WO2020087766A1 - 一种苯并呋喃衍生物的用途 - Google Patents

一种苯并呋喃衍生物的用途 Download PDF

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WO2020087766A1
WO2020087766A1 PCT/CN2019/000113 CN2019000113W WO2020087766A1 WO 2020087766 A1 WO2020087766 A1 WO 2020087766A1 CN 2019000113 W CN2019000113 W CN 2019000113W WO 2020087766 A1 WO2020087766 A1 WO 2020087766A1
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agent
inflammatory
mass ratio
oral
thickener
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PCT/CN2019/000113
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English (en)
French (fr)
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曹华
郭鹏峰
王恩明
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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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • 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
    • 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
    • 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
    • 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

Definitions

  • the invention belongs to the application field of organic benzofuran derivatives, and particularly relates to the application of a benzofuran derivative.
  • Toothpaste is a cleaning product commonly used in daily life and has a long history. With the continuous development of science and technology, the continuous improvement and perfection of process equipment, various types of toothpaste have come out one after another. At present, it mainly includes ordinary clean toothpaste and bactericidal anti-inflammatory toothpaste. With the continuous improvement of people's living standards, tooth decay and tooth inflammatory diseases are particularly common. Therefore, antibacterial and anti-inflammatory toothpaste has become the mainstream of research.
  • Chinese patent application CN102871881A discloses an anti-inflammatory toothpaste.
  • the anti-inflammatory ingredients clove basil oil, borax and ginger oil are added to the effective ingredients of the toothpaste, which effectively improves the blood circulation of the gums, periodontal tissue and oral mucosa, and improves The supply of oral mucosa tissue nutrients enhances the disease resistance of gums, periodontal, teeth and oral mucosa.
  • borax is highly toxic. It is a banned product for food additives all over the world. If the human body consumes too much boron, it will cause cumulative poisoning of multiple organs. Therefore, it is urgent to develop a less toxic toothpaste. demand.
  • Chinese patent application CN108056988A discloses an anti-inflammatory toothpaste.
  • the anti-inflammatory toothpaste uses peppermint oil, paeonol, marigold, honeysuckle, and dandelion. It also has whitening and tooth whitening ingredients. , The curative effect is slow, and it needs long-term use to achieve a complete anti-inflammatory effect.
  • the present invention provides a use of benzofuran derivatives.
  • the benzofuran derivative provided by the present invention is used for preparing sterilization and anti-inflammatory daily necessities.
  • the benzofuran derivative is used for preparing sterilization and anti-inflammatory toothpaste, which has significant antibacterial, anti-inflammatory and gingival prevention Bleeding, improving the oral environment and analgesic effects, without adding any hormone drugs, has the advantages of high safety and low side effects.
  • benzofuran derivative is used to prepare toothpaste, which has functions of killing oral bacteria, eliminating oral inflammation, preventing gum bleeding, and / or improving oral environment.
  • the oral bacteria are one or more of Streptococcus A, Anaerobic Streptococcus, Staphylococcus epidermidis, Neisseria, and Lactobacillus.
  • oral inflammation is symptoms of oral redness, oral ulcer erosion.
  • a bactericidal anti-inflammatory toothpaste including the following components and their weight percentages:
  • bactericidal anti-inflammatory toothpaste includes the following components and their weight percentages:
  • bacteriostatic agent consists of honeysuckle essential oil and formula I
  • the benzofuran derivatives are composed 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 flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 4: 3-1; the foaming agent is ten Sodium dialkyl sulfate; the friction agent is calcium carbonate powder; and the thickener is hydroxyethyl cellulose.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3;
  • the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 2: 1.
  • a preparation method of bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1. After stirring and dissolving, add the flavoring agent and continue stirring to obtain the raw material mixture;
  • step S3 The paste prepared in step S3 is allowed to stand for 1-3 hours, allowed to cool naturally to room temperature, and then canned and packaged.
  • step S3 vacuum is applied to achieve a vacuum degree of 0.09-0.1 Mpa, and the time for vacuuming is 30-60 min; the temperature during the kneading and grinding is 45 ° C.
  • the present invention has the following beneficial effects:
  • the moisturizing agent of the present invention is compounded with propylene glycol and sorbitol to form a protective film on the surface of the gums to effectively prevent gum pollution and protect teeth and gums for a long time.
  • the flavoring agent of the present invention is compounded by lemon essential oil and eugenol, which has the effects of detoxification, deodorization and sterilization. It can also eliminate fatigue and invigorate the spirit while adjusting the odor and taste of toothpaste.
  • the bacteriostatic agent of the present invention is compounded with honeysuckle essential oil and the benzofuran derivative described in Formula I, which has good bactericidal and anti-inflammatory effects. At the same time, it cooperates with the flavoring agent composed of lemon essential oil and eugenol to achieve good The effect of sterilization and anti-inflammatory, deodorization and detoxification, hemostasis and pain relief and adjustment of the oral environment.
  • the present invention uses humectants, flavoring agents, foaming agents, friction agents, thickeners and bacteriostatic agents to coordinate with each other, and has obvious antibacterial and bactericidal effects, anti-inflammatory and analgesic, hemostasis and swelling.
  • Example 1 a bactericidal anti-inflammatory toothpaste
  • the bactericidal anti-inflammatory toothpaste consists of the following components and their mass percentage:
  • the benzofuran derivative is composed of a mass ratio of 7: 3.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 2; the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 4: 1; the foaming agent is sodium lauryl sulfate; The friction agent is calcium carbonate powder; the thickener is hydroxyethyl cellulose.
  • the preparation method of the bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1. After stirring and dissolving, add the flavoring agent and continue stirring to obtain the raw material mixture;
  • step S3 Stir, knead, and grind the raw material mixture prepared in step S2 at a temperature of 45 ° C, and at the same time evacuate for 30 min to bring the vacuum degree to 0.09 MPa to obtain a paste;
  • step S4 The paste prepared in step S3 is allowed to stand for 1 hour to allow it to cool naturally to normal temperature, and then canned and packaged.
  • Example 2 A bactericidal anti-inflammatory toothpaste
  • the bactericidal anti-inflammatory toothpaste includes the following components and their weight percentages:
  • the benzofuran derivative is composed of a mass ratio of 7: 6.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 4; the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 4: 3; the foaming agent is sodium lauryl sulfate; The friction agent is calcium carbonate powder; the thickener is hydroxyethyl cellulose.
  • the preparation method of the bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1. After stirring and dissolving, add the flavoring agent and continue stirring to obtain the raw material mixture;
  • step S3 Stir, knead, and grind the raw material mixture prepared in step S2 at a temperature of 45 ° C, and at the same time evacuate for 60 min to achieve a vacuum of 0.1 MPa to obtain a paste;
  • step S4 The paste prepared in step S3 is allowed to stand for 3 hours to allow it to naturally cool to normal temperature, and then canned and packaged.
  • Example 3 A bactericidal anti-inflammatory toothpaste
  • the bactericidal anti-inflammatory toothpaste includes the following components and their weight percentages:
  • bacteriostatic agent consists of honeysuckle essential oil and formula I
  • the benzofuran derivatives are composed in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3; the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 2: 1; the foaming agent is sodium lauryl sulfate; The friction agent is calcium carbonate powder; the thickener is hydroxyethyl cellulose.
  • the preparation method of the bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1. After stirring and dissolving, add the flavoring agent and continue stirring to obtain the raw material mixture;
  • step S3 Stir, knead, and grind the raw material mixture prepared in step S2 at a temperature of 45 ° C, and at the same time evacuate for 40 min, so that the degree of vacuum reaches 0.1 MPa to obtain a paste;
  • step S4 The paste prepared in step S3 is allowed to stand for 2 hours to allow it to naturally cool to normal temperature, and then canned and packaged.
  • Example 4 A bactericidal anti-inflammatory toothpaste
  • the bactericidal anti-inflammatory toothpaste includes the following components and their weight percentages:
  • bacteriostatic agent consists of honeysuckle essential oil and formula I
  • the benzofuran derivatives are composed in a mass ratio of 7: 4.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 2; the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 4: 1; the foaming agent is sodium lauryl sulfate; The friction agent is calcium carbonate powder; the thickener is hydroxyethyl cellulose.
  • the preparation method of the bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1, stir and dissolve, add flavoring agent, and continue stirring to obtain a raw material mixture;
  • step S3 Stir, knead, and grind the raw material mixture prepared in step S2 at a temperature of 45 ° C, and at the same time evacuate for 50 min to bring the vacuum degree to 0.09 MPa to obtain a paste;
  • step S4 The paste prepared in step S3 is allowed to stand for 2.5 hours to allow it to naturally cool to normal temperature, and then canned and packaged.
  • the bactericidal anti-inflammatory toothpaste includes the following components and their weight percentages:
  • the benzofuran derivative is composed of 1: 1 mass ratio.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3; the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 2: 1; the foaming agent is sodium lauryl sulfate; The friction agent is calcium carbonate powder; the thickener is hydroxyethyl cellulose.
  • the preparation method of the bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1. After stirring and dissolving, add the flavoring agent and continue stirring to obtain the raw material mixture;
  • step S3 Stir, knead, and grind the raw material mixture prepared in step S2 at a temperature of 45 ° C, and at the same time evacuate for 40 min, so that the degree of vacuum reaches 0.1 MPa to obtain a paste;
  • step S4 The paste prepared in step S3 is allowed to stand for 2 hours to allow it to naturally cool to normal temperature, and then canned and packaged.
  • Comparative Example 1 is basically the same as Example 3, except that the mass ratio of the bacteriostatic agent honeysuckle essential oil and the benzofuran derivative of Formula I is changed from 7: 5 to 1: 1.
  • the bactericidal anti-inflammatory toothpaste includes the following components and their weight percentages:
  • bacteriostatic agent is honeysuckle essential oil.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3; the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 2: 1; the foaming agent is sodium lauryl sulfate; The friction agent is calcium carbonate powder; the thickener is hydroxyethyl cellulose.
  • the preparation method of the bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1. After stirring and dissolving, add the flavoring agent and continue stirring to obtain the raw material mixture;
  • step S3 Stir, knead, and grind the raw material mixture prepared in step S2 at a temperature of 45 ° C, and at the same time evacuate for 40 min, so that the degree of vacuum reaches 0.1 MPa to obtain a paste;
  • step S4 The paste prepared in step S3 is allowed to stand for 2 hours to allow it to naturally cool to normal temperature, and then canned and packaged.
  • Comparative Example 2 is basically the same as Example 3, except that the bacteriostatic agent is a single component honeysuckle essential oil.
  • the bactericidal anti-inflammatory toothpaste includes the following components and their weight percentages:
  • bacteriostatic agent consists of honeysuckle essential oil and formula I
  • the benzofuran derivatives are composed in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 1: 1; the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 2: 1; the foaming agent is sodium lauryl sulfate; The friction agent is calcium carbonate powder; the thickener is hydroxyethyl cellulose.
  • the preparation method of the bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1. After stirring and dissolving, add the flavoring agent and continue stirring to obtain the raw material mixture;
  • step S3 Stir, knead, and grind the raw material mixture prepared in step S2 at a temperature of 45 ° C, and at the same time evacuate for 40 min, so that the degree of vacuum reaches 0.1 MPa to obtain a paste;
  • step S4 The paste prepared in step S3 is allowed to stand for 2 hours to allow it to naturally cool to normal temperature, and then canned and packaged.
  • Comparative Example 3 is basically the same as Example 3, except that the mass ratio of the moisturizer propylene glycol and sorbitol is changed from 5: 3 to 1: 1.
  • the bactericidal anti-inflammatory toothpaste includes the following components and their weight percentages:
  • bacteriostatic agent consists of honeysuckle essential oil and formula I
  • the benzofuran derivatives are composed in a mass ratio of 7: 5.
  • the humectant is composed of propylene glycol and sorbitol in a mass ratio of 5: 3; the flavoring agent is composed of lemon essential oil and eugenol in a mass ratio of 1: 1; the foaming agent is sodium lauryl sulfate; The friction agent is calcium carbonate powder; the thickener is hydroxyethyl cellulose.
  • the preparation method of the bactericidal anti-inflammatory toothpaste includes the following steps:
  • step S2 Add the bacteriostatic agent to the mixed solution prepared in step S1. After stirring and dissolving, add the flavoring agent and continue stirring to obtain the raw material mixture;
  • step S3 Stir, knead, and grind the raw material mixture prepared in step S2 at a temperature of 45 ° C, and at the same time evacuate for 40 min, so that the degree of vacuum reaches 0.1 MPa to obtain a paste;
  • step S4 The paste prepared in step S3 is allowed to stand for 2 hours to allow it to naturally cool to normal temperature, and then canned and packaged.
  • Comparative Example 4 is basically the same as Example 3, except that the mass ratio of the lemon essential oil and eugenol is changed from 2: 1 to 1: 1.
  • Test example one clinical trial
  • Test materials Example 1, Example 2, Example 3, Example 4, Comparative Example 1, Comparative Example 2, Comparative Example 3 and Comparative Example 4 prepared bactericidal anti-inflammatory toothpaste.
  • Test subjects Randomly select 180 cases with inflammation of the gums, swelling and pain of the gums, redness and swelling of the oral cavity, and erosion of oral ulcers, 90 males and one female.
  • Test method 180 cases were randomly divided into 9 groups, 20 cases in each group, using Example 1, Example 2, Example 3, Example 4, Comparative Example 1, Comparative Example 2, Comparative Example 3 and The bactericidal anti-inflammatory toothpaste prepared in Comparative Example 4 and recorded as Example 1, Group 2, Group 3, Group 3, Example 4, Group 1, Group 2, Group 3, Group 4 and Group 4
  • the control group uses the commercially available Yunnan Baiyao anti-inflammatory toothpaste, which is recorded as the control group.
  • the oral hygiene education should be uniformly taught and the correct brushing method should be taught. It is required to brush the teeth twice a day, 3 minutes each time. After 1 week of toothpaste, the clinical effects were evaluated in two stages.
  • the evaluation criteria were: recovery: inflammation of the gums, swelling of the gums, swelling of the oral cavity, and symptoms of oral ulcer erosion completely disappeared; basic healing: inflammation of the gums, swelling and swelling of the gums, disappearance of oral swelling, oral The symptoms of ulcer erosion improved; effective: gum inflammation, gum swelling, and oral swelling improved; ineffective: gum inflammation, gum swelling, oral redness, and oral ulcer erosion symptoms did not improve.
  • Test results The test results are shown in Table 1.
  • Test example two oral colony count
  • Test materials Example 1, Example 2, Example 3, Example 4, Comparative Example 1, Comparative Example 2, Comparative Example 3 and Comparative Example 4 prepared bactericidal anti-inflammatory toothpaste.
  • Example 1 After coating, 5 equidistant holes were punched in the medium with a sterile stainless steel punch with an outer diameter of 4 mm.
  • Draw 30 ⁇ L of antibacterial and anti-inflammatory toothpaste solution prepared in Example 1, Example 2, Example 3, Example 4, Comparative Example 1, Comparative Example 2, Comparative Example 3 and Comparative Example 4 add an equal amount of normal saline in the middle hole as a control Group, make a mark.
  • the bacteria were cultured at 37 ° C for 24h, and the diameter of the inhibition zone (in mm of inhibition diameter) was measured. The test was repeated 5 times, and the average value of 5 times was used as the inhibition zone diameter.
  • the antibacterial and anti-inflammatory toothpaste prepared by the present invention has an antibacterial diameter greater than 25.8 mm for Streptococcus A, an antibacterial diameter greater than 34.5 mm for anaerobic streptococci, and an antibacterial diameter greater than 33.2 mm for Staphylococcus epidermidis.
  • the antibacterial diameter of Neisseria is greater than 32.7mm, and the antibacterial diameter of Lactobacillus is greater than 31.6mm.
  • the comparative example 1, the comparative example 2, the comparative example 3 and the comparative example 4 have a lower bacteriostatic effect than the bactericidal anti-inflammatory toothpaste prepared in Examples 1-4 of the present invention, indicating that the lemon essential oil and eugenol provided by the present invention , Honeysuckle essential oil and benzofuran derivatives shown in formula I cooperate with each other to enhance the bacteriostatic effect.

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Abstract

式Ⅰ的苯并呋喃衍生物用于制备杀菌、消炎日用品的用途。该苯并呋喃衍生物用于杀菌消炎牙膏的用途，所述杀菌消炎牙膏具有抑菌、消炎、防止牙龈出血、改善口腔环境和镇痛的效果，同时不添加激素类药物。

Description

一种苯并呋喃衍生物的用途 技术领域
本发明属于有机苯并呋喃衍生物用途领域，具体涉及一种苯并呋喃衍生物的用途。
背景技术
牙膏是日常生活中常用的清洁用品，有着很悠久的历史。随着科学技术的不断发展，工艺装备的不断改进和完善，各种类型的牙膏相继问世，目前主要包括普通的清洁型牙膏和杀菌消炎型牙膏。而随着人们生活水平的不断提高，蛀牙以及牙齿炎症疾病尤为常见，因此，抑菌消炎型牙膏成为研究的主流。
中国专利申请CN102871881A公开了一种消炎牙膏，该牙膏有效成分中添加消炎成分丁香罗勒油、硼砂和生姜油，有效地改善了牙龈、牙周组织和口腔黏膜的血液循环，提高了牙周组织和口腔黏膜组织养分的供给，增强牙龈、牙周、牙齿和口腔黏膜的抗病能力。然而，硼砂毒性较高，为世界各国食品添加物的禁用品，若人体摄入过多的硼，会引发多脏器的蓄积性中毒，因此，研发一种毒性较小的牙膏成为一种迫切需求。
中国专利申请CN108056988A公开了一种消炎牙膏，该牙膏消炎成分采用薄荷油，丹皮，万寿菊，金银花，蒲公英，同时加入美白牙齿的成分，具有美白消炎双重效果，但该牙膏采用重要成分进行消炎，疗效较慢，需要长期使用，才能达到彻底消炎的效果。
因此，研发一种消炎效果好，疗效快，毒性低的牙膏成为一种必要。
发明内容
为了解决现有技术中的不足，本发明提供了一种苯并呋喃衍生物的用途。本发明提供的苯并呋喃衍生物用于制备杀菌、消炎日用品的用途，所述苯并呋喃衍生物用于制备杀菌消炎牙膏的用途，所述杀菌消炎牙膏具有显著的抑菌、消炎、防止牙龈出血、改善口腔环境和镇痛效果，同时还不添加任何激素类药物，具有安全性高、副作用低的优点。
本发明通过以下技术方案实现：
式I的苯并呋喃衍生物用于制备杀菌、消炎日用品的用途，
Figure PCTCN2019000113-appb-000001
进一步的，所述苯并呋喃衍生物用于制备牙膏，所述牙膏具有杀灭口腔细菌、消灭口腔炎症、防止牙龈出血和/或改善口腔环境的功能。
进一步的，所述口腔细菌为甲型链球菌、厌氧链球菌、表皮葡萄球菌、奈瑟氏菌、乳杆菌中的一种或多种。
进一步的，所述口腔炎症为口腔红肿、口腔溃疡糜烂症状。
一种杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂15-30％、调味剂0.6-1％、发泡剂1.3-2.0％、摩擦剂20-40％、增稠剂0.1-1％、抑菌剂1-3％，去离子水23-62％；所述抑菌剂由金银花精油和式I所述的苯并呋喃衍生物按质量比7∶3-6组成。
进一步的，所述杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂22％、调味剂0.8％、发泡剂1.7％、摩擦剂27％、增稠剂0.7％、抑菌剂2.8％、去离子水45％；所述抑菌剂由金银花精油和式I所述的苯并呋喃衍生物按质量比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；所述调味剂为由柠檬精油和丁香酚按质量比4∶3-1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
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；所述调味剂为由柠檬精油和丁香酚按质量比2∶1组成。
一种杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物进行搅拌、捏合、研磨，同时抽真空，得到膏体；
S4、将步骤S3制得的膏体静置1-3小时，使其自然冷却至常温，装罐、包装，即得。
进一步的，所述步骤S3中，抽真空使真空度达到0.09-0.1Mpa，抽真空的时间为30-60min；所述捏合、研磨时温度为45℃。
与现有技术相比，本发明具有如下有益效果：
(1)本发明保湿剂采用丙二醇和山梨醇复配，在牙龈表面形成一层保护膜，有效防止牙龈污染，长效保护牙齿及牙龈。
(2)本发明调味剂采用由柠檬精油和丁香酚按复配，具有解毒、除臭、杀菌的功效，在调节牙膏气味口感的同时，还具有消除疲倦、振奋精神的作用。
(3)本发明抑菌剂采用金银花精油和式I所述的苯并呋喃衍生物复配，具有良好的杀菌消炎作用，同时，与由柠檬精油和丁香酚组成的调味剂相互协同，达到良好的杀菌消炎、除臭解毒、止血止痛和调节口腔环境的功效。
(4)本发明采用保湿剂、调味剂、发泡剂、摩擦剂、增稠剂和抑菌剂相互协调，具有明显的抑菌杀菌，消炎止痛，止血消肿的作用。
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、一种杀菌消炎牙膏
所述杀菌消炎牙膏，由以下组分及其质量百分比组成：
保湿剂15％、调味剂0.6％、发泡剂1.3％、摩擦剂20％、增稠剂0.1％、抑菌剂1％，去离子水62％；所述抑菌剂由金银花精油和式I 所述的苯并呋喃衍生物按质量比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；所述调味剂由柠檬精油和丁香酚按质量比4∶1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
所述杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物在温度为45℃时，进行搅拌、捏合、研磨，同时抽真空的时间为30min，使真空度达到0.09Mpa，得到膏体；
S4、将步骤S3制得的膏体静置1小时，使其自然冷却至常温，装罐、包装，即得。
实施例2、一种杀菌消炎牙膏
所述杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂30％、调味剂1％、发泡剂2.0％、摩擦剂40％、增稠剂1％、抑菌剂3％，去离子水23％；所述抑菌剂由金银花精油和式I所述的苯并呋喃衍生物按质量比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；所述调味剂由柠檬精油和丁香酚按质量比4∶3组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
所述杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物在温度为45℃时，进行搅拌、捏合、研磨，同时抽真空的时间为60min，使真空度达到0.1Mpa，得到膏体；
S4、将步骤S3制得的膏体静置3小时，使其自然冷却至常温，装 罐、包装，即得。
实施例3、一种杀菌消炎牙膏
所述杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂22％、调味剂0.8％、发泡剂1.7％、摩擦剂27％、增稠剂0.7％、抑菌剂2.8％、去离子水45％；所述抑菌剂由金银花精油和式I所述的苯并呋喃衍生物按质量比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；所述调味剂由柠檬精油和丁香酚按质量比2∶1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
所述杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物在温度为45℃时，进行搅拌、捏合、研磨，同时抽真空的时间为40min，使真空度达到0.1Mpa，得到膏体；
S4、将步骤S3制得的膏体静置2小时，使其自然冷却至常温，装罐、包装，即得。
实施例4、一种杀菌消炎牙膏
所述杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂25％、调味剂0.9％、发泡剂1.6％、摩擦剂35％、增稠剂0.5％、抑菌剂2％，去离子水35％；所述抑菌剂由金银花精油和式I所述的苯并呋喃衍生物按质量比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；所述调味剂由柠檬精油和丁香酚按质量比4∶1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
所述杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入 调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物在温度为45℃时，进行搅拌、捏合、研磨，同时抽真空的时间为50min，使真空度达到0.09Mpa，得到膏体；
S4、将步骤S3制得的膏体静置2.5小时，使其自然冷却至常温，装罐、包装，即得。
对比例1、一种杀菌消炎牙膏
所述杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂22％、调味剂0.8％、发泡剂1.7％、摩擦剂27％、增稠剂0.7％、抑菌剂2.8％、去离子水45％；所述抑菌剂由金银花精油和式I所述的苯并呋喃衍生物按质量比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；所述调味剂由柠檬精油和丁香酚按质量比2∶1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
所述杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物在温度为45℃时，进行搅拌、捏合、研磨，同时抽真空的时间为40min，使真空度达到0.1Mpa，得到膏体；
S4、将步骤S3制得的膏体静置2小时，使其自然冷却至常温，装罐、包装，即得。
对比例1与实施例3基本相同，不同在于，所述抑菌剂金银花精油和式I所述的苯并呋喃衍生物的质量比由7∶5变为1∶1。
对比例2、一种杀菌消炎牙膏
所述杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂22％、调味剂0.8％、发泡剂1.7％、摩擦剂27％、增稠剂0.7％、抑菌剂2.8％、去离子水45％；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；所述调味剂为 由柠檬精油和丁香酚按质量比2∶1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
所述杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物在温度为45℃时，进行搅拌、捏合、研磨，同时抽真空的时间为40min，使真空度达到0.1Mpa，得到膏体；
S4、将步骤S3制得的膏体静置2小时，使其自然冷却至常温，装罐、包装，即得。
对比例2与实施例3基本相同，不同在于，所述抑菌剂为单一成分金银花精油。
对比例3、一种杀菌消炎牙膏
所述杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂22％、调味剂0.8％、发泡剂1.7％、摩擦剂27％、增稠剂0.7％、抑菌剂2.8％、去离子水45％；所述抑菌剂由金银花精油和式I所述的苯并呋喃衍生物按质量比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；所述调味剂为由柠檬精油和丁香酚按质量比2∶1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
所述杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物在温度为45℃时，进行搅拌、捏合、研磨，同时抽真空的时间为40min，使真空度达到0.1Mpa，得到膏体；
S4、将步骤S3制得的膏体静置2小时，使其自然冷却至常温，装 罐、包装，即得。
对比例3与实施例3基本相同，不同在于，所述保湿剂丙二醇和山梨醇的质量比由5∶3变为1∶1。
对比例4、一种杀菌消炎牙膏
所述杀菌消炎牙膏，包括以下组分及其重量百分比：
保湿剂22％、调味剂0.8％、发泡剂1.7％、摩擦剂27％、增稠剂0.7％、抑菌剂2.8％、去离子水45％；所述抑菌剂由金银花精油和式I所述的苯并呋喃衍生物按质量比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；所述调味剂为由柠檬精油和丁香酚按质量比1∶1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
所述杀菌消炎牙膏的制备方法，包括如下步骤：
S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
S3、将步骤S2制得的原料混合物在温度为45℃时，进行搅拌、捏合、研磨，同时抽真空的时间为40min，使真空度达到0.1Mpa，得到膏体；
S4、将步骤S3制得的膏体静置2小时，使其自然冷却至常温，装罐、包装，即得。
对比例4与实施例3基本相同，不同在于，所述调味剂柠檬精油和丁香酚的质量比由2∶1变为1∶1。
试验例一、临床试验
1、试验材料：实施例1、实施例2、实施例3、实施例4、对比例1、对比例2、对比例3和对比例4制备的杀菌消炎牙膏。
2、试验对象：随机选取180名有牙龈发炎、牙龈肿痛、口腔红肿、口腔溃疡糜烂症状的病例，男女各90名。
3、试验方法：随机将180名病例分为9组，每组20例，分别使用实施例1、实施例2、实施例3、实施例4、对比例1、对比例2、对比例3和对比例4制备的杀菌消炎牙膏，并记为实施例1组、实施例2 组、实施3组、实施例4组、对比例1组、对比例2组、对比例3组和对比例4组，对照组使用市售的云南白药消炎牙膏，记为对照组，实验前统一进行口腔卫生教育并教会正确的刷牙方式，要求每天早晚刷牙2次，每次3min，对每个病例进行用前以及用牙膏1周后两个阶段的临床效果评价，评价标准：痊愈：牙龈发炎、牙龈肿痛、口腔红肿、口腔溃疡糜烂症状完全消失；基本痊愈：牙龈发炎、牙龈肿痛、口腔红肿消失，口腔溃疡糜烂症状好转；有效：牙龈发炎、牙龈肿痛、口腔红肿好转；无效：牙龈发炎、牙龈肿痛、口腔红肿、口腔溃疡糜烂症状均未出现好转。
4、试验结果：试验结果如表1所示。
表1临床试验效果数据
表1 临床试验效果数据
Figure PCTCN2019000113-appb-000002
由表1可知，实施例1-4组痊愈人数均大于10人，且无效人数均小于1人，其中实施例3组效果最好，无效人数为0，为本发明的最佳实施例，相比而言，对比例1-4组与对照组的痊愈人数均小于8人，无效人数均大于5人，结果表明，本发明制备的杀菌消炎牙膏具有良好的杀菌消炎、止痛消肿作用，并且对口腔红肿、口腔溃疡糜烂有很好的疗效。
试验例二、口腔菌落计数
1、试验材料：实施例1、实施例2、实施例3、实施例4、对比例1、对比例2、对比例3和对比例4制备的杀菌消炎牙膏。
2、供试菌的制备
在无菌操作室中分别将甲型链球菌、厌氧链球菌、表皮葡萄球菌、奈瑟氏菌和乳杆菌接种至牛肉膏培养液中，在30-32℃条件下进行常规培养。
3、试验方法：
采用琼脂打孔扩散法，将无菌培养皿分为9组，每组5个，将灭菌后的牛肉膏培养液倒入无菌培养皿中，每皿15～20mL，待其凝固后用无菌移液管吸取0.1mL甲型链球菌、厌氧链球菌、表皮葡萄球菌、奈瑟氏菌和乳杆菌供试菌加到培养皿上，涂布均匀，每组每个培养皿加入不同的菌种。
涂布完毕后，然后用外径4mm的灭菌不锈钢打孔器在培养基上打5个等距离的孔。将实施例1、实施例2、实施例3、实施例4、对比例1、对比例2、对比例3和对比例4制备的杀菌消炎牙膏用无菌水完全溶解，用微量加样器分别吸取实施例1、实施例2、实施例3、实施例4、对比例1、对比例2、对比例3和对比例4制备的杀菌消炎牙膏溶液30μL，中间一孔添加等量生理盐水做对照组，做好标记。将细菌置于37℃下培养24h，量取抑菌圈直径(抑菌直径mm计)，试验重复5次，以5次平均值为抑菌圈直径。
4、试验结果
试验结果如表1所示。
表1杀菌消炎牙膏的抑菌试验数据
Figure PCTCN2019000113-appb-000003
由表1可知，本发明制备的杀菌消炎牙膏对甲型链球菌的抑菌直径大于25.8mm，对厌氧链球菌的抑菌直径大于34.5mm、对表皮葡萄球菌的抑菌直径大于33.2mm、对奈瑟氏菌的抑菌直径大于32.7mm，对乳杆菌的抑菌直径大于31.6mm，对甲型链球菌、厌氧链球菌、表皮葡萄球菌、奈瑟氏菌和乳杆菌具有显著的抑制作用，而对比例1、对比例2、对比例3和对比例4的抑菌效果比本发明实施例1-4制备的杀菌消炎牙膏的效果差，说明本发明提供的齐柠檬精油、丁香酚、金银花精油和式I所示的苯并呋喃衍生物相互协同起到增强抑菌的作用。
上述实施例仅例示性说明本发明的原理及其功效，而非用于限制本发明。任何熟悉此技术的人士皆可在不违背本发明的精神及范畴下，对上述实施例进行修饰或改变。因此，举凡所属技术领域中具有通常知识者在未脱离本发明所揭示的精神与技术思想下所完成的一切等效修饰或改变，仍应由本发明的权利要求所涵盖。

Claims (10)

  1. 式I的苯并呋喃衍生物用于制备杀菌、消炎日用品的用途，
    Figure PCTCN2019000113-appb-100001
  2. 如权利要求1所述的用途，其特征在于，所述苯并呋喃衍生物用于制备牙膏，所述牙膏具有杀灭口腔细菌、消灭口腔炎症、防止牙龈出血和/或改善口腔环境的功能。
  3. 如权利要求2所述的用途，其特征在于，所述口腔细菌为甲型链球菌、厌氧链球菌、表皮葡萄球菌、奈瑟氏菌、乳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，所述口腔炎症为口腔红肿、口腔溃疡糜烂症状。
  5. 一种杀菌消炎牙膏，其特征在于，包括以下组分及其质量百分比：
    保湿剂15-30％、调味剂0.6-1.0％、发泡剂1.3-2.0％、摩擦剂20-40％、增稠剂0.1-1.0％、抑菌剂1.0-3.0％，去离子水23-62％；所述抑菌剂由金银花精油和权利要求1所述的苯并呋喃衍生物按质量比7∶3-6组成。
  6. 如权利要求5所述的杀菌消炎牙膏，其特征在于，包括以下组分及其质量百分比：
    保湿剂22％、调味剂0.8％、发泡剂1.7％、摩擦剂27％、增稠剂0.7％、抑菌剂2.8％、去离子水45％；所述抑菌剂由金银花精油和权利要求1所述的苯并呋喃衍生物按质量比7∶5组成。
  7. 如权利要求5或6所述的杀菌消炎牙膏，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；所述调味剂由柠檬精油和丁香酚按质量比4∶3-1组成；所述发泡剂为十二烷基硫酸钠；所述摩擦剂为碳酸钙粉末；所述增稠剂为羟乙基纤维素。
  8. 如权利要求7所述的杀菌消炎牙膏，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；所述调味剂由柠檬精油和丁香酚按质量比2∶1组成。
  9. 一种如权利要求5所述的杀菌消炎牙膏的制备方法，其特征在于，包括如下步骤：
    S1、将保湿剂、发泡剂、摩擦剂和增稠剂溶解于去离子水中，得到混合溶液；
    S2、将抑菌剂加入步骤S1制得的混合溶液中，搅拌溶解后，加入调味剂，继续搅拌，得到原料混合物；
    S3、将步骤S2制得的原料混合物进行搅拌、捏合、研磨，同时抽真空，得到膏体；
    S4、将步骤S3制得的膏体静置1-3小时，使其自然冷却至常温，装罐、包装，即得。
  10. 如权利要求9所述的杀菌消炎牙膏的制备方法，其特征在于：所述步骤S3中，抽真空使真空度达到0.09-0.1Mpa，抽真空的时间为30-60min；所述捏合、研磨时温度为45℃。
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