，计算细胞黑色素相对含量，其结果见表1。
黑素合成相对含量＝A1/A0，其中Al是样品组的吸光度，A0是空白组的吸光度。
表1各组中黑素合成相对含量
| 组别 | 黑素合成相对含量 |
| 空白组 | 1 |
| 对照组 | 0.58±0.62 |
| 25μmol·L<sup>-1</sup>的NADH处理组 | 0.87±0.21 |
| 50μmol·L<sup>-1</sup>的NADH处理组 | 0.79±0.57 |
| 100μmol·L<sup>-1</sup>的NADH处理组 | 0.64±0.34 |
| 200μmol·L<sup>-1</sup>的NADH处理组 | 0.51±0.83 |
如表1所示，25～200μmol·L-1范围内的NADH处理黑素瘤细胞48小时后，呈浓度依赖性抑制黑素细胞中的黑素合成(P＜0.05)，而200μmol·L-1NADH对黑素合成抑制作用最强，与空白组相比，黑素含量减少约49％(0.51±0.83；P<0.01)。说明NADH在抑制细胞产生黑色素上具有显著的影响。
实施例2
NADH在抑制皮肤黑色素及减小皮肤损伤中的人体试验：
以健康的年龄为30～40岁的18名女子作为对象，随机分成6组，每组3人。实验组4组：测定前一小时内分别在测定部位涂抹25～200μmol·L-1范围内的NADH，每天一次。对照组1组：以相同方法涂抹200μmol·L-1的曲酸。空白组1组：仅涂抹生理盐水。在被验者的上臂涂抹部位上附着具有直径1.5cm孔的不透明胶布，然后照射各被验者的最小红斑量(MED；Minimumerythma dose)1.5～2倍左右的紫外线B而诱导皮肤的黑化。用分光测色计CM-1000测定UV照射后的黑色素指数和红斑指数随时间的变化。
根据毛培坤等《化妆品功能性评价和分析方法》(中国轻工业出版社，1998)的方法作如下测定：利用构成皮肤色的色素的特定的反射分光特性，根据皮肤中血红蛋白和黑色素的吸收光谱选择光源，将568nm和655nm作为二种特定波长，参照日本工业标准JIS Z8722扩散照明/垂直受光方式。用分光测色计(CM-1000)，用脉冲氖灯作光源，测定反射光的强度。接触式测定直径是8mm。用下列式计算出红斑和色素沉着的程度作为红斑指数和黑色素指数。
红斑指数＝lg(1/G)-lg(1/R)
黑色素指数＝lg(1/R)
公式中：G—绿色光的反射光的强度，R—红色光的反射光的强度。
结果显示在表2和表3中，表中数值表示测定平均值。
表2黑色素指数表
| 组别 | 0天 | 7天 | 14天 | 21天 | 28天 | 56天 |
| 空白组 | 50.2 | 53.6 | 57.1 | 62.5 | 65.7 | 69.5 |
| 对照组 | 50.2 | 51.7 | 55.4 | 58.1 | 61.9 | 65.3 |
| 25μmol·L<sup>-1</sup>的NADH | 50.2 | 51.2 | 54.7 | 57.8 | 60.6 | 63.7 |
| 50μmol·L<sup>-1</sup>的NADH | 50.2 | 51.0 | 54.1 | 57.3 | 60.2 | 63.2 |
| 100μmol·L<sup>-1</sup>的NADH | 50.2 | 50.9 | 52.9 | 55.4 | 57.7 | 59.4 |
| 200μmol·L<sup>-1</sup>的NADH | 50.2 | 50.5 | 52.0 | 54.1 | 56.0 | 58.6 |
表3红斑指数值
| 组别 | 0天 | 7天 | 14天 | 21天 | 28天 | 56天 |
| 空白组 | 10.5 | 11.7 | 12.5 | 13.8 | 14.6 | 16.8 |
| 对照组 | 10.5 | 11.5 | 12.3 | 13.1 | 13.9 | 15.3 |
| 25μmol·L<sup>-1</sup>的NADH | 10.5 | 11.3 | 12.0 | 12.6 | 13.5 | 14.7 |
| 50μmol·L<sup>-1</sup>的NADH | 10.5 | 11.1 | 11.6 | 12.2 | 13.1 | 14.0 |
| 100μmol·L<sup>-1</sup>的NADH | 10.5 | 10.8 | 11.0 | 11.7 | 12.8 | 13.7 |
| 200μmol·L<sup>-1</sup>的NADH | 10.5 | 10.6 | 10.8 | 11.3 | 12.0 | 12.9 |
由表2的数据可以看出，NADH能有效抑制皮肤黑色素；表3的结果表明，NADH能减少紫外线对皮肤的损伤，对皮肤起到保护作用。
实施例3
公开了一种以NADH为活性组分抑制皮肤色素的药物组合物：
取5份白术提取物、1份茯苓提取物、3份山茱萸提取物、4份猪苓提取物、1份沙苑蒺藜提取物以及1份甘草提取物混合，以质量计加8倍量的水溶解，搅拌均匀后，加入5份的NADH和5份NMN，在室温下充分搅拌混匀后升温至50℃真空浓缩后，得到组合物。将组合物按常规方法与药用辅料制成片剂。
以上所揭露的仅为本发明较佳实施例而已，当然不能以此来限定本发明之权利范围，因此依本发明权利要求所作的等同变化，仍属本发明所涵盖的范围。
Claims (10)
1.NADH及其盐在制备皮肤色素抑制剂中的应用。
2.根据权利要求1所述的应用，其特征在于，所述NADH及其盐为胃肠道给药或非胃肠道给药，胃肠道给药包括口服给药，非胃肠道给药包括注射给药。
3.根据权利要求2所述的应用，其特征在于，口服给药时NADH的单次剂量为0.1～10mg/kg，注射给药时NADH的单次剂量为0.1～2mg/kg，每日给药1～3次。
4.根据权利要求1所述的应用，其特征在于，所述NADH作为皮肤色素抑制剂是基于NADH能增加人体内NAD+的水平，达到抑制或预防由紫外光引起的皮肤DNA损伤，并且NADH作为人体内天然的氢供体，进一步清除人体内有害的氧自由基。
5.一种抑制皮肤色素产生的化妆品组合物，其特征在于，所述化妆品组合物以NADH和/或其药理学上可接受的盐为唯一活性成分。
6.根据权利要求5所述的化妆品组合物，其特征在于，其还包括NMN作为辅助剂，NADH或其盐与NMN的重量比为(1-10):(1-10)。
7.根据权利要求5所述的化妆品组合物，其特征在于，其还包括化妆品中可接受的辅料。
8.一种抑制皮肤色素产生的药物组合物或保健品组合物，其特征在于，其以NADH和/或其药理学上可接受的盐作为唯一活性成分。
9.据权利要求8所述的药物组合物或保健品组合物，其特征在于，其还包括NMN作为辅助剂，NADH或其盐与NMN的重量比为(1-10):(1-10)。
10.据权利要求8所述的药物组合物或保健品组合物，其特征在于，所述药物组合物包括以下重量配比的组分：NADH 1～10份，NMN 1～10份，白术提取物1～10份，茯苓提取物1～10份，山茱萸提取物1～10份，猪苓提取物1～10份，沙苑蒺藜提取物1～10份和甘草提取物1～10份。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910988662.7A CN110638827A (zh) | 2019-10-17 | 2019-10-17 | Nadh及其盐在制备皮肤色素抑制剂中的应用 |
| PCT/CN2020/118815 WO2021073426A1 (zh) | 2019-10-17 | 2020-09-29 | Nadh 及其盐在制备皮肤色素抑制剂中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910988662.7A CN110638827A (zh) | 2019-10-17 | 2019-10-17 | Nadh及其盐在制备皮肤色素抑制剂中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110638827A true CN110638827A (zh) | 2020-01-03 |
Family
ID=68994326
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910988662.7A Pending CN110638827A (zh) | 2019-10-17 | 2019-10-17 | Nadh及其盐在制备皮肤色素抑制剂中的应用 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN110638827A (zh) |
| WO (1) | WO2021073426A1 (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021073426A1 (zh) * | 2019-10-17 | 2021-04-22 | 泓博元生命科技（深圳）有限公司 | Nadh 及其盐在制备皮肤色素抑制剂中的应用 |
| CN112791008A (zh) * | 2021-01-29 | 2021-05-14 | 中粮集团有限公司 | 辅酶在抗衰老美容护肤品中的应用及含辅酶的护肤品及其制备方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH1059839A (ja) * | 1996-08-21 | 1998-03-03 | Noevir Co Ltd | 皮膚外用剤 |
| JP2001048773A (ja) * | 1999-08-10 | 2001-02-20 | Naris Cosmetics Co Ltd | 化粧料 |
| CN108969396A (zh) * | 2018-10-09 | 2018-12-11 | 泓博元生命科技（深圳）有限公司 | 一种含nmn的凝胶护肤品及其制备方法 |
| CN109350557A (zh) * | 2018-05-25 | 2019-02-19 | 泓博元生命科技（深圳）有限公司 | 包含nadh和神经酰胺的抗衰老组合物、护肤品及其制备方法与应用 |
| CN109985056A (zh) * | 2013-10-30 | 2019-07-09 | 可劳迈戴斯有限公司 | 用于在治疗皮肤病中局部使用的烟酰胺核苷组合物 |
| CN110237089A (zh) * | 2019-06-19 | 2019-09-17 | 泓博元生命科技（深圳）有限公司 | Nadh和/或nmn防治男性***功能障碍的应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104352513B (zh) * | 2014-11-14 | 2017-04-05 | 邦泰生物工程(深圳)有限公司 | Nadh或盐在制备治疗苯丙酮尿症药物或保健品的应用 |
| CN109646423A (zh) * | 2018-12-03 | 2019-04-19 | 泓博元生命科技（深圳）有限公司 | 含nadh的生物高分子纳米球及其制备方法与应用 |
| CN110638827A (zh) * | 2019-10-17 | 2020-01-03 | 泓博元生命科技（深圳）有限公司 | Nadh及其盐在制备皮肤色素抑制剂中的应用 |
-
2019
- 2019-10-17 CN CN201910988662.7A patent/CN110638827A/zh active Pending
-
2020
- 2020-09-29 WO PCT/CN2020/118815 patent/WO2021073426A1/zh active Application Filing
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH1059839A (ja) * | 1996-08-21 | 1998-03-03 | Noevir Co Ltd | 皮膚外用剤 |
| JP2001048773A (ja) * | 1999-08-10 | 2001-02-20 | Naris Cosmetics Co Ltd | 化粧料 |
| CN109985056A (zh) * | 2013-10-30 | 2019-07-09 | 可劳迈戴斯有限公司 | 用于在治疗皮肤病中局部使用的烟酰胺核苷组合物 |
| CN109350557A (zh) * | 2018-05-25 | 2019-02-19 | 泓博元生命科技（深圳）有限公司 | 包含nadh和神经酰胺的抗衰老组合物、护肤品及其制备方法与应用 |
| CN108969396A (zh) * | 2018-10-09 | 2018-12-11 | 泓博元生命科技（深圳）有限公司 | 一种含nmn的凝胶护肤品及其制备方法 |
| CN110237089A (zh) * | 2019-06-19 | 2019-09-17 | 泓博元生命科技（深圳）有限公司 | Nadh和/或nmn防治男性***功能障碍的应用 |
Non-Patent Citations (3)
| Title |
|---|
| 史晓凤等: "皮肤的光学性质研究", 《发光学报》 * |
| 彭冠杰，郭清泉主编: "《美白化妆品科学与技术》", 30 June 2019 * |
| 朱海琴等: "烟酰胺在皮肤局部外用中的进展", 《临床皮肤科杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021073426A1 (zh) * | 2019-10-17 | 2021-04-22 | 泓博元生命科技（深圳）有限公司 | Nadh 及其盐在制备皮肤色素抑制剂中的应用 |
| CN112791008A (zh) * | 2021-01-29 | 2021-05-14 | 中粮集团有限公司 | 辅酶在抗衰老美容护肤品中的应用及含辅酶的护肤品及其制备方法 |
| CN112791008B (zh) * | 2021-01-29 | 2022-06-21 | 中粮集团有限公司 | 辅酶在抗衰老美容护肤品中的应用及含辅酶的护肤品及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021073426A1 (zh) | 2021-04-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5804168A (en) | Pharmaceutical compositions and methods for protecting and treating sun damaged skin | |
| US20120258060A1 (en) | Methods for protecting the skin from radiation insults | |
| Mathews-Roth | Plasma concentrations of carotenoids after large doses of beta-carotene | |
| WO2009067095A1 (en) | Topical cosmetic skin lightening compositions and methods of use thereof | |
| US20090028895A1 (en) | Methods and compositions for reducing facial lines and wrinkles | |
| KR20060130631A (ko) | 피부 침착을 감소시키기 위한 통합 조성물과 방법 | |
| KR101902911B1 (ko) | 산수국 추출물을 함유하는 자외선에 의한 인간 피부세포 손상 개선용 조성물 | |
| CN110638827A (zh) | Nadh及其盐在制备皮肤色素抑制剂中的应用 | |
| KR20060114774A (ko) | (20Ｓ)-진세노사이드 Ｒｇ3을 함유하는 주름 예방 및개선용 화장료 | |
| US20100178286A1 (en) | Methods and compositions for reducing facial lines and wrinkles | |
| KR20100124132A (ko) | 효소처리를 이용한 혼합생약재 추출물을 함유하는 피부 주름개선용 화장료 조성물 및 그 추출방법 | |
| CN113425639A (zh) | 一种抗氧化组合物及其应用、产品 | |
| US20100166683A1 (en) | Composition of external preparation for uv-protection comprising rehmannia glutinosa extracts | |
| KR20100121352A (ko) | 피부노화 예방 및 미용 효과를 지니는 복합생약 조성물 그리고 피부노화 예방 및 개선용 건강 기능 식품 | |
| EP3851095A1 (en) | Use of combretum micranthum extract in cosmetics | |
| KR20190018264A (ko) | 홍삼 추출물의 미백 활성을 증가시키는 방법 및 이를 이용한 피부 미백 조성물 | |
| US11110117B2 (en) | Skin preparation composition for external use containing complex hyaluronic acid | |
| CN109925248B (zh) | 一种含有根皮素、三七总皂苷抗皮肤光老化作用的护肤组合物 | |
| CN106729150A (zh) | 一种皮肤美白祛斑的药物配方 | |
| KR20010093861A (ko) | 천련자 추출물을 함유하는 미백용 조성물 | |
| KR20110043019A (ko) | 피부 미백 효능을 가지는 식물 추출물로 이루어진 조성물 및 이를 포함하는 화장료 조성물 | |
| KR19990048305A (ko) | 피부미백용 조성물 | |
| CN108836927A (zh) | 一种祛斑组合物 | |
| KR20020008268A (ko) | 오배자 추출물을 함유하는 테스토스테론 5알파-리덕타아제저해제 | |
| CN115154360B (zh) | 一种具有美白祛斑及保湿功效的组合物及其应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200103 |