WO2021098874A1 - 毛发护理组合物及其制备方法 - Google Patents

毛发护理组合物及其制备方法 Download PDF

Info

Publication number
WO2021098874A1
WO2021098874A1 PCT/CN2020/130814 CN2020130814W WO2021098874A1 WO 2021098874 A1 WO2021098874 A1 WO 2021098874A1 CN 2020130814 W CN2020130814 W CN 2020130814W WO 2021098874 A1 WO2021098874 A1 WO 2021098874A1
Authority
WO
WIPO (PCT)
Prior art keywords
care composition
weight
hair
hair care
nicotinamide mononucleotide
Prior art date
Application number
PCT/CN2020/130814
Other languages
English (en)
French (fr)
Inventor
潘永强
卢锦春
王骏
Original Assignee
百瑞全球有限公司
潘永强
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 百瑞全球有限公司, 潘永强 filed Critical 百瑞全球有限公司
Priority to JP2022529830A priority Critical patent/JP2023517413A/ja
Priority to EP20890137.1A priority patent/EP4062897A4/en
Publication of WO2021098874A1 publication Critical patent/WO2021098874A1/zh

Links

Images

Classifications

    • 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
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • 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
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A61K8/442—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof substituted by amido group(s)
    • 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
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A61K8/463—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfuric acid derivatives, e.g. sodium lauryl sulfate
    • 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
    • A61K8/67—Vitamins
    • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
    • 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
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • 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
    • A61K8/67—Vitamins
    • A61K8/678—Tocopherol, i.e. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
    • A61Q1/02—Preparations containing skin colorants, e.g. pigments
    • A61Q1/10—Preparations containing skin colorants, e.g. pigments for eyes, e.g. eyeliner, mascara
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • 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
    • A61Q5/006—Antidandruff preparations
    • 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
    • A61Q5/02—Preparations for cleaning the hair
    • 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
    • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
    • 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
    • A61Q5/12—Preparations containing hair conditioners
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q9/00—Preparations for removing hair or for aiding hair removal
    • A61Q9/02—Shaving preparations

Definitions

  • the invention belongs to the field of personal care, and in particular relates to a hair care composition containing nicotinamide mononucleotide or its salt or its hydrate.
  • Nicotinamide mononucleotide is the most direct precursor that is transformed into coenzyme I (Nicotinamide adenine dinucleotide, NAD+) in the human body.
  • coenzyme I Natural Organic acid deficiency adenine dinucleotide
  • Coenzyme I is mainly used to transport hydrogen ions (H-) in the biological reactions of cells in the human body, and is an indispensable substance in biological reactions such as regulating metabolism, gene repair and even regulating the biological clock. This shows that the level of Coenzyme I in cells is closely related to health.
  • the hair care composition must be effectively and evenly distributed on the skin, so that the main active functional component nicotinamide mononucleotide in the care composition can contact the epidermis and hair follicles and directly reach the cells.
  • the hair care composition must be mainly liquid with different viscosities.
  • the stability of nicotinamide mononucleotide in liquid is poor, and the half-life of aqueous solution is generally 14 days. Due to the indeterminate nature of nicotinamide mononucleotide in the liquid state, there are technical difficulties in the application of nicotinamide mononucleotide. This is also the main reason for the failure to produce and launch related products in the market.
  • TP enzymatic process or enzymatic reaction.
  • a hair care composition comprises nicotinamide mononucleotide or its salt or its hydrate, and a basic component for stabilizing nicotinamide mononucleotide or its salt or its hydrate.
  • the nicotinamide mononucleotide or its salt or its hydrate is in a solid, liquid or mist state.
  • the nicotinamide mononucleotide or its salt or its hydrate accounts for 0.01% to 25% by weight of the total weight of the hair care composition, preferably a hair care composition 0.1% to 20% by weight of the total weight, more preferably 0.1% to 15% by weight of the total weight of the hair care composition.
  • the hair care composition also contains water,
  • the content of water is 50-95% by weight, preferably 60-92% by weight, more preferably 65-90% by weight.
  • the content of anionic surfactant is 15-65% by weight, preferably 25-45% by weight, more preferably 30-40% by weight;
  • the content of amphoteric surfactant is 1-15% by weight, preferably 1.5-8% by weight, more preferably 2-7% by weight; optionally, the content of cationic surfactant is 0.01-0.09% by weight %, preferably 0.02-0.08% by weight, more preferably 0.03-0.08% by weight;
  • the content of antioxidant is 0.5-3% by weight, preferably 0.9-2.5% by weight, more preferably 1.5-2% by weight;
  • the content of the acidity regulator is 0.05-1% by weight, preferably 0.2-0.85% by weight, more preferably 0.3-0.7% by weight;
  • the content of the pH buffering agent is 1-3% by weight, preferably 1.5-2.5% by weight, more preferably 2-2.5% by weight.
  • the cationic surfactant is at least one selected from polyquaternium-10, guar hydroxypropyltrimethylammonium chloride or a mixture thereof.
  • the eyebrow care products are eyebrow care liquid, eyebrow care spray and eyebrow care cream
  • the eyelash care products are eyelash care liquid assembly
  • the beard care products are beard care liquid, beard care spray and beard care cream.
  • the hair care composition also contains functional additives to enrich the appearance, texture, smell and user experience of the hair care composition.
  • a method for preparing a hair care composition includes the following steps:
  • aqueous solution for stabilizing the basic component of nicotinamide mononucleotide or its salt or its hydrate in liquid or gaseous state
  • the nicotinamide mononucleotide or its salt or its hydrate is mixed with the aqueous solution and the pH value is adjusted to obtain a hair care composition.
  • the basic components for stabilizing nicotinamide mononucleotide or its salt or its hydrate include anionic surfactants, amphoteric surfactants, cationic surfactants, nonionic surfactants, antioxidants, pH buffers, and One or more of acidity regulators.
  • the method includes:
  • the present invention provides a hair care composition which takes nicotinamide mononucleotide as the main active ingredient and can stably maintain the activity of nicotinamide mononucleotide or its salt or its hydrate for a long time, thereby By providing nicotinamide mononucleotide to the mitochondria in hair follicle stem cells and epidermal cells, the coenzyme I level of hair follicle stem cells and epidermal cells is increased, which promotes the normal energy production of cells and activates their vitality.
  • the nicotinamide mononucleotide in the present invention is the precursor of coenzyme I, which is directly converted to coenzyme I after absorption by cells, and is not subject to multiple enzymatic reactions in the body.
  • nicotinamide mononucleotide is a small molecule, which the human body can quickly absorb and reach the epidermal cells.
  • the hair care composition of the present invention can directly increase the level of coenzyme I for hair follicle stem cells and epidermal cells; compared to only oral nicotinamide mononucleotide supplements, the method of the present invention is more significant in improving hair problems, short More obvious effects can be presented within time. Therefore, this invention is suitable for middle-aged and elderly people who are concerned about hair loss and gradual whitening of hair, or hair growth is slow and thin. It is also suitable for people who are concerned about hair health.
  • Figure 1 shows the comparison results of the stability of Example 1, Example 15, Example 16 and 0.5% nicotinamide mononucleotide aqueous solution in 25 days under general conditions.
  • Fig. 2 shows the comparison results of the stability of Example 1, Example 15, Example 16 and 0.5% nicotinamide mononucleotide aqueous solution in 25 days under accelerated conditions.
  • Figures 3(a)-(d) respectively show the hair growth of female test subjects using the nicotinamide mononucleotide-containing hair essence of Example 4 at 0 days, 30 days, 60 days, and 120 days photo.
  • Fig. 4 shows the variation of the average hairline gap between female testers using the hair serum containing nicotinamide mononucleotide of Example 4 with the number of days.
  • hair follicle cells use glutamine as a substrate for ATP synthesis, and the coenzyme I used by this synthesis pathway is doubled.
  • the increase in age causes the level of Coenzyme I in the body to decrease year by year, and the level of Coenzyme I in the hair follicle cells will also decrease accordingly. Therefore, the synthesis of ATP will be more difficult and cannot satisfy the normal cell operation.
  • Hair follicle cells are activated by lactic acid at the same time: lactate dehydrogenase expressed in the cell is a catalytic enzyme, which uses hydrogen ions provided by reduced coenzyme I to synthesize lactic acid into lactic acid. In the absence of lactic acid, hair follicle cells cannot grow new hair; it can be seen that the simultaneous occurrence of both conditions is directly related to the decrease of coenzyme I levels in the cells.
  • Coenzyme I is an indispensable biochemical substance for maintaining the health of hair follicles and promoting hair growth. Therefore, increasing the level of Coenzyme I in the body has become a root-cause countermeasure for slow hair growth, whitening of hair color, and loss of hair. Although taking oral nicotinamide mononucleotide supplements can effectively increase the overall level of coenzyme I in the body, it can only supplement the effective ingredients required by hair and hair follicle cells in a limited way, and cannot be in place immediately, so the effect needs to be taken for a long time. Can gradually manifest.
  • the present invention provides a hair care composition containing nicotinamide mononucleotide.
  • the composition can be used directly on the scalp, scalp, epidermis, and hair follicles to directly supplement and increase the level of Coenzyme I in hair follicles and epidermal cells in the most effective way, so as to increase the synthesis of ATP and the proliferation of lactic acid, thereby Keep hair follicles healthy and activate hair follicle cells to promote hair regrowth;
  • the hair care composition can be used to soothe, improve, or even reverse various hair and hair problems of middle-aged and elderly people, and has a health care effect on hair health and helps to grow hair For use.
  • the hair care composition of the present invention is obtained by adding nicotinamide mononucleotide to specific stabilizing basic ingredients (for example, adding specific surfactants, additives, antioxidants, etc., and a specific range of ingredient ratios). Because the user directly coats the scalp, hair and skin when using hair care products, the main active functional ingredient nicotinamide mononucleotide in the product is absorbed by hair follicles and epidermal cells and passed through nicotinamide mononucleotide in the mitochondria Coenzyme I is synthesized by adenosyltransferase and ATP.
  • specific stabilizing basic ingredients for example, adding specific surfactants, additives, antioxidants, etc., and a specific range of ingredient ratios.
  • the coenzyme I participates in the biochemical synthesis of ATP and lactic acid in hair follicles and epidermal cells. In addition, during the synthesis of lactic acid, coenzyme I is then converted into reduced coenzyme I, which becomes the coenzyme required for the catalytic process of pyruvate synthesis to lactic acid as a medium for hydrogen ion transport.
  • the hair care composition of the present invention increases the level of Coenzyme I in hair follicles and epidermal cells to solve the problem of hair graying and shedding due to aging, and can maintain the health of the hair and accelerate the hair growth cycle.
  • Nicotinamide mononucleotide also maintains excellent liquid stability in the hair care composition. Therefore, the hair care composition of the present invention can maintain its activity compared with general nicotinamide mononucleotide aqueous solutions.
  • the invention promotes the usability and commercial plasticity of nicotinamide mononucleotide in hair care compositions, solves the long-term industrial production problem of nicotinamide mononucleotide in liquid stability, and gives users a solution to the problem of hair Rooted and new based on biochemical research s solution.
  • the present invention provides a hair care composition
  • a hair care composition comprising nicotinamide mononucleotide or its salt or its hydrate, and a stabilizing nicotinamide mononucleotide or its salt or its hydrate
  • Basic ingredients include anionic surfactants, amphoteric surfactants, cationic surfactants, neutral surfactants, antioxidants, pH buffering agents and acidity adjustment One or more of the agents.
  • the care composition of the present invention can maintain the stability of nicotinamide mononucleotide or its salt or its hydrate in an aqueous care composition for a long time, so as to make hair containing nicotinamide mononucleotide or its salt or its hydrate
  • the care composition can maintain its effective quality for a long time.
  • the hair care composition comprises nicotinamide mononucleotide or a salt or hydrate thereof.
  • the physical form of nicotinamide mononucleotide or its salt or its hydrate can be solid, liquid or mist state.
  • the chemical structure of nicotinamide mononucleotide can be acid type, salt type, crystal water type, hydrate type or other accessory forms.
  • the purity of the physical form and chemical structure may be 5% to 99.8%, preferably 80% to 99.8%, more preferably 97.5% to 99.5%.
  • the content of the nicotinamide mononucleotide or its salt or its hydrate is 0.01 wt% to 25 wt%, preferably 0.01 wt% to 20% by weight, more preferably 0.1% to 15% by weight.
  • the hair care composition contains a basic ingredient for stabilizing nicotinamide mononucleotide or its salt or its hydrate.
  • the basic ingredient package for stabilizing nicotinamide mononucleotide or its salt or its hydrate includes anionic surfactants, amphoteric surfactants, cationic surfactants, neutral surfactants, antioxidants, pH buffers and acidity One or more of the regulators.
  • the anionic surfactant can also stabilize nicotinamide mononucleotide or its salt or its hydrate.
  • the anionic surfactant can be fatty alcohol polyether sulfate, ammonium laureth sulfate, sodium laureth sulfate, sodium lauryl sulfate, ammonium lauryl sulfate, sodium methyl cocoyl taurate , Laureth-5 carboxylic acid and sodium lauryl glucose carboxylate and other single components or mixtures.
  • the content of the anionic surfactant is 15-65% by weight, preferably the content is 25-45% by weight, and more preferably the content is 30-40% by weight.
  • This surfactant can exhibit both anionic and cationic properties, and has excellent biocompatibility.
  • the amphoteric surfactant can not only be used as a decontamination agent, but also can stabilize nicotinamide mononucleotide or its salt or its hydrate.
  • the amphoteric surfactant may be an alkyl amino acid type amphoteric surfactant or an alkyl amphoteric carboxylate.
  • Amphoteric surfactants may include single ingredients or mixtures of cocamidopropyl betaine, cocamide monoethanolamine, lauryl glucoside, and coco methyl dextran.
  • the content of the amphoteric surfactant is 1-15 wt%, preferably 1.5-8 wt%, more preferably 2-7 wt%.
  • amphoteric surfactants include alkyl amphoteric carboxylic acids or their salts, for example, alkyl amphoteric dipropionic acid, alkyl amphoteric diacetic acid, alkyl amphoteric glycine and alkali metal salts of alkyl amphoteric propionic acid, wherein the alkyl Represents an alkyl group having 6 to 20 carbon atoms. More preferably, the alkyl group is derived from coconut oil or is a lauryl compound, such as coco amphoteric dipropionate. This coconut oil-based amphoteric dipropionate surfactant and the same type of amphoteric surfactant can be the same and sold under the trademark Miranol series.
  • amphoteric surfactants include:
  • ⁇ Lauroyl amphoteric diacetate obtained from a mixture of lauric acid and myristic acid (sold under the trademark MIRANOL BM CONC.);
  • ⁇ hexanoyl amphoteric acetate sold under the trademark MIRANOL SM CONC.
  • amphoteric surfactant used is coco amphoteric acetate.
  • amphoteric surfactants account for about 0.1% to about 7% by weight, preferably about 0.2% to about 4% by weight, more preferably 0.3% to 3% by weight.
  • Cationic surfactants can provide cations, which can provide functional effects for hair care compositions: cations will be attached to the hair during cleansing, which can make the hair straight, reduce the formation of knots in the hair, and make it easy to comb. At the same time, cations can interact with nicotinamide mononucleotide in aqueous solution to improve its stability in liquid state.
  • the cationic surfactant may include an amine salt heterocyclic quaternary ammonium salt type cationic surfactant.
  • cationic surfactants include cetyl trimethyl ammonium chloride, dodecyl trimethyl ammonium chloride, tricetyl methyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride , And at least one of two (partially hydrogenated tallow) dimethyl ammonium chloride, polyquaternium-10, guar hydroxypropyltrimethylammonium chloride, etc., preferably polyquaternium-10 , Guar hydroxypropyl trimethyl ammonium chloride or polyethylene glycol.
  • the cationic surfactant is 0.01-0.09% by weight, preferably 0.02-0.08% by weight, more preferably 0.03-0.08% by weight.
  • the hair care composition may also include other surfactants, such as nonionic surfactants and other amphoteric surfactants.
  • Nonionic surfactants can function as emulsifiers and stabilizers in the composition.
  • the term "nonionic surfactant” as used herein includes mixtures of nonionic surfactants.
  • Examples of useful nonionic surfactants also include condensates of ethylene oxide and a hydrophobic portion, wherein the average hydrophilic-lipophilic balance (HLB) of the hydrophobic portion is between about 8 and about 16, and more It is preferably between about 10 and about 12.5.
  • HLB hydrophilic-lipophilic balance
  • These surfactants include condensation products of aliphatic primary or secondary alcohols and ethylene oxide having a linear or branched configuration of about 8 to about 24 carbon atoms, wherein ethylene oxide is About 2 moles to about 40 moles, preferably about 2 moles to about 9 moles.
  • the aliphatic alcohol contains about 9 to about 18 carbon atoms, and is ethoxylated with about 3 moles to about 12 moles of ethylene oxide per mole of the aliphatic alcohol.
  • Particularly preferred is the ethylene oxide ethoxylation of primary alcohols having about 12 to about 15 carbon atoms and about 5 moles to about 9 moles per mole of alcohol.
  • One such material is sold by Shell Chemical Company under the trade name Neodol 25-9.
  • Other commercially available nonionic surfactants are Neodol 25-6.5 and Neodol 25-7 sold by Shell Chemical Company.
  • nonionic surfactants include condensation products of alkylphenols having about 6 to about 12 carbon atoms and about 3 moles to about 30 moles, preferably about 5 moles to about 14 moles of ethylene oxide.
  • examples of such surfactants are sold by Rhodia, Inc. under the trade names IGEPAL CO 530, IGEPAL CO 630, IGEPAL CO720, and IGEPAL CO 730.
  • the most preferably used nonionic surfactant is a mixed linear alcohol ethoxylate, such as Laureth-7 sold by Rhodia, Inc. under the trade name RHODASURF L-790.
  • Antioxidants can effectively prevent the generation of oxidation, preventing substances from producing oxidation products such as free radicals during the oxidation process and carrying out subsequent unpredictable chemical reactions with the main components of them, which may cause the main components to deteriorate and deteriorate over a long period of time. degradation. Nicotinamide mononucleotide will undergo oxidation reaction in the liquid state and degrade into nicotinamide and other substances. Therefore, the use of antioxidants can effectively protect the stability of nicotinamide mononucleotide in the liquid state. Antioxidants can be divided into two categories: synthetic antioxidants and natural antioxidants.
  • antioxidants Two types protect liquid nicotinamide mononuclear
  • the chemical structure of the acid is different, and it is preferable to use natural antioxidants.
  • Natural antioxidants can be further subdivided into amino acid antioxidants, vitamin antioxidants, preferably L-cysteine, DL-methionine, vitamin A, vitamin C, vitamin E, vitamin P, and sodium phytate. Ingredients or mixtures.
  • the antioxidants also exert a certain degree of antiseptic function, which synergistically helps the overall stability of the hair care composition.
  • the content of the antioxidant is 0.5-3% by weight, preferably 0.9-2.5% by weight, more preferably 1.5-2% by weight.
  • the stability of nicotinamide mononucleotide in the liquid state will be improved in a weakly acidic environment. Therefore, acidity regulators are needed to adjust the pH in the hair care combination.
  • the acidity regulator of the hair care combination may be a single component of citric acid, oxalic acid, lactic acid, etc., or a mixture thereof.
  • pH adjusting agent content based on the total weight of the hair care composition, pH adjusting agent content of 1-3% by weight, preferably 1.5 to 2.5 wt%, more preferably 2-2.5 wt%.
  • Nicotinamide mononucleotide or its salt or its hydrate is generally very unstable in the composition and easily degraded. Therefore, the hair care composition of the present invention further includes an additive for stabilizing the activity of nicotinamide mononucleotide or its salt or hydrate.
  • the stabilizer may be one or more selected from the group consisting of sialic acid, theanine, ⁇ -carotene, and sodium phosphate.
  • the hair care composition can be added with other different ingredients to enrich its appearance, texture, fragrance, characteristic function and user experience effect, as long as the ingredient or its combination does not undergo any chemical reaction with nicotinamide mononucleotide to cause nicotinamide
  • the single nucleotide can be significantly degraded during the shelf life.
  • this component can improve the stability of nicotinamide mononucleotide or its salt or its hydrate in liquid to a certain extent.
  • conditioning agents such as propylene glycol
  • propylene glycol can be used to increase the hair care composition
  • Liquid viscosity manufacturers can adjust the viscosity according to the positioning of their products to increase the content of propylene glycol in the hair care composition to increase the viscosity proportionally; in a specific embodiment of the present invention, based on the hair care composition
  • the total weight of the product, the content of other components is 0.01-1% by weight, preferably 0.1-0.8% by weight, more preferably 0.2-0.6% by weight.
  • a co-solvent can also be added to the hair care composition to adjust the physical texture of the composition, especially the transparency in the liquid look and feel of the hair care composition.
  • Sodium xylene sulfonate can provide liquid products in hair care products such as shampoos, hair conditioners and essences to increase the degree of transparency in the products; sodium xylene sulfonate can increase the ability of water molecules in the liquid to dissolve ingredients. Promote the various ingredients in the hair care composition to be more fully joined.
  • the nicotinamide mononucleotide in the hair care composition can have higher solubility in the hair care composition, and can be made into specific products such as high-concentration nicotinamide mononucleotide essence to meet the different needs and expectations of users .
  • sodium xylene sulfonate can fuse nicotinamide mononucleotide with other ingredients to achieve part of the product in the hair care composition. It can provide more than one functional effect at the same time, which can be understood as a hair care composition Among them, nicotinamide mononucleotide or its derivatives are used to promote the levels of Coenzyme I in various tissues of the head, including hair, scalp, hair follicles and their cells, to improve the health of the hair and head, as well as other The purpose of the hair care composition, such as cleaning, styling coordination, smell change, etc., should also be regarded as part of the function of the hair care composition. In a specific embodiment of the present invention, based on the total weight of the hair care composition, the content of sodium xylene sulfonate is 0.01-10% by weight, preferably 0.1-5% by weight, more preferably 1-3% by weight.
  • Foaming agents can also be added to the hair care composition to increase the cleansing and repairing functions of some monofunctional or multifunctional products in the composition, such as shampoo and conditioner.
  • the foam can produce a larger contact space, which can make the main ingredients and other ingredients in the hair care composition effectively diffuse on the head, thereby making favorable conditions for the hair, scalp, hair follicles, etc. to absorb the main ingredient nicotinamide mononuclear Glycolic acid or its derivatives are added to the cell to increase the level of Coenzyme I, especially the level of the mitochondria in the cell to cope with daily metabolism and biocatalysis, and can also protect and repair environmental pollution and damage caused by UV exposure.
  • Foam can also extend the residence time of the ingredients on the head: the tension between the foams can maintain each other, so that it can easily stay between the hair and scalp without affecting the effect of the difference in the shape of the head. Therefore, the addition of a foaming agent to the hair care composition also plays a certain physical role in enhancing the result of Coenzyme I.
  • the foaming agent that can be used in the hair care composition can be a quaternary ammonium polyethylene glycol alkyl amino acid sugar surfactant, which can be betaine, cocamidopropyl betaine, cocoyl monoethanolamine, sodium cocoyl glycinate , Sodium lauryl glucose carboxylate, olive oil fatty acid polyethylene glycol ester mono (carboxymethyl) ether sodium salt, etc.
  • the above-mentioned foaming agents can be added according to the function of the product, and these foaming agents can be used in a single or a mixture of multiple proportions in the product ingredients to condition the product The most suitable foam condition achieves the best use effect and user experience.
  • the foaming agent is preferably betaine, sodium cocoyl glycinate and sodium lauryl glucose carboxylate, more preferably sodium cocoyl glycinate.
  • the content of sodium cocoylglycinate is 0.01-10% by weight, preferably 0.1-5% by weight, more preferably 0.5-1% by weight. It is used in the case of mixing in various proportions, and the combination of sodium cocoyl glycinate and sodium lauryl glucose carboxylate is the most preferable combination.
  • the mixing ratio of sodium cocoyl glycinate and sodium lauryl glucose carboxylate is 2:1 for the fine foam formula, and the larger foam is 1:2; the size of the foam can be based on the sodium cocoyl glycinate and sodium lauryl glucose carboxylate in the mixture.
  • the coordination ratio of sodium lauryl glucose carboxylate is adjusted.
  • the content of the total mixture is 0.01-10% by weight, preferably 0.1-5% by weight, more preferably 0.5-1% by weight.
  • the hair care composition can also be added with other additives to enrich its appearance, fragrance, feeling of use and function; in terms of appearance, the hair care composition can be added with general food pigments, and darker colors such as yellow, brown, blue and Black has a more obvious performance in preventing light, and it also has a certain effect on the stability of the main and other ingredients of the hair care composition.
  • the content of the edible pigment is 0.01-1% by weight, preferably 0.05-0.1% by weight, more preferably 0.05-0.08% by weight. Fragrance is more important in products in hair care compositions, such as shampoos, conditioners, and essences. It can increase the user's satisfaction with the products and solve the problem of hair odor.
  • the hair care composition can be added with harmless fragrance or refined plant mineral sesame oil as the main fragrance source, more preferably refined plant mineral sesame oil. Since there is no odor in the formula of the hair care composition, the aroma provided by the additives should actually be reflected in the hair care composition without any difference between the aroma of the composition after the addition and the attribute aroma of the additives. If this happens, it should be considered that there is an unpredictable chemical reaction between the additive and the hair care composition, which may affect the chemical structure of the nicotinamide mononucleotide in the hair care composition, thereby changing the hair care The function of the composition and its stability.
  • Refined plant-mineral sesame oils are mostly inert substances, and should not have the above-mentioned special conditions after being added to the hair care composition.
  • the content of the refined plant mineral oil is 0.001-0.1% by weight, preferably 0.005-0.01% by weight, more preferably 0.08-0.01% by weight.
  • the hair care composition can be added with functional additives to meet the needs of different users, and can help increase the Coenzyme I level of hair, scalp and hair follicle cells, and promote the hair care composition to show compliance in a short period of use. Significant effect expected by users.
  • the level of coenzyme I decreases, it is difficult for the epidermal cells of the head to synthesize ATP to meet the daily high energy demand.
  • the withering of epidermal cells will increase the scalp.
  • the cell's immune ability will also decrease and the chance of infection will increase;
  • hoarding is difficult to drain from sweat and head oil on the epidermis of the head. Dust is also more likely to be attached to the head due to the increase in surface area.
  • Inflammation of the epidermis of the head also tends to occur frequently, which is a severe itching phenomenon known in the field.
  • the phenomenon of head itching forces the patient to touch the scalp with his hands, but when the head itch becomes more severe, the patient will frequently stroke the scalp or even make it feel firm, so as to remove the unpleasant feeling in the shortest time.
  • the patient caused damage to the epidermis of the head, especially the damage to the hair sacs.
  • the dead head capsule cells also lose the ability to grow hair. Part of this physical damage is permanent. Even increasing the level of Coenzyme I failed to promote cell recovery.
  • Functional additives can be pain Shuyuan material and scalp inhibitor, in which peppermint oil and zinc pyrithione are used as functional additives of hair care composition to achieve the purpose; peppermint oil can give the user a cool feeling when it touches the epidermis of the head, disturbing the head The unpleasant feeling of itching; therefore, the user can avoid scratching the head due to itching and damaging the tissues and cells in the process.
  • the content of peppermint oil is 0.05-0.1% by weight, preferably 0.05-0.09% by weight, more preferably 0.06-0.08% by weight.
  • Zinc pyrithione is an antibacterial agent, which can inhibit the growth of Gram-negative and positive bacteria and molds.
  • the content of zinc pyrithione is 0.1-1.5% by weight, preferably 0.5-1% by weight, more preferably 0.8-1% by weight.
  • the hair care product form of the hair care composition is at least one selected from the group consisting of shampoo, conditioner, essence, soap, spray, cream, wax, gel, ointment Shape or any liquid and solid. Therefore, the hair care product of the present invention can simultaneously have other functions such as cleaning, repairing, anti-dandruff and fixing hair styling.
  • shampoo containing nicotinamide mononucleotide also has a cleansing effect, that is, generally removes oil and odor from the hair; shampoo also has foaming properties to easily penetrate into the hair and scalp.
  • the shampoo may contain water, nicotinamide mononucleotide or its salt or its hydrate, surfactants, acidity regulators, perfumes, etc. as auxiliary materials to preserve the functions and characteristics of the shampoo And durability.
  • the content of water is 30% to 90% by weight based on the total weight of the shampoo.
  • the hair care composition also includes eyebrow care products, eyelash care products, and beard care products.
  • Eyebrow care products mainly include eyebrow care lotion and eyebrow care cream; eyebrow care lotion and eyebrow care cream contain 0.01-3% (w/v) of nicotinamide mononucleotide or its salt or its hydrate as the main component, adding auxiliary materials Including sage oil, green tea extract, white beeswax, etc.
  • the eyelash care products are assembled with eyelash care liquid, and the eyelashes are applied to the eyelashes with the eyelash brush so that the upper and lower eyelashes and the hair follicles can be in contact.
  • the main component of mascara is also nicotinamide mononucleotide or its salt or its hydrate, and because the growth rate of eyelashes is slower than that of hair, the main component needs to be more to stimulate its growth cycle, so nicotinamide in mascara
  • the mononucleotide or its salt or its hydrate is 1-10% (w/v)
  • the auxiliary materials are tea tree extract and cysteine. Since the use of mascara is closer to the essence of the eye, the composition of the mascara must not contain eye-sensitive, volatile substances and materials used to treat eye diseases.
  • the purpose of the eyelash care solution assembly is to allow users who are concerned about the health of eyelashes, especially for users with slower and short eyelash growth, to improve their condition, and to help users in eye health care and personal grooming.
  • the beard care products are beard care lotion, beard care spray and beard care cream; the main ingredient of beard care products is 0.1-2% nicotinamide mononucleotide or its salt or its hydrate, with mint extract and burdock powder as auxiliary materials Or its extracts, vitamin A, vitamin E and cysteine, etc., using water, low concentration ethanol 0.01-0.05% (v/v) or beeswax as a medium to make liquid, spray and paste for users to press Make a choice according to their preferences.
  • the purpose of beard care liquid, beard care spray and beard care cream is to accelerate the growth of beard, maintain or restore the original color and the health of hair follicles.
  • the principle is consistent with the above-mentioned hair care composition, thereby providing users with personal styling A healthy product in scientific research.
  • the present invention also provides a method for preparing a hair care composition, comprising the following steps: providing nicotinamide mononucleotide or a salt or hydrate thereof; providing a stabilizing nicotinamide mononucleotide or An aqueous solution of the basic component of its salt or its hydrate; and mixing nicotinamide mononucleotide or its salt or its hydrate with the aqueous solution and adjusting the pH value, thereby obtaining a hair care composition.
  • the basic component for stabilizing nicotinamide mononucleotide or its salt or its hydrate includes one of anionic surfactants, amphoteric surfactants, cationic surfactants, antioxidants, pH buffers and acidity regulators, or Many kinds.
  • the method includes:
  • the essence is mainly used to increase the levels of coenzyme I and reduced coenzyme I in hair follicle cells, and also relieve scalp itching or inflammation, so as to promote the health of hair follicle stem cells and activate their activity to Carry out the synthesis of ATP and lactic acid.
  • the main component of the essence is nicotinamide mononucleotide or its salt or its hydrate, and its content is 3% to 25% by weight of the total component weight, preferably 5% to 15% by weight, more preferably 8% to 12% by weight.
  • the preparation method of shampoo is as follows. Add ammonium laureth sulfate, cocoyl glutamate TEA salt and MIRANOL to the container as surfactants.
  • the content of these three surfactants can be different or equal, mainly for different hair types. When the content of surfactant is equal, it will be neutral hair. Taking normal hair as an example, based on the total weight of the shampoo, the content of the three surfactants is 0.1% to 10% by weight, preferably 0.5% to 10% by weight, more preferably 1% to 10% by weight. weight%.
  • the user can apply the shampoo evenly to the head according to the amount of personal preference and it is recommended to massage the head for 2-5 minutes. After completion, it can be rinsed off; the shampoo should be used at least once a day and should be used continuously to achieve the target effect.
  • nicotinamide mononucleotide 2.5 grams were added and stirred at a speed of about 100 rpm for 15 minutes until completely uniform, and pure water was added to the total amount of 500 ml and stirred until completely uniform.
  • the pH value of the eyebrow care solution needs to be between 4.75-5.
  • 1M sodium citrate solution or 1M citric acid solution can be used.
  • the same method of using eyebrow care solution is to put about 1ml of the liquid on the fingertips in the morning and evening, then lightly apply to the eyebrows, and swipe back and forth until the eyebrows are completely absorbed by the eyebrows.
  • Test 1 Comparison of the effectiveness of shampoo containing nicotinamide mononucleotide and control shampoo
  • Table 9 lists the average hair gap between the hair lines of the female testers using the nicotinamide mononucleotide-containing hair serum of Example 4 on different days.
  • Fig. 4 shows the variation of the average hairline gap between female testers using the hair serum containing nicotinamide mononucleotide of Example 4 with the number of days.
  • the nicotinamide mononucleotide aqueous solution (2.5g nicotinamide mononucleoside dissolved in 500 ml of pure water) and Example 1, Example 15 and Example 16 were compared for the stability test of nicotinamide mononucleotide. Specifically, the samples were placed in general conditions (temperature ⁇ 22 degrees Celsius and ⁇ 65% humidity) and accelerated conditions (temperature ⁇ 37 degrees Celsius and ⁇ 85% humidity). A 30-day study is carried out every day by high performance liquid chromatography to observe the stability of nicotinamide mononucleotide in each group. The results of stability can refer to Figure 1 and Figure 2, and the test method and instrument can be used. Refer to Table 10.
  • Control 1 Use only oral nicotinamide mononucleotide supplements
  • the trial participants used oral nicotinamide mononucleotide supplements (obtained from Gene Harbor (Hong Kong) Biotechnology Co., Ltd.: product name-NMN9000), and took two capsules totaling 300 mg every morning after breakfast; at the same time, the trial participants shampooed their hair every day After using 5ml of hair essence, three months later, the trial participants will conduct a questionnaire survey: assess their physical health, hair growth speed, hair color change and the number of new hair growth.

Abstract

一种毛发护理组合物及其制备方法。毛发护理组合物包含烟酰胺单核苷酸或其盐或其水合物，以及用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分。该毛发护理组合物的成分能提升烟酰胺单核苷酸在液态中的稳定性，为解决头发和毛发的衰老和生长问题和烟酰胺单核苷酸在液态中的稳定性带来崭新的方向，并为烟酰胺单核苷酸的应用方式带来多样化的突破。

Description

毛发护理组合物及其制备方法 技术领域
本发明属于个人护理领域，具体涉及一种含有烟酰胺单核苷酸或其盐或其水合物的毛发护理组合物。
背景技术
近年生物化学类研究发现，人体内的辅酶I水平会随年岁增长而逐步下降。相关的研究亦提出辅酶I水平的减少与身体出现各新陈代谢减慢、机能衰退而引发关联疾病如糖尿病等、或因细胞失去自动修复机能而出现癌症等有密切关系。针对以上情况，补充体内辅酶I水平是一个直接和有效的方案。国内外科研均对提升辅酶I作出不同的机理、动物和病理临床研究，均一致肯定补充辅酶I能有效改善上述健康的问题，更在动物实验中证实此方法能提升年老小鼠的运动能力；相反，对照组的小鼠在年老时运动能力较弱。
烟酰胺单核苷酸(Nicotinamide mononucleotide,NMN)是人体内转化成辅酶I(Nicotinamide adenine dinucleotide,NAD+)最直接的前体。 研究证明烟酰胺单核苷酸是最直接的方式迅速提升人体各器官及细胞内的辅酶I水平。辅酶I主要为人体内各细胞的生物反应中传送氢离子(H-)，并作为调控新陈代谢、基因修复以至调节生理时钟等生物反应中不可或缺的物质。由此可见，细胞中的辅酶I水平与健康有着密切的关系。
毛发的生长亦与辅酶I有密切的关系：近年的毛发生长项目研究发现，乳酸的合成和其水平于毛囊细胞中均为启动毛发生长循环的重要原素，与此同时，研究人员发现毛囊细胞亦需要大量的ATP方能维持其正常运作。辅酶I和其还原型辅酶I是毛囊细胞中合成乳酸的重要原料:当细胞中的辅酶I水平下降，乳酸无法合成，其水平因而减少而导致毛发生长暂停。
辅酶I亦是细胞腺粒体中ATP合成一个不可或缺的底物:辅酶I的下降亦导致毛囊细胞中的腺粒体不能合成足够ATP，难而支持其细胞的日常运作。毛囊细胞在同时缺乏乳酸和ATP的情况时，头发的生长无可避免地渐趋缓慢甚至脱落，毛囊的凋零下色素细胞亦随之减少，促使发色转白。上述的现象与身体机能衰退皆为衰老的后果，源自身体上辅酶I的减少。恢复身体的辅酶I水平可以以运动和控制热量吸收的方式进行，但成效因人而异且不能长久实行。口服烟酰胺单核苷酸补充剂提供了一个简便和直接的方式，并能有效提升体内辅酶I整体水平。虽然口服烟酰胺单核苷酸补能对身体上 各健康状况都有明显的改善和提升，但却不能针对头发和毛发问题，未能在最短的时间内对头髪和其他部位的毛发作出仪容上的改善。为解决上述问题，开发以烟酰胺单核苷酸为主要活性功能成分的毛发护理组合物为最佳方案。
毛发护理组合物的使用须能有效地平均分布在皮肤上，使护理组合物中主要活性功能成分烟酰胺单核苷酸能接触表皮和毛囊并直达细胞之中。为达成这个目的，毛发护理组合物须以不同黏度的液态为主。但是烟酰胺单核苷酸于液态的稳定性较差，水溶液的半衰期一般为14天。碍于烟酰胺单核苷酸于液态中的不穏定性，为烟酰胺单核苷酸在相关应用上存在技术性难题。这也是市场上未能生产和推出相关产品的主要原因。TP)的酶法工艺或者酶法反应。
发明内容
为了解决至少上述一个问题，本发明提供了一种毛发护理组合物及其制备方法。本发明的毛发护理组合物的成分能提升烟酰胺单核苷酸在液态中的稳定性上提供了解决方案，为解决头发和毛发的衰老和生长问题和烟酰胺 单核苷酸在液态中的稳定性带来崭新的方向，并为烟酰胺单核苷酸的应用方式带来多样化的突破。
具体而言，本发明提供了：
一种毛发护理组合物，包含烟酰胺单核苷酸或其盐或其水合物，以及用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分。
其中，烟酰胺单核苷酸或其盐或其水合物为固态、液态或雾态。
其中，用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分包含阴离子表面活性剂、两性表面活性剂、阳离子表面活性剂、抗氧化剂、pH缓冲剂和酸度调节剂中的一种或者多种。
其中，毛发护理组合物的形式为洗发水、护发素、精华液、肥皂、喷雾、乳霜、发蜡、啫喱和膏体中的任意一者。
其中，毛发护理组合物为眉毛护理产品、眼睫毛护理产品和胡须护理产品中的任意一者。
其中，基础成分包含用以防止烟酰胺单核苷酸在液态或雾态时降解的成分，如选自唾液酸、茶氨酸、β-胡萝卜素和磷酸钠中的一种或多种。
其中，以烟酰胺单核苷酸计，所述烟酰胺单核苷酸或其盐或其水合物占所述毛发护理组合物总重量的0.01重量％至25重量％，优选为毛发护理 组合物总重量的0.1重量％-20重量％，更优选为毛发护理组合物总重量的0.1重量％-15重量％。
其中，毛发护理组合物还包含水，
任选地，基于所述毛发护理组合物的总重量，水的含量为50-95重量％，优选为60-92重量％，更优选为65-90重量％。
其中，相对于毛发护理组合物的总重量，
阴离子表面活性剂的含量为15-65重量％，优选为25–45重量％，更优选为30-40重量％；
任选地，两性表面活性剂的含量为1-15重量％，优选为1.5-8重量％，更优选为2-7重量％；；任选地，阳离子表面活性剂的含量为0.01-0.09重量％，优选为0.02-0.08重量％，更优选为0.03-0.08重量％；
任选地，抗氧化剂的含量为0.5-3重量％，优选为0.9-2.5重量％，更优选为1.5-2重量％；
任选地，酸度调节剂的含量为0.05-1重量％，优选为0.2-0.85重量％，更优选为0.3-0.7重量％；以及
任选地，pH缓冲剂的含量为1-3重量％，优选为1.5-2.5重量％，更优选为2-2.5重量％。
其中，阴离子表面活性剂选自月桂醇聚醚硫酸酯钠、月桂基硫酸钠、月桂基硫酸铵、甲基椰油酰基牛磺酸钠、月桂醇聚醚-5羧酸、月桂基葡萄糖羧酸钠和其混合物中的至少一者。
其中，两性表面活性剂为烷基两性羧酸盐、烷基氨基酸盐、椰油酰胺丙基甜菜碱、椰油酰胺单乙醇胺、月桂基葡糖苷、椰油基甲基葡聚糖或其混合物中的至少一者。
其中，阳离子表面活性剂为选自聚季铵盐-10、瓜儿胶羟丙基三甲基氯化铵或其混合物中的至少一者。
其中，抗氧化剂为选自L-半胱氨酸、DL-蛋氨酸、维生素A、维生素C、维生素E、植酸钠或其混合物中的至少一者。
其中，酸度调节剂为选自柠檬酸、草酸、乳酸、盐酸或其混合物中的至少一者。
其中，眉毛护理产品为眉毛护理液、眉毛护理喷雾和眉毛护理膏；所述的眼睫毛护理产品为眼睫毛护理液组装；所述的胡须护理产品为胡须护理液、胡须护理喷雾和胡须护理膏。
其中，毛发护理组合物中还包含用以丰富毛发护理组合物的外观、质感、气味和用家体验的功能性添加剂。
其中，功能性添加剂选自增感剂、增泡剂、香味剂、功能性辅料或其任意组合。
一种制备毛发护理组合物的方法，包括下列步骤：
提供烟酰胺单核苷酸或其盐或其水合物；
提供用于稳定液态或气态中的烟酰胺单核苷酸或其盐或其水合物的基础成分的水溶液；以及
将烟酰胺单核苷酸或其盐或其水合物与所述水溶液混合并且调节pH值，从而得到毛发护理组合物。
其中，用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分包含阴离子表面活性剂、两性表面活性剂、阳离子表面活性剂、非离子表面活性剂、抗氧化剂、pH缓冲剂和酸度调节剂中的一种或者多种。
其中，该方法包括：
(1)将一种或多种阴离子表面活性剂混合，得到第一类表面活性剂；
(2)将一种或多种两性表面活性剂混合，得到第二类表面活性剂；
(3)任选地将一种或多种阳离子表面活性剂混合，得到第三类表面活性剂；
(4)将第一类表面活性剂、第二类表面活性剂和任选的第三类表面活性剂混合成得复合表面活性剂；
(5)将烟酰胺单核苷酸加至复合表面活性剂中，以得到混合物
(6)将pH在缓冲液加入混合物并使用酸度调节剂使混合物的pH值为4.85-7.0，从而得毛发护理组合物；以及
(7)将抗氧化剂加入混合物从而得毛发护理组合物。
本发明具有至少以下一种优点和积极效果：
1.本发明提供了一种毛发护理组合物，该组合物以烟酰胺单核苷酸为主要有效成分并且能够长期稳定地保持烟酰胺单核苷酸或其盐或其水合物的活性，从而通过将烟酰胺单核苷酸提供至毛囊干细胞和表皮细胞中的线粒体来提升毛囊干细胞和表皮细胞的辅酶I水平，促使细胞的正常能量生产和激活其活力。
2.与烟酸、烟酰胺和其他衍生物等相比，本发明中的烟酰胺单核苷酸是辅酶I的最前体，细胞吸收后直接转化至辅酶I，不受制于体内多重酶反应。同时，烟酰胺单核苷酸为小分子，人体能迅速吸收并达到表皮细胞。
3.本发明的毛发护理组合物能直接为毛囊干细胞和表皮细胞提升辅酶I水平；相对只以口服烟酰胺单核苷酸补充剂，本发明的做法于改善毛发问题 上更为显着，短时间内能呈现更明显的效果。因此，此发明除适合关注脱发和发色逐渐变白等问题的中年和老年人士，或毛发生长较缓慢和稀
Figure PCTCN2020130814-appb-000001
的人士使用，也适合一般对头发健康关注人士。
附图简要说明
图1示出在一般状况下实例1、实例15、实例16与0.5％烟酰胺单核苷酸水溶液在25天的稳定性比较结果。
图2示出在加速状况下实例1、实例15、实例16与0.5％烟酰胺单核苷酸水溶液在25天的稳定性比较结果。
图3(a)-(d)分别示出了使用了实例4的含有烟酰胺单核苷酸的头发精华液的女测试者在0天、30天、60天和120天时的头发生长情况的照片。
图4示出了使用实例4的含有烟酰胺单核苷酸的头发精华液的女测试者发线平均头发差距随着天数的变化。
具体实施方式
以下通过具体实施方案的描述对本发明作进一步说明，但这并非是对本发明的限制，本领域技术人员根据本发明的基本思想，可以做出各种修改或改进，但是只要不脱离本发明的基本思想，均在本发明的范围之内。
头发生长缓慢、逐渐变白和脱落乃衰老最明显的表征，其中原因可为毛囊细胞缺乏ATP的供应；毛囊细胞于线粒体中经醣解等生化反应合成能量分子ATP，以提供足够能量维持毛发生长和毛囊正常运作。研究报道指出毛囊细胞在低ATP水平下会逐渐死亡，从而毛发停止生长、色素细胞减少以至渐变灰白、继而脱落并凋零。毛囊细胞中的ATP合成与其他细胞有异：身体一般细胞大多使用葡萄糖进行，所需的辅酶I较少。毛囊细胞较少利用此方法进行ATP合成，除而代之，毛囊细胞更多利用谷氨酰胺为底物进行ATP合成，而该合成途径需要利用的辅酶I则以倍增。在多种原因下，年岁的增长使身体里的辅酶I水平逐年下跌，毛囊细胞中的辅酶I水平也将随之下降，因此ATP的合成将会更为困难，无法满足正常细胞的运作。毛囊细胞同时由乳酸激活：乳酸在细胞内表达的乳酸脱氢酶为催化酶，使用还原型辅酶I中提供的氢离子予丙酮酸合成为乳酸。在缺乏乳酸的情况下，毛囊细胞不能生长新发；由此可见，两种情况同时出现下均与细胞中的辅酶I水平下降有着直接的关系。
辅酶I是保持毛囊健康与促进毛发生长上不可或缺的生化物质。因此，提升身体内的辅酶I水平成为解决头发生长缓慢、发色转白和脱落的根源对策。服用口服烟酰胺单核苷酸补充剂虽能有效的提升体内辅酶I整体水平，但对头发和毛囊细胞所需的有效成分只能作有限的补充，同时不能即时到位，故此效果需要服用长时间才能逐渐体现。
为解决上述问题，本发明提供了一种包含烟酰胺单核苷酸的毛发护理组合物。该组合物能直接在头髪、头皮、表皮和毛囊上使用，以最有效的方式直接补充及提升毛囊和表皮细胞中辅酶I水平，逹至其提升ATP合成和乳酸的增生的目的，藉此保持毛囊健康和激活毛囊细胞以促进毛发重新生长；该毛发护理组合物可用于舒缓、改善、甚至逆转中年和老年人士的各头发和毛发问题，并对毛发健康作保健作用及有助增长毛发之用。
本发明的毛发护理组合物是通过将烟酰胺单核苷酸加入到特定的稳定用基础成分(例如加入特定表面活性剂、添加剂、抗氧化剂等和其特定范围的成分比例)中而获得的。由于用者在使用毛发护理产品时直接涂上头皮、头发和皮肤上，产品中的主要活性功能成分烟酰胺单核苷酸被毛囊和表皮细胞所吸收并在线粒体中经烟酰胺单核苷酸腺苷转移酶与ATP合成得辅酶I。该辅酶I参与毛囊和表皮细胞中的ATP和乳酸生化合成。另外，乳酸合成 时辅酶I再转化成为还原型辅酶I后，成为丙酮酸合成至乳酸的催化过程中所需的辅酶以作为当中氢离子传输的介质。本发明的毛发护理组合物提升毛囊和表皮细胞中的辅酶I水平以解决因为衰老而导致毛发变灰白和脱落的问题，并能保持毛发的健康和加快毛发的生长周期。
烟酰胺单核苷酸在毛发护理组合物中还保持了优异的液态稳定性，因此本发明的毛发护理组合物可以较一般烟酰胺单核苷酸的水溶液保持其活性。本发明促使烟酰胺单核苷酸在毛发护理组合物的使用性和商业化可塑性，解决了长期以来烟酰胺单核苷酸在液态稳定性上的工业化生产难题，给予使用者在毛发问题上一个以生物化学科研为基础的根源性且新
Figure PCTCN2020130814-appb-000002
的解决方案。
在一个方面中，本发明提供了一种毛发护理组合物，其包含烟酰胺单核苷酸或其盐或其水合物，以及用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分。用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分包括阴离子表面活性剂、两性表面活性剂、阳离子表面活性剂、中性表面活性剂、抗氧化剂、pH缓冲剂和酸度调节剂中的一种或者多种。本发明的护理组合物能够长期保持烟酰胺单核苷酸或其盐或其水合物在水性的护理组合物中的 稳定性，使含有烟酰胺单核苷酸或其盐或其水合物的毛发护理组合物能长时间保持其有效质量。
烟酰胺单核苷酸或其盐或其水合物
在本发明的各个实施方案中，毛发护理组合物包含烟酰胺单核苷酸或其盐或其水合物。烟酰胺单核苷酸或其盐或其水合物的物理形态可为固态、液态或雾态。烟酰胺单核苷酸的化学结构可为酸型、盐型、结晶水型、水合物型或其他附属形态。该物理形态和化学结构的纯度可以为5％至99.8％，优选为80％至99.8％，更优选为97.5％至99.5％。
在本发明的具体实施方案中，基于毛发护理组合物的总重量，所述烟酰胺单核苷酸或其盐或其水合物的含量为0.01重量％至25重量％，优选为0.01重量％至20重量％，更优选为0.1重量％至15重量％。
基础成分
本发明的一个特征是毛发护理组合物包含用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分。用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分包包含阴离子表面活性剂、两性表面活性剂、阳离子表面活性剂、中性表面活性剂、抗氧化剂、pH缓冲剂和酸度调节剂中的一种或者多种。
阴离子表面活性剂
在本发明的毛发护理组合物中，阴离子表面活性剂也能够稳定烟酰胺单核苷酸或其盐或其水合物。阴离子表面活性剂可以为脂肪醇聚醚硫酸盐，还可以是月桂醇聚醚硫酸铵、月桂醇聚醚硫酸酯钠、月桂基硫酸钠、月桂基硫酸铵、甲基椰油酰基牛磺酸钠、月桂醇聚醚-5羧酸和月桂基葡萄糖羧酸钠等中单一成分或混合物。
在本发明的具体实施方案中，基于毛发护理组合物的总重量，阴离子表面活性剂的含量为15-65重量％，优选含量为25–45重量％，更优选含量为30-40重量％。
两性表面活性剂
这种表面活性剂既可以表现出阴离子特性，又能够表现出阳离子特性，并且具有优异的生物兼容性。
在本发明的毛发护理组合物，两性表面活性剂不仅能够用作去污，而且还能够稳定烟酰胺单核苷酸或其盐或其水合物。两性表面活性剂可以为烷基氨基酸型两性表面活性剂或者烷基两性羧酸盐。两性表面活性剂可以包括椰油酰胺丙基甜菜碱、椰油酰胺单乙醇胺、月桂基葡糖苷和椰油基甲基葡聚糖等单一成分或混合物。
在本发明的具体实施方案中，基于毛发护理组合物的总重量，两性表面活性剂的含量为1-15重量％，优选为1.5-8重量％，更优选为2-7重量％。
其他两性表面活性剂包括烷基两性羧酸或其盐，例如，烷基两性二丙酸、烷基两性二乙酸、烷基两性甘氨酸和烷基两性丙酸的碱金属盐，其中所述烷基表示具有6至20个碳原子的烷基。更优选的是所述烷基衍生自椰油或为月桂基的化合物，例如椰油基两性二丙酸盐。这种椰油基两性二丙酸盐表面活性剂和同类型的两性表面活性剂可以一致并以商标Miranol系列来销售。
市售有用的两性表面活性剂包括：
×椰油基两性乙酸盐(以商标MIRANOL ULTRA C-32和MIRAPON FA来销售)；
×椰油基两性丙酸盐(以商标MIRANOL CMSF CONC.和MIRAPON FAS来销售)；
×椰油基两性二乙酸盐(以商标MIRANOL C2M CONC.和MIRAPON FB来销售)；
×月桂酰两性乙酸盐(以商标MIRANOL HM CONC.和MIRAPON LA来销售)；
×月桂酰两性二乙酸盐(以商标MIRANOL H2M CONC.和MIRAPON LB来销售)；
×月桂酰两性二丙酸盐(以商标MIRANOL H2M-SF CONC.和MIRAPON LBS来销售)；
×由月桂酸和肉豆蔻酸的混合物获得的月桂酰两性二乙酸盐(以商标MIRANOL BM CONC.来销售)；
×椰油基两性丙基磺酸盐(以商标Miranol CS CONC.来销售)；
×己酰基两性二乙酸盐(以商标MIRANOL S2M CONC.来销售)；
×己酰基两性乙酸盐(以商标MIRANOL SM CONC.来销售)；
×己酰基两性二丙酸盐(以商标MIRANOL S2M-SF CONC.来销售)；以及
×硬脂酰基两性乙酸盐(以商标MIRANOL DM来销售)。
使用的最优选的其他两性表面活性剂是椰油基两性乙酸盐。
基于毛发护理组合物的总重量，其他两性表面活性剂占约0.1重量％至约7重量％，优选为约0.2重量％至约4重量％，更优选0.3重量％至3重量％。
阳离子表面活性剂
阳离子表面活性剂能提供阳离子，可为毛发护理组合物提供功能性的效用：阳离子在淸洁时将附上毛发上，可令毛发顺直，减少毛发形成打结，易于梳理。与此同时，阳离子可与烟酰胺单核苷酸在水溶液态中相互作用而提升其在液态中的稳定性。阳离子表面活性剂可以包括胺盐杂环季铵盐型阳离子表面活性剂。阳离子表面活性剂的具体例子包括鲸蜡基三甲基氯化铵、十二烷基三甲基氯化铵、三鲸蜡基甲基氯化铵、硬脂基二甲基苄基氯化铵、和二(部分氢化的牛油)二甲基氯化铵、聚季铵盐-10、瓜儿胶羟丙基三甲基氯化铵等中的至少一种，优选聚季铵盐-10、瓜儿胶羟丙基三甲基氯化铵或聚乙二醇。
在本发明的具体实施方案中，基于毛发护理组合物的总重量，阳离子表面活性剂为0.01-0.09重量％，优选为0.02-0.08重量％，更优选为0.03-0.08重量％。
在本发明的一些实施方案中，毛发护理组合物还可以包含其他表面活性剂，例如非离子表面活性剂和其他两性表面活性剂。
非离子表面活性剂在组合物中可起到乳化剂和稳定剂的作用。本文中所用的术语“非离子表面活性剂”包括非离子表面活性剂的混合物。
有用的非离子表面活性剂的例子还包括环氧乙烷和疏水性部分的缩合物，其中所述疏水性部分的平均亲水亲油平衡值(HLB)在约8至约16之间，更优选在约10至约12.5之间。这些表面活性剂包括具有约8至约24个碳原子的直链或支链构型的脂族伯醇或仲醇和环氧乙烷的缩合产物，其中相对于每摩尔醇，环氧乙烷为约2摩尔至约40摩尔，优选约2摩尔至约9摩尔。
在优选的实施方案中，所述脂族醇包含约9至约18个碳原子，并且每摩尔脂族醇与约3摩尔至约12摩尔的环氧乙烷乙氧基化。特别优选的是具有约12至约15个碳原子的伯醇和约5摩尔至约9摩尔/摩尔醇的环氧乙烷乙氧基化。一种这类的材料由Shell Chemical Company公司以商品名Neodol 25-9来销售。其他市售非离子表面活性剂由Shell Chemical Company公司销售的Neodol 25-6.5和Neodol 25-7。
其他合适的非离子表面活性剂包括具有约6至约12个碳原子的烷基酚和约3摩尔至约30摩尔、优选约5摩尔至约14摩尔的环氧乙烷的缩合产 物。这种表面活性剂的例子由Rhodia,Inc.公司以商品名IGEPAL CO 530、IGEPAL CO 630、IGEPAL CO720和IGEPAL CO 730销售。最优选使用的非离子表面活性剂是混合的线性醇的乙氧基化物，例如由Rhodia,Inc.公司以商品名RHODASURF L-790销售的Laureth-7。
抗氧化剂
抗氧化剂能有效的防止氧化作用的产生，免于物质在氧化过程中产生如自由基等的氧化产物并与当中的主要成分进行后续不可预知的化学反应而致该主要成分在长时间下变质和降解。烟酰胺单核苷酸于液态中会出现氧化反应并降解为烟酰胺等物质，因此，使用抗氧化剂能有效保护烟酰胺单核苷酸在液态中的稳定性。抗氧化剂可分为人工合成抗氧化剂和天然抗氧化剂两大类。两类抗氧化剂对保护液态烟酰胺单核
Figure PCTCN2020130814-appb-000003
酸的化学结构表现不同，优选采用天然抗氧化剂。天然抗氧化剂中可再细分为氨基酸类抗氧化剂、维生素类抗氧化剂，优选L-半胱氨酸、DL-蛋氨酸、维生素A、维生素C、维生素E、维生素P和植酸钠等中的单一成分或混合物。所述的抗氧化剂除本质功效外，皆同时发挥一定程度的防腐剂功效，对毛发护理组合物整体的稳定性有协同性的帮助。
在本发明的具体实施方案中，基于毛发护理组合物的总重量，抗氧化剂的含量为0.5-3重量％，优选为0.9-2.5重量％，更优选为1.5-2重量％。
酸度调节剂
烟酰胺单核苷酸于液态中的稳定性在弱酸性的环境下会有所提高，因此，毛发护理组合中需要利用酸度调节剂来进行pH的调控。毛发护理组合的酸度调节剂可为柠檬酸、草酸和乳酸等中的单一成分或其混合物。
在本发明的具体实施方案中，基于毛发护理组合物的总重量， 酸度调 节剂的含量为1-3重量％，优选为1.5-2.5重量％，更优选为2-2.5重量％。
稳定剂
烟酰胺单核苷酸或其盐或其水合物通常在组合物中是非常不稳定地，容易降解。因此，本发明的毛发护理组合物还包含用于稳定烟酰胺单核苷酸或其盐或其水合物的活性的添加剂。
稳定剂可以是选自唾液酸、茶氨酸、β-胡萝卜素和磷酸钠中的一种或多种。
其他成分
毛发护理组合物可添加其他的不同成分以丰富其外观、质感、香味、特性功能和用户的体验效果，只要该成分或其组合不会与烟酰胺单核苷酸进行 任何化学反应而引致烟酰胺单核苷酸在保质期中出现明显降解即可。与此同时，该成分可以在一定程度上提高烟酰胺单核苷酸或其盐或其水合物在液体中的稳定性。
在外观和质感上，毛发护理组合物中可添加调节剂(如丙二醇)使其外观成透明、不透明或颜色，和其质感成水性至不同程度的黏度状态：丙二醇可用于增加毛髪护理组合物的液态黏度，生产商可根据其产品的定位作黏度的调节，以提高丙二醇在毛发护理组合物中的含量可使其黏度作比例性的增加；在本发明的具体实施方案中，基于毛发护理组合物的总重量，其他成分(例如，丙二醇)的含量为0.01-1重量％，优选为0.1-0.8重量％，更优选为0.2-0.6重量％。
毛发护理组合物中亦可加入助溶剂以调整组合物中的物理质感，特别是毛发护理组合物中的液态观感中的透澈度。二甲苯磺酸钠可以为头发护理产品中如洗发水、护发液和精华液等液态产品提供增加产品中的透澈程度；二甲苯磺酸钠能增加液体中水分子对成份的溶解能力，促使毛发护理组合物中的各成份能有更充分的接合。毛发护理组合物中的烟酰胺单核苷酸能在毛发护理组合物中有着更高的溶解度，制成特定产品如高浓度烟酰胺单核苷酸精华液等以满足使用者的不同需要和期望。再者，二甲苯磺酸钠可使烟酰胺 单核苷酸与其他成分相互融合以达至毛发护理组合物中的部分产物可同时提供多于一种的功能作用，这可理解为毛发护理组合物中以利用烟酰胺单核苷酸或其衍生物以促使头部各组织包括毛发、头皮、毛囊和其细胞中的辅酶I水平达致毛发和头部的健康得以改善外，还可达到其他的目的如清洁、造型协调、气味改变等，也应视为毛发护理组合物中功能的一部分。在本发明的具体实施方案中，基于毛发护理组合物的总重量，二甲苯磺酸钠的含量为0.01-10重量％，优选为0.1-5重量％，更优选为1-3重量％。
毛发护理组合物中亦可加入起泡剂以増加组合物中的一些单功能性或多功能性产物如洗发水、护发素等的清洁和修护功能。泡沫能产生较大的接触空间，可以使毛发护理组合物中的主要成分和其他成分能有效的在头部上扩散，从而制做有利条件使毛发、头皮、毛囊等吸收主要成分烟酰胺单核苷酸或其衍生物至细胞中以提升当中的辅酶I水平，特别是该细胞中的线粒体内的水平以应付日常的新陈代谢及生物催化作用，也可以保护和修复环境污染、紫外线接触的损伤。
泡沫亦可延长成分在头部的停留时间：泡沫之间的张力能相互维系，使其轻易的停留于毛发和头皮间并不受头形的差异而影响其效果。因此，毛发护理组合物中加入起泡剂对提升辅酶I的结果亦起了一定的物理作用。毛 发护理组合物中可使用的起泡剂可为季铵聚乙二醇烷基氨基酸醣类表面活性剂，可以为甜菜碱、椰油酰胺丙基甜菜碱、椰油酰单乙醇胺、椰油酰甘氨酸钠、月桂基葡萄糖羧酸钠、橄榄油脂肪酸聚乙二醇酯单(羧甲基)醚钠盐等。在毛发护理组合物的成分中，可按产品的功能加入上述的起泡剂，而这些起泡剤可在产品成分中为单一或多种比例性的混合情况下使用，以调理出对该产品最合适的泡沫状况而达致最佳的使用效果和用家体验。作为毛发护理组合物的成分，起泡剂优选为甜菜碱、椰油酰甘氨酸钠和月桂基葡萄糖羧酸钠，更优选为椰油酰甘氨酸钠。在本发明的具体实施方案中，基于毛发护理组合物的总重量，椰油酰甘氨酸钠的含量为0.01-10重量％，优选为0.1-5重量％，更优选为0.5-1重量％。以多种比例性的混合情况下使用，椰油酰甘氨酸钠和月桂基葡萄糖羧酸钠的配合为最优选的组合。椰油酰甘氨酸钠和月桂基葡萄糖羧酸钠的配合比例以2:1为细小泡沫的配方，较大的泡沫则以1:2的份量；泡沫的大小可按混合物中椰油酰甘氨酸钠和月桂基葡萄糖羧酸钠的配合作比例性作调节。在本发明的具体实施方案中，基于毛发护理组合物的总重量，总混合物的含量为0.01-10重量％，优选为0.1-5重量％，更优选为0.5-1重量％。
毛发护理组合物亦可加入其他添加物以丰富其外观、香气和使用感觉和功能；外观上，毛发护理组合物可加入一般的食用颜料，选用较深的颜色如黄色、啡色、蓝色和黑色在避光上会有着较明显的表现，亦是对毛发护理组合物的主要和其他成分的稳定有着一定的作用。在本发明的具体实施方案中，基于毛发护理组合物的总重量，食用颜料的含量为0.01-1重量％，优选为0.05-0.1重量％，更优选为0.05-0.08重量％。香气在毛发护理组合物中的产品如洗发水、护发素和精华液中较为重要，可增加使用者对产品的满意程度，同时解决毛发出现异味的情况。毛发护理组合物中可加入无害香精或精炼植物矿物类香油为主要香气来源，更优选为精炼植物矿物类香油。由于毛发护理组合物的配方中没有气味，因此添加物所提供的香气应实在的反应于毛发护理组合物中而不存在添加后组合物的香气与添加物的属性香气有着任何差异性的结果。若然此情况出现，即应视为添加物与毛发护理组合物出现不可预知的化学反应，对毛发护理组合物中的烟酰胺单核苷酸或会构成化学结构上的影响，从而改变毛发护理组合物的功能和其稳定性。精炼植物矿物类香油多为惰性物质，加入毛发护理组合物中后理应不会出现上述特殊状况。在本发明的具体实施方案中，基于毛发护理组合物的总重量，精炼植物 矿物类香油的含量为0.001-0.1重量％，优选为0.005-0.01重量％，更优选为0.08-0.01重量％。
毛发护理组合物可加入功能添加物以满足不同用户的需求，并能相扶提升毛发、头皮和毛囊细胞的辅酶I水平的效果，促使毛发护理组合物能在短时间的使用期上表现出符合用户预期的显着效果。头部表皮细胞在辅酶I水平下降的时候难以合成ATP以应付日常的高能量需求，表皮细胞的凋零将导致头皮増加，与此同时，细胞的免疫能力亦因此下降而促使感染的机会提高；头皮囤积除影响社交感观外，头部表皮上的汗水和头油难于排疏，灰尘亦因为表面积的增加而更容易附于头上，在生理健康的下降与头部发生的恶化同步聚焦下，头部表皮出现炎症状况也趋之频生，即为本领域内所认知的剧烈头痒现象。头痒现象逼使患者用手抚摸，而然当头痒程度加剧时患者亦随之频繁挥抚头皮甚至使其劲度抓弄，务求在最短时间中去除不快感。患者在过程中对头部表皮造成损伤，特别是对毛嚢的伤害是严重，除可使毛发脱落，死去的头囊细胞亦因此失去生发的能力，而这类物理性伤害部分属永久性，即使提升辅酶I的水平亦未能促使细胞回复功能。功能添加物可为痛
Figure PCTCN2020130814-appb-000004
舒媛物和头皮抑制物，其中以薄荷油和吡硫鎓锌为毛发护理组合物的功能添加物可达到目的；薄荷油在接触头部表皮时可给予使用者一种凉快的感觉， 干扰头痒的不悦感；因此，使用者便可避免因感到头痒而出手抓弄头部并在过程中伤害其组织和细胞。在本发明的具体实施方案中，基于毛发护理组合物的总重量，薄荷油的含量为0.05-0.1重量％，优选为0.05-0.09重量％，更优选为0.06-0.08重量％。吡硫鎓锌为抗菌剂，可抑制革兰氏阴性、阳性细菌以及霉菌生长，普遍用于去除头屑成分并且有不错的功效。在本发明的具体实施方案中，基于毛发护理组合物的总重量，吡硫鎓锌的含量为0.1-1.5重量％，优选为0.5-1重量％，更优选为0.8-1重量％。
在本发明的一些实施方案中，毛发护理组合物的头发护理产品形式为选自以下中的至少一种：洗发水、护发素、精华液、肥皂、喷雾、乳霜、发蜡、啫喱、膏状或任何液体和固体。因此，本发明的头发护理产品可同时具有其他功能如清洁、修护、去屑和固定头发造型等。例如，含有烟酰胺单核苷酸的洗发水也具有清洁功效，即一般去除头发上的油脂和异味；洗发水亦具有泡沫性，以易于渗透于毛发和头皮之中。
在本发明的具体实施方案中，洗发水可含有水、烟酰胺单核苷酸或其盐或其水合物、表面活性剂、酸度调节剂、香料等作为辅料，以保存洗发水的功能、特性和持久性。在更具体实施方案中，基于所述洗发水的总重量，水的含量为30重量％至90重量％。
毛发护理组合物中除头发产品外还包括眉毛护理产品、眼睫毛护理产品和胡须护理产品。眉毛护理产品主要包括眉毛护理液和眉毛护理膏；眉毛护理液和眉毛护理膏含有0.01-3％(w/v)的烟酰胺单核苷酸或其盐或其水合物为主要成分，加入辅料包括鼠尾草油、绿茶抽取物、白蜂蜡等。眼睫毛护理产品为眼睫毛护理液组装，配合眼睫毛刷将眼睫毛液涂上眼睫毛的部分，使上、下眼睫毛部分和其毛囊部分均能接触。眼睫毛液的主要成分亦为烟酰胺单核苷酸或其盐或其水合物，而因应眼睫毛的生长速度比头发较慢，主要成分需较多以刺激其生长周期，因此眼睫毛液中的烟酰胺单核苷酸或其盐或其水合物为1-10％(w/v)，而辅料为茶树抽取物和半胱氨酸。由于眼睫毛液的使用较接近眼精，眼睫毛液的成分不能含有对眼睛敏感、挥发性物质和用于治疗眼疾的物料。眼睫毛护理液组装的目的为让关注眼睫毛健康的用户，特别为眼睫毛生长较慢和短的用家一个可以改善其情况的选择，为用户无论在眼部健康护理和个人仪容上带来帮助。胡须护理产品为胡须护理液、胡须护理喷雾和胡须护理膏；胡须护理产品的主要成分为0.1-2％的烟酰胺单核苷酸或其盐或其水合物，配合辅料薄荷抽取物、牛蒡粉或其抽取物、维生素A、维生素E和半胱氨酸等，以水、低浓度乙醇0.01-0.05％(v/v)或蜂蜡为介体以制成液态、喷雾和膏状以供用户按其喜好作选择。胡须护理液、胡 须护理喷雾和胡须护理膏的目的为加快胡须的生长、保持或回复原本色泽和毛囊的健康，其原理与上述的毛发护理组合物相符，借此为用家在个人造型上提供一个科研上的健康产品。
在另一个方面中，本发明还提供一种制备毛发护理组合物的方法，包括下列步骤：提供烟酰胺单核苷酸或其盐或其水合物；提供用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分的水溶液；以及将烟酰胺单核苷酸或其盐或其水合物与所述水溶液混合并且调节pH值，从而得到毛发护理组合物。用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分包含阴离子表面活性剂、两性表面活性剂、阳离子表面活性剂、抗氧化剂、pH缓冲剂和酸度调节剂中的一种或者多种。
优选地，该方法包括：
(1)将一种或多种脂肪醇聚醚硫酸盐阴离子表面活性剂混合，得到第一类表面活性剂；
(2)将一种或多种烷基酰基氨基酸型两性表面活性剂混合，得到第二类表面活性剂；
(3)将一种或多种阳离子表面活性剂混合，得到第三类表面活性剂；
(4)将第一类表面活性剂、第二类表面活性剂和第三类表面活性剂混合成得复合表面活性剂；
(5)将烟酰胺单核苷酸加至复合表面活性剂中，以得到混合物；以及(6)将氨基酸类抗氧化剂加入混合物并使用酸度调节剂使混合物的pH值为4.85-7.0，从而得毛发护理组合物。
在更具体实施方案中，表面活性剂可为月桂醇聚醚硫酸铵、椰油脂酰基谷氨酸TEA盐和MIRANOL；其中所述洗发水的总重量，月桂醇聚醚硫酸铵的含量为0.2重量％至1.9重量％、椰油脂酰基谷氨酸TEA盐的含量为0.1重量％至1.5重量％和MIRANOL的含量为0.3重量％至3重量％。在更具体实施方案中，酸度调节剂为磷酸二氢钾，洗发水的pH为4.5至5.5。在更具体实施方案中，香料可为有机香熏油，其中可选择不同香气以配合市场需要，有机香熏油的含量为0.1重量％至0.5重量％。在另一更具体实施方案中，香料可为不同有机香熏油，其中可选择不同香气以配合市场需要，有机香熏油的含量为0.1重量％至0.5重量％。在更具体实施方案中，洗发水还可包含遮光剂、防腐剂等，这些成分的含量不应超过洗发水重量的0.05重量％。
在本发明的具体实施方案中，精华液为主要用于提升毛囊细胞中的辅酶I和还原型辅酶I的水平，也舒缓头皮痕痒或发炎情况，以促进毛囊干细胞的健康并激活其活性以进行ATP和乳酸的合成。因此，精华素的主要成分为烟酰胺单核苷酸或其盐或其水合物，其含量为总成分重量的3重量％至25重量％，优选为5重量％至15重量％，更优选为8重量％至12重量％。在更具体实施方案中，精华液的成分为绿茶抽取物、薄荷油、鼠尾草油、牛蒡粉、蜂蜡和水等。另外，还可向精华液中加入乙酰谷胱甘肽和谷胱甘肽。
此外，只要毛发护理组合物为外用的毛发用品，在产品中加入烟酰胺单核苷酸，或该产品提升毛囊和表皮细胞中的辅酶I水平以达至防止、修护、改善或逆转因衰老，应视作为本专利申请的范围之中。
以下以洗发水和精华液为例，对根据本发明的毛发护理组合物的制备进行描述。
洗发水的制备方法如下。向容器中加入月桂醇聚醚硫酸铵、椰油脂酰基谷氨酸TEA盐和MIRANOL作为表面活性剂，这三种表面活性剂的含量可以是不同或相等的，主要是配合不同发质，三种表面活性剂的含量相等时则为中性发质。以中性发质为例，基于洗发水的总重量，三种表面活性剂的含量共为0.1重量％至10重量％，优选为0.5重量％至10重量％，更优选为 1重量％至10重量％。加入表面活性剂和维生素后，先加入纯水至总重量的80重量％，再加入酸度调节剂；酸度调节剂可为磷酸二氢钾或其他缓冲物，溶液的pH优选为4.8至6，更优选为5至5.5。调节pH至4.5-5.5后可加入烟酰胺单核苷酸或其盐或其水合物，基于洗发水的总重量，烟酰胺单核苷酸或其盐或其水合物的含量为0.01重量％至25重量％,优选为0.1重量％至5重量％，更优选为0.1重量％至1重量％。然后，可加入有机香熏油、遮光剂、防腐剂等，这些成分的总含量不超过洗发水总重量的5％。搅拌均匀后再加纯水至总量即可使用。
使用者可随个人喜好的份量将洗发水均匀涂到头上并建议在头上按摩2-5分钟，完成后可以冲洗干净；洗发水最少每天使用一次并应持续使用，以达致目标效果。
精华液的制备方法如下。首先向容器中加入牛蒡粉、绿茶抽取物和烟酰胺单核苷酸；其中基于精华液的总重量，牛蒡粉的含量为1重量％至5重量％，优选为1重量％至4重量％，更优选为1重量％至2.5重量％；绿茶抽取物的含量为1重量％至5重量％，优选为2重量％至4重量％，更优选为2重量％至2.5重量％；烟酰胺单核苷酸的含量为3重量％至25重量％，优选为5重量％至15重量％，更优选为8重量％至12重量％，并加入辅助物料 唾液酸、茶氨酸、甘草酸、谷胱甘肽和S-乙酰-L-谷胱甘肽。然后，加入纯水至总重量的80％后，加入酸度调节剂磷酸二氢钾至pH为5至5.2，并搅拌至均匀。向上述溶液中分别加入薄荷油和鼠尾草油；其中基于精华液的总重量，薄荷油的含量为0.1重量％至1.5重量％，优选为0.1重量％至1.2重量％，更优选为0.1重量％至1重量％；鼠尾草油的含量为0.1重量％至1.5重量％，优选为0.1重量％至1.2重量％，更优选为0.1重量％至1重量％。最后，加入已于62至65摄氏度热熔的白蜂蜡，含量为总重量的0.1％；加入纯水至原定分量并搅拌至完全溶解。
用者在洗发后可直接将5-10ml精华液涂于头皮和发根位置，用手轻按头部并均匀的将精华液分散于头皮上，待精华液完全吸收之后便可。精华液最少每天使用一次并应持续使用，以达致目标效果。
以下通过实例子的方式进一步解释或说明本发明内容，但这些实施例不应被理解为对本发明保护范围的限制。
例子
以下例子中未注明具体条件的，均按常规条件或制造商建议的条件进行。
实施例中所用材料和设备的描述如下：
烟酰胺单核苷酸：得自基因港(香港)生物科技有限公司；
月桂醇聚醚硫酸铵：得自济宁百川化工有限公司；
椰油脂酰基谷氨酸TEA盐：得自北京灵宝科技有限公司；
MIRANOL：得自苏州源太润化工有限公司；
牛蒡粉：得自兴化市宏升食品有限公司；
绿茶抽取物：得自陕西横岭天然生物制品有限公司；
薄荷油：得自江西吉平天然植物油有限公司；
鼠尾草油：得自深圳奥斯汀贸易有限公司；
磷酸二氢钾：得自江苏紫东食品有限公司；
白蜂蜡：得自广州日油科技有限公司；
S-乙酰-L-谷胱甘肽:得自基因港(香港)生物科技有限公司；
谷胱甘肽:得自基因港(香港)生物科技有限公司；
茶氨酸:得自Merck,USA；
唾液酸:得自Merck,USA；
甘草酸:得自Merck,USA；
小型搅拌器(LIAEBO LSJB120):得自江苏常州；
pH测量仪(雷磁PHB-4):得自上海
实例1：含有烟酰胺单核苷酸的中性发质用洗发水
制作500ml含有烟酰胺单核苷酸的中性发质用洗发水。加入250ml水、25g月桂醇聚醚硫酸铵、25g椰油脂酰基谷氨酸TEA盐、1g MIRANOL、50g维生素C；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；利用pH测量仪(雷磁PHB-4,上海)测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5。然后，加入烟酰胺单核苷酸5克，加入纯水至总量500ml并搅拌至完全均匀。
实例2：含有烟酰胺单核苷酸的干性发质用洗发水
制作500ml含有烟酰胺单核苷酸的中性发质用洗发水。加入250ml水、40g月桂醇聚醚硫酸铵、10g椰油脂酰基谷氨酸TEA盐、50g 维生素 C；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；利用pH测量仪(雷磁PHB-4,上海)测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5。然后，加入烟酰胺单核苷酸5克，加入纯水至总量500ml并搅拌至完全均匀。
实例3：含有烟酰胺单核苷酸的油性发质用洗发水
制作500ml含有烟酰胺单核苷酸的中性发质用洗发水。加入250ml水、10g月桂醇聚醚硫酸铵、40g椰油脂酰基谷氨酸TEA盐、50g 维生素 C；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；利用pH测量仪(雷磁PHB-4,上海)测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5。然后，加入烟酰胺单核苷酸5克，加入纯水至总量500ml并搅拌至完全均匀。
实例4：含有烟酰胺单核苷酸的头发精华液
制作50ml含有烟酰胺单核苷酸的毛发精华液。加入25ml水并按顺序加入0.5g牛蒡粉、0.4g唾液酸、0.2g谷胱甘肽、0.05gS-乙酰-L-谷胱甘肽、0.1g茶氨酸、0.2g甘草酸、0.5g绿茶抽取物、5g维生素C和5g烟酰胺单核苷酸。随后，加入纯水至总量35ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；加入0.5g月桂醇聚醚硫酸铵；利用pH测量仪测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5，然后，加入薄荷油500ul、鼠尾草油500ul，搅拌中分五次加入已于摄氏62-65度加热的白蜂蜡，总量为0.1g；搅拌器以250rpm的速度进行搅拌15分钟至完全溶解便完成。
实例5：含有烟酰胺单核苷酸的止头痒功能洗发水
制作500ml含有烟酰胺单核苷酸的中性发质用洗发水。加入250ml水、25g月桂醇聚醚硫酸铵、25g椰油脂酰基谷氨酸TEA盐、50g 维生素 C；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；利用pH测量仪测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5。然后，加入烟酰胺单核苷酸2.5克和加入薄荷油2.5ml以约100rpm的速度进行搅拌15分钟至完全均匀，加入纯水至总量500ml并搅拌至完全均匀。
实例6：含有烟酰胺单核苷酸的去头屑功能洗发水
制作500ml含有烟酰胺单核苷酸的中性发质用洗发水。加入250ml水、25g月桂醇聚醚硫酸铵、25g椰油脂酰基谷氨酸TEA盐、50g 维生素C和5g吡硫鎓锌；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；利用pH测量仪测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5。然后，加入烟酰胺单核苷酸2.5克，加入纯水至总量500ml并搅拌至完全均匀。
实例7：含有烟酰胺单核苷酸的多功能洗发水
含有烟酰胺单核苷酸的多功能洗发水为同时拥有止头痒和去头屑功能的产品：制作500ml含有烟酰胺单核苷酸的中性发质用洗发水。加入250ml水、25g月桂醇聚醚硫酸铵、25g椰油脂酰基谷氨酸TEA盐、50g 维生素C和5g吡硫鎓锌；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的 速度进行搅拌15分钟至完全均匀；利用pH测量仪测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5。然后，加入烟酰胺单核苷酸2.5克和加入薄荷油2.5ml以约100rpm的速度进行搅拌15分钟至完全均匀，加入纯水至总量500ml并搅拌至完全均匀。
实例8:含有烟酰胺单核苷酸的眉毛护理液
制备50ml含有烟酰胺单核苷酸的眉毛护理液的方法为先加入0.5g烟酼胺单核苷酸，然后加入0.5g的绿茶抽取物，以20ml纯水将材料于搅拌下至完全溶解。按以下次序和分量在溶液中加入配料，并保持搅拌:1.0.25g半胱胺酸盐酸盐；2.0.25g维生素C；3.0.1g维生素E；4.0.5ml鼠尾草油；5.0.05g柠檬酸钠；6.0.1g柠檬酸；7.0.05g椰油脂酰基氨酸盐；搅拌至完全溶解后再加入纯水至50ml，并以pH测量仪检测其pH值。眉毛护理液的pH值需要在4.75-5之间。调节眉毛护理液的pH可以使用1M柠檬酸钠溶液或1M柠檬酸溶液。眉毛护理液的使用同方法为于早上和晚间将约1ml的液体放在指尖上后轻涂上眉目处，并以来回方向轻扫至眉毛液于眉毛处完全吸收即可。
实例9:含有烟酰胺单核苷酸的眉毛护理膏
制备50g含有烟酰胺单核苷酸的眉毛护理液的方法为先加入0.5g烟酼胺单核苷酸，然后加入0.5g的绿茶抽取物，以20ml纯水将材料于搅拌下至完全溶解。按以下次序和分量在溶液中加入配料，并保持搅拌:1.0.25g半胱胺酸盐酸盐；2.0.25g维生素C；3.0.1g维生素E；4.0.5ml鼠尾草油；5.0.05g柠檬酸钠；6.0.1g柠檬酸；7.0.05g椰油脂酰基氨酸盐；搅拌至完全溶解后再加入纯水至45ml，并以pH测量仪检测其pH值，溶液的pH值需要在4.75-5之间，调节溶液的pH可以使用1M柠檬酸钠溶液或1M柠檬酸溶液。完成后在搅拌的情况下，以逐少的份量批次性加入已于摄氏62-65度加热的白蜂蜡共2g，溶液亦将逐渐由液态变成固态呈膏状。眉毛护理膏的使用同方法为于早上和晚间将少许放在指尖上后轻涂上眉目处，并以来回方向轻扫至眉毛液于眉毛处完全吸收即可。
实例10:含有烟酰胺单核苷酸的眼睫毛护理组装
制备50ml含有烟酰胺单核苷酸的眼睫毛护理液的方法为先加入5g的烟酰胺单核苷酸、1g的茶树抽取物、1g的绿茶抽取物、0.5g的L-半胱氨酸盐酸盐、0.5g的维生素C和0.1g的维生素D，加入40ml纯水以搅拌的方式至完全溶解后，使用pH检测仪进行检测，以0.5M的NaOH将溶液调至pH6.75-7,并以0.22uM滤膜过滤即完成。用家使用时将眼
Figure PCTCN2020130814-appb-000005
毛刷沾上约1- 2ml眼睫毛护理液，沿眼廉位置轻扫轻至眼睫毛部位至完全吸收，建议于早上和晚上使用。
实例11:含有烟酰胺单核苷酸的胡须护理液
制备50ml的胡须护理液的方法为先加入0.5g的烟酰胺单核苷酸、0.1g的牛蒡粉、0.08g的维生素A、0.05g的维生素E、0.1g的L-半胱氨酸盐酸盐，加入40ml的纯水以搅拌的方式至完全溶解后，使用pH检测仪进行量度，以1M NaOH调节溶液的pH值至5.25-5.5。完成调节后加入0.01g椰酸甘油和0.05ml的无水乙醇，搅拌至完全溶解后便告完成。用家可于早上和晚上使用，将1-2ml的护理液涂在胡须生长处并轻轻按摸，待护理液完全被皮肤吸收后即可。
实例12:含有烟酰胺单核苷酸的胡须护理膏
制备50g的胡须护理液的方法为先加入0.5g的烟酰胺单核苷酸、0.1g的牛蒡粉、0.08g的维生素A、0.05g的维生素E、0.1g的L-半胱氨酸盐酸盐，加入40ml的纯水以搅拌的方式至完全溶解后，使用pH检测仪进行量度，以1M NaOH调节溶液的pH值至5.25-5.5。完成调节后加入0.01g椰酸甘油，搅拌至完全溶解，然后以逐少量批次性的加入1g的已于摄氏60-65度预热的白蜂蜡并继续搅拌，溶液将随时间逐渐变为固态，当成膏状即完 成。用家可于早上和晚上使用，将少许的护理膏涂在胡须生长处并重复按摸待至皮肤吸收。
实例13：洗发水原型(没有加入烟酰胺单核苷酸)
制作500ml洗发水原型。加入250ml水、25g月桂醇聚醚硫酸铵、25g椰油脂酰基谷氨酸TEA盐和50g维生素C；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；利用pH测量仪测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5，加入纯水至总量500ml并搅拌至完全均匀。
实例14：头发精华液原型(没有加入烟酰胺单核苷酸)
制作50ml含有烟酰胺单核苷酸的毛发精华液。加入25ml水并按顺序加入0.5g牛蒡粉、0.4g唾液酸、0.2g谷胱甘肽、0.05gS-乙酰-L-谷胱甘肽、0.1g茶氨酸、0.2g甘草酸、0.5g绿茶抽取物、5g维生素C。随后，加入纯水至总量35ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；加入0.5g月桂醇聚醚硫酸铵；利用pH测量仪测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5，然后，加入薄荷油500ul、鼠尾草油500ul，搅拌中分五次加入已于摄氏62-65度加热的白蜂蜡，总量为0.1g；搅拌器以250rpm的速度进行搅拌15分钟至完全溶解便完成。
实例15：(比较例，加入抗氧化剂)
制作500ml实例5的溶解液。加入250ml水和50g维生素C；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；利用pH测量仪测量溶液的pH，并利用磷酸二氢钾和磷酸氢二钾调节酸碱值至pH 5.5。然后，加入烟酰胺单核苷酸5克，加入纯水至总量500ml并搅拌至完全均匀。
实例16：(比较例，只加入低剂量的表面活性剂)
制作500ml洗发水原型。加入250ml水、0.25g月桂醇聚醚硫酸铵、0.25g椰油脂酰基谷氨酸TEA盐和50g维生素C；加入纯水至总量400ml，并利用小型搅拌器以约100rpm的速度进行搅拌15分钟至完全均匀；利用pH测量仪测量溶液的pH，并利用磷酸二氢钾调节酸碱值至pH5.5。然后，加入烟酰胺单核苷酸5克，加入纯水至总量500ml并搅拌至完全均匀。
测试1-含有烟酰胺单核苷酸洗发水与对照组洗发水的效用比较
招募16位男和16位女测试者，年龄需达50岁或以上。测试前研究人员会对参与者头发的发色、生长速度、头屑状况和头发分布进行评估并给予分数(表1-4，方法表11)，并需确认在过去的一年内没有进行染发、电发和 负离子头发处理。参加者亦需承诺在研究进行后的90天不能进行上述相关事宜，倘若须要进行发型修剪或护理，参加者需联络项目主任作相应的研究安排，其中包括重新评估。
研究以性别分为两批进行，以双盲实验的方式由研究人员随机派发按上述的实例1或13制备的洗发水。研究需要参与者最少每24小时使用指定的洗发水洗发一次。每次洗发使用2-5ml的洗发水，洗头时同时让洗发水与泡沫停留于头上不少于2分钟后，及后以温水冲洗干净。测试者在每30天进行评估，而整个测试为期个90天。测试结果如下表5-6所示。
表1-发色评估
评分 状况
1 目测头发均为灰白色
2 目测50％以上的头发为灰白色，有少部分为黑色
3 目测70％以上的头发为黑色，只有少部分为灰白色
4 目测大部分头发为黑色，灰白色头发不明显
表2-生长速度
评分 状况
1 没有增长
2 三十天内增长少于2mm
3 三十天内增长于2mm-4mm
4 三十天内增长大于4mm
表3-头屑状况
评分 状况
1 目测明显大范围头屑
2 目测部分头屑
3 少量头屑
4 头屑数量不明显或没有
表4-头发分布
评分 状况
1 出现大范围集中性秃头情况
2 部分范围出现秃头
3 少量秃头或头发长度不均
4 没有秃头或头发长度不均情况
表5-男测试者结果
Figure PCTCN2020130814-appb-000006
Figure PCTCN2020130814-appb-000007
表6-女测试者结果
Figure PCTCN2020130814-appb-000008
测试2-含有烟酰胺单核苷酸头发精华液与对照组头发精华液的效用比较
分别按实例4制备含有烟酰胺单核苷酸头发精华液和按实例14制备头发精华液原型。招募8位男士和8位女士为参加者作研究对象。参加者须健 康良好，年龄达50歳或以上。测试前研究人员会对参与者头发的发色、生长速度、头屑状况和头发分布进行评估并给予分数(可参考表1-4)，并需确认在过去的一年内没有进行染发、电发、负离子头发处理或所有影响头发生长状况有关的事宜，其中包括手术和疗程等。参加者亦需承诺在研究进行后的90天不能进行上述相关事宜，倘若须要进行发型修剪或护理，参加者需联络项目主任作相应的研究安排，其中包括重新评估。
研究以性别分为两批进行，以双盲实验的方式由研究人员随机派发按上述的实例4制备含有烟酰胺单核苷酸头发精华液或按14制备的原型头发精华液。研究者需要每天使用2次，指定在早上和晚上洗发后，只利用干布抹干而不采用热风筒的情况下，将毛发弄干并即时使用5-10ml毛发精华液，涂于头皮上并进行按摩以均匀分散，此动作应不少于五分钟，直至毛发精华液被头皮完全吸收。测试者在研究开始前和开始后每30日进行评估，整个研究为期90日。测试结果如下表7-9和图3-4所示。
表7-男测试者结果
Figure PCTCN2020130814-appb-000009
Figure PCTCN2020130814-appb-000010
表8-女测试者结果
Figure PCTCN2020130814-appb-000011
还对女测试者的头发生长情况进行了拍照并且计算了头发生长密度。结果参见图3(a)-(d)、图4和表9。图3(a)-(d)分别示出了使用了实例4的含有烟酰胺单核苷酸的头发精华液的女测试者在不同天数的头发生长情况的照片。具体来说，该图证明了女测试者在使用头发精华液90天内的效果；红线为头发分轴；发线平均差距距离为使用Adobe Photoshop CS软件在轴线上取六个点度量两旁头发的距离，距离较大可视为头发分布较稀疏，较少则可视为头发分布较浓密。
此外，表9列出了使用实例4的含有烟酰胺单核苷酸的头发精华液的女测试者在不同天数的发线平均头发差距。图4示出了使用实例4的含有烟酰胺单核苷酸的头发精华液的女测试者发线平均头发差距随着天数的变化。
表9
使用天数 法线平均头发差距(像素)
0 75.02
30 58.18
60 40.37
90 34.86
测试3：烟酰胺单核苷酸的稳定性测试
将烟酰胺单核苷酸水溶液(2.5g烟酰胺单核苷溶解于500ml的纯水中)和实例1、实例15和实例16作出烟酰胺单核苷酸的稳定性测试对比。具体来说，将样品放置于于一般状况(温度摄氏～22度和～65％的湿度)和加速状况(温度摄氏～37度和～85％的湿度)进行。以高效液相色谱法每天进行检测为期三十日的研究，以观测烟酰胺单核苷酸在各组的稳定性，稳定性的结果可参考图1和图2，而测试的方法和仪器可参考表10。
表10
Figure PCTCN2020130814-appb-000012
Figure PCTCN2020130814-appb-000013
对照1：只使用口服烟酰胺单核苷酸补充剂
试用者使用口服烟酰胺单核苷酸补充剂(得自基因港(香港)生物科技有限公司：品名-NMN9000)，每天早上于早饭后服用两颗胶囊共300mg；三个月后试用者进行问卷调查：评估其身体健康状况、毛发生长速度、毛发颜色变化和新生长毛发数量。试用者回馈在精神状态、体力、睡眠质素和皮肤都有显着改善。具体地说，试用者表示其深层睡眠时间有所延长、运动能力和回复速度増强，以及在过去三个月身体未曾出现任何病痛或症状；年老人士时常出现的囗干、上火、间歇性精神不振、发冷发热的情况也大为减少， 个人感观上听力和视力都有进步，两方面都比以往更为灵敏。研究人员在进行检测中发现试用者的后脑位置近颈项上有一小撮黑色毛发长出，与三个月前的同一位置仍是白发有巨大差异。毛发生长速度、毛发颜色变化和新生长毛发对比率在观察后与三个月前有轻微改进，但相对使用含有烟酰胺单核苷酸的中性发质用洗发水和使用含有烟酰胺单核苷酸的毛发精华液的效果较为缓慢。试用者认为服用后毛发减少脱落为最明显的效果，而头皮发痒和头屑则明显减少。
对照2：同时服用烟酰胺单核苷酸补充剂并使用含有烟酰胺单核苷酸的头发精华液
试用者使用口服烟酰胺单核苷酸补充剂(得自基因港(香港)生物科技有限公司：品名-NMN9000)，每天早上于早饭后服用两颗胶囊共300mg；同时，试用者于每天洗发后使用5ml毛发精华液，三个月后试用者进行问卷调查：评估其身体健康状况、毛发生长速度、毛发颜色变化和新生长毛发数量。试用者反应身体状况比以前有明显改善：体力比以前为佳，最明显为行山和上落楼梯时没有气喘和力有不逮的感觉，皮肤较以前紧致；睡眠时间比以往为短但醒后精神充沛，没有懒床或再睡的情况出现。失眠与尿频的次数有所减少，生活质素改善不少。毛发生长速度、毛发颜色变化和新生长毛发 对比率在观察后与三个月前有显着分别，特别是于使用前仍是一片白发中明显有黑发长出，占毛发的20％左右；研究人员取出白发与黑发丝各十条于电子显微镜下作仔细研究，作出以下总结：
表11
Figure PCTCN2020130814-appb-000014
相对只服用口服烟酰胺单核苷酸补充剂，这位试用者的毛发生长情况更为明显，而且在生长出的毛发中发现呈黑色的更多。
应当理解的是，本发明的应用并不限于上述的实施例。对本领域普通技术人员来说，可以根据上述说明加以改进或变换，所有这些改进和变换都应属于本发明所附权利要求的保护范围。
表12
Figure PCTCN2020130814-appb-000015
Figure PCTCN2020130814-appb-000016
Figure PCTCN2020130814-appb-000017
Figure PCTCN2020130814-appb-000018
Figure PCTCN2020130814-appb-000019

Claims (20)

  1. 一种毛发护理组合物，其特征在于包含烟酰胺单核苷酸或其盐或其水合物，以及用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分。
  2. 根据权利要求1所述的毛发护理组合物，其特征在于所述的烟酰胺单核苷酸或其盐或其水合物为固态、液态或雾态。
  3. 根据权利要求1或2所述的毛发护理组合物，其特征在于所述的用于稳定烟酰胺单核苷酸或其盐或其水合物的基础成分包含阴离子表面活性剂、两性表面活性剂、阳离子表面活性剂、抗氧化剂、pH缓冲剂和酸度调节剂中的一种或者多种。
  4. 根据权利要求1-3中任意一者所述的毛发护理组合物，其特征在于所述毛发护理组合物的形式为洗发水、护发素、精华液、肥皂、喷雾、乳霜、发蜡、啫喱和膏体中的任意一者。
  5. 根据权利要求1-4中任意一项所述的毛发护理组合物，其特征在于所述毛发护理组合物为眉毛护理产品、眼睫毛护理产品和胡须护理产品中的任意一者。
  6. 根据权利要求1所述的毛发护理组合物，其特征在于所述基础成分包含用以防止烟酰胺单核苷酸在液态或雾态时降解的成分，如选自唾液酸、茶氨酸、β-胡萝卜素和磷酸钠中的一种或多种。
  7. 根据权利要求1-6中任意一项所述的毛发护理组合物，其特征在于以烟酰胺单核苷酸计，所述烟酰胺单核苷酸或其盐或其水合物占所述毛发护理组合物总重量的0.01重量％至25重量％，优选为毛发护理组合物总重量的0.1重量％-20重量％，更优选为毛发护理组合物总重量的0.1重量％-15重量％。
  8. 根据权利要求1-7中任意一项所述的毛发护理组合物，其特征在于所述毛发护理组合物还包含水，
    任选地，基于所述毛发护理组合物的总重量，水的含量为50-95重量％，优选为60-92重量％，更优选为65-90重量％。
  9. 根据权利要求3所述的毛发护理组合物，其特征在于相对于毛发护理组合物的总重量，
    阴离子表面活性剂的含量为15-65重量％，优选为25–45重量％，更优选为30-40重量％；
    任选地，两性表面活性剂的含量为1-15重量％，优选为1.5-8重量％，更优选为2-7重量％；任选地，阳离子表面活性剂的含量为0.01-0.09重量％，优选为0.02-0.08重量％，更优选为0.03-0.08重量％；
    任选地，抗氧化剂的含量为0.5-3重量％，优选为0.9-2.5重量％，更优选为1.5-2重量％；
    任选地，酸度调节剂的含量为0.05-1重量％，优选为0.2-0.85重量％，更优选为0.3-0.7重量％；以及
    任选地，pH缓冲剂的含量为1-3重量％，优选为1.5-2.5重量％，更优选为2-2.5重量％。
  10. 根据权利要求3或9所述的毛发护理组合物，其特征在于所述阴离子表面活性剂选自月桂醇聚醚硫酸酯钠、月桂基硫酸钠、月桂基硫酸铵、甲基椰油酰基牛磺酸钠、月桂醇聚醚-5羧酸、月桂基葡萄糖羧酸钠和其混合物中的至少一者。
  11. 根据权利要求3或9所述的毛发护理组合物，其特征在于所述两性表面活性剂为烷基两性羧酸盐、烷基氨基酸盐、椰油酰胺丙基甜菜碱、椰油酰胺单乙醇胺、月桂基葡糖苷、椰油基甲基葡聚糖或其混合物中的至少一者。
  12. 根据权利要求3或9所述的毛发护理组合物，其特征在于所述阳离子表面活性剂为选自聚季铵盐-10、瓜儿胶羟丙基三甲基氯化铵或其混合物中的至少一者。
  13. 根据权利要求3或9所述的毛发护理组合物，其特征在于所述抗氧化剂为选自L-半胱氨酸、DL-蛋氨酸、维生素A、维生素C、维生素E、植酸钠或其混合物中的至少一者。
  14. 根据权利要求3或9所述的毛发护理组合物，其特征在于所述酸度调节剂为选自柠檬酸、草酸、乳酸、盐酸或其混合物中的至少一者。
  15. 根据权利要求5所述的毛发护理组合物，其中所述的眉毛护理产品为眉毛护理液、眉毛护理喷雾和眉毛护理膏；所述的眼睫毛护理产品为眼睫毛护理液组装；所述的胡须护理产品为胡须护理液、胡须护理喷雾和胡须护理膏。
  16. 根据权利要求1-15中任意一项所述的毛发护理组合物，其特征在于所述毛发护理组合物中还包含用以丰富毛发护理组合物的外观、质感、气味和用家体验的功能性添加剂。
  17. 根据权利要求16所述的毛发护理组合物，其特征在于所述功能性添加剂选自增感剂、增泡剂、香味剂、功能性辅料或其任意组合。
  18. 一种制备毛发护理组合物的方法，其特征在于包括下列步骤：
    提供烟酰胺单核苷酸或其盐或其水合物；
    提供用于稳定液态或气态中的烟酰胺单核苷酸或其盐或其水合物的基础成分的水溶液；以及
    将烟酰胺单核苷酸或其盐或其水合物与所述水溶液混合并且调节pH值，从而得到毛发护理组合物。
  19. 根据权利要求18所述的方法，其特征在于所述的用于稳定液态或气态中的烟酰胺单核苷酸或其盐或其水合物的基础成分包含阴离子表面活性剂、两性表面活性剂、阳离子表面活性剂、非离子表面活性剂、抗氧化剂、pH缓冲剂和酸度调节剂中的一种或者多种。
  20. 根据权利要求19所述的方法，其特征在于该方法包括：
    (1)将一种或多种阴离子表面活性剂混合，得到第一类表面活性剂；
    (2)将一种或多种两性表面活性剂混合，得到第二类表面活性剂；
    (3)任选地将一种或多种阳离子表面活性剂混合，得到第三类表面活性剂；
    (4)将第一类表面活性剂、第二类表面活性剂和任选的第三类表面活性剂混合成得复合表面活性剂；
    (5)将烟酰胺单核苷酸加至复合表面活性剂中，以得到混合物
    (6)将pH在缓冲液加入混合物并使用酸度调节剂使混合物的pH值为4.85-7.0，从而得毛发护理组合物；以及
    (7)将抗氧化剂加入混合物从而得毛发护理组合物。
PCT/CN2020/130814 2019-11-21 2020-11-23 毛发护理组合物及其制备方法 WO2021098874A1 (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2022529830A JP2023517413A (ja) 2019-11-21 2020-11-23 毛髪ケア組成物及びその調製方法
EP20890137.1A EP4062897A4 (en) 2019-11-21 2020-11-23 HAIR CARE COMPOSITION AND ASSOCIATED PREPARATION METHOD

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201911146375.8A CN112823778A (zh) 2019-11-21 2019-11-21 毛发护理组合物及其制备方法
CN201911146375.8 2019-11-21

Publications (1)

Publication Number Publication Date
WO2021098874A1 true WO2021098874A1 (zh) 2021-05-27

Family

ID=75907388

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/130814 WO2021098874A1 (zh) 2019-11-21 2020-11-23 毛发护理组合物及其制备方法

Country Status (4)

Country Link
EP (1) EP4062897A4 (zh)
JP (1) JP2023517413A (zh)
CN (1) CN112823778A (zh)
WO (1) WO2021098874A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115025000A (zh) * 2022-05-19 2022-09-09 广州市金宸生物科技有限公司 一种具有抗皱、紧致功能的美白组合物及其应用

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111588729A (zh) * 2020-06-16 2020-08-28 无锡脑镁素生物医药科技有限公司 β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用
CN114191329B (zh) * 2021-12-17 2023-05-12 百瑞全球有限公司 口腔护理添加剂、口腔护理组合物、制备方法、成套用具及其应用
CN114588076A (zh) * 2022-04-08 2022-06-07 杭州悦萱堂化妆品有限公司 无硅护发素

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007002640A1 (en) * 2005-06-24 2007-01-04 Arizona Board Of Regents On Behalf Of The University Of Arizona Method for treating hair growth disorders, such as female pattern alopecia, and compositions useful therefore
WO2019078177A1 (ja) * 2017-10-16 2019-04-25 めぐみ 田中 ニコチンアミドモノヌクレオチドを含む化粧品組成物
CN109908067A (zh) * 2019-04-11 2019-06-21 聂乐明 用于生发和防止脱发的组合物及其制备方法和应用
CN111588729A (zh) * 2020-06-16 2020-08-28 无锡脑镁素生物医药科技有限公司 β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6352825B2 (ja) * 2015-01-23 2018-07-04 株式会社ベスビオ 化粧料
WO2016210232A1 (en) * 2015-06-25 2016-12-29 N.V. Perricone Llc Niacinamide mononucleotide formulations for skin aging
JP6949002B6 (ja) * 2015-08-05 2021-11-17 メトロ インターナショナル バイオテック，エルエルシー ニコチンアミドモノヌクレオチド誘導体及びそれらの使用
GB2542881B (en) * 2015-10-02 2020-01-01 Carr Andrew Crystal forms of ß-nicotinamide mononucleotide
JP6803854B2 (ja) * 2015-12-21 2020-12-23 昭和電工株式会社 ニコチンアミドモノヌクレオチド誘導体、その塩、その製造方法、皮膚外用剤、化粧料、食品添加剤
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
CN110338412A (zh) * 2019-07-16 2019-10-18 深圳市弘创农业科技有限公司 含烟酰胺单核苷酸和冰叶日中花的组合物及其制备和应用
WO2021234009A1 (fr) * 2020-05-20 2021-11-25 Nuvamid Sa Compositions cosmetiques anti-age comprenant du nmn

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007002640A1 (en) * 2005-06-24 2007-01-04 Arizona Board Of Regents On Behalf Of The University Of Arizona Method for treating hair growth disorders, such as female pattern alopecia, and compositions useful therefore
WO2019078177A1 (ja) * 2017-10-16 2019-04-25 めぐみ 田中 ニコチンアミドモノヌクレオチドを含む化粧品組成物
CN109908067A (zh) * 2019-04-11 2019-06-21 聂乐明 用于生发和防止脱发的组合物及其制备方法和应用
CN111588729A (zh) * 2020-06-16 2020-08-28 无锡脑镁素生物医药科技有限公司 β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
See also references of EP4062897A4 *
YOSHINO JUN; BAUR JOSEPH A.; IMAI SHIN-ICHIRO: "NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR", CELL METABOLISM, vol. 27, no. 3, 14 December 2017 (2017-12-14), pages 513 - 526, XP085357896, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2017.11.002 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115025000A (zh) * 2022-05-19 2022-09-09 广州市金宸生物科技有限公司 一种具有抗皱、紧致功能的美白组合物及其应用
CN115025000B (zh) * 2022-05-19 2024-03-22 广州市金宸生物科技有限公司 一种具有抗皱、紧致功能的美白组合物及其应用

Also Published As

Publication number Publication date
EP4062897A4 (en) 2024-04-17
JP2023517413A (ja) 2023-04-26
EP4062897A1 (en) 2022-09-28
CN112823778A (zh) 2021-05-21

Similar Documents

Publication Publication Date Title
WO2021098874A1 (zh) 毛发护理组合物及其制备方法
WO2015035585A1 (zh) 一种含高效防脱复合剂的香波组合物
CN107595735A (zh) 一种含艾叶的氨基酸洁面乳及其制备方法
KR20140107784A (ko) 탈모 방지 및 모발 성장 촉진용 조성물
AU2014361780A1 (en) Exfoliative hair retention-promoting formulation
JP2010163418A (ja) 化粧料
AU2012238087B2 (en) Topical palmitoyl glutathione formulations
CN105476950A (zh) 无添加天然保湿泡沫洁面乳
KR20150066811A (ko) 양모ㆍ육모 촉진용 화장료 조성물
JP2015034131A (ja) イチジク発酵抽出物及びその製造方法、並びにイチジク発酵抽出物を配合する化粧料
JP2012116898A (ja) 洗浄剤組成物
JP2005047910A (ja) 皮脂分泌抑制用組成物
CN104814882A (zh) 局部酰基谷胱甘肽制剂
JP2006028026A (ja) 育毛剤
CN112076134A (zh) 一种诺丽果植物精华洗发液及其制备方法
CN104287982B (zh) 一种调节头皮油脂平衡的去屑组合物
JP5216414B2 (ja) 育毛剤
JP2007039397A (ja) ビール酵母で発酵させたアルコール飲料からコラーゲン産生促進作用を有する組成物を製造する方法及びその組成物
JP2009114170A (ja) 育毛剤
JP2015093844A (ja) グリセリンおよびグリシンを含む組成物
JP2020183377A (ja) Ｓｖｃｔ発現促進剤
JPH03167113A (ja) 養毛剤
JP2011148773A (ja) 頭皮頭髪化粧料
KR101850770B1 (ko) 효소 식품 및 콜라겐을 유효성분으로 함유하는 갱년기 여성 손톱 개선용 조성물
CN110200873A (zh) 一种酒糟保湿洗发水

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20890137

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2022529830

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2020890137

Country of ref document: EP

Effective date: 20220621