WO2020087763A1 - 一种6-氟咪唑并吡啶衍生物的用途 - Google Patents

一种6-氟咪唑并吡啶衍生物的用途 Download PDF

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Publication number
WO2020087763A1
WO2020087763A1 PCT/CN2019/000018 CN2019000018W WO2020087763A1 WO 2020087763 A1 WO2020087763 A1 WO 2020087763A1 CN 2019000018 W CN2019000018 W CN 2019000018W WO 2020087763 A1 WO2020087763 A1 WO 2020087763A1
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mass ratio
surfactant
antioxidant
thickener
hand sanitizer
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PCT/CN2019/000018
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English (en)
French (fr)
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曹华
郭鹏峰
陈龙斌
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广东药科大学
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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
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • 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
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • 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
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention belongs to the use field of organic compounds, and particularly relates to the use of a 6-fluoroimidazopyridine derivative.
  • the imidazopyridine derivative is a synthetic compound, which is mainly used in intermediates and active ingredients of antihypertensive and anticancer drugs. Studies have shown that such compounds also have a strong effect of destroying bacteria, fungi and viruses. Therefore, it is also used in anti-inflammatory drugs.
  • Chinese patent application CN1646530A discloses a series of nitrosated imidazolidines, which have gastric secretion inhibitory, anti-inflammatory and antibacterial properties.
  • hand sanitizer has become an ideal skin care cleanser.
  • some specific ingredients in the commercially available hand sanitizer can It has the effect of disinfection and sterilization, but the sterilization effect is general, and the sterilization substance in the hand sanitizer may irritate the skin of the hand, which is not suitable for people who are prone to skin allergies.
  • Cidal and antibacterial hand sanitizers there are many types of bactericidal and antibacterial hand sanitizers, and there have been a lot of researches on organic compound composition hand sanitizers.
  • Chinese patent application CN105686964A discloses a moisturizing antibacterial hand sanitizer, which includes nonionic surfactants, Anionic surfactant, amphoteric surfactant, moisturizing emollient, bacteriostatic agent, chelating agent, sodium citrate, white oil, essence, in which the bacteriostatic agent is trichlorodiphenyl urea or chloroxylenol, the Moisturizing antibacterial hand sanitizer has good decontamination, antibacterial moisturizing and moisturizing functions, but long-term application will cause skin damage. Therefore, many plant extracts such as antibacterial hand washing liquid came into being, such as China
  • Patent application CN108295005A discloses a plant-derived antibacterial hand sanitizer.
  • the antibacterial component of the plant-derived antibacterial hand sanitizer is a plant-derived antibacterial agent.
  • the plant-derived antibacterial agent is tea meal extract, ginger extract, locust tree Rice extract, gardenia extract, seaweed extract and mint extract.
  • the hand sanitizer has good bactericidal and bacteriostatic properties, but its bactericidal effect is general compared to organic compound compositions.
  • the present invention provides the use of 6-fluoroimidazopyridine derivatives.
  • the 6-fluoroimidazopyridine derivative provided by the present invention is used in a bacteriostatic hand sanitizer, which has multiple functions of decontamination, sterilization, skin care, and bacteriostasis, and at the same time, the bacteriostasis provided by the present invention
  • the hand sanitizer also has good anti-allergic effects, high safety, and good application prospects.
  • the 6-fluoroimidazopyridine derivative is used to prepare a hand washing liquid, and the hand washing liquid has functions of killing bacteria, inhibiting bacteria, and inhibiting viruses.
  • the bacteria are one or more of Escherichia coli, Staphylococcus, Pseudomonas aeruginosa, Streptococcus, and Mycobacterium tuberculosis.
  • the virus is one or more of hepatitis virus, influenza virus, and measles virus.
  • An antibacterial hand sanitizer including the following components and their mass percentage:
  • the bacteriostatic agent consists of honeysuckle essential oil and 6-fluoroimidazopyridine according to formula I The derivative is composed of 7: 3-6 by mass ratio.
  • antibacterial hand sanitizer includes the following components and their mass percentage:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 2-4;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant is sodium fatty acid;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee flower oil and eugenol in a mass ratio of 4: 1-3;
  • the antioxidant is ascorbic acid and grape seed
  • the oil is composed of a mass ratio of 1-2: 3;
  • the pH adjusting agent is citric acid.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the surfactant is sodium fatty acid;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1;
  • the antioxidant is composed of ascorbic acid and grape seed oil in a mass ratio 2: 3 composition;
  • the pH adjuster is citric acid.
  • a preparation method of antibacterial hand washing liquid includes the following steps:
  • step S2 Add the moisturizer and fragrance to the mixed solution prepared in step S1, warm to room temperature, stir and dissolve, and then continue to stir the bacteriostatic agent to obtain a raw material mixture;
  • step S3 Add a pH adjusting agent to the raw material mixture prepared in step S2, adjust the pH to 7.5-8, continue to mix evenly, and fill and fill the jar.
  • the safety test shows that the 6-fluoroimidazopyridine derivative provided by the present invention and honeysuckle essential oil can be used as a bacteriostatic agent, which can effectively prevent skin allergies, has high safety, and also has good effects of itching and analgesia.
  • Tests show that the 6-fluoroimidazopyridine derivative provided by the present invention, as one of the bacteriostatic agents, has a good antibacterial and anti-inflammatory effect, and also has a good effect of whitening and moisturizing.
  • the 6-fluoroimidazopyridine derivatives provided by the present invention are used for preparing sterilization and bacteriostatic daily necessities, and have good sterilization, bacteriostasis and anti-inflammatory functions on skin.
  • the antibacterial agent of the antibacterial hand sanitizer provided by the present invention is compounded with honeysuckle essential oil and the 6-fluoroimidazopyridine derivative described in Formula I, on the one hand, it maintains the good anti-inflammatory skin care function of honeysuckle essential oil, and on the other hand
  • the efficacy of the synergies with each other improves the sterilization speed and sterilization efficiency of the hand sanitizer, improves the bacteriostatic efficiency, and also improves the anti-inflammatory repair function.
  • the essence of the antibacterial hand sanitizer provided by the present invention is compounded with bee flower essential oil and eugenol. On the one hand, the compound essence is added to the hand sanitizer to make the hand sanitizer fragrance pleasant.
  • the liquid has good refreshing effect.
  • the antioxidant of the antibacterial hand sanitizer provided by the present invention is compounded with ascorbic acid and grape seed oil, which can not only effectively reduce the roughness and aging of the skin, but also effectively supplement vitamins and improve the skin tenderness.
  • the 6-fluoroimidazopyridine derivatives and humectants, cationic surfactants, nonionic surfactants, anionic surfactants, thickeners, flavors, antioxidants, pH adjusters provided by the present invention
  • the agent and the bacteriostatic agent honeysuckle essential oil are coordinated with each other, showing excellent antibacterial and anti-inflammatory effects, and at the same time showing a good whitening effect.
  • Honeysuckle essential oil is mainly used to purify the extract of honeysuckle-chlorogenic acid, this substance can promote human metabolism, regulate human function, improve immunity, and have antibacterial, anti-inflammatory, immune regulation and other functions.
  • Bee flower essential oil essential oil extracted from lemon balm, the main components are citral, geraniol, citronellol, etc.
  • the aroma is rich and it is used in the processing of fruit juice drinks, which can improve the flavor of the drink, improve the palatability, and at the same time antiseptic Role, extend the fresh-keeping period.
  • Grape seed oil Grape seed is refined by the most advanced cold-pressing method and contains two important elements, linoleic acid and proanthocyanidins, of which linoleic acid is a fatty acid that is essential for the body and cannot be synthesized by the body. It has the effects of resisting free radicals, anti-aging, and strengthening the elasticity of the circulatory system, while proanthocyanidins have the effect of protecting the elasticity of blood vessels and preventing cholesterol from accumulating on the walls of blood vessels.
  • Example 1 a bacteriostatic hand sanitizer
  • the antibacterial hand sanitizer consists of the following components and their mass percentage:
  • bacteriostatic agent consists of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 3.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 2; the cationic surfactant is coconut oleoyl diethanolamine; the nonionic surfactant is dodecyl glycoside; the anionic surfactant It is fatty acid sodium; the thickener is hydroxyethyl cellulose; the flavor is composed of bee flower oil and eugenol in a mass ratio of 4: 1; the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 1: 3 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid includes the following steps:
  • step S2 Add the moisturizer and fragrance to the mixed solution prepared in step S1, warm to room temperature, stir and dissolve, and then continue to stir the bacteriostatic agent to obtain a raw material mixture;
  • step S3 Add a pH adjusting agent to the raw material mixture prepared in step S2, adjust the pH to 7.5, continue to mix evenly, and then fill the jar and package.
  • Example 2 A bacteriostatic hand sanitizer
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 6.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 4; the cationic surfactant is coconut oleoyl diethanolamine; the nonionic surfactant is dodecyl glycoside; the anionic surfactant It is fatty acid sodium; the thickener is hydroxyethyl cellulose; the essence is composed of bee flower oil and eugenol in a mass ratio of 4: 3; the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 2: 3 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid includes the following steps:
  • step S2 Add the humectant and flavor to the mixed solution prepared in step S1, warm to room temperature, stir and dissolve, and continue to stir the bacteriostatic agent to obtain a raw material mixture;
  • Example 3 A bacteriostatic hand sanitizer
  • An antibacterial hand sanitizer including the following components and their mass percentage:
  • bacteriostatic agent consists of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 4.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 2; the cationic surfactant is coconut oleoyl diethanolamine; the nonionic surfactant is dodecyl glycoside; the anionic surfactant It is fatty acid sodium; the thickener is hydroxyethyl cellulose; the essence is composed of bee flower essential oil and eugenol at a mass ratio of 4: 3; the antioxidant is composed of ascorbic acid and grape seed oil at a mass ratio of 1: 3 Composition; The pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid includes the following steps:
  • step S2 Add the moisturizer and fragrance to the mixed solution prepared in step S1, warm to room temperature, stir and dissolve, and then continue to stir the bacteriostatic agent to obtain a raw material mixture;
  • Example 4 A bacteriostatic hand sanitizer
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 4.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 2; the cationic surfactant is coconut oleoyl diethanolamine; the nonionic surfactant is dodecyl glycoside; the anionic surfactant It is fatty acid sodium; the thickener is hydroxyethyl cellulose; the essence is composed of bee flower essential oil and eugenol at a mass ratio of 4: 3; the antioxidant is composed of ascorbic acid and grape seed oil at a mass ratio of 1: 3 Composition; The pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid includes the following steps:
  • step S2 Add the moisturizer essence to the mixed solution prepared in step S1, warm to room temperature, stir and dissolve, and then continue to stir the bacteriostatic agent to obtain a raw material mixture;
  • step S3 Add a pH adjusting agent to the raw material mixture prepared in step S2, adjust the pH to 7.5, continue to mix evenly, and then fill the jar and package.
  • Example 5 A bacteriostatic hand sanitizer
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1;
  • the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 2: 3 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid includes the following steps:
  • step S2 Add the moisturizer and fragrance to the mixed solution prepared in step S1, warm to room temperature, stir and dissolve, and then continue to stir the bacteriostatic agent to obtain a raw material mixture;
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 1: 1.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1;
  • the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 2: 3 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 1 is basically the same as Example 5, except that the ratio of the bacteriostatic agent honeysuckle essential oil and the 6-fluoroimidazopyridine derivative described in Formula I is changed from 7: 5 to 1: 1.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • Moisturizer 14% cationic surfactant 1.3%, nonionic surfactant 1.7%, anionic surfactant 23%, thickener 1.7%, fragrance 0.6%, bacteriostatic agent 3.0%, antioxidant 0.7%, pH adjustment Agent 3%, deionized water 51%; the bacteriostatic agent is honeysuckle essential oil.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1;
  • the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 2: 3 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 2 is basically the same as Example 5, except that the bacteriostatic agent of Comparative Example 2 is a single component honeysuckle essential oil.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is the 6-fluoroimidazopyridine derivative of formula I.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1;
  • the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 2: 3 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 3 is basically the same as Example 5, except that the bacteriostatic agent of Comparative Example 3 is a single component 6-fluoroimidazopyridine derivative of Formula I.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 1: 1;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1;
  • the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 2: 3 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 4 is basically the same as Example 5, except that the ratio of the moisturizer propylene glycol and sorbitol of Comparative Example 4 is changed from 5: 3 to 1: 1.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is propylene glycol; the cationic surfactant is coconut oleoyl diethanolamine; the nonionic surfactant is dodecyl glycoside; the anionic surfactant is sodium fatty acid; and the thickener is Hydroxyethyl cellulose; the essence is composed of bee flower oil and eugenol in a mass ratio of 2: 1; the antioxidant is composed of ascorbic acid and grape seed oil in a mass ratio of 2: 3; the pH adjusting agent is citric acid .
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 5 is basically the same as Example 5, except that the humectant of Comparative Example 5 is a single component of propylene glycol.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is sorbitol; the cationic surfactant is coconut oleoyl diethanolamine; the nonionic surfactant is dodecyl glycoside; the anionic surfactant is sodium fatty acid; the thickener It is hydroxyethyl cellulose; the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1; the antioxidant is composed of ascorbic acid and grape seed oil in a mass ratio of 2: 3; and the pH adjuster is lemon acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 6 is basically the same as Example 5, except that the moisturizer of Comparative Example 6 is a single component sorbitol.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee flower oil and eugenol in a mass ratio of 1: 1;
  • the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 2: 3 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 7 is basically the same as Example 5, except that the ratio of the essence of bee flower essential oil and eugenol in Comparative Example 7 is changed from 2: 1 to 1: 1.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickening agent is hydroxyethyl cellulose;
  • the essence is bee flower essential oil;
  • the antioxidant is composed of ascorbic acid and grape seed oil in a mass ratio of 2: 3; and the pH adjusting agent is citric acid .
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 8 is basically the same as Example 5, except that the essence of Comparative Example 8 is bee flower essential oil. Comparative Example 9. An antibacterial hand sanitizer
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickener is hydroxyethyl cellulose;
  • the flavor is eugenol;
  • the antioxidant is composed of ascorbic acid and grape seed oil in a mass ratio of 2: 3; and the pH adjuster is citric acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 9 is basically the same as Example 5, except that the flavor of Comparative Example 9 is eugenol.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the cationic surfactant is coconut oleoyl diethanolamine;
  • the nonionic surfactant is dodecyl glycoside;
  • the anionic surfactant It is fatty acid sodium;
  • the thickener is hydroxyethyl cellulose;
  • the essence is composed of bee flower oil and eugenol in a mass ratio of 2: 1;
  • the antioxidant is ascorbic acid and grape seed oil in a mass ratio of 1: 1 Composition;
  • the pH adjusting agent is citric acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 10 is basically the same as Example 5, except that the ratio of the antioxidant ascorbic acid to grape seed oil in Comparative Example 10 is changed from 2: 3 to 1: 1.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3; the cationic surfactant is coconut oleoyl diethanolamine; the nonionic surfactant is dodecyl glycoside; the anionic surfactant It is fatty acid sodium; the thickener is hydroxyethyl cellulose; the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1; the antioxidant is ascorbic acid; and the pH adjuster is citric acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 11 is basically the same as Example 5, except that the antioxidant of Comparative Example 11 is ascorbic acid.
  • the antibacterial hand sanitizer includes the following components and their mass percentages:
  • bacteriostatic agent is composed of honeysuckle essential oil and the 6-fluoroimidazopyridine derivative of formula I in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3; the cationic surfactant is coconut oleoyl diethanolamine; the nonionic surfactant is dodecyl glycoside; the anionic surfactant It is fatty acid sodium; the thickener is hydroxyethyl cellulose; the essence is composed of bee essential oil and eugenol in a mass ratio of 2: 1; the antioxidant is grape seed oil; and the pH adjuster is lemon acid.
  • the preparation method of the antibacterial hand washing liquid is basically the same as that in Example 5.
  • Comparative Example 12 is basically the same as Example 5, except that the antioxidant of Comparative Example 12 is grape seed oil.
  • Test material antibacterial hand sanitizer prepared in Examples 1-5.
  • Test method Randomly divide 60 healthy adult rabbits into 10 groups, 6 in each group, shear the back of rabbits in groups 1, 2, 3, 4, and 5 with a diameter of 5 cm, and divide 6, 7, 8, Cut the outer skin of the rabbits in groups 9 and 10 with a diameter of 4 cm, and apply the antibacterial hand sanitizer prepared in Examples 1-5, wash off after 3 minutes, apply 3 times a day, 0.5 mL each time, and apply continuously 15 days, observe the rabbit skin phenomenon.
  • Test results The application site was visually observed without any abnormal changes such as papules, hyperemia, and erythema, and the back of the rabbits in the damaged skin group basically healed, and there were no abnormal changes. Then the rabbits were sacrificed, the application site was cut out, and histopathological examination was performed. The results showed that the skin at the application site was the same as normal skin, and no abnormalities were found. It shows that the antibacterial hand-washing liquid prepared by the invention does not have any irritant reaction to the skin.
  • Test example two skin allergy test
  • Test material antibacterial hand sanitizer prepared in Examples 1-5.
  • Test method randomly divide 30 healthy guinea pigs into 5 groups, 6 in each group, cut their backs with a diameter of 3.5 cm, and apply the antibacterial hand sanitizer prepared in Examples 1-5 respectively, and administer them every other day. Each administration of 0.5mL, 3 consecutive doses, and then on the 14th day after the first dose, double the dose, observe the situation of guinea pigs after application of the drug.
  • Test results The results showed that all groups of guinea pigs did not show any allergic phenomena such as sneezing, hair twitching, twitching, nose scratching, and difficulty breathing, indicating that the antibacterial hand sanitizer prepared by the present invention did not have any allergic reactions.
  • Test example three in vitro antifungal test
  • Test materials the antibacterial hand sanitizer prepared in Examples 1-5 and the antibacterial hand sanitizer prepared in Comparative Examples 1-3.
  • Test object The standard strains used in this experiment are Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus, and Mycobacterium tuberculosis, all of which are cited from the Bacterial Strain Preservation Center of the Institute of Dermatology, Chinese Academy of Medical Sciences.
  • Test method Take 90 sterilized test tubes, transplant the above bacteria into a sterilized tube, one tube for each bacterium, and dilute the antibacterial hand washing solution prepared in Examples 1-5 and Comparative Examples 1-3, respectively, and add , One tube only added culture medium without bacteriostatic hand washing liquid, as a growth control, adjusted to a density of 10 5 CFU / mL. Add 50 ⁇ L of suspension to each tube with a micro sampler, mix well, put in a 28 ° C incubator for 7 days, transfer 0.05 mL from each tube into the medium, test and record the results of sterilization and bacteriostasis.
  • Test result The result judges that the growth control tube is only added with culture medium and bacterial solution, and no drug is added. Only when the growth control tube grows well, and other test tubes are added with the drug, the growth of the bacteria is inhibited, the test is successful.
  • the groups of Examples 1-5 showed good inhibitory effect on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus and Mycobacterium tuberculosis, and the bacteriostatic effect was significantly better than the control Groups 1-3, of which the group 5 of Example 5 has the best bacteriostatic effect, which is the best embodiment of the present invention.
  • the results show that the bacteriostatic hand sanitizer prepared by the present invention is effective against E. coli, staphylococcus, Pseudomonas aeruginosa, chain Cocci and Mycobacterium tuberculosis have good bactericidal and bacteriostatic effects.
  • Test Example IV Experimental test of virus suppression
  • Test materials antibacterial hand sanitizer prepared in Examples 1-5 and Comparative Examples 1-12.
  • Test subjects monkey embryonic kidney cells (MA104) and canine kidney cells (MDCK): after the cells grow into a single layer, pass them by 1: 3, continue culturing, and pass the next day.
  • Human laryngeal epidermoid carcinoma cell (Hep-2) cells After the cells grow into a monolayer, they are passaged at 1: 2, and the culture is continued, and the passage is carried out the next day.
  • Test results The test results are shown in Table 2.
  • the antibacterial hand washing liquid prepared by the invention has the effect of inhibiting hepatitis virus, influenza virus and measles virus.
  • Test example 5 Clinical trials
  • Test materials antibacterial hand sanitizer prepared in Examples 1-5 and Comparative Examples 1-12.
  • Test subjects 180 test subjects, aged 15-75 years, male and female half.
  • Test methods and judging criteria On the basis of obtaining the basis of animal toxicology test and pharmacological and pharmacological effect test, on the premise of patient Listeiness, 180 testers are divided into 18 groups on average, 10 persons in each group, male and female In each half, distribute the antibacterial hand sanitizer prepared in Examples 1-5 and Comparative Examples 1-12 to each member, and ask the group members to decontaminate the test sample in accordance with the normal hand washing method, the freshness after washing, and after washing Lubricity, moisture retention after washing and aroma refreshing were scored respectively as Groups 1-5 and Comparative Examples 1-12, a group using Shufujia antibacterial hand sanitizer was recorded as a control group, and the scoring principle adopted a 5-point scale , Where the evaluation levels range from 0-1 (very poor), 1-2 (poor), 2-3 (satisfactory), 3-4 (good), and 4-5 (very good).
  • Example 5 has the best effect and is the best example of the present invention; at the same time, it has a strong killing inhibitory effect on hepatitis virus, influenza virus and measles virus.

Abstract

本发明属于有机化合物用途领域，具体涉及一种6-氟咪唑并吡啶衍生物的用途。本发明提供的式(I)的6-氟咪唑并吡啶衍生物用于制备杀菌、抑菌日用品的用途，所述6-氟咪唑并吡啶衍生物应用于抑菌洗手液的用途，所述抑菌洗手液，兼具有去污、杀菌、护肤、抑菌多重功效，同时本发明提供的抑菌洗手液还具有良好的抗过敏效果，安全性高，具有良好的应用前景。

Description

一种6-氟咪唑并吡啶衍生物的用途 技术领域
本发明属于有机化合物用途领域，具体涉及一种6-氟咪唑并吡啶衍生物的用途。
背景技术
咪唑并吡啶衍生物是一种人工合成的化合物，主要应用于抗高血压、抗癌药物的中间体及有效成分，研究表明，该类化合物还具有较强的消灭细菌、真菌及病毒的作用，因此也被应用于消炎药物中，其中，中国专利申请CN1646530A公开了一系列亚硝基化咪唑吡啶，该类化合物具有胃分泌抑制、消炎和抗菌特性。
专家认为，疾病会通过鼻、口、眼、手等途径传播，为了全面预防疾病，勤于洗手成为最好的方法。在过去，香皂是人们洗手的清洁日用品，但随着人们对日用化妆品性能的要求不断提高，洗手液成为了一种理想的护肤清洁液，目前市售的洗手液，有些特定的成分可以起到消毒、杀菌的作用，但杀菌效果一般，且洗手液中的杀菌物质可能会刺激手部皮肤，对于皮肤容易过敏的人不适合使用。
杀菌抑菌洗手液的种类繁多，目前已有大量研究从事有机化合物组合物洗手液，例如中国专利申请CN105686964A公开了一种保湿抑菌洗手液，该保湿抑菌洗手液包括非离子表面活性剂，阴离子表面活性剂，两性表面活性剂，保湿润 肤剂，抑菌剂，螯合剂，柠檬酸钠，白油，香精，其中抑菌剂为三氯均二苯脲或氯代二甲苯酚，该保湿抑菌洗手液具有良好的去污、抑菌保湿、滋润功能，但长期应用，会对皮肤造成损伤。因此较多植物提取物类抑菌洗手液应运而生，例如中国
专利申请CN108295005A公开了一种植物源抑菌洗手液，该植物源抑菌洗手液的抑菌成分为植物源抑菌剂，所述植物源抑菌剂为茶粕提取物、生姜提取物、槐米提取物、栀子提取物、海藻提取物和薄荷提取物。该洗手液具有良好的杀菌、抑菌性能，但与有机化合物组合物相比，其杀菌效果一般。
综上所述，现有技术中的洗手液大多数产品功能单一、杀菌效果一般，成本较高，甚至对皮肤还有伤害，因此，需要一种兼具去污、杀菌、护肤多重功效的洗手液。
发明内容
针对现有技术中的不足，本发明提供了一种6-氟咪唑并吡啶衍生物的用途。本发明提供的6-氟咪唑并吡啶衍生物应用于抑菌洗手液的用途，所述抑菌洗手液，兼具有去污、杀菌、护肤、抑菌多重功效，同时本发明提供的抑菌洗手液还具有良好的抗过敏效果，安全性高，具有良好的应用前景。
本发明通过以下技术方案实现：
式I的6-氟咪唑并吡啶衍生物用于制备杀菌、抑菌日用品的用途，
Figure PCTCN2019000018-appb-000001
进一步的，所述6-氟咪唑并吡啶衍生物用于制备洗手液，所述洗手液具有杀灭细菌、抑制细菌、抑制病毒的功能。
进一步的，所述细菌为大肠杆菌、葡萄球菌、绿脓杆菌、链球菌、结核杆菌中的一种或多种。
进一步的，所述病毒为肝炎病毒、流感病毒、麻疹病毒中的一种或几种。
一种抑菌洗手液，包括以下组分及其质量百分比：
保湿剂10-20％、阳离子表面活性剂0.5-2％、非离子表面活性剂0.5-2％、阴离子表面活性剂15-30％、增稠剂1-3％、香精0.1-0.9％、抑菌剂2.4-3.6％、抗氧化剂0.5-1.5％，pH调节剂2-5％、去离子水32-68％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶3-6组成。
进一步的，所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
进一步的，所述保湿剂由丙二醇和山梨醇按质量比5∶2-4组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比4∶1-3组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比1-2∶3组成；所述pH调节剂为柠檬酸。
进一步的，所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
一种抑菌洗手液的制备方法，包括如下步骤：
S1、将阳离子表面活性剂、非离子表面活性剂、阴离子表面活性剂、增稠剂和抗氧化剂溶解于去离子水中，2-8℃搅拌均匀，得到混合溶液；
S2、将保湿剂和香精加入步骤S1制得的混合溶液中，升温至室温，搅拌溶解后，抑菌剂，继续搅拌，得到原料混合物；
S3、向步骤S2制得的原料混合物中加入pH调节剂，调节至pH＝7.5-8，继续搅拌均匀，装罐、包装，即得。
安全性试验表明，本发明提供的6-氟咪唑并吡啶衍生物与金银花精油复配作为抑菌剂，能够有效的防止皮肤过敏，安全性高，同时还具有止痒镇痛的良好的效果。
试验表明，本发明提供的6-氟咪唑并吡啶衍生物作为抑菌剂之一的抑菌洗手液，具有良好的杀菌消炎效果，同时还具有美白润肤的良好效果。
与现有技术相比，本发明的有益效果如下：
(1)本发明提供的6-氟咪唑并吡啶衍生物用于制备杀菌、抑菌日用品的用途，对皮肤具有很好的杀菌、抑菌和消炎的功能。
(2)本发明提供的抑菌洗手液的抑菌剂采用金银花精油和式I所述的6-氟咪唑并吡啶衍生物复配，一方面保持了金银花精油良好消炎护肤功能，另一方面两者功效相互协同，提高了洗手液的杀菌速度和杀菌效率，提高了抑菌效率，同时还提高了消炎修复功能。
(3)本发明提供的抑菌洗手液的香精采用蜂花精油和丁香酚复配，一方面在洗手液中加入复合香精，使洗手液香气怡人，另一方面，蜂花精油的加入洗手液具有提神的良好功效。
(4)本发明提供的抑菌洗手液的抗氧化剂由抗坏血酸和葡萄籽油复配，不仅可以有效降低皮肤粗糙老化程度，同时还能有效补充维生素，提高皮肤柔嫩程度。
(5)本发明提供的本发明提供的6-氟咪唑并吡啶衍生物与保湿剂、阳离子表面活性剂、非离子表面活性剂、阴离子表面活性剂、增稠剂、香精、抗氧化剂、pH调节剂以及抑菌剂金银花精油相互协调，表现出 优异的抑菌消炎效果，同时表现出良好的美白效果。
金银花精油：金银花精油主要是提纯金银花的提取物的主要成分-绿原酸，这种物质能促进人体新陈代谢、调节人体功能、提高免疫力，具有抑菌、抗炎、调节免疫等作用。
蜂花精油：为香蜂草萃取的精油，主要成分有柠檬醛、香叶醇、香茅醇等，香气香味浓郁，用于果汁饮品加工，能改善饮品风味，提高嗜口性、同时起防腐作用，延长保鲜期。
葡萄籽油：是葡萄种子经由最高级的冷压方式精制而成，含有两种重要的元素，亚麻油酸和原花色素，其中亚麻油酸是人体必需而又为人体所不能合成的脂肪酸，具有抵抗自由基、抗老化、强化循环系统弹性的功效，而原花色素具有保护血管弹性、阻止胆固醇囤积在血管壁上的功效。
实施例
以下通过实施例形式的具体实施方式，对本发明的上述内容作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下实施例。
实施例1、一种抑菌洗手液
所述抑菌洗手液，由以下组分及其质量百分比组成：
保湿剂10％、阳离子表面活性剂0.5％、非离子表面活性剂0.5％、阴离子表面活性剂15％、增稠剂1％、香精0.1％、抑菌剂2.4％、抗氧化剂0.5％，pH调节剂2％、去离子水68％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶3组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶2组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所 述香精由蜂花精油和丁香酚按质量比4∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比1∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，包括如下步骤：
S1、将阳离子表面活性剂、非离子表面活性剂、阴离子表面活性剂、增稠剂和抗氧化剂在预溶锅中溶解于去离子水中，2℃搅拌均匀，得到混合溶液；
S2、将保湿剂和香精加入步骤S1制得的混合溶液中，升温至室温，搅拌溶解后，抑菌剂，继续搅拌，得到原料混合物；
S3、向步骤S2制得的原料混合物中加入pH调节剂，调节至pH＝7.5，继续搅拌均匀，装罐、包装，即得。
实施例2、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂20％、阳离子表面活性剂2％、非离子表面活性剂2％、阴离子表面活性剂30％、增稠剂3％、香精0.9％、抑菌剂3.6％、抗氧化剂1.5％，pH调节剂5％、去离子水32％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶6组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶4组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比4∶3组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，包括如下步骤：
S1、将阳离子表面活性剂、非离子表面活性剂、阴离子表面活性剂、增稠剂和抗氧化剂在预溶锅中溶解于去离子水中，8℃搅拌均匀，得到混合溶液；
S2、将保湿剂和香精加入步骤S1制得的混合溶液中，升温至室温， 搅拌溶解后，抑菌剂，继续搅拌，得到原料混合物；
S3、向步骤S2制得的原料混合物中加入pH调节剂，调节至pH＝8，继续搅拌均匀，装罐、包装，即得。
实施例3、一种抑菌洗手液
一种抑菌洗手液，包括以下组分及其质量百分比：
保湿剂13％、阳离子表面活性剂0.9％、非离子表面活性剂1.3％、阴离子表面活性剂20％、增稠剂2.5％、香精0.8％、抑菌剂2.8％、抗氧化剂1.2％，pH调节剂2.3％、去离子水58％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶4组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶2组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比4∶3组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比1∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，包括如下步骤：
S1、将阳离子表面活性剂、非离子表面活性剂、阴离子表面活性剂、增稠剂和抗氧化剂在预溶锅中溶解于去离子水中，5℃搅拌均匀，得到混合溶液；
S2、将保湿剂和香精加入步骤S1制得的混合溶液中，升温至室温，搅拌溶解后，抑菌剂，继续搅拌，得到原料混合物；
S3、向步骤S2制得的原料混合物中加入pH调节剂，调节至pH＝8，继续搅拌均匀，装罐、包装，即得。
实施例4、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂19％、阳离子表面活性剂1.5％、非离子表面活性剂0.9％、阴离子表面活性剂27％、增稠剂1.4％、香精0.3％、抑菌剂3.3％、抗 氧化剂0.6％，pH调节剂4％、去离子水42％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶4组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶2组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比4∶3组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比1∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，包括如下步骤：
S1、将阳离子表面活性剂、非离子表面活性剂、阴离子表面活性剂、增稠剂和抗氧化剂在预溶锅中溶解于去离子水中，3℃搅拌均匀，得到混合溶液；
S2、将保湿剂香精加入步骤S1制得的混合溶液中，升温至室温，搅拌溶解后，抑菌剂，继续搅拌，得到原料混合物；
S3、向步骤S2制得的原料混合物中加入pH调节剂，调节至pH＝7.5，继续搅拌均匀，装罐、包装，即得。
实施例5、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，包括如下步骤：
S1、将阳离子表面活性剂、非离子表面活性剂、阴离子表面活性剂、增稠剂和抗氧化剂在预溶锅中溶解于去离子水中，7℃搅拌均匀，得到混合溶液；
S2、将保湿剂和香精加入步骤S1制得的混合溶液中，升温至室温，搅拌溶解后，抑菌剂，继续搅拌，得到原料混合物；
S3、向步骤S2制得的原料混合物中加入pH调节剂，调节至pH＝8，继续搅拌均匀，装罐、包装，即得。
对比例1、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比1∶1组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法与实施例5基本相同。
对比例1与实施例5基本相同，不同在于，对比例1抑菌剂金银花精油和式I所述的6-氟咪唑并吡啶衍生物的比例由7∶5变为1∶1。
对比例2、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗 氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂为金银花精油。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例2与实施例5基本相同，不同在于，对比例2的抑菌剂为单一组分金银花精油。
对比例3、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂为式I所述的6-氟咪唑并吡啶衍生物。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例3与实施例5基本相同，不同在于，对比例3的抑菌剂为单一组分式I所述的6-氟咪唑并吡啶衍生物。
对比例4、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂由丙二醇和山梨醇按质量比1∶1组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例4与实施例5基本相同，不同在于，对比例4的保湿剂丙二醇和山梨醇的比例由5∶3变为1∶1。
对比例5、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂为丙二醇；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例5与实施例5基本相同，不同在于，对比例5的保湿剂为单一组分丙二醇。
对比例6、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂为山梨醇；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例6与实施例5基本相同，不同在于，对比例6的保湿剂为单一组分山梨醇。
对比例7、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比1∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例7与实施例5基本相同，不同在于，对比例7的香精蜂花精油和丁香酚的比例由2∶1变为1∶1。
对比例8、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精为蜂花精油；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例8与实施例5基本相同，不同在于，对比例8的香精为蜂花精油。对比例9、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精为丁香酚；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例9与实施例5基本相同，不同在于，对比例9的香精为丁香酚。
对比例10、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比1∶1组成；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例10与实施例5基本相同，不同在于，对比例10的抗氧化剂抗坏血酸和葡萄籽油的比例由2∶3变为1∶1。
对比例11、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所 述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂为抗坏血酸；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例11与实施例5基本相同，不同在于，对比例11的抗氧化剂为抗坏血酸。
对比例12、一种抑菌洗手液
所述抑菌洗手液，包括以下组分及其质量百分比：
保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和式I所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂为葡萄籽油；所述pH调节剂为柠檬酸。
所述抑菌洗手液的制备方法，与实施例5基本相同。
对比例12与实施例5基本相同，不同在于，对比例12的抗氧化剂为葡萄籽油。
试验例一、皮肤刺激性试验
1、试验材料：实施例1-5制备的抑菌洗手液。
2、实验对象：选取3Kg左右的健康成年家兔60只。
3、试验方法：将60只健康成年家兔随机分为10组，每组6只，将1、2、3、4、5组的家兔背部剪毛，直径5cm，将6、7、8、9、10组的家兔背部剪下直径为4cm的外表皮肤，分别涂抹实施例1-5制备的抑菌洗手液，3min后洗掉，每日涂抹3次，每次涂抹0.5mL，连续涂 抹15天，观察家兔皮肤现象。
4、试验结果：肉眼观察涂药部位，无任何丘疹、充血、红斑等异常改变，且破损皮肤组家兔的背部基本愈合，亦未见异常改变。然后将家兔处死，剪下涂药部位，做病理组织学检查，结果表明，涂药部位皮肤与正常皮肤一样，均未见异常。表明本发明制备的抑菌洗手液对皮肤无任何刺激性反应。
试验例二、皮肤过敏性试验
1、试验材料：实施例1-5制备的抑菌洗手液。
2、实验对象：选取500g左右的健康豚鼠30只。
3、试验方法：将30只健康豚鼠随机分为5组，每组6只，将其背部剪毛，直径为3.5cm，分别涂抹实施例1-5制备的抑菌洗手液，隔天给药，每次给药0.5mL，连续给药3次，再在首次给药后的第14日，2倍量给药，观察涂抹药剂后豚鼠的状况。
4、试验结果：结果表明，几组豚鼠均未出现任何喷嚏、竖毛、抽搐、搔鼻、呼吸困难等过敏现象，表明本发明制备的抑菌洗手液无任何过敏性反应。
试验例三、体外抗真菌测试
1、试验材料：实施例1-5制备的抑菌洗手液和对比例1-3制备的抑菌洗手液。
2、试验对象：本实验采用的标准菌株为大肠杆菌、葡萄球菌、绿脓杆菌、链球菌、结核杆菌，均引自中国医学科学院皮肤病学研究所细菌菌种保存中心。
3、试验方法：取灭菌试管90管，将上述细菌移植入灭菌管，每种细菌一管，并分别将实施例1-5和对比例1-3制备的抑菌洗手液稀释后加入，一管只加培养液不加抑菌洗手液，作为生长对照，调节至密度为10 5CFU/mL。用微量加样器每管加50μL悬液，混匀，放入28℃温箱培 养7d，从各管中分别取0.05mL转入培养基，测试并记录杀菌抑菌结果。
4、试验结果：结果判定生长对照管只加培养基和菌液不加药，只有当生长对照管生长良好，其它试管随药物的加入，则菌生长受抑时才证明试验成功。
结果如表1所示：
表1 体外真菌测试数据
Figure PCTCN2019000018-appb-000002
由表1可知，与生长对照组相比，实施例1-5组对大肠杆菌、葡萄球菌、绿脓杆菌、链球菌、结核杆菌表现出良好的抑制效果，且抑菌效果明显优于对比例1-3组，其中，实施例5组的抑菌效果最好，为本发明的最佳实施例，结果表明，本发明制备的抑菌洗手液对大肠杆菌、葡萄球菌、绿脓杆菌、链球菌、结核杆菌具有良好的杀菌抑菌效果。
试验例四、抑制病毒实验测试
1、试验材料：实施例1-5、对比例1-12制备的抑菌洗手液。
2、试验对象：猴胚胎肾细胞(MA104)、犬肾细胞(MDCK)：待细胞长成单层后，按1∶3传代，继续培养，隔天进行传代。人喉表皮样癌细胞(Hep-2)细胞：待细胞长成单层后，按1∶2传代，继续培养，隔天进行传代。
3、分别将肝炎病毒、流感病毒、麻疹病毒1mL与0.25％胰酶20μL混匀，放于37℃、5％CO 2恒温培养箱内作用1h，接种于已经长成单层的MA104细胞、MDCK细胞和Hep-2细胞上，分别加入用维持液稀释的实施例1-5、对比例1-12制备的抑菌洗手液，再在恒温培养箱内作用1h后，并设细胞对照组，其中细胞对照组相同操作加入相同量的维持液，置于37℃、5％CO 2培养箱中培养12h。MTT法测试细胞存活率。
4、试验结果：试验结果如表2所示。
表2 抑制病毒MTT数据
Figure PCTCN2019000018-appb-000003
Figure PCTCN2019000018-appb-000004
由表2可知，与对照组和对比例1-12组相比，实施例1-5组细胞存活率高，其中，实施例5组效果最好，为本发明的最佳实施例，结果表明，本发明制备的抑菌洗手液具有抑制肝炎病毒、流感病毒、麻疹病毒的效果。
试验例五、临床试验
1、试验材料：实施例1-5、对比例1-12制备的抑菌洗手液。
2、试验对象：选取180例试验者，年龄15-75岁，男女各半。
3、试验方法及评判标准：在经过动物毒理试验和药理药效实验取得依据的基础上，在患者自愿的前提下，将180例试验者，平均分为18组，每组10人，男女各半，将实施例1-5、对比例1-12制备的抑菌洗手液分发给每个成员，要求小组成员按照正常洗手方式依次对测试样品的去污能力、洗后清爽度、洗后润滑度、洗后保湿度以及香气提神度进行评分，分别记为实施例1-5组和对比例1-12组，一组使用舒肤佳抑菌洗手液记为对照组，评分原则采用5分制，其中评估等级从0-1(极差)、1-2(差)、2-3(满意)、3-4(好)、4-5(很好)。
4、最终结果取平均值，具体参见表3。
表3 临床测试评分数据
Figure PCTCN2019000018-appb-000005
由表3可知，与对比例1-12组相比，本发明实施例1-5均具有良好的去污能力、洗后清爽度、洗后润滑度、洗后保湿度、香气提神度效果，其中，实施例5的效果最好，为本发明的最佳实施例；同时对肝炎病毒、流感病毒、麻疹病毒具有较强的杀伤抑制效果。

Claims (9)

  1. 式I的6-氟咪唑并吡啶衍生物用于制备杀菌、抑菌日用品的用途，
    Figure PCTCN2019000018-appb-100001
  2. 如权利要求1所述的用途，其特征在于，所述6-氟咪唑并吡啶衍生物用于制备洗手液，所述洗手液具有杀灭细菌、抑制细菌、抑制病毒的功能。
  3. 如权利要求2所述的用途，其特征在于，所述细菌为大肠杆菌、葡萄球菌、绿脓杆菌、链球菌、结核杆菌中的一种或多种。
  4. 如权利要求2所述的用途，其特征在于，所述病毒为肝炎病毒、流感病毒、麻疹病毒中的一种或几种。
  5. 一种抑菌洗手液，其特征在于，包括以下组分及其质量百分比：
    保湿剂10-20％、阳离子表面活性剂0.5-2％、非离子表面活性剂0.5-2％、阴离子表面活性剂15-30％、增稠剂1-3％、香精0.1-0.9％、抑菌剂2.4-3.6％、抗氧化剂0.5-1.5％，pH调节剂2-5％、去离子水32-68％；所述抑菌剂由金银花精油和权利要求1所述的6-氟咪唑并吡啶衍生物按质量比7∶3-6组成。
  6. 如权利要求5所述的抑菌洗手液，其特征在于，包括以下组分及其质量百分比：保湿剂14％、阳离子表面活性剂1.3％、非离子表面活性剂1.7％、阴离子表面活性剂23％、增稠剂1.7％、香精0.6％、抑菌剂3.0％、抗氧化剂0.7％、pH调节剂3％、去离子水51％；所述抑菌剂由金银花精油和权利要求1所述的6-氟咪唑并吡啶衍生物按质量比7∶5组成。
  7. 如权利要求5或6所述的抑菌洗手液，其特征在于，所述保湿剂 由丙二醇和山梨醇按质量比5∶2-4组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比4∶1-3组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比1-2∶3组成；所述pH调节剂为柠檬酸。
  8. 如权利要求7所述的抑菌洗手液，其特征在于，所述保湿剂由丙二醇和山梨醇按质量比5∶3组成；所述阳离子表面活性剂为椰子油酰二乙醇胺；所述非离子表面活性剂为十二烷基糖苷；所述阴离子表面活性剂为脂肪酸钠；所述增稠剂为羟乙基纤维素；所述香精由蜂花精油和丁香酚按质量比2∶1组成；所述抗氧化剂由抗坏血酸和葡萄籽油按质量比2∶3组成；pH调节剂为柠檬酸。
  9. 一种如权利要求5所述的抑菌洗手液的制备方法，其特征在于，包括如下步骤：
    S1、将阳离子表面活性剂、非离子表面活性剂、阴离子表面活性剂、增稠剂和抗氧化剂溶解于去离子水中，2-8℃搅拌均匀，得到混合溶液；
    S2、将保湿剂和香精加入步骤S1制得的混合溶液中，升温至室温，搅拌溶解后，加入抑菌剂，继续搅拌，得到原料混合物；
    S3、向步骤S2制得的原料混合物中加入pH调节剂，调节至pH＝7.5-8，继续搅拌均匀，装罐、包装，即得。
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