WO2023108866A1 - 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 - Google Patents

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 Download PDF

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WO2023108866A1
WO2023108866A1 PCT/CN2022/074521 CN2022074521W WO2023108866A1 WO 2023108866 A1 WO2023108866 A1 WO 2023108866A1 CN 2022074521 W CN2022074521 W CN 2022074521W WO 2023108866 A1 WO2023108866 A1 WO 2023108866A1
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oral care
adenine dinucleotide
nicotinamide
oral
nicotinic acid
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PCT/CN2022/074521
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English (en)
French (fr)
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王骏
潘永强
卢锦春
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百瑞全球有限公司
王骏
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Priority to JP2023547884A priority Critical patent/JP2024516919A/ja
Priority to US17/792,977 priority patent/US20240173239A1/en
Priority to EP22735066.7A priority patent/EP4230263A4/en
Publication of WO2023108866A1 publication Critical patent/WO2023108866A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A23G4/12—Chewing gum characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • A23G4/126—Chewing gum characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins containing vitamins, antibiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/042—Gels
    • 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
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • 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
    • 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
    • A61K8/673—Vitamin B group
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/592—Mixtures of compounds complementing their respective functions
    • A61K2800/5922—At least two compounds being classified in the same subclass of A61K8/18
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/88—Two- or multipart kits
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/92—Oral administration

Definitions

  • the invention belongs to the field of personal care, and in particular relates to an oral care additive, an oral care composition, a preparation method, a complete set of utensils and applications thereof, in particular to the use of an additive mainly composed of ⁇ -nicotinamide mononucleotide for current and Among the new oral care products to increase its efficacy.
  • Oral diseases mainly include irregular dentition, dental caries, gingival inflammation and bleeding, gingival recession and periodontitis, etc., which have been listed by China and the World Health Organization as one of the five key chronic diseases for prevention and treatment. They are closely related to cardiovascular and cerebrovascular diseases, cancer and diabetes, etc. Traditional chronic diseases are listed among them. The number of patients with oral diseases in China has increased year by year. According to the data, the number of patients in 2018 has exceeded 694 million, which reflects that the situation is quite serious. Among the many oral diseases, dental caries, gingival inflammation and bleeding are the most common symptoms. Most of the reasons are poor oral hygiene, which leads to long-term accumulation of dental plaque on the teeth and gums, and the bacteria in it will produce toxins to stimulate tissues and cause diseases.
  • Oral hygiene is an important part of the prevention and treatment of oral diseases. Our country has been actively promoting and educating the importance of oral hygiene for many years. In addition to instilling the importance of brushing teeth every day from young children, and investing a lot of resources to promote residents' knowledge of health care and improve behavior, However, it still fails to stop the increasing prevalence of oral cavity, especially the rising trend among Chinese adults.
  • the main countermeasures of oral care are to focus on oral cleaning.
  • this kind of countermeasures only focuses on prevention and treatment, and the method is single. For adults, especially those who have already suffered from oral diseases, these measures can only delay their condition but fail to bring about substantial improvement.
  • the present invention provides an oral care additive, its application in oral care composition, oral care composition, preparation method and use method of oral care composition, especially using the additive to add to existing Oral care products to increase the efficacy of the product (such as treatment, prevention or alleviation of oral diseases, such as periodontal disease or gingival inflammation); the invention also proposes the application and method of the product with the additive as the main component.
  • the oral care additive proposed by the present invention is mainly composed of ⁇ -nicotinamide mononucleotide, which can be added to existing oral care products in combination to increase the ⁇ -nicotinamide adenine dinucleotide in gingival tissue. Nucleotide levels and at the same time exert the original efficacy of the product.
  • the present invention also proposes a new oral care product with the additive as the main component, including chewing gum and oral gelling agent containing ⁇ -nicotinamide mononucleotide, which provides a suitable platform for the combination of the additive, and provides a solution for different oral health conditions. Provide convenience to users.
  • the present invention provides:
  • An oral care additive comprising at least one main component selected from niacin or its derivatives and nicotinamide or its derivatives.
  • niacin or its derivatives and nicotinamide or its derivatives are selected from ⁇ -nicotinic acid riboside and its salts, ⁇ -nicotinic acid mononucleotide and its salts, Oxidized ⁇ -nicotinic acid adenine dinucleotide and its salt, reduced ⁇ -nicotinic acid adenine dinucleotide and its salt, oxidized ⁇ -nicotinic acid adenine dinucleotide and its salt, reduced form ⁇ -nicotinic acid adenine dinucleotide phosphate and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide phosphate and its salts, ⁇ -nicotinamide riboside and its salts, ⁇ -nicotinamide mononucleotide and its salts, oxidized ⁇ -nicotinic acid riboside and its salt
  • the vitamin is selected from at least one of vitamin A, vitamin B, vitamin C, vitamin D and vitamin K.
  • the coenzyme is selected from glutathione or its derivatives, adenosine triphosphate and its derivatives, pyrroloquinoline quinone or its derivatives, adenosylmethionine or its derivatives, coenzyme A or At least one of its derivatives, coenzyme Qs or derivatives thereof.
  • the derivatives are ⁇ -nicotinic acid riboside or its salt, ⁇ -nicotinic acid mononucleotide or its salt, ⁇ -nicotinamide riboside or its salt, ⁇ -nicotinic acid riboside or its salt, Nicotinamide mononucleotide or its salt, oxidized ⁇ -nicotinamide adenine dinucleotide or its salt, or reduced ⁇ -nicotinamide adenine dinucleotide or its salt;
  • the vitamins are vitamin B, vitamin C or vitamin K.
  • the coenzyme is glutathione or its derivatives or pyrroloquinoline quinone or its derivatives.
  • oral care additive according to any of the above, wherein said oral care additive is in solid, liquid or gaseous form.
  • the solid state is selected from at least one of powder, paste, gel and crystal, optionally, the liquid state is selected from solution, slurry, essential oil and non-Newtonian fluid at least one of; and optionally, the gaseous state is selected from liquefied spray.
  • the content of the main component is 0.1-100% (weight/weight) of the total weight of the oral care additive, preferably 0.1-90% (weight/weight), more preferably 0.1-50% (weight/weight).
  • the main component: the vitamin: the weight ratio of the coenzyme is (0.1-99%): (0.1-99%) (0.1-99%), preferably (0.1 -75%): (0.1-12.5%) (0.1-12.5%), more preferably (0.1-50%): (0.1-25%) (0.1-25%).
  • An oral care composition characterized by comprising the oral care additive described in any one of 1-11.
  • the content of the oral care additive is 0.1-50% (weight/weight) of the total weight of the oral care composition, preferably 0.1-25% (weight/weight) , more preferably 0.3-15% (weight/weight).
  • the oral care composition is at least one selected from the group consisting of toothpaste, mouthwash, oral spray and dentifrice.
  • oral care composition according to any of the above, said oral care composition being a chewing gum or an oral gel.
  • said chewing gum further comprising at least one of resins, waxes, phospholipids, flavorings and elastomers;
  • the oral gel further comprises glycerin, sorbitol, gum tragacanth, sodium benzoate and peppermint oil.
  • a method of preparing an oral care composition comprising the steps of:
  • an oral care additive comprising at least one main ingredient selected from niacin or its derivatives and niacinamide or its derivatives;
  • the oral care additive is incorporated into a carrier that facilitates absorption of the oral care additive by the gum tissue of the oral cavity.
  • the carrier is at least one of toothpaste, mouthwash, mouth spray, dentifrice, chewing gum and oral gel.
  • the oral care additive further comprises an auxiliary ingredient selected from at least one of vitamins and coenzymes.
  • the nicotinic acid or its derivatives and nicotinamide or its derivatives are selected from ⁇ -nicotinic acid riboside and its salts, ⁇ -nicotinic acid mononucleotide and its salts, oxidation Type ⁇ -nicotinic acid adenine dinucleotide and its salts, reduced ⁇ -nicotinic acid adenine dinucleotide and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide and its salts, reduced ⁇ - Nicotinic acid adenine dinucleotide phosphate and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide phosphate and its salts, ⁇ -nicotinamide riboside and its salts, ⁇ -nicotinamide mononucleotide and Its salt, oxidized
  • An oral care kit comprising the oral care composition described in any one of the above and teethers.
  • the present invention proposes a kind of oral care additive, its application and related method, with one or more niacin or derivatives thereof or nicotinamide or derivatives thereof (preferably ⁇ -nicotinamide mononucleotide and oxidized ⁇ -nicotinamide adenine dinucleotide phosphate and its salts) as the main components, used to supplement and enhance the level of ⁇ -nicotinamide adenine dinucleotide in gum tissue; use the composition in the oral cavity It is a new breakthrough in health care. Oral care products are no longer limited to a single function of maintaining oral hygiene or relieving tooth sensitivity;
  • All the substances in the oral care additive proposed by the present invention are natural and harmless and exist in various organisms. They are safe and reliable and will not cause adverse reactions or effects on the oral health of ordinary users. They are suitable for daily use by people of any age ;
  • the present invention proposes to add oral care additives to existing oral care products such as toothpaste and mouthwash, which is simple; the combination of additives will not react scientifically with the ingredients in oral care products, so the combination of additives will not affect or reduce the The original function and efficacy of oral care products; when users use the oral care products, they can clean the mouth and at the same time absorb the ingredients of the additive combination in the process to supplement and enhance the ⁇ -nicotinamide adenine dinucleoside in the gums acid levels, a two-pronged approach for more comprehensive oral care without extra time.
  • One of the new oral care compositions proposed by the present invention is chewing gum containing oral care additives; this product is suitable for users with normal chewing ability, and can supplement and enhance the ⁇ in the gums by chewing gum anytime and anywhere. - Levels of nicotinamide adenine dinucleotide.
  • the additives in the chewing gum are released by the user while chewing. Since the process of chewing the gum is generally longer, the chances of being directly absorbed by the capillaries in the gums are increased.
  • This method can not only effectively utilize the physical characteristics of chewing gum to load a high amount of additives in it, but also utilize the habit of using chewing gum, that is, when chewing in the mouth, it will stick to the gums, and the additives in the chewing gum can be used in the most direct and
  • the stable method allows capillary absorption in the gum tissue, which is more direct and long-lasting than other methods of use.
  • Another new oral care composition proposed by the present invention is an oral gel containing oral care additives; this product is suitable for people with poor chewing ability and dentures. Most of these people are elderly or patients with severe periodontal disease, and they need to supplement and increase the level of nicotinamide adenine dinucleotide to promote gum health, reduce gum inflammation, and promote the proliferation of gum capillaries to avoid gum recession , and this function is lacking in existing oral care products, especially designed for this type of people; oral gel is mainly water-based, and natural sedative ingredients such as broccoli can be added to give users a soothing effect. The user only needs to inject the oral gel into the braces and put it into the saliva cavity.
  • the oral gel directly contacts the surface of the gums to create the most direct conditions for the gums to absorb directly.
  • the water-based gel allows the user to freeze it before use. Use it at a warm temperature, allowing users to make the most suitable choice for their own experience.
  • Fig. 1 shows the stability study result of embodiment 6 (represented as oral care additive in the figure) and embodiment 7 (represented as ⁇ -nicotinamide mononucleotide in the figure) over time;
  • Fig. 2 shows the growth effect of oral tissue cells in the culture medium without oral care additive and with different doses of the oral care additive of Example 2.
  • Oral disease has become the most important public health problem in our country.
  • the number of people suffering from dental caries and periodontal disease has exceeded one-third of the total population, and this situation is gradually increasing.
  • the existing population The problem of aging, I am afraid that in the foreseeable few years, oral diseases will be the highest among the chronic diseases in our country, and will make a heavy burden on China's health care. Therefore, the society should pay attention to the importance of oral diseases.
  • "Healthy China 2030" Planning Outline and "China's Medium- and Long-Term Plan for the Prevention and Treatment of Chronic Diseases (2017-2025)” both put forward the importance of oral health, and further strengthened the publicity work on oral health and improved the public's action on oral health and positivity.
  • ⁇ -nicotinamide adenine dinucleotide is an important coenzyme in biology. In addition to regulating various biological functions in the body, it is also responsible for activating longevity protein genes and suppressing inflammatory cytokines. Therefore, using it can improve gum tissue Substances at the level of ⁇ -nicotinamide adenine dinucleotide are very important for oral care.
  • ⁇ -nicotinamide mononucleotide is the direct precursor of ⁇ -nicotinamide adenine dinucleotide, which is converted into ⁇ -nicotinamide adenine dinucleotide by enzyme in cells; ⁇ -nicotinamide mononucleotide It has high stability and safety, and is easily absorbed by the human body. It is an ideal substance to increase the level of ⁇ -nicotinamide adenine dinucleotide in the gums.
  • niacin or its derivatives and nicotinamide or its derivatives which may include ⁇ -nicotinic acid riboside and its salts
  • ⁇ -nicotinic acid mononucleotide and its salt oxidized ⁇ -nicotinic acid adenine dinucleotide and its salt, reduced ⁇ -nicotinic acid adenine dinucleotide and its salt, oxidized ⁇ -nicotinic acid Adenine dinucleotide and its salts, reduced ⁇ -nicotinic acid adenine dinucleotide phosphate and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide phosphate and its salts, ⁇ -nicotinamide nucleus Glycosides and their salts, ⁇ -nicotinamide mononucleotide and its salt
  • the inventor of the present invention believes that the level of ⁇ -nicotinamide adenine dinucleotide in such people is relatively low, and the level in the body should be increased as soon as possible, and it is necessary to absorb it directly in the gums; according to scientific research in recent years, absorbing nicotinamide or Derivatives can increase the level of ⁇ -nicotinamide adenine dinucleotide in organisms, and it is pointed out that the use of ⁇ -nicotinamide mononucleotide, the precursor of ⁇ -nicotinamide adenine dinucleotide, has both efficacy and safety. for the ideal.
  • the present inventors investigated the possibility of applying this substance.
  • the results confirm that ⁇ -nicotinamide mononucleotide is easily absorbed by the body and can be quickly converted into ⁇ -nicotinamide adenine dinucleotide in the body and increase the level of this substance in the body.
  • Studies have also pointed out that increasing the level of ⁇ -nicotinamide adenine dinucleotide can significantly improve the body's metabolism, biological clock and physical functions.
  • ⁇ -nicotinamide mononucleotide to increase ⁇ -nicotinamide adenine dinucleotide can promote the proliferation of capillaries in muscles to improve function, and can be used to promote the proliferation of gingival capillaries to prevent periodontal Tooth loss caused by receding gums.
  • ⁇ -nicotinamide mononucleotide is a more natural substance with high stability, and studies have also proved that it is safe for the human body. People from all over the world have begun to take it and received good feedback. Therefore, the inventors believe that ⁇ -nicotinamide mononucleotide is the most suitable main component of the additive.
  • ⁇ -nicotinamide adenine dinucleotide is an important coenzyme in the body. Every cell and tissue in the body relies on its existence for various types of physiological reactions. Relying on oral ⁇ -nicotinamide mononucleotide cannot actually deal with oral problems , it is necessary to allow ⁇ -nicotinamide mononucleotide to enter the gums in a more direct way and be absorbed by the capillaries in it, so as to directly increase the level of ⁇ -nicotinamide adenine dinucleotide in the gums.
  • the inventor believes that the application and method of increasing the level of ⁇ -nicotinamide adenine dinucleotide in the gums should be based on the convenience of the user, and it will complement each other with the existing habit of oral hygiene.
  • the present invention proposes a kind of oral care additive, oral care composition, its application and method, provides brand-new means on the basis of traditional oral care, increases the effect of existing oral care product and provides new application and method, makes new The scientific results can be practically applied to the general public to create more favorable conditions for oral health by combining oral cleaning and increasing the level of ⁇ -nicotinamide adenine dinucleotide in the gums to meet the public's needs for personal health and public health requirements Benefit.
  • the oral care additives and their applications in this paper break away from the current inherent thinking and mode of focusing on oral hygiene in oral health care.
  • the new thinking is to improve the level of ⁇ -nicotinamide adenine dinucleotide and integrate into the existing oral care habits.
  • the public brings a more comprehensive oral health experience and builds a more solid foundation for my country's public health.
  • the present invention provides an oral care additive comprising at least one main component selected from niacin or its derivatives and niacinamide or its derivatives.
  • Nicotinic acid or its derivatives and nicotinamide or its derivatives can be selected from ⁇ -nicotinic acid riboside and its salts, ⁇ -nicotinic acid mononucleotide and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide and its salts, reduced ⁇ -nicotinic acid adenine dinucleotide and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide and its salts, reduced ⁇ -nicotinic acid adenine dinucleotide phosphate and Its salt, oxidized ⁇ -nicotinic acid adenine dinucleotide phosphate and its salt, ⁇ -nicotinamide riboside and its salt, ⁇ -nicotinamide mononucleotide and its salt, oxidized ⁇ -nicotinamide adenine Dinucleot
  • the main function of the oral care additive is to increase and supplement the level of ⁇ -nicotinamide adenine dinucleotide in the oral cavity
  • the oral care additive combination contains at least one direct or indirect functional substance, which can be one One or more kinds of niacin or its derivatives and nicotinamide or its derivatives: one or more kinds of niacin or its derivatives may contain niacin, ⁇ -nicotinic acid riboside and its salts, ⁇ -nicotinic acid Acid mononucleotide and its salt, oxidized ⁇ -nicotinic acid adenine dinucleotide and its salt, reduced ⁇ -nicotinic acid adenine dinucleotide and its salt, oxidized ⁇ -nicotinic acid adenine dinucleotide Nucleotides and salts thereof, reduced ⁇ -nicotinic acid adenine dinucleotide phosphate
  • the total percentage by weight of the at least one direct or indirect functional substance in the entire cavity care additive should be 0.1-100% (w/w), preferably 0.1-90% (w/w), more preferably 0.1- 50% (w/w).
  • Direct or indirect functional substances in oral care additives can preferably be ⁇ -nicotinamide mononucleotide, ⁇ -nicotinamide riboside, oxidized ⁇ -nicotinamide adenine dinucleotide, reduced ⁇ -nicotinamide adenine Purine dinucleotide, ⁇ -nicotinic acid mononucleotide and ⁇ -nicotinic acid riboside, more preferably ⁇ -nicotinamide mononucleotide, ⁇ -nicotinamide riboside and oxidized ⁇ -nicotinamide adenine di Nucleotides, and the use of ⁇ -nicotinamide mononucleotide is the best.
  • the oral care additive further contains auxiliary ingredients selected from at least one of vitamins and coenzymes.
  • the vitamin may be selected from at least one of vitamin A, vitamin B, vitamin C, vitamin D and vitamin K.
  • the coenzyme may be selected from at least one of glutathione or its derivatives, adenosine triphosphate and its derivatives, pyrroloquinoline quinone or its derivatives, adenosylmethionine or its derivatives.
  • niacin or derivatives thereof and niacinamide or derivatives thereof are ⁇ -nicotinic acid riboside or a salt thereof, ⁇ -nicotinic acid mononucleotide or a salt thereof, ⁇ -nicotinic acid Amide riboside or a salt thereof, ⁇ -nicotinamide mononucleotide or a salt thereof, an oxidized ⁇ -nicotinamide adenine dinucleotide or a salt thereof, or a reduced ⁇ -nicotinamide adenine dinucleotide or a salt thereof salt;
  • the vitamin is vitamin B, vitamin C or vitamin K; and the coenzyme is glutathione or a derivative thereof or pyrroloquinoline quinone or a derivative thereof, coenzyme A or a derivative thereof, coenzyme Q or a derivative thereof at least one of the objects.
  • Oral care additives can be in solid, liquid and gaseous form.
  • the solid state may be selected from powder, paste, gel and crystal.
  • the liquid form can be selected from solutions, slurries, essential oils and non-Newtonian fluids; the gaseous form can be selected from liquefied sprays.
  • the content of at least one main component may be 0.1-100% (weight/weight), preferably 0.1-90% (weight/weight), of the total weight of the oral care additive, More preferably 0.1-50% (weight/weight).
  • the main component the vitamin: the weight ratio of the coenzyme is (0.1-99%): (0.1-99%) (0.1-99%), preferably (0.1-75%): (0.1-12.5 %)(0.1-12.5%), more preferably (0.1-50%):(0.1-25%):(0.1-25%).
  • the oral care agent herein has the advantage of high stability, it will neither chemically interact with the compounds in existing oral care products, nor affect or reduce the existing efficacy of the product
  • the second aspect herein provides an oral care composition comprising the above-mentioned oral care additive.
  • the oral care composition herein may comprise at least one selected from niacin or derivatives thereof and niacinamide or derivatives thereof.
  • the content of oral care additives can be 0.1-50% (weight/weight), preferably 0.1-25% (weight/weight), more preferably 0.3-15% ( weight/weight).
  • the oral care composition may be at least one selected from toothpaste, mouthwash, mouth spray, and dentifrice. These are all existing oral care products.
  • Oral care compositions can also be novel oral care products such as chewing gum or oral gels.
  • Cavity care compositions can also be in solid, liquid and gaseous form.
  • the solid state may be selected from powder, paste, gel and crystal.
  • the liquid state may be selected from solutions, slurries, essential oils and non-Newtonian fluids.
  • the gaseous form can be selected from liquefied sprays.
  • chewing gum may also contain at least one of resins, waxes, phospholipids, flavoring agents and elastomers.
  • the chewing gum containing the oral care additive in the novel oral care product is the carrier of the oral care additive; the carrier has the advantages of large loading capacity and easy portability, and the carrier can be firmly attached to the surface of the user's gums directly Favorable conditions for the gums and their capillaries to absorb the oral care additive composition substances released in the chewing gum, the user also releases the substances when chewing and is absorbed by the gums and their capillaries through saliva.
  • oral gels can also contain glycerin, sorbitol, gum tragacanth, sodium benzoate and peppermint oil.
  • the oral gel containing the oral care additive in the new oral care product is the carrier of the oral care additive and is used in conjunction with the braces; the carrier can be attached to the surface of the gums to allow the gums to absorb the oral care additive composition, suitable for For those with poor chewing ability, dentures and tooth loss.
  • the chewing gum and oral gel containing oral care additives can be added with different tastes and colors to meet user needs; wherein the oral gel can be used at 10-40 degrees Celsius.
  • the present invention prepares a chewing gum containing a combination of oral care additives for the convenience of the general user.
  • Chewing gum is mainly based on resin, wax and elastomer, and the material used in the present invention is based on plant components. Decompose naturally.
  • the use of edible carriers that are oral care additive combinations has many advantages: the ingredients of chewing gum are inert materials, and will not chemically react with the substances in the oral care additive combination during production; 0.1-20% (w/w) of the oral cavity
  • the care additive combination can be added to the chewing gum in a solid or liquid state, the composition of the oral care additive combination will not change, and the stability will maintain 95% or more of the content of functional ingredients under normal storage conditions for three months; the chewing gum can be added to a variety of Natural flavorings to make the taste and taste suitable for users.
  • the present invention further creates favorable conditions for the main component of the additive, ⁇ -nicotinamide mononucleotide, to be absorbed by the gums and their capillaries based on the chewing gum habit of the user.
  • the oral care additive composition loaded in the chewing gum will be released in the gums; 2.
  • Chewing gum will stimulate the secretion of saliva, and the substances in the chewing gum will also be absorbed by the body through saliva; 3 .
  • chewing gum there will be frequent contact between the gums and the gum, and the user will naturally attach the chewing gum to the gums and teeth.
  • a chewing gum containing a combination of oral care additives is also convenient for users to carry and use, and users can use it anytime and anywhere to supplement the level of beta-nicotinamide adenine dinucleotide in the gums.
  • the inventors have prepared another novel oral care product comprising a combination of oral care additives.
  • This product is an oral gel, which is used by a group of people with low chewing ability, people who use dentures and people with oral diseases who have lost part of their teeth; add 10% (w/w) of Oral care additive combination (beta-nicotinamide mononucleotide:S-acetylglutathione:vitamin C is 6:2:2), 15% (w/w) glycerin, 15% (w/w) Sorbitol, 2% (w/w) gum tragacanth, 2.5% (w/w) sodium benzoate, 0.1% (w/w) peppermint oil, add pure water to constant volume and stir at 250rpm for 12 hours to Liquid paste.
  • the user injects oral gel evenly into the two teethers, and then puts the teethers into the upper and lower jaws respectively and closes the lips tightly to prevent the teethers from falling out. The user takes them out after 10 minutes Put the teether on and rinse your mouth with water to complete.
  • the ingredients in the oral care additive package in the oral gel are absorbed by the gums and capillaries for their intended use.
  • the components of the oral gel are all inert materials, which will not chemically react with the functional components in the oral care additive combination.
  • the oral care additive combination can be stabilized, and its stability is higher than that of the oral care additive combination of the oral gel under normal storage conditions. The content is still maintained at 95% or above.
  • the oral gel can be cooled to not lower than 10 degrees Celsius or kept warm to not higher than 37 degrees Celsius before use, and its physical properties, functionality and stability will not be affected by temperature changes.
  • the oral care additive has the advantage of high stability, neither chemically interacts with the compounds in the existing oral care products, nor affects or reduces the existing efficacy of the products.
  • a third aspect of this paper provides a method for preparing an oral care composition, comprising the following steps:
  • an oral care additive comprising at least one main ingredient selected from niacin or its derivatives and niacinamide or its derivatives;
  • the oral care additive is incorporated into a carrier that facilitates absorption of the oral care additive by the gum tissue of the oral cavity.
  • the carrier is at least one of toothpaste, mouthwash, mouth spray, dentifrice, chewing gum, and oral gel.
  • the oral care additive may further contain auxiliary ingredients selected from at least one of vitamins and coenzymes.
  • the niacin or its derivatives and nicotinamide or its derivatives can be selected from ⁇ -nicotinic acid riboside and its salts, ⁇ -nicotinic acid mononucleotide and its salts, oxidized ⁇ -nicotinic acid adenine dinucleoside Nucleic acid and its salts, reduced ⁇ -nicotinic acid adenine dinucleotide and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide and its salts, reduced ⁇ -nicotinic acid adenine dinucleotide Phosphoric acid and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide phosphate and its salts, ⁇ -nicotinamide riboside and its salts, ⁇ -nico
  • a fourth aspect of the present invention provides an oral care kit comprising an oral care composition and a teether.
  • the oral care composition may comprise at least one selected from niacin or its derivatives and nicotinamide or its derivatives
  • this paper proposes an oral care additive combination, wherein the oral care additive combination can be one or more of niacin and its derivatives, nicotinamide and its derivatives, vitamins and coenzymes as the main composed of ingredients.
  • Nicotinic acid or its derivatives include niacin, ⁇ -nicotinic acid riboside and its salts, ⁇ -nicotinic acid mononucleotide and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide and its salts, reduced form ⁇ -Nicotinic acid adenine dinucleotide and its salts, oxidized ⁇ -nicotinic acid adenine dinucleotide and its salts, reduced ⁇ -nicotinic acid adenine dinucleotide phosphate and its salts, and oxidized ⁇ - -Nicotinic acid adenine dinucleotide phosphate and its salts
  • the oral care composition selects ⁇ -nicotinamide mononucleotide, glutathione derivative S-acetylglutathione and vitamin C to be added to the toothpaste.
  • the ratio by weight of ⁇ -nicotinamide mononucleotide: S-acetylglutathione: vitamin C is 6:2:2 and mixed in the container in powder form, and then 1% of the total weight of the toothpaste Add and stir with a spoon until no solids are visible.
  • the same combination and ratio is added to a mouthwash and dissolved.
  • the toothpaste and mouthwash with the additive combination are compared with the original items for color, odor, stability and antibacterial control experiments to prove that the additive combination will not affect the physical and functional properties of oral care products.
  • the direct or indirect functional substances in the combination may preferably be ⁇ -nicotinamide mononucleotide, ⁇ -nicotinamide riboside, oxidized ⁇ -nicotinamide adenine dinucleotide, reduced ⁇ -nicotinamide adenine Purine dinucleotide, ⁇ -nicotinic acid mononucleotide and ⁇ -nicotinic acid riboside, more preferably ⁇ -nicotinamide mononucleotide, ⁇ -nicotinamide riboside and oxidized ⁇ -nicotinamide adenine di Nucleotides, especially ⁇ -nicotinamide mononucleotide and oxidized ⁇ -nicotinamide adenine dinucleotide are the best.
  • the present invention also provides the application of any of the above oral care additives in the preparation of an oral care composition for treating, preventing or alleviating oral diseases.
  • ⁇ -nicotinamide mononucleotide from Gene Harbor (Hong Kong) Biotechnology Co., Ltd.;
  • Oxidized ⁇ -nicotinamide adenine dinucleotide from Gene Harbor (Hong Kong) Biotechnology Co., Ltd.;
  • Sodium ascorbate (i.e. vitamin C): purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.;
  • Negro toothpaste purchased from Market Place by Jasons;
  • Powder gum base purchased from Glee gum
  • Sorbitol purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.;
  • Peppermint extract purchased from Guangzhou Baiyu Biotechnology Co., Ltd.;
  • Sodium phosphate (sodium dihydrogen phosphate monohydrate and disodium hydrogen phosphate): purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.
  • Embodiment 1 preparation contains the solid-state oral care additive of ⁇ -nicotinamide mononucleotide
  • Preparation of 100g solid oral care additive in a sterilized 500ml beaker, add ⁇ -nicotinamide mononucleotide, S-acetylglutathione and sodium aspirate in sequence, these three substances are in the oral care additive
  • the weight of S-acetylglutathione is 60g
  • the weight of S-acetylglutathione is 20g
  • the weight of sodium aspirate is 20g.
  • the three substances are all in powder form.
  • Example 2 Preparation of solid oral care additives containing ⁇ -nicotinamide mononucleotide and oxidized ⁇ -nicotinamide adenine dinucleotide
  • the three substances are all in powder form. After adding to the beaker, stir with a spatula no less than 20 times until the substances are completely mixed; take 10mg of the mixed sample and dissolve it in 1ml of pure water to analyze it by high performance liquid chromatography in Annex 1 content of functional ingredients.
  • Example 3 Preparation of solid oral care additives containing ⁇ -nicotinamide adenine dinucleotide and oxidized ⁇ -nicotinamide adenine dinucleotide
  • the weight of ⁇ -nicotinamide mononucleotide is 40g
  • the weight of oxidized ⁇ -nicotinamide adenine dinucleotide is 40g
  • the weight of glutathione is 10g
  • the weight of sodium aspirate is 10g.
  • the four substances are all in the form of powder. After adding to the beaker, stir with a spatula no less than 20 times until the substances are completely mixed; take 10mg of the mixed sample and dissolve it in 1ml of pure water to analyze it by high performance liquid chromatography in Annex 1 content of functional ingredients.
  • Embodiment 4 preparation contains the liquid oral care additive of ⁇ -nicotinamide mononucleotide
  • Embodiment 5 Preparation contains the liquid oral care additive of ⁇ -nicotinamide adenine dinucleotide
  • Toothpaste containing oral care additives and toothpaste without oral care additives were also studied for antibacterial efficacy: the two toothpastes were tested with E. coli according to the method in Annex 2; The average antibacterial zone diameter is 20.2+1.1, and the average antibacterial zone diameter of the toothpaste without oral care additives is 20.3+1.3; the experimental results show that the diameter of the antibacterial zone of the toothpaste containing oral care additives and the toothpaste without oral care additives is between The three concentrations tested are all very close, which proves that the two have the same antibacterial efficacy, and the combination of oral care additives does not affect the original efficacy of the toothpaste.
  • the toothpaste containing the combination of oral care additives in normal packaging was stored at 25 degrees Celsius and the humidity was maintained at 60%.
  • the high performance liquid chromatography method of 1 is afraid that this method is used to analyze the content of ⁇ -nicotinamide mononucleotide, the main component of the oral care additive combination, and study the change of its content in toothpaste; the experimental results are shown in Figure 1, which proves the oral care additive.
  • the main component ⁇ -nicotinamide mononucleotide has excellent stability in toothpaste.
  • the toothpaste containing the combination of oral care additives in normal packaging was stored at 25 degrees Celsius and the humidity was maintained at 60%.
  • the HPLC method of 1 is afraid that this method is used to analyze the content of ⁇ -nicotinamide mononucleotide, the main component of oral care additive combination, to study the change of its content in toothpaste; see Figure 1 for the results.
  • a double-blind test on the physical color, smell and taste of mouthwashes containing oral care additives and mouthwashes without oral care additives the researchers first labeled the above two mouthwashes as sample 3 and sample 4, and then provided them to 10 testers used and compared the color, smell and taste of the two samples, and asked the testers whether there were any differences in the above three senses between sample 1 and sample 2. The results showed that 8 of the 10 testers believed that the two samples had no difference in color, smell and taste.
  • Antibacterial efficacy studies were also carried out on the mouthwash containing oral care additives and the mouthwash without oral care additives: the two mouthwashes were tested according to the method in Annex 3, and E. coli was tested; The average antibacterial zone diameter of the mouthwash of nursing additive is 24.4mm, and the average antibacterial zone diameter of the mouthwash not containing oral care additive is 24.1mm; The antibacterial zone diameters of the mouthwash were very close under the three concentrations tested, which proved that the two had the same antibacterial efficacy, and the combination of oral care additives did not affect the original efficacy of the mouthwash.
  • the mouthwash containing the oral care additives in the original packaging was stored at 25 degrees Celsius and 60% humidity.
  • use the high performance liquid chromatography method in Annex 1 to analyze the content of ⁇ -nicotinamide mononucleotide, the main component of oral care additives, to study the change of its content in mouthwash; the experimental results show that ⁇ -nicotinamide mononucleotide in toothpaste after six months -
  • the content of nicotinamide mononucleotide is 94.5% of the content of the initial experimental sample, which proves that the main component of oral care additives, ⁇ -nicotinamide mononucleotide, has superior stability in mouthwash.
  • the pre-mixed oral care additives, sorbitol and xylitol powders are stacked on a flat surface, and the melted powder gum base is placed in the center of the powder pile, and the powder is evenly adhered to the colloid by kneading. After completion, add 0.85g of mint extract and 3-5 drops of bright blue at the same time and continue kneading until the colloid is light blue on average.
  • the colloid is evenly dispersed in a plate of 6cm (length) x 6cm (width) x 1cm (height) and cut into a cube of 20mm (length) x 20mm (width) x 1cm (height) with a knife, and it is completed after air-drying at room temperature for 12 hours
  • the whole preparation process; each piece of mint-flavored chewing gum containing the oral care additive weighs about 4g, and contains 40mg of the oral care additive.
  • Toothpaste containing oral care additives and toothpaste without oral care additives were also studied for antibacterial efficacy: the two toothpastes were tested with E. coli according to the method in Annex 2; The average antibacterial zone diameter is 20.2+1.1, and the average antibacterial zone diameter of the toothpaste without oral care additives is 20.3+1.3; the experimental results show that the diameter of the antibacterial zone of the toothpaste containing oral care additives and the toothpaste without oral care additives is between The three concentrations tested are all very close, which proves that the two have the same antibacterial efficacy, and the combination of oral care additives does not affect the original efficacy of the toothpaste.
  • the toothpaste containing the combination of oral care additives in normal packaging was stored at 25 degrees Celsius and the humidity was maintained at 60%.
  • the high-performance liquid chromatography method of 1 was used to analyze the total content of ⁇ -nicotinamide mononucleotide and oxidized ⁇ -nicotinamide adenine dinucleotide, the main components of oral care additive combination, to study the change of its content in toothpaste; the experiment
  • HGF-1 cells human gingival fibroblasts; Human gingival fibroblast
  • the cell growth changes of the cells in the medium containing different concentrations (12-50ug/mL) of oral care additives and blank samples were compared for 48 hours.
  • HGF-1 medium ATCC-formulated Dulbecco's Modified Eagle's Medium+10% fetal bovine serum
  • a 12-well cell culture plate was used in the experiment. 2.5x 104 HGF-1 was added to each well and placed in a cell culture incubator (at a constant temperature of 37 degrees Celsius, 5% carbon dioxide) for three hours, and the cell culture medium in the well was sucked away.
  • HGF-1 medium containing 12ug/ml oral care additives to the three wells in a row, add HGF-1 medium containing 24ug/ml oral care additives to the other three wells in a row, add 24ug /ml of HGF-1 medium with oral care additives, finally add HGF-1 medium without oral care additives to the in-line three wells and place them in the cell incubator, replace the medium in the sample wells for 24 hours, and cultivate for 48 hours Then use a cell counter to calculate the average number of cells in this medium. In the control experiment, the average cell number of the HGF-1 medium containing 12ug/ml oral care additive was 7.8% higher than that of the blank sample.
  • the average cell mass of the HGF-1 medium was 8.4% and 8.8% higher than that of the blank sample respectively. See Figure 2 for specific results. This result shows that oral care additives can promote the growth of oral tissues, thereby alleviating, preventing or treating oral diseases, such as gingival inflammation, etc. to a certain extent.
  • nucleoside and mononucleotide content of nicotinic acid or its derivatives by HPLC such as ⁇ - ⁇ -nicotinamide mononucleotide, ⁇ -nicotinamide adenine dinucleotide, ⁇ -nicotinamide riboside , ⁇ -nicotinic acid mononucleotide, nicotinic acid adenine dinucleotide, ⁇ -nicotinic acid riboside, etc.
  • the operation method is as follows:
  • Annex 2 Bacteriostatic testing of toothpastes containing combinations of oral care additives

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Abstract

一种口腔护理添加剂、口腔护理组合物、其制备方法、口腔护理成套用具及其应用。口腔护理添加剂的主要成分包含一种或多种的烟酸、烟酰胺或其衍生物以补充和提升口腔中β-烟酰胺腺嘌呤二核苷酸的水平，组合成分还可同时包含各类维生素和辅酶以辅助主要成分的功能。该添加剂和其应用方法保留现有口腔护理产品的功能并同时增添全新的效能，促使使用者有更全面的口腔健康管理体验。

Description

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 技术领域
本发明属于个人护理领域，具体涉及一种口腔护理添加剂、口腔护理组合物、制备方法、成套用具及其应用，特别涉及使用以β-烟酰胺单核苷酸为主要成分的添加剂用于现行和新型的口腔护理产品之中以增添其功效。
背景技术
口腔疾病主要包括齿列不齐、龋齿、牙龈发炎和流血、牙龈萎缩和牙周炎等，已被中国和世界卫生组织列入五大重点防治慢性病之一，与心脑血管疾病、癌症和糖尿病等传统慢性疾病并列其中。中国的口腔疾病患者随年增长，根据数据在2018的患者数目已超过6.94亿人，反映情况相当严重。在众多的口腔疾病中以龋齿、牙龈发炎和流血的病征较为普遍，原由多为口腔清洁欠佳，导致牙菌膜长期积聚在牙齿和牙龈边，而当中的细菌会产生毒素刺激组织而引发疾病。口腔清洁是防治口腔疾病的重要一环，我国多年来均积极推广和教育口腔清洁的重要性，除由幼童阶段灌输每天刷牙的重要性，并且投放大量资源推动居民普及保健知识和改善行为，但是仍未能制止口腔患病率越来越高的问题，特别在中国成年人的上升趋势。
人口老化和吸烟亦是口腔疾病的主要成因，特别是随着中国的人口老化问题越趋严重，当2030年中国60岁以上的老年人口将占整体人口的四分之一时，口腔疾病的患者人数必定居高不下，对国家在口腔保健的负担将会更为沉重。口腔疾病不仅为病人带来咀嚼不便：近年的研究均发现牙周病与其他慢性疾病包括糖尿病、癌症和心血管疾病有关联。因此，口腔健康可以被认知为公共健康发展的最前线；若然不正视牙腔疾病可以引发的严重性和相关性，大众的健康情况将无 可避免的倒退，而且基于口腔疾病的普及性，在可预计的将来肯定成为中国医疗保健的缺口，如现在不将其堵上，对民众和社会的利益构成重大风险。
现时口腔护理的主要对策以着重口腔清洁为重，在口腔护理产品中添加多种消除口腔中滋生的微生物并抑制其繁殖速度以减低牙菌膜和牙石的形成，例如每天早晚使用含氟的牙膏以正确的方式刷牙和使用漱口水、进食后使用牙线清理口腔中的残余物和定期到牙科诊所进行牙齿检查；这些对策在预防口腔疾病中皆有积极的作用，应继续推广和实行；然而，这类对策只以防治为主，做法单一，对成年人特别是已经患上口腔疾病的患者来说，这些措施只能延缓其病况而未能带来实质的改善，而且对一类非因口腔细菌而引致口腔疾病的患者，例如牙齿排列不良、磨牙或长期吸烟人士引致牙龈或其毛细血管萎缩，则功效不大。此外，近年研究发现口腔疾病，特别是牙龈发炎和流血、牙龈和其毛细血管萎缩而引起的牙周病和牙骨退化可以是因为炎性细胞因子在牙龈组织增加而造成。当牙龈发炎和牙周病时，身体的免疫系统产生活性氧化物和炎性细胞因子对抗细菌和病源体的入侵，但这些物质亦会对牙龈组织进行破坏。研究发现激活牙龈组织的长寿蛋白基因1(Sirtuin 1)和抑压当中炎性细胞因子的持续产生是改善上述情况的有效对策。
口腔护理产品在多年内仍只着重于消减细菌的功能上发展或添加化学物质而物理的方式应对如牙齿和牙龈敏感等问题上，做法因循守旧，多年来口腔护理产品在功能上的发展仍原地踏步，纵使普罗大众对口腔护理的意识日益增加，口腔疾病患者人数仍连年递增，对我国的公共健康形成前所未有的挑战。
因此，仍然需要新的(优选在至少一个方面改进的)口腔护理添加剂以及使用该添加剂的口腔护理组合物。
发明内容
为了解决上述问题，本发明提供了一种口腔护理添加剂、其在口腔护理组合物中的应用、口腔护理组合物、口腔护理组合物的制备方 法、使用方法，特别是使用该添加剂添加至现有的口腔护理产品之中以增添该产品的功效(例如治疗、预防或者缓解口腔疾病，比如牙周病或者牙龈发炎等)；本发明同时提出以该添加剂为主要成分的产品的应用和方法。
本发明所提出的口腔护理添加剂是以β-烟酰胺单核苷酸为主要成分，其可以按照组合的方式添加至现有的口腔护理产品中以提升牙龈组织中的β-烟酰胺腺嘌呤二核苷酸的水平并同时发挥该产品的原有功效。本发明还提出以该添加剂主要成分的新型口腔护理产品，包括含有β-烟酰胺单核苷酸的口香糖和口腔胶凝剂，为该添加剂组合提供合适的使用平台，并且为不同口腔健康情况的使用者提供使用上的便利。
具体而言，本发明提供了：
1.一种口腔护理添加剂，包含选自烟酸或其衍生物以及烟酰胺或其衍生物中的至少一种主成分。
2.根据上述任意的口腔护理添加剂，其中所述烟酸或其衍生物以及烟酰胺或其衍生物选自β-烟酸核苷及其盐、β-烟酸单核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸磷酸及其盐、β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸及其盐、还原型β-烟酰胺腺嘌呤二核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐中的至少一者。
3.根据上述任意的口腔护理添加剂，所述口腔护理添加剂还包含选自维生素和辅酶中的至少一者的辅助成分。
4.根据上述任意的口腔护理添加剂，所述维生素选自维生素A类、维生素B类、维生素C类、维生素D类和维生素k类中的至少一者。
5.根据上述任意的口腔护理添加剂，所述辅酶选自谷胱甘肽或其衍生物、三磷酸腺苷及其衍生物、吡咯喹啉醌或其衍生物、腺苷蛋氨酸或其衍生物、辅酶A或其衍生物、辅酶Q类或其衍生物中的 至少一者。
6.根据上述任意的口腔护理添加剂，所述的衍生物为β-烟酸核苷或其盐、β-烟酸单核苷酸或其盐、β-烟酰胺核苷或其盐、β-烟酰胺单核苷酸或其盐、氧化型β-烟酰胺腺嘌呤二核苷酸或其盐、或者还原型β-烟酰胺腺嘌呤二核苷酸或其盐；
所述维生素为维生素B类、维生素C类或维生素K类；以及
所述辅酶为谷胱甘肽或其衍生物或者吡咯喹啉醌或其衍生物。
7.根据上述任意的口腔护理添加剂，其中所述口腔护理添加剂为固态、液态或气态的形式。
8.根据上述任意的口腔护理添加剂，所述固态选自粉状、膏状、凝胶和结晶体中的至少一者，任选地，所述液态选自溶液、浆体、精油和非牛顿流体中的至少一者；并且任选地，所述气态选自液化喷雾。
9.根据上述任意的口腔护理添加剂，所述固态选自凝胶，所述液态选自溶液；并且所述气态选自液化喷雾。
10.根据上述任意的口腔护理添加剂，所述主成分的含量为所述口腔护理添加剂总重量的0.1-100％(重量/重量)，优选为0.1-90％(重量/重量)，更优选为0.1-50％(重量/重量)。
11.根据上述任意的口腔护理添加剂，所述主成分：所述维生素：所述辅酶的重量比为(0.1-99％):(0.1-99％)(0.1-99％)，优选为(0.1-75％):(0.1-12.5％)(0.1-12.5％)，更优选为(0.1-50％):(0.1-25％)(0.1-25％)。
12.一种口腔护理组合物，特征在于包含1-11中任意一项所述的口腔护理添加剂。
13.根据上述任意的口腔护理组合物，所述的口腔护理添加剂的含量为所述口腔护理组合物总重量的0.1-50％(重量/重量)，优选为0.1-25％(重量/重量)，更优选为0.3-15％(重量/重量)。
14.根据上述任意的口腔护理组合物，所述口腔护理组合物为选自牙膏、漱口水、口腔喷剂和洁牙粉的至少一者。
15.根据上述任意的口腔护理组合物，所述口腔护理组合物为口 香糖或口腔凝胶剂。
16.根据上述任意的口腔护理组合物，所述口腔护理组合物为固态、液态或气态的形式。
17.根据上述任意的口腔护理组合物，所述口香糖还包含树脂、腊、磷脂、调味剂和弹性体中的至少一者；
优选地，所述口腔凝胶剂还包含甘油、山梨糖醇、黄蓍树胶、苯甲酸钠和薄荷油。
18.一种口腔护理组合物的制备方法，包括下列步骤：
提供口腔护理添加剂，该口腔护理添加剂包含选自烟酸或其衍生物以及烟酰胺或其衍生物中的至少一种主成分；以及
将所述口腔护理添加剂加入到有助于该口腔护理添加剂被口腔牙龈组织吸收的载体中。
19.根据上述任意所述的方法，所述载体为牙膏、漱口水、口腔喷剂、洁牙粉、口香糖和口腔凝胶剂中的至少一者。
20.根据上述任意所述的方法，所述口腔护理添加剂还包含选自维生素和辅酶中的至少一者的辅助成分。
21.根据上述任意所述的方法，所述烟酸或其衍生物以及烟酰胺或其衍生物选自β-烟酸核苷及其盐、β-烟酸单核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸磷酸及其盐、β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸及其盐、还原型β-烟酰胺腺嘌呤二核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐中的至少一者。
22.一种口腔护理成套用具，包括上述任意一项所述的口腔护理组合物以及牙胶套。
23.上述任意的口腔护理添加剂在制备用于治疗、预防或者缓解口腔疾病的口腔护理组合物中的应用。
本发明有以下的特点和积极效果：
1.本发明提出了一种口腔护理添加剂、其应用和相关方法，添加剂中以一种或多种的烟酸或其衍生物或烟酰胺或其衍生物(优选β-烟酰胺单核苷酸和氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐)为主要成分，用于补充和提升牙龈组织中的β-烟酰胺腺嘌呤二核苷酸的水平；使用该组合物于口腔保健之中是一新的突破，口腔护理产品不再只局限于维持口腔清洁或舒缓牙齿敏感症状的单一功能；
2.本发明所提出的口腔护理添加剂中的所有物质均为天然无害并存在于各生物之中，安全可靠并不会对一般使用者的口腔健康产生不良反应和影响，适合任何年龄人士每天使用；
3.本发明提出将口腔护理添加剂加入现有的口腔护理产品如牙膏和漱口水中，做法简易；添加剂组合不会与口腔护理产品中的成分发生科学反应，因此添加剂组合不会影响或降低该口腔护理产品的原有功能和功效；使用者在使用该口腔护理产品的时候既可以清洁口腔并同时在过程中吸收添加剂组合的成分以补充和提升牙龈中的β-烟酰胺腺嘌呤二核苷酸的水平，以双管齐下的方式进行更全面的口腔护理而毋需额外时间。
4.本发明提出的其中一个新型口腔护理组合物为含有口腔护理添加剂的口香糖；该产品适合一般嘴嚼能力正常的使用者，可以在随时随地透过嘴嚼口香糖以补充和提升牙龈中的β-烟酰胺腺嘌呤二核苷酸的水平。使用者在咀嚼的時候释放口香糖中的添加剂，由于咀嚼口香糖的過程時間一般較長，因此增加了并被牙龈中的毛细血管直接吸收的機會。此做法不但能有效利用口香糖的物理特性上载高量的添加剂于其中，而且利用了使用口香糖的习惯，即不停在口腔中咀嚼时会黏附在牙龈之上，口香糖中的添加剂能以最直接和稳定的方式让牙龈组织中的毛细血管吸收，比其他使用方法更为直接和持久。
5.本发明提出的另一个新型口腔护理组合物为含有口腔护理添加剂的口腔凝胶；该产品适合咀嚼能力不佳和使用假牙人士使用。这类人士多为年老或牙周病的严重患者，更需要补充和提升烟酰胺腺嘌吟二核苷酸的水平以促进牙龈健康、减少牙龈发炎和促进牙龈毛细血管的增生而避免牙龈萎缩，而这方面的功能是现有口腔护理产品所缺乏 的，特别是专为这一类人士而设计；口腔凝胶以水性为主，可加入簿荷等天然镇静成分给使用者以舒缓作用。使用者只需将口腔凝胶注入牙套之中并放入口水腔之中，口腔凝胶直接接触牙龈表层创造最直接的条件让牙龈直接吸收，同时水性凝胶能让使用者在使用前以冷冻至保温的温度下使用，让使用者作出最合乎自身体验效果的选择。
附图简要说明
图1示出实施例6(图中表示为口腔护理添加剂)和实施例7(图中表示为β-烟酰胺单核苷酸)随时间变化的稳定性研究结果；
图2示出不添加口腔护理添加剂以及添加不同剂量的实施例2的口腔护理添加剂的培养基中口腔组织细胞的生长效果。
具体实施方案
以下通过具体实施方式的描述对本发明作进一步说明，但这并非是对本文的限制，本领域技术人员根据本文的基本思想，可以做出各种修改或改进，但是只要不脱离本文的基本思想，均在本文的范围之内。
口腔疾病已经成为我国最值得重视的公共卫生问题，现时患有龋齿和牙周病等的人数已超越整体人口数量的三分之一，而且这情况有逐渐上升的趋势，加上既有的人口老化问题，恐怕在可预见的数年口腔疾病便高据我国慢性疾病之首，将会为中国的保健作出沉重的负担。因此，社会应重视口腔疾病的重要性。《“健康中国2030”规划纲要》和《中国防治慢性病中长期规划(2017—2025年)》中皆提出口腔健康的重要性，落实进一步加强口腔健康的宣传工作并提升大众对口腔健康的行动性和积极性。上述的政策和措施逐步到位，特别是在青少年的口腔健康上已取得阶段性的成效，然而我国的口腔疾病人数仍居高不下，为这日积月累的公共健康问题注入新的思维可望有所收获。
随着近年的科技发展日新月异，科学界对口腔健康和疾病的研究亦更为广泛，特别是在β-烟酰胺腺嘌呤二核苷酸对口腔健康的重要性更为了解和清晰。
β-烟酰胺腺嘌呤二核苷酸是生物中的重要辅酶，除为身体中调控各生物功能外，更同时负责激活长寿蛋白基因和抑压炎性细胞因子的作用，因此使用能提升牙龈组织里β-烟酰胺腺嘌呤二核苷酸水平的物质对口腔护理十分重要。β-烟酰胺单核苷酸是β-烟酰胺腺嘌呤二核苷酸的直接前体，在细胞中经酶转化成β-烟酰胺腺嘌呤二核苷酸；β-烟酰胺单核苷酸具有高稳定性和安全性，而且容易被人体吸收，是成为提升牙龈中β-烟酰胺腺嘌呤二核苷酸水平的理想物质。
此外，直接施用其他烟酸或其衍生物以及烟酰胺或其衍生物也具有上述类似的作用，这些烟酸或其衍生物以及烟酰胺或其衍生物可以包括β-烟酸核苷及其盐、β-烟酸单核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸磷酸及其盐、β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸及其盐、还原型β-烟酰胺腺嘌呤二核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐中的至少一者。
本发明人注意到口腔疾病如牙龈炎和牙周病的患者多集中于成年人至老年人的年龄层，而这些患者多因为年纪渐大而病况日益严重，甚至影响其咀嚼能力而降低其生活质素。本发明人认识到这种衰老的情况和近年间科学研究证实人体中β-烟酰胺腺嘌呤二核苷酸的水平随年岁增长而逐步减少有密切的关联，并发现近年的研究亦指出β-烟酰胺腺嘌呤二核苷酸在牙龈炎症上发挥保护作用并以激活牙龈中的长寿蛋白基因1以抑制牙周病中所产生的活性氧化物对牙龊组织的破坏，因此本发明人认为牙龈中β-烟酰胺腺嘌呤二核苷酸的水平对口腔健康至关重要。本发明人认为这类人士自身的β-烟酰胺腺嘌呤二核苷酸的水平较低，应尽快提升体内水平，同时有必要直接在牙龈中吸收；根据近年的科学研究，吸收烟酰胺或其衍生物可以提升生物中的β-烟酰胺腺嘌呤二核苷酸水平，而当中指出使用β-烟酰胺腺嘌呤二核苷酸的最前体β-烟酰胺单核苷酸在效能和安全上皆为理想。
因此，本发明人研究了应用该物质的可能性。结果证实β-烟酰胺单核苷酸易于被人体吸收并能在身体中快速转化成β-烟酰胺腺嘌呤二核苷酸并提升该物质在体内水平。研究亦指出提升β-烟酰胺腺嘌呤二核苷酸水平对身体的新陈代谢、生理时钟和身体机能皆有明显的改善。其中，研究证实以β-烟酰胺单核苷酸提升β-烟酰胺腺嘌呤二核苷酸，能促进肌肉中的毛细血管增生以改善机能，则可以用于促进牙龈毛细血管的增生防治牙周病中的牙龈萎缩而引发的脱齿症。β-烟酰胺单核苷酸更为天然物质，稳定性高，而且研究亦证明其对人体安全，各国民众已开始服用并获得良好的回馈。因此，发明人认为以β-烟酰胺单核苷酸为添加剂中的主要成分最为合适。β-烟酰胺腺嘌呤二核苷酸为身体重要的辅酶，身体各细胞组织皆依赖其存在以进行各类型的生理反应，依赖口服β-烟酰胺单核苷酸未能实质以此应对口腔问题，需要以更直接的方式让β-烟酰胺单核苷酸进入牙龈并被其中的毛细血管吸收，方能直接提升牙龈的中的β-烟酰胺腺嘌呤二核苷酸水平。如此同时，本发明人认为提升牙龈中β-烟酰胺腺嘌呤二核苷酸水平的应用和方法应以方便使用者为主，配合现有口腔清洁的习惯更会相得益彰。
因此，本发明提出一种口腔护理添加剂、口腔护理组合物、其应用和方法，在传统口腔护理基础上提供崭新的手段，增加现有口腔护理产品的功效并且提供新的应用和方法，使新的科学成果能实际应用于普罗大众身上，以融合口腔清洁和提升牙龈中的β-烟酰胺腺嘌呤二核苷酸水平创造更有利口腔健康的条件以符合大众对个人健康的需求和公共卫生的利益。
本文的口腔护理添加剂及其应用破除了目前口腔健康护理中偏重口腔清洁的固有思维和模式，以提升β-烟酰胺腺嘌呤二核苷酸水平为新思维，融入现有的口腔护理习惯，为大众带来更全面的口腔健康体验，为我国的公共健康打造更稳固的基石。
在一个方面中，本发明提供一种口腔护理添加剂，包含选自烟酸或其衍生物以及烟酰胺或其衍生物中的至少一种主成分。
烟酸或其衍生物以及烟酰胺或其衍生物可以选自β-烟酸核苷及其盐、β-烟酸单核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、 还原型β-烟酸腺嘌呤二核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸磷酸及其盐、β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸及其盐、还原型β-烟酰胺腺嘌呤二核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐中的至少一者。
优选地，口腔护理添加剂以提升和补充口腔中的β-烟酰胺腺嘌呤二核苷酸的水平为主要功能，口腔护理添加剂组合中含有最少一种直接或间接的功能性物质，其中可以为一种或多种的烟酸或其衍生物中和烟酰胺或其衍生物：一种或多种的烟酸或其衍生物可包含烟酸、β-烟酸核苷和其盐、β-烟酸单核苷酸和其盐、氧化型β-烟酸腺嘌呤二核苷酸和其盐、还原型β-烟酸腺嘌呤二核苷酸和其盐、氧化型β-烟酸腺嘌呤二核苷酸和其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸和其盐和氧化型β-烟酸腺嘌呤二核苷酸磷酸和其盐；一种或多种的烟酰胺或其衍生物包含烟酰胺、β-烟酰胺核苷或其盐、β-烟酰胺单核苷酸或其盐、氧化型β-烟酰胺腺嘌呤二核苷酸和其盐、还原型β-烟酰胺腺嘌呤二核苷酸和其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸和其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸和其盐。
所述最少一种直接或间接的功能性物质在整个腔护理添加剂的重量百分比总和应为0.1-100％(w/w)，优选为0.1-90％(w/w)，更优选为0.1-50％(w/w)。
口腔护理添加剂中直接或间接的功能性物质可以优选为β-烟酰胺单核苷酸、β-烟酰胺核苷、氧化型β-烟酰胺腺嘌呤二核苷酸、还原型β-烟酰胺腺嘌呤二核苷酸、β-烟酸单核苷酸和β-烟酸核苷，更优选为β-烟酰胺单核苷酸、β-烟酰胺核苷和氧化型β-烟酰胺腺嘌呤二核苷酸，更以使用β-烟酰胺单核苷酸为最佳。
优选地，口腔护理添加剂还包含选自维生素和辅酶中的至少一者的辅助成分。
维生素可以选自维生素A类、维生素B类、维生素C类、维生 素D类和维生素k类中的至少一者。
辅酶可以选自谷胱甘肽或其衍生物、三磷酸腺苷及其衍生物、吡咯喹啉醌或其衍生物、腺苷蛋氨酸或其衍生物中的至少一者。
在口腔护理添加剂的一个优选实施方案中，烟酸或其衍生物以及烟酰胺或其衍生物为β-烟酸核苷或其盐、β-烟酸单核苷酸或其盐、β-烟酰胺核苷或其盐、β-烟酰胺单核苷酸或其盐、氧化型β-烟酰胺腺嘌呤二核苷酸或其盐、或者还原型β-烟酰胺腺嘌呤二核苷酸或其盐；维生素为维生素B类、维生素C类或维生素K类；以及辅酶为谷胱甘肽或其衍生物或者吡咯喹啉醌或其衍生物、辅酶A或其衍生物、辅酶Q类或其衍生物中的至少一者。
口腔护理添加剂可以为固态、液态和气态。固态可以选自粉状、膏状、凝胶和结晶体。液态可选自溶液、浆体、精油和非牛顿流体；气态可选自液化喷雾。
根据本文的口腔护理添加剂的一个实施方案，至少一种主成分的含量可以为所述口腔护理添加剂总重量的0.1-100％(重量/重量)，优选为0.1-90％(重量/重量)，更优选为0.1-50％(重量/重量)。
优选地，主成分：所述维生素：所述辅酶的重量比为(0.1-99％):(0.1-99％)(0.1-99％)，优选为(0.1-75％):(0.1-12.5％)(0.1-12.5％)，更优选为(0.1-50％):(0.1-25％)：(0.1-25％)。
本文的口腔护理剂具有高稳定性的优势，既不会与现有口腔护理产品中的化合物发生化学作用，也不影响或降低该产品的既有效能
本文的第二方面提供一种口腔护理组合物，包含上述的口腔护理添加剂。换言之，本文的口腔护理组合物可以包含选自烟酸或其衍生物以及烟酰胺或其衍生物中的至少一种。
在一个实施方案中，口腔护理添加剂的含量可以为口腔护理组合物总重量的0.1-50％(重量/重量)，优选为0.1-25％(重量/重量)，更优选为0.3-15％(重量/重量)。
在一个实施方案中，口腔护理组合物可以为选自牙膏、漱口水、口腔喷剂和洁牙粉的至少一者。这些均是现有的口腔护理产品。
口腔护理组合物还可以为新型口腔护理产品，例如口香糖或口腔 凝胶剂。
腔护理组合物也可以为固态、液态和气态的形式。固态可以选自粉状、膏状、凝胶和结晶体。液态可选自溶液、浆体、精油和非牛顿流体。气态可选自液化喷雾。
作为新型的口腔护理产品，口香糖还可以包含树脂、腊、磷脂、调味剂和弹性体中的至少一者。在一个实施方案中，新型口腔护理产品中含有口腔护理添加剂的口香糖为口腔护理添加剂的载体；该载体有着载样量大和易于携带的优点，并使用该载体可以稳固依附在使用者牙龈表面上直接让牙龈和其毛细血管吸收口香糖中释放的口腔护理添加剂组合物质的有利条件，使用者亦在咀嚼时释出物质并以唾液为介体被牙龈和其毛细血管吸收。
作为新型的口腔护理产品，口腔凝胶剂还可以包含甘油、山梨糖醇、黄蓍树胶、苯甲酸钠和薄荷油。在一个实施方案中，新型口腔护理产品中含有口腔护理添加剂的口腔凝胶剂为口腔护理添加剂的载体，配合牙套使用；该载体配合牙套可以依附在牙龈表面让牙龈吸收口腔护理添加剂组合物质，適合咀嚼能力欠佳、配带假牙和脱齿症患者使用。
所述的含有口腔护理添加剂的口香糖和口腔凝胶可以加入不同的味道和颜色而符合使用者所需；其中所述的口腔凝胶可以于摄氏10-40度下使用。
在一个实施例中，本发明为便利一般使用者而制备了一种含有口腔护理添加剂组合的口香糖。口香糖主要以树脂、腊和弹性体为主要成分，本发明所应用的材料则以植物成分为基础，主要成分包括人心果树液、阿拉伯胶和卵磷脂等，有着与普通口香糖的特性和功能并可以自然分解。使用为口腔护理添加剂组合的食用载体有着多项的优势：口香糖成分均为隋性物料，制作时不会与口腔护理添加剂组合中的物质发生化学反应；0.1-20％(w/w)的口腔护理添加剂组合可以以固态或液态的方式加入口香糖中，口腔护理添加剂组合的成分不会改变，稳定性在三个月的正常存放条件下功能成分的含量维持95％或以上；口香糖可以加入多种天然调味剂以制作使用者 合适的口感和味道。
在另一个实施例中，本该发明进一步以使用者咀嚼口香糖的习惯制造有利的条件将添加剂中的主要成分β-烟酰胺单核苷酸被牙龈和其毛细血管吸收。1.使用者在每次咀嚼口香糖时会释放口气糖中载入的口腔护理添加剂组合物质于牙龈中；2.咀嚼口香糖同时会刺激唾液分泌，口香糖当中的物质亦会经唾液被身体吸收；3.咀嚼口香糖时牙龈和口香糖会有频密的接触，使用者会自然的将口气糖依附在牙龈和牙齿的部位，这时候制造了长时间接触牙龈组织的有利条件让口腔护理组合物直接被牙龈吸收并输送至毛细血管中。一种含有口腔护理添加剂组合的口香糖同时方便使用者携带和使用，使用者能随时随地使用以补充牙龈中的β-烟酰胺腺嘌呤二核苷酸的水平。
在另一个实施例中，发明人制备另一种含有口腔护理添加剂组合的新型口腔护理产品。该产品为口腔凝胶，为一类咀嚼能力低下人士、使用假牙者和已脱落部分牙齿的口腔疾病人士所使用；按次序在容器中以成品的总重量计算加入10％(w/w)的口腔护理添加剂组合(β-烟酰胺单核苷酸:S-乙酰谷胱甘肽:维生素C为6:2:2)，15％(w/w)的甘油、15％(w/w)的山梨糖醇、2％(w/w)的黄蓍树胶、2.5％(w/w)的苯甲酸钠、0.1％(w/w)的薄荷油，加入纯水定容并以250rpm搅拌12小时至液态膏状。使用者在使用前将口腔凝胶均匀地注入两个牙胶套中，然后将牙胶套分别放入上颚和下颚并合紧双唇，避免牙胶套跌出，使用者在10min后拿出牙胶套并用清水漱口便告完成。口腔凝胶中的口腔护理添加剂组合中的成分会被牙龈和毛细血管吸以达致使用目标。口腔凝胶成分皆为隋性物料，不会与口腔护理添加剂组合中的功能成分发生化学反应，同时间可以稳定口腔护理添加剂组合，其稳定性在一般存放条件下口腔凝胶的口腔护理添加剂组合的含量仍保持95％或以上。口腔凝胶可以用前降温至不低于摄氏10度以下或保温至不高于摄氏37度，其物理性、功能性和稳定性不会因温度的变化而有所影响。
根据本发明，口腔护理添加剂有高稳定性的优势，既不会与现有口腔护理产品中的化合物发生化学作用，也不影响或降低该产品的 既有效能。
本文的第三方面提供了一种口腔护理组合物的制备方法，包括下列步骤：
提供口腔护理添加剂，该口腔护理添加剂包含选自烟酸或其衍生物以及烟酰胺或其衍生物中的至少一种主成分；以及
将所述口腔护理添加剂加入到有助于该口腔护理添加剂被口腔牙龈组织吸收的载体中。
在一个实施方案中，载体为牙膏、漱口水、口腔喷剂、洁牙粉、口香糖和口腔凝胶剂中的至少一者。
如上所述，口腔护理添加剂还可以包含选自维生素和辅酶中的至少一者的辅助成分。所述烟酸或其衍生物以及烟酰胺或其衍生物可以选自β-烟酸核苷及其盐、β-烟酸单核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸磷酸及其盐、β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸及其盐、还原型β-烟酰胺腺嘌呤二核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐中的至少一者。
本文的第四方面提供了一种口腔护理成套用具，包括口腔护理组合物以及牙胶套。口腔护理组合物可以包含选自烟酸或其衍生物以及烟酰胺或其衍生物中的至少一种
根据一个实施方案中，本文提出一种口腔护理添加剂组合，其中所述的口腔护理添加剂组合可以为一种或多种的烟酸及其衍生物、烟酰胺及其衍生物、维生素和辅酶为主要成分所组合而成。烟酸或其衍生物包括烟酸、β-烟酸核苷及其盐、β-烟酸单核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸及其盐和氧化型β-烟酸腺嘌呤二核苷酸磷酸及其盐；烟酰胺衍生物包括烟酰胺、β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧 化型β-烟酰胺腺嘌呤二核苷酸及其盐、还原型β-烟酰胺腺嘌呤二核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐；维生素包括维生素A类、维生素B类、维生素C类、维生素D类和维生素k类；辅酶包括谷胱甘肽及其衍生物、三磷酸腺苷及其衍生物、吡咯喹啉醌及其衍生物、腺苷蛋氨酸及其衍生物、辅酶A或其衍生物、辅酶Q类或其衍生物中的至少一者；优选地，组合中的烟酸或其衍生物可以为β-烟酸核苷及其盐和β-烟酸单核苷酸及其盐；优选地，组合中的烟酰胺或其衍生物可以为β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸及其盐和还原型β-烟酰胺腺嘌呤二核苷酸及其盐；优选地，组合中的维生素可以为维生素B类,维生素C类和维生素K类；优选地，组合中的辅酶可以为谷胱甘肽及其衍生物和吡咯喹啉醌及其衍生物；该组合中的最主要目的为补充和提升牙龈中的β-烟酰胺腺嘌呤二核苷酸水平，因此发明人提出该组合中以β-烟酰胺单核苷酸为主要成分，并以组合中所包括的其他物质为辅助成分。
本发明人提出可以将组合中的物质直接加入现有的口腔护理产品中，加入的组合份量可以为0.1-10％(w/v)。根据本文的一个实施例，口腔护理组合物选取β-烟酰胺单核苷酸、谷胱甘肽衍生物S-乙酰谷胱甘肽和维生素C加入牙膏之中。按组合物的总重量以重量比例β-烟酰胺单核苷酸:S-乙酰谷胱甘:维生素C的6:2:2以粉状混分于容器中，再以牙膏总重量的1％加入并以匙子混合搅拌至没有明显固体。在另一个实施例中，同样的组合和比例加入漱口水中并溶解。加入添加剂组合的牙膏和漱口水与原始物品进行颜色、气味和稳定性和抗菌性的对照实验，以证明添加剂组合不会对口腔护理产品的物理性和功能性有所影响。
所述组合中直接或间接的功能性物质可以优选为β-烟酰胺单核苷酸、β-烟酰胺核苷、氧化型β-烟酰胺腺嘌呤二核苷酸、还原型β-烟酰胺腺嘌呤二核苷酸、β-烟酸单核苷酸和β-烟酸核苷，更优选为β-烟酰胺单核苷酸、β-烟酰胺核苷和氧化型β-烟酰胺腺嘌呤二核苷酸，更以使用β-烟酰胺单核苷酸和氧化型β-烟酰胺腺嘌呤二核苷酸为最佳。
本发明还提供了上述任意的口腔护理添加剂在制备用于治疗、预防或者缓解口腔疾病的口腔护理组合物中的应用。
以下通过实例的方式进一步解释或说明本发明内容，但这些实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。除非特别说明，否则所述百分比为重量百分比。
下列例子中所用材料和设备的描述如下：
β-烟酰胺单核苷酸：来自基因港(香港)生物科技有限公司；
氧化型β-烟酰胺腺嘌呤二核苷酸：来自基因港(香港)生物科技有限公司；
S-乙酰谷胱甘肽:来自基因港(香港)生物科技有限公司；
抗坏血酸钠(即维生素C):购自上海阿拉丁生化科技有限公司；
黑人牙膏:购自Market Place by Jasons；
高露洁三重功效牙膏:购自Market Place by Jasons；
李施德林全护配方漱口水：购自Market Place by Jasons；
粉末胶基:购自Glee gum；
山梨醇:购自上海阿拉丁生化科技有限公司；
薄荷萃取物:购自广州佰宇生物科技有限公司；
亮蓝:购自山东谷康生物工程有限公司；
磷酸钠(磷酸二氢钠一水物和磷酸氢二钠):购自上海阿拉丁生化科技有限公司。
实施例1:制备含有β-烟酰胺单核苷酸的固态口腔护理添加剂
制备100g固态口腔护理添加剂：在一个已灭菌的500ml烧杯中，按次序加入β-烟酰胺单核苷酸、S-乙酰谷胱甘肽和抗血酸钠，该三种物质在口腔护理添加剂组合的重量比例为β-烟酰胺单核苷酸：谷胱甘肽：抗血酸钠＝6:2:2，即在100克固态口腔护理添加剂中，β-烟酰胺单核苷酸的重量为60g、S-乙酰谷胱甘肽的重量为20g和抗血酸钠的重量为20g。三种物质皆为粉状，加入烧杯后以药匙搅拌不少于二十次至各物质完全混合；取10mg混合样并溶解于1ml的纯水中以附件 一的高效液相色谱发分析其中功能成分的含量。
实施例2：制备含有β-烟酰胺单核苷酸和氧化型β-烟酰胺腺嘌呤二核苷酸的固态口腔护理添加剂
制备100g固态口腔护理添加剂组合物：在一个已灭菌的500ml烧杯中，按次序加入β-烟酰胺单核苷酸、氧化型β-烟酰胺腺嘌呤二核苷酸、S-乙酰谷胱甘肽和抗血酸钠，该四种物质在口腔护理添加剂组合的重量比例为β-烟酰胺单核苷酸：氧化型β-烟酰胺腺嘌呤二核苷酸：谷胱甘肽：抗血酸钠＝3:3:2:2，即在100克固态口腔护理添加剂組合中，β-烟酰胺单核苷酸的重量为30g、氧化型β-烟酰胺腺嘌呤二核苷酸的重量为30gS-乙酰谷胱甘肽的重量为20g和抗血酸钠的重量为20g。三种物质皆为粉状，加入烧杯后以药匙搅拌不少于二十次至各物质完全混合；取10mg混合样并溶解于1ml的纯水中以附件一的高效液相色谱发分析其中功能成分的含量。
实施例3:制备含有β-烟酰胺腺嘌呤二核苷酸和氧化型β-烟酰胺腺嘌呤二核苷酸的固态口腔护理添加剂
制备100g固态口腔护理添加剂。在一个已灭菌的500ml烧杯中，按次序加入烟酰胺腺嘌吟二核苷酸、氧化型β-烟酰胺腺嘌呤二核苷酸、谷胱甘肽和抗血酸钠，该四种物质在口腔护理添加剂组合的重量比例为β-烟酰胺单核苷酸：氧化型β-烟酰胺腺嘌呤二核苷酸：S-乙酰谷胱甘肽：抗血酸钠＝4:4:1:1，即在100克固态口腔护理添加剂中，β-烟酰胺单核苷酸的重量为40g、氧化型β-烟酰胺腺嘌呤二核苷酸的重量为40g、谷胱甘肽的重量为10g和抗血酸钠的重量为10g。四种物质皆为粉状，加入烧杯后以药匙搅拌不少于二十次至各物质完全混合；取10mg混合样并溶解于1ml的纯水中以附件1的高效液相色谱法分析其中功能成分的含量。
实施例4:制备含有β-烟酰胺单核苷酸的液态口腔护理添加剂
制备100ml液态口腔护理添加剂。在一个已灭菌的500ml烧杯中，按次序加入β-烟酰胺单核苷酸、谷胱甘肽和抗血酸钠，该三种物质在口腔护理添加剂组合的重量比例为β-烟酰胺单核苷酸：谷胱甘肽：抗血酸钠＝6:2:2，即β-烟酰胺单核苷酸的重量为600mg、S-乙酰谷胱甘 肽的重量为200mg和抗血酸钠的重量为200mg。三种物质皆为粉状，加入烧杯后以酸度调节剂溶液溶解，该酸度调节剂为食用级磷酸钠；1g的口腔护理添加剂组合加入99ml的0.1M磷酸钠酸度调节剂溶液(pH 6.5)溶解得1％(w/v)的液态口腔护理添加剂组合；取1mL的液态口腔护理添加剂组合中以附件一的高效液相色谱分析其中功能成分的含量。
实施例5:制备含有β-烟酰胺腺嘌呤二核苷酸的液态口腔护理添加剂
制备100ml液态口腔护理添加剂。在一个已灭菌的500ml烧杯中，按次序加入β-烟酰胺腺嘌呤二核苷酸、谷胱甘肽和抗血酸钠，该三种物质在口腔护理添加剂组合的重量比例为β-烟酰胺单核苷酸：谷胱甘肽：抗血酸钠＝4:4:2，即β-烟酰胺单核苷酸的重量为400mg、谷胱甘肽的重量为400mg和抗血酸钠的重量为200mg。三种物质皆为粉状，加入烧杯后以酸度调节剂溶液溶解，该酸度调节剂为食用级磷酸钠；1g的口腔护理添加剂组合加入99ml的0.1M磷酸钠酸度调节剂溶液(pH 6.5)溶解得1％(w/v)的液态口腔护理添加剂组合；取1mL的液态口腔护理添加剂组合中以附件一的高效液相色谱方法分析其中功能成分的含量。
实施例6:制备含有口腔护理添加剂的牙膏
制备100g含有口腔护理添加剂的牙膏，按实施例1的方法制备固态口腔护理添加剂并且取1g并加入已灭菌的塑料袋之中，然后加入99g的黑人牙膏，再于塑料袋中反复混合口腔护理添加剂组合和牙膏至完全混和即告完成；取1g含有口腔护理添加剂组合的黑人牙膏完全混合于纯水中并以13,000rpm离心5min后取上清液使用高效液相色谱法分析其含量；含有口腔护理添加剂的牙膏和不含有口腔护理添加剂的牙膏在物理上的气味和味道作双盲测试：研究员首先将上述两种牙膏分别标示为样1和样2，然后提供给10位测试者使用并对两样的颜色、气味和味道作比较，询问测试者样品1和样品2在上述三种感观上有否差异。结果显示10位测试者中9位测试者均认为两样在颜色、气味和味道均没有差异。
含有口腔护理添加剂的牙膏和不含有口腔护理添加剂的牙膏亦进行了抗菌功效研究：两种牙膏按附件2的方法以大肠杆菌进行测试；在三组的对照实验中，含有口腔护理添加剂的牙膏的平均抑菌圈直径为20.2+1.1，不含有口腔护理添加剂的牙膏平均抑菌圈直径为20.3+1.3；实验结果显示含有口腔护理添加剂的牙膏和不含有口腔护理添加剂的牙膏的抑菌圈直径在三种浓度的测试下皆非常接近，证明两者在抗菌功效上相同，口腔护理添加剂组合没有影响牙膏原来的效能。
研究人员对含有口腔护理添加剂的牙膏进行稳定性测试，在为期六个月的实验期中，以正常包装含有口腔护理添加剂组合的牙膏存放于摄氏25度和湿度维持在60％的环境下，以附件1的高效液相色谱方恐怕這個法对口腔护理添加剂组合的主要成分β-烟酰胺单核苷酸进行含量分析研究其含量在牙膏中的变化；实验结果请参见图1，证明口腔护理添加剂的主要成分β-烟酰胺单核苷酸在牙膏有优越的稳定性。
实施例7：制备含有口腔护理添加剂的牙膏
制备100g含有β-烟酰胺单核苷酸作为口腔护理添加剂的牙膏并且取1g并加入已灭菌的塑料袋之中，然后加入99g的黑人牙膏，再于塑料袋中反复混合口腔护理添加剂组合和牙膏至完全混和即告完成；取1g含有口腔护理添加剂组合的黑人牙膏完全混合于纯水中并以13,000rpm离心5min后取上清液使用高效液相色谱法分析其含量；含有口腔护理添加剂的牙膏和不含有口腔护理添加剂的牙膏在物理上的气味和味道作双盲测试：研究员首先将上述两种牙膏分别标示为样1和样2，然后提供给10位测试者使用并对两样的颜色、气味和味道作比较，询问测试者样品1和样品2在上述三种感观上有否差异。结果显示10位测试者中9位测试者均认为两样在颜色、气味和味道均没有差异。
研究人员对含有口腔护理添加剂的牙膏进行稳定性测试，在为期六个月的实验期中，以正常包装含有口腔护理添加剂组合的牙膏存放于摄氏25度和湿度维持在60％的环境下，以附件1的高效液相色谱方恐怕這個法对口腔护理添加剂组合的主要成分β-烟酰胺单核苷酸进行 含量分析研究其含量在牙膏中的变化；结果请参见图1。
实施例8:制备含有口腔护理添加剂的漱口水
制备100ml含有口腔护理添加剂的漱口水，按实施例1的方法制备固态口腔护理添加剂并且取1g并加入已消毒的烧杯之中，然后加入99g(即约99ml容量)的李施德林全护配方漱口水，再于烧杯中以250rpm磁搅拌30min至完全溶解即告完成；取1ml含有口腔护理添加剂的李施德林全护配方漱口水使用附件1的高效液相色谱法分析其含量。
含有口腔护理添加剂的漱口水和不含有口腔护理添加剂的漱口水在物理上的颜色、气味和味道作双盲测试：研究员首先将上述两种漱口水分别标示为样品3和样品4，然后提供给10位测试者使用并对两样本的颜色、气味和味道作比较，询问测试者样品1和样品2在上述三种感观上有否差异。结果显示10位测试者中8位测试者均认为两样本在颜色、气味和味道均没有差异。
含有口腔护理添加剂的漱口水和不含有口腔护理添加剂的漱口水还进行了抗菌功效研究：两种漱口水按附件3的方法进行，以大肠杆菌进行测试；在三组的对照实验中，含有口腔护理添加剂的漱口水的平均抑菌圈直径为24.4mm，不含有口腔护理添加剂的漱口水的平均抑菌圈直径为24.1mm；实验结果显示含有口腔护理添加剂的漱口水和不含有口腔护理添加剂的漱口水的抑菌圈直径在三种浓度的测试下皆非常接近，证明两者在抗菌功效上相同，口腔护理添加剂组合没有影响漱口水原来的效能。
研究人员对含有口腔护理添加剂组合的漱口水进行稳定性测试，在为期六个月的实验期中，以原有包装含有口腔护理添加剂的漱口水存放于摄氏25度和湿度维持在60％的环境下，以附件1的高效液相色谱方法对口腔护理添加剂的主要成分β-烟酰胺单核苷酸进行含量分析以研究其含量在漱口水中的变化；实验结果显示六个月后牙膏中的β-烟酰胺单核苷酸含量是初次实验样本含量的94.5％，证明口腔护理添加剂主要成分β-烟酰胺单核苷酸在漱口水中有优越的稳定性。
实施例9:制备含有口腔护理添加剂的薄荷味口香糖
制备200g含有口腔护理添加剂的薄荷味口香糖，按实施例1的方法制备固态口腔护理添加剂并取2g混入16.5g的山梨糖醇和16.5g的木糖醇以药匙完全混合后备用。烧杯中加入100g粉末胶基、70g山梨糖醇香和15g的大豆卵磷脂，以微波炉的中度热力加热5分钟。完成后不停搅拌降温至摄氏40度或以下便可取出。预先拌好的口腔护理添加剂、山梨糖醇和木糖醇粉末堆放于平面上，将已融化的粉末胶基置于粉末堆的中央，以揉捏的方式将粉末平均的黏附在胶体之上，当完成后同时加入0.85g的薄荷萃取精华液和3-5滴的亮蓝并继续揉捏至胶体平均呈现浅蓝色。胶体平均分散于6cm(长)x6cm(阔)x 1cm(高)的盘中并以刀切成20mm(长)x20mm(阔)x 1cm(高)的正方体，在室温中风干12小时后即完成整个制备工序；每粒含有口腔护理添加剂的薄荷味口香糖重量约4g，内含有口腔护理添加剂40mg。
实施例10:制备含有口腔护理添加剂的口腔凝胶
制备100g含有口腔护理添加剂的口腔凝胶，按实施例1的方法制备固态口腔护理添加剂并取10g备用；烧杯中按次序加入15g黄蓍树胶、15g甘油和15g山梨糖醇，加热至摄氏70度并持续搅拌至流质便可终止取出。在持续搅拌下于室温放置并降温至摄氏40度，按次序加入10g口腔护理添加剂组合、2.5g苯甲酸钠和100mg的簿菏萃取物，在室温持续搅拌12hr后完成整个制备过程。
实施例11-制备含有口腔护理添加剂的牙膏
制备100g含有口腔护理添加剂的牙膏。将1g按照实施例2所制备的口腔护理添加剂加入99g的黑人牙膏，再于塑料袋中反复混合口腔护理添加剂和牙膏至完全混和即告完成；取1g含有口腔护理添加剂的黑人牙膏完全混合于纯水中并以13,000rpm离心5min后取上清液使用高效液相色谱法分析其含量；含有口腔护理添加剂的牙膏和不含有口腔护理添加剂的牙膏在物理上的气味和味道作双盲测试：研究员首先将上述两种牙膏分别标示为样1和样2，然后提供给10位测试者使用并对两样的颜色、气味和味道作比较，询问测试者样品1和样品2在上述三种感观上有否差异。结果显示10位测试者中9位测试者均认为两样在颜色气味和味道均没有差异。
含有口腔护理添加剂的牙膏和不含有口腔护理添加剂的牙膏亦进行了抗菌功效研究：两种牙膏按附件2的方法以大肠杆菌进行测试；在三组的对照实验中，含有口腔护理添加剂的牙膏的平均抑菌圈直径为20.2+1.1，不含有口腔护理添加剂的牙膏平均抑菌圈直径为20.3+1.3；实验结果显示含有口腔护理添加剂的牙膏和不含有口腔护理添加剂的牙膏的抑菌圈直径在三种浓度的测试下皆非常接近，证明两者在抗菌功效上相同，口腔护理添加剂组合没有影响牙膏原来的效能。
研究人员对含有口腔护理添加剂的牙膏进行稳定性测试，在为期六个月的实验期中，以正常包装含有口腔护理添加剂组合的牙膏存放于摄氏25度和湿度维持在60％的环境下，以附件1的高效液相色谱方法对口腔护理添加剂组合的主要成分β-烟酰胺单核苷酸和氧化型β-烟酰胺腺嘌呤二核苷酸进行總含量分析研究其含量在牙膏中的变化；实验结果显示六个月后牙膏中的β-烟酰胺单核苷酸和还原型β-烟酰胺腺嘌呤二核苷酸的总含量是初次实验样本含量的96.3％，证明口腔护理添加剂组合主要成分β-烟酰胺单核苷酸和氧化型β-烟酰胺腺嘌呤二核苷酸在牙膏有优越的稳定性。
测试例
为进一步测试口腔护理添加剂组合在口腔组织的功效进行了细胞培养的对照测试，实验上选用了HGF-1细胞(人类牙龈成纤维细胞；Human gingival fibroblast)为实验细胞模组，通过对照实验的方式对比该细胞在含有不同浓度(12-50ug/mL)的口腔护理添加剂和空白样的培养基中在48小时的细胞增长变化。
按实施例2的方法制备100g口腔护理添加剂，分别加入12mg、24mg和50mg的口腔护理添加物溶解于各1000mL的HGF-1培养基(ATCC-formulated Dulbecco's Modified Eagle's Medium+10％胎牛血清)中，组成三组口腔护理添加剂浓度不同的HGF-1培养基，空白样则为不添加口腔护理添加剂的HGF-1培养基。实验使用12孔细胞培养板，在每一孔中加入2.5x 10 4的HGF-1并放置于细胞培养箱(恒温摄氏37度,5％二氧化碳)三小时，抽走孔内的细胞培养基，直列三孔 中加入含12ug/ml口腔护理添加剂的HGF-1培养基，另一直列三孔中加入含24ug/ml口腔护理添加剂的HGF-1培养基，在另一直列三孔中加入含24ug/ml口腔护理添加剂的HGF-1培养基，最后在直列三孔中加入不含口腔护理添加剂的HGF-1培养基并放置于细胞培养箱中，24小时更换样孔内培养基，培养48小时后使用细胞计数仪计算该种培养基中的平均细胞数量。对照试验中使用含12ug/ml口腔护理添加剂的HGF-1培养基的平均细胞数量较空白样高7.8％，使用含24ug/ml口腔护理添加剂的HGF-1培养基和含50ug/ml口腔护理添加剂的HGF-1培养基的平均细胞量较空白样分別高8.4％和8.8％。具体结果请参见图2。该结果表明，口腔护理添加剂能够促进口腔组织的生长，从而可在一定程度上减轻、预防或者治疗口腔疾病，如牙龈炎症等。
本发明不受上述具体文字描述的限制，本发明可在权利要求书所概括的范围内做各种修改或改变。这些改变均在本发明要求保护的范围之内。
附件一
以高效液相分析烟酸或其衍生物的核苷和单核苷酸含量(例如β-β-烟酰胺单核苷酸、β-烟酰胺腺嘌呤二核苷酸、β-烟酰胺核苷、β-烟酸单核苷酸、烟酸腺嘌呤二核苷酸、β-烟酸核苷等)的条件
操作方法如下:
固态口腔护理添加剂:
使用纯水进行适当的稀释使用高效液相色谱进行分析
液态口腔护理添加剂:
使用纯水进行适当的稀释使用高效液相色谱进行分析
牙膏:
取10mg牙膏于小管中，加入1mL纯水，混合1min
以10,000rpm离心5min，抽取水相
取0.5mL水相，使用0.22um针筒过滤器进行过滤
使用纯水进行适当的稀适使用高效液相色谱进行分析
漱口水
使用纯水进行适当的稀适使用高效液相色谱进行分析
高效液相色谱分析条件
Figure PCTCN2022074521-appb-000001
Figure PCTCN2022074521-appb-000002
Figure PCTCN2022074521-appb-000003
附件二：含有口腔护理添加剂组合的牙膏抑菌测试
以LB培养基接种大肠杆菌，在摄氏37度和220rpm的条件下培养24小时后，取0.8mL含大肠杆菌培养基接种于
LB琼脂平板上并风干1小时；平板的中心位置使用已灭菌的不锈杆圆柱棒制做一个直径5mm、深至平板底部的中空圆洞；取1g含有口腔护理添加剂组合的牙膏并加入1mL的已灭菌纯水彻底混合后，取0.15mL的混合液滴加至圆洞中；该平板在摄氏37度的恒温培养箱中放置24hr,取出并使用直尺量度该平板上的抑菌圈直径长度。
附件三：含有口腔护理添加剂组合的漱口水抑菌测试
以LB培养基接种大肠杆菌，在摄氏37度和220rpm的条件下培养24小时后，取0.8mL含大肠杆菌培养基接种于
LB琼脂平板上并风干1小时；平板的中心位置使用已灭菌的不锈杆圆柱棒制做一个直径5mm、深至平板底部的中空圆洞；取1g含有口腔护理添加剂组合的漱口水并加入1mL的已灭菌纯水彻底混合后，取0.15mL的混合液滴加至圆洞中；该平板在摄氏37度的恒温培养箱中放置24hr,取出并使用直尺量度该平板上的抑菌圈直径长度。

Claims (22)

  1. 一种口腔护理添加剂，其特征在于包含选自烟酸或其衍生物以及烟酰胺或其衍生物中的至少一种主成分。
  2. 根据权利要求1所述的口腔护理添加剂，其特征在于所述烟酸或其衍生物以及烟酰胺或其衍生物选自β-烟酸核苷及其盐、β-烟酸单核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸磷酸及其盐、β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸及其盐、还原型β-烟酰胺腺嘌呤二核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐中的至少一者。
  3. 根据权利要求1或2所述的口腔护理添加剂，其特征在于所述口腔护理添加剂还包含选自维生素和辅酶中的至少一者的辅助成分。
  4. 根据权利要求3所述的口腔护理添加剂，其特征在于所述维生素选自维生素A类、维生素B类、维生素C类、维生素D类和维生素K类中的至少一者。
  5. 根据权利要求3或4所述的口腔护理添加剂，其特征在于所述辅酶选自谷胱甘肽或其衍生物、三磷酸腺苷及其衍生物、吡咯喹啉醌或其衍生物、腺苷蛋氨酸或其衍生物、辅酶A或其衍生物、辅酶Q类或其衍生物中的至少一者。
  6. 根据权利要求2所述的口腔护理添加剂，其特征在于所述的衍生物为β-烟酸核苷或其盐、β-烟酸单核苷酸或其盐、β-烟酰胺核苷 或其盐、β-烟酰胺单核苷酸或其盐、氧化型β-烟酰胺腺嘌呤二核苷酸或其盐、或者还原型β-烟酰胺腺嘌呤二核苷酸或其盐；
    所述维生素为维生素B类、维生素C类或维生素K类；以及
    所述辅酶为谷胱甘肽或其衍生物或者吡咯喹啉醌或其衍生物。
  7. 根据权利要求1-6中任意一项所述的口腔护理添加剂，其中所述口腔护理添加剂为固态、液态或气态的形式。
  8. 根据权利要求7所述的口腔护理添加剂，其特征在于所述固态选自粉状、膏状、凝胶和结晶体中的至少一者，任选地，所述液态选自溶液、浆体、精油和非牛顿流体中的至少一者；并且任选地，所述气态选自液化喷雾。
  9. 根据权利要求1到7中任意一项所述的口腔护理添加剂，其特征在于所述主成分的含量为所述口腔护理添加剂总重量的0.1-100％(重量/重量)，优选为0.1-90％(重量/重量)，更优选为0.1-50％(重量/重量)。
  10. 根据权利要求3所述的口腔护理添加剂，其特征在于所述主成分：所述维生素：所述辅酶的重量比为(0.1-99％):(0.1-99％)(0.1-99％)，优选为(0.1-75％):(0.1-12.5％)(0.1-12.5％)，更优选为(0.1-50％):(0.1-25％)(0.1-25％)。
  11. 一种口腔护理组合物，特征在于包含权利要求1-10中任意一项所述的口腔护理添加剂。
  12. 根据权利要求11所述的口腔护理组合物，其特征在于所述的口腔护理添加剂的含量为所述口腔护理组合物总重量的0.1-50％(重量/重量)，优选为0.1-25％(重量/重量)，更优选为0.3-15％(重量/重量)。
  13. 根据权利要求11或12所述的口腔护理组合物，其特征在于所述口腔护理组合物为选自牙膏、漱口水、口腔喷剂和洁牙粉的至少一者。
  14. 根据权利要求11或12所述的口腔护理组合物，其特征在于，所述口腔护理组合物为口香糖或口腔凝胶剂。
  15. 根据权利要求11或12所述的口腔护理组合物，其特征在于，所述口腔护理组合物为固态、液态或气态的形式。
  16. 根据权利要求14所述的口腔护理组合物，其特征在于，所述口香糖还包含树脂、腊、磷脂、调味剂和弹性体中的至少一者；
    优选地，所述口腔凝胶剂还包含甘油、山梨糖醇、黄蓍树胶、苯甲酸钠和薄荷油。
  17. 一种口腔护理组合物的制备方法，其特征在于包括下列步骤：
    提供口腔护理添加剂，该口腔护理添加剂包含选自烟酸或其衍生物以及烟酰胺或其衍生物中的至少一种主成分；以及
    将所述口腔护理添加剂加入到有助于该口腔护理添加剂被口腔牙龈组织吸收的载体中。
  18. 根据权利要求17所述的方法，其特征在于所述载体为牙膏、漱口水、口腔喷剂、洁牙粉、口香糖和口腔凝胶剂中的至少一者。
  19. 根据权利要求17或18所述的方法，其特征在于所述口腔护理添加剂还包含选自维生素和辅酶中的至少一者的辅助成分。
  20. 根据权利要求17或18所述的方法，其特征在于所述烟酸或 其衍生物以及烟酰胺或其衍生物选自β-烟酸核苷及其盐、β-烟酸单核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸及其盐、还原型β-烟酸腺嘌呤二核苷酸磷酸及其盐、氧化型β-烟酸腺嘌呤二核苷酸磷酸及其盐、β-烟酰胺核苷及其盐、β-烟酰胺单核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸及其盐、还原型β-烟酰胺腺嘌呤二核苷酸及其盐、氧化型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐或还原型β-烟酰胺腺嘌呤二核苷酸磷酸及其盐中的至少一者。
  21. 一种口腔护理成套用具，其特征在于包括权利要求11-16中任意一项所述的口腔护理组合物以及牙胶套。
  22. 权利要求1-10所述的口腔护理添加剂在制备用于治疗、预防或者缓解口腔疾病的口腔护理组合物中的应用。
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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1302196A1 (de) * 2001-10-16 2003-04-16 Habinger, René, Ing. Mag. Intelligenzfördernde Zahncreme
EP2052712A1 (en) * 2007-10-26 2009-04-29 3M Innovative Properties Company Dental composition
JP2016175901A (ja) * 2015-03-18 2016-10-06 第一三共ヘルスケア株式会社 Ｌ−アスパラギン酸またはその塩、及びニコチンアミドを含有する口腔ケア用組成物
CN106265423A (zh) * 2016-08-23 2017-01-04 广州立白企业集团有限公司 具有清火消痛作用的口腔护理组合物
WO2018091300A1 (en) * 2016-11-18 2018-05-24 Unilever N.V. Oral care composition for oral biofilm removal
CN109350622A (zh) * 2018-10-17 2019-02-19 深圳市龙格生技术有限公司 烟酰胺核糖及其衍生物与吡咯喹啉醌及其钠盐的组合工艺
US20210069096A1 (en) * 2019-09-06 2021-03-11 BeautyPaste LLC Enhanced Toothpaste And Kits
CN113151378A (zh) * 2021-04-13 2021-07-23 百瑞全球有限公司 制备烟酸或其衍生物的核苷、烟酸腺嘌呤二核苷酸、烟酸单核苷酸的方法、酶组合物及应用

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6228347B1 (en) * 1997-12-01 2001-05-08 Thione International, Inc. Antioxidant gel for gingival conditions
US20040101494A1 (en) * 2002-11-26 2004-05-27 Scott Douglas Craig Chewable solid unit dosage forms and methods for delivery of active agents into occlusal surfaces of teeth
US20060024247A1 (en) * 2004-07-28 2006-02-02 Bioactives, Llc Oral care formulations comprising highly bioavailable Coenzyme Q-10 cyclodextrin complex
ES2375391B1 (es) * 2010-08-17 2013-07-31 Vitae Natural Nutrition, S.L. Composición de complemento nutricional.
WO2016210232A1 (en) * 2015-06-25 2016-12-29 N.V. Perricone Llc Niacinamide mononucleotide formulations for skin aging
CA3130704A1 (en) * 2019-02-21 2020-08-27 ChromaDex Inc. Use of nicotinamide riboside, nicotinic acid riboside, reduced nicotinyl riboside compounds, and nicotinyl riboside compound derivatives in formulations
CN112823778A (zh) * 2019-11-21 2021-05-21 百瑞全球有限公司 毛发护理组合物及其制备方法
CN111374310A (zh) * 2020-04-16 2020-07-07 上海益跬尔生物科技有限公司 一种食用复方线粒体能量增强配方

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1302196A1 (de) * 2001-10-16 2003-04-16 Habinger, René, Ing. Mag. Intelligenzfördernde Zahncreme
EP2052712A1 (en) * 2007-10-26 2009-04-29 3M Innovative Properties Company Dental composition
JP2016175901A (ja) * 2015-03-18 2016-10-06 第一三共ヘルスケア株式会社 Ｌ−アスパラギン酸またはその塩、及びニコチンアミドを含有する口腔ケア用組成物
CN106265423A (zh) * 2016-08-23 2017-01-04 广州立白企业集团有限公司 具有清火消痛作用的口腔护理组合物
WO2018091300A1 (en) * 2016-11-18 2018-05-24 Unilever N.V. Oral care composition for oral biofilm removal
CN109350622A (zh) * 2018-10-17 2019-02-19 深圳市龙格生技术有限公司 烟酰胺核糖及其衍生物与吡咯喹啉醌及其钠盐的组合工艺
US20210069096A1 (en) * 2019-09-06 2021-03-11 BeautyPaste LLC Enhanced Toothpaste And Kits
CN113151378A (zh) * 2021-04-13 2021-07-23 百瑞全球有限公司 制备烟酸或其衍生物的核苷、烟酸腺嘌呤二核苷酸、烟酸单核苷酸的方法、酶组合物及应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4230263A4 *

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