Traditional Chinese medicine oral gargle for tissue repair and preparation method thereof
By combining the small molecule peptide of plant extract with the new organic compound HMPA, the problem of traditional oral gargle dysregulation and poor repair effect on oral bacterial dysbiosis and achieving efficient antibacterial, anti-inflammatory and tissue repair effects.
Patent Information
- Application Number
- CN202510053319.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-14
- Publication Date
- 2025-05-13
AI Technical Summary
Traditional oral gargle relies on chemical synthesis of antibacterial ingredients, resulting in oral bacterial imbalance, weakening immune defense, and difficulty in effectively repairing oral tissue. At the same time, the oral products containing Chinese medicine ingredients in the market are extensive, the ingredients are not fully dissolved, the formula design is not scientific enough, and it is difficult to meet the high requirements of oral health.
The small molecule peptide of plant extracts (such as honeysuckle, perilla, and Agastache extract) is combined with the new organic compound HMPA (3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl)propanamide), and a unique small molecule peptide sequence is obtained through enzymatic lysis, separation and purification technology. Combined with HMPA, a synergistic effect is formed to achieve antibacterial, anti-inflammatory and tissue repair.
It has achieved precise inhibition of harmful bacteria and triggered the oral tissue repair process. It has a more targeted and more efficient system to ensure the stability of the active ingredients of the gargle and significantly improve the oral tissue repair effect.
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of biomedicine, and in particular to a tissue repair Chinese medicine oral rinse and a preparation method thereof. Background Art
[0002] Traditional oral rinses mostly rely on chemically synthesized antibacterial ingredients. Common ingredients such as chlorhexidine can quickly inhibit bacterial growth, but they lack consideration for the balance of oral microecology. Long-term use can easily lead to oral flora imbalance, thereby weakening the oral cavity's own immune defense function, hindering the mucosal repair process and causing repeated inflammation that is difficult to heal.
[0003] At the same time, the number of oral products containing Chinese herbal ingredients on the market is gradually increasing, but the current situation is not optimistic. On the one hand, the extraction process is relatively extensive, mostly using simple water boiling or low-concentration alcohol extraction, resulting in the inability to fully dissolve many highly active ingredients contained in Chinese herbal medicines such as honeysuckle, perilla, and patchouli; on the other hand, the formula design is not scientific enough, simply mixing several extracts without deeply exploring the synergistic effects of the various ingredients, making the product weak in anti-inflammatory and oral tissue repair, and difficult to meet consumers' high requirements for oral health.
[0004] With the vigorous development of biotechnology and materials science, the physiological activities of small molecule peptides are constantly being revealed, and their application in the fields of medicine and skin care has achieved remarkable results; new organic compounds are carefully designed to carry a variety of functional groups and show unique antioxidant and targeted delivery properties. Introducing these cutting-edge results into the field of oral rinses and combining them with traditional Chinese medicine extracts is expected to break the current dilemma and develop innovative products that can accurately inhibit harmful bacteria and promote oral tissue repair in all directions. Summary of the invention
[0005] The invention provides a tissue repair Chinese medicine oral rinse, comprising plant extract, tocopherol acetate, xylitol, polysorbate, preservative, sodium citrate, purified water and organic compound 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide; the plant extract is a plant extract small molecule peptide; the plants are honeysuckle, perilla and patchouli.
[0006] Preferably, the amino acid sequence of the small molecule peptide from the honeysuckle extract is tryptophan-cysteine-valine-arginine-leucine-glycine-proline; the amino acid sequence of the small molecule peptide from the perilla extract is methionine-phenylalanine-histidine-tyrosine-isoleucine-serine-threonine; the amino acid sequence of the small molecule peptide from the patchouli extract is lysine-arginine-glutamic acid-alanine-glycine-asparagine-leucine.
[0007] Preferably, the gargle comprises: 80-82 parts of purified water, 3-6 parts of honeysuckle extract, 2-4 parts of perilla extract, 2-3 parts of patchouli extract, 6-8 parts of xylitol, 3-4 parts of organic compound 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide, 2-3 parts of tocopherol acetate, 1-1.2 parts of polysorbate 80, and the preservatives are 0.4-0.5 parts of sodium benzoate or methylparaben and 0.4-0.5 parts of sodium citrate.
[0008] Preferably, the plant may also be Centella asiatica, mint and perilla, or Astragalus, Phellodendron bark and Bletilla striata tuber; or Hamamelis virginiana, Cineraria officinalis and Seabuckthorn, or Rose, Osmanthus fragrans and Clove; or Licorice, Gynostemma pentaphyllum and Rosemary.
[0009] Preferably, the method for preparing the tissue repair Chinese medicine oral rinse comprises the following steps:
[0010] (1) preparing plant extract small molecule peptides and synthesizing the organic compound 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide respectively for later use;
[0011] (2) adding xylitol and tocopherol acetate to water at 40-50° C. and stirring until dissolved to obtain a base solution;
[0012] (3) adding polysorbate 80, stirring, and adding plant extract small molecule peptides and 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide, and continuing stirring;
[0013] (4) pH value is adjusted to 5.5-6.5, preservative is added, stirred and sterilized by microporous filter membrane filtration to obtain tissue repair Chinese medicine oral rinse. Preferably, the method for preparing the plant-derived small molecule peptide is as follows: the plant is crushed, ultrasonically extracted with ethanol-water mixture to obtain a crude extract, the crude extract is hydrolyzed with protease, the enzyme is inactivated, and then the target extract small molecule peptide is obtained by ultrafiltration, ion exchange chromatography and drying.
[0014] Preferably, the mass volume ratio of the crushed plant to the ethanol-water mixture is 1:10-15, the concentration of ethanol in the ethanol-water mixture is 60-85%; the extraction temperature is 45-70°C, and the extraction time is 30min-4h.
[0015] Preferably, the concentration of the crude extract is 10-20wt%; the protease is trypsin, papain or alkaline protease; the amount of the protease is 2-3wt% of the crude extract; the enzymolysis temperature is 37-45°C, and the time is 4-5h.
[0016] Preferably, the preparation steps of the organic compound 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl)propionamide are:
[0017] 1) mixing hydroxyanisole, epichlorohydrin, anhydrous carbonic acid as a catalyst and toluene as a solvent, heating the mixture under reflux for reaction, filtering, and removing the solvent by distillation under reduced pressure to obtain an intermediate product, 4-(chloropropoxy)-2-methoxyphenol;
[0018] 2) stirring the intermediate product and ethanolamine to react in a system with a pH value of 9-10; then neutralizing, distilling under reduced pressure to remove the solvent, and purifying by recrystallization to obtain the product 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide.
[0019] Preferably, in step 1), the molar ratio of p-hydroxyanisole to epichlorohydrin is 1:1.2; the heating reflux reaction time is 6-8 hours; in step 2), the molar ratio of the intermediate product to ethanolamine is 0.8:1; the heating reaction temperature is 60-70°C and the time is 4-6 hours.
[0020] Beneficial technical effects:
[0021] The new small molecule peptide sequence, HMPA and traditional Chinese medicine extracts work together to form a synergistic effect in antibacterial, anti-inflammatory and tissue repair, far exceeding the single antibacterial mode of existing mouthwashes. Targeted tissue repair mechanism: obtained through special enzymatic hydrolysis, separation and purification processes, this unique small molecule peptide sequence gives it outstanding antibacterial and anti-inflammatory properties, accurately strikes harmful oral bacteria, and triggers the tissue repair process; the unique small molecule peptide sequence can specifically identify and act on damaged cell targets, and cooperate with HMPA to accelerate cell regeneration and tissue remodeling, which is more targeted. Stable and efficient system guarantee: from moisturizing, preservation to pH adjustment, all ingredients work together to maintain the stability of the active ingredients of the mouthwash and ensure the repair effect. DETAILED DESCRIPTION
[0022] Example 1
[0023] Key formulas and components: Purified water: 80 parts, as a basic solvent, provides a medium for uniformly dispersing the ingredients in the mouthwash system, ensuring the mouthwash has a stable and uniform texture and is easy to store and use. Small molecule peptides from honeysuckle extract: the sequence is tryptophan-cysteine-valine-arginine-leucine-glycine-proline (WCVRGLP), 5 parts. Obtained through a special enzymatic hydrolysis, separation and purification process, this unique sequence gives it outstanding antibacterial and anti-inflammatory properties, accurately strikes harmful oral bacteria, and triggers the tissue repair process. During preparation, the honeysuckle is first crushed, extracted with a hot reflux extraction of an ethanol-water mixture in a specific ratio, the crude extract is hydrolyzed by protease, and then the target small molecule peptide is obtained by ultrafiltration, ion exchange chromatography and other means.
[0024] Small molecule peptide from Perilla extract: The sequence is methionine-phenylalanine-histidine-tyrosine-isoleucine-serine-threonine (MFHYIST), 3 copies. The unique amino acid sequence not only helps regulate oral flora, but also accelerates the renewal of damaged mucosal cells and promotes repair. The extraction process includes steps such as crushing, solvent extraction, enzymatic hydrolysis, and multi-stage membrane filtration separation.
[0025] Patchouli extract small molecule peptide: the sequence is lysine-arginine-glutamic acid-alanine-glycine-asparagine-leucine (KREAGNL), 2 parts. It can enhance the overall antibacterial and antiviral ability, and cooperate with the first two to build a healthy microenvironment for oral repair. The extraction method is similar to the above.
[0026] The preparation process of the honeysuckle extract small molecule peptide is as follows: extraction: take dry, mildew-free honeysuckle, crush it to 20-40 mesh, add 70% ethanol solution at a solid-liquid ratio of 1:10 (g / mL), perform ultrasonic-assisted extraction at 50°C for 30 minutes, the ultrasonic power is 300W, repeat the extraction twice, combine the extracts, and concentrate under reduced pressure to recover ethanol to obtain a crude honeysuckle extract.
[0027] Enzymatic hydrolysis: The crude extract of honeysuckle is prepared into a solution with a concentration of 10% with deionized water, the pH is adjusted to 7.5, and trypsin is added according to 2% of the substrate protein mass, and the solution is hydrolyzed at 45°C for 4 hours. After the hydrolysis is completed, the temperature is raised to 90°C to inactivate the enzyme for 10 minutes. Separation and purification: After cooling, centrifugation is performed, and the supernatant is taken, and the peptides in the range of 5-10kDa are collected, and then further purified by ion exchange chromatography, and freeze-dried to obtain the small molecule peptides of honeysuckle extract. Sequencing: Take an appropriate amount of freeze-dried small molecule peptides of honeysuckle extract and re-dissolve them with deionized water to a concentration of 1mg / mL. Add an equal volume of acetonitrile for protein precipitation, centrifuge and take the supernatant, and after vacuum concentration and drying, use liquid chromatography tandem mass spectrometry (LC-MS / MS) for sequencing. The sample is injected into a high performance liquid chromatograph, and acetonitrile-water (containing 0.1% formic acid) is used as the mobile phase for gradient elution to separate the peptides. It then entered the mass spectrometer and ionized in the positive ion mode of the electrospray ion source (ESI). By detecting the mass-to-charge ratio of the ion fragments and combining with database retrieval, the amino acid sequence of the small molecule peptide was determined to be tryptophan-cysteine-valine-arginine-leucine-glycine-proline (WCVRGLP).
[0028] The preparation process of the small molecule peptide of the perilla extract is as follows: extraction: select the whole perilla plant, wash and dry it, crush it to 30-50 mesh, add 60% ethanol at a solid-liquid ratio of 1:12 (g / mL), reflux and extract at 65°C for 2 hours, filter, collect the filtrate, repeat the extraction of the filter residue once, combine the two filtrates, and remove the ethanol under reduced pressure and concentrate to obtain the perilla crude extract. Enzymolysis: The perilla crude extract is prepared into a 15% aqueous solution, the pH is adjusted to 6.8, 3% of the substrate mass of papain is added, and the enzyme is hydrolyzed at 37°C for 5 hours, and then heated to 95°C for 15 minutes to kill the enzyme. Separation and purification: Cool and centrifuge, take the supernatant, first grade it through 15kDa and 8kDa ultrafiltration membranes, collect 8-15kDa peptide segments, and then purify it with gel filtration chromatography, freeze-dry, and obtain the perilla extract small molecule peptide. Sequencing: Accurately weigh the freeze-dried perilla small molecule peptide and dissolve it to 0.5mg / mL with ultrapure water. Three volumes of pre-cooled acetone were added to precipitate the protein, and the precipitate was collected after centrifugation, vacuum dried, and then redissolved. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) sequencing was performed by mixing the sample with the matrix α-cyano-4-hydroxycinnamic acid in a ratio of 1:1 and spotting on the target plate. The sample was ionized under laser irradiation, and the ion mass was determined according to the flight time. The amino acid sequence was determined to be methionine-phenylalanine-histidine-tyrosine-isoleucine-serine-threonine (MFHYIST) by software analysis.
[0029] The preparation process of the small molecule peptide of Patchouli extract is as follows: Extraction: Take the dried leaves of Patchouli, crush them into 40-60 mesh particles, add 80% ethanol in a ratio of 1:15 (g / mL), soak and extract at 50°C for 3 hours, filter, retain the filtrate, repeat the extraction twice, combine the filtrate, and recover the ethanol by vacuum distillation to obtain a crude Patchouli extract. Enzymolysis: The crude Patchouli extract is made into a 20% solution, the pH is adjusted to 8, 2.5% alkaline protease of the substrate weight is added, enzymolysis is carried out at 40°C for 3.5 hours, and then the enzyme is inactivated at 100°C for 10 minutes. Separation and purification: After cooling, centrifugation is performed, the supernatant is passed through 20kDa and 10kDa ultrafiltration membranes, 10-20kDa peptide segments are collected, and then separated by reversed-phase high-performance liquid chromatography, freeze-dried for standby use, and a small molecule peptide of Patchouli extract is obtained.
[0030] Sequencing: Take an appropriate amount of freeze-dried small molecule peptide from Patchouli bark and dilute it to 0.8 mg / mL with pH 7.0 phosphate buffer. Add an appropriate amount of trichloroacetic acid to precipitate the macromolecular protein, centrifuge and take the supernatant, freeze-dry and sequence using the Edman degradation method. The sample is coupled to the reaction column of the sequencer, reacted with phenyl isothiocyanate, and the N-terminal amino acid is gradually cut off. After derivatization, it is detected by high-performance liquid chromatography, and each amino acid is determined in turn. The sequence is lysine-arginine-glutamic acid-alanine-glycine-asparagine-leucine (KREAGNL).
[0031] Novel organic compound (3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide, abbreviated as HMPA): 3 parts, which is carefully designed and synthesized through multi-step organic synthesis. The phenolic hydroxyl group, methoxy group, amide group and ether bond in the molecule work synergistically. The phenolic hydroxyl group is responsible for anti-oxidation and antibacterial; the methoxy group enhances the antibacterial effect; the amide group is conducive to adhesion to oral tissue and achieves sustained release; the ether bond improves stability and jointly assists tissue repair. The design principle of the novel organic compound HMPA is that the phenolic hydroxyl group in the molecule has antioxidant and antibacterial properties, can remove free radicals in the oral cavity, and inhibit the growth of harmful bacteria; the methoxy group enhances the antibacterial activity of the phenolic hydroxyl group through electronic effects and broadens the antibacterial spectrum; the amide group has good affinity with the surface proteins of the oral mucosa, which is conducive to adhesion and achieves slow release of the effective ingredients; the ether bond improves the overall chemical stability and fat solubility of the compound, helps penetrate the biological membrane, enables it to better act on the oral tissue, and synergistically promotes oral tissue repair. Its synthesis process is as follows:
[0032] Etherification reaction: In a three-necked flask equipped with a stirrer, a thermometer and a reflux condenser, add p-hydroxyanisole (1.0 mol), epichlorohydrin (1.2 mol) and an appropriate amount of anhydrous potassium carbonate as a catalyst, use toluene as a solvent, and heat under reflux for 6-8 hours. After the reaction is completed, cool to room temperature, filter to remove solid impurities, and remove toluene by vacuum distillation to obtain the intermediate product 4-(chloropropoxy)-2-methoxyphenol;
[0033] Amidation reaction: The intermediate product (0.8 mol) obtained above is added to a three-necked flask containing ethanolamine (1.0 mol), and then an appropriate amount of sodium hydroxide is added to adjust the pH of the system to 9-10, and the reaction is stirred at 60-70°C for 4-6 hours. After the reaction is completed, it is cooled, and the pH is adjusted to neutral with dilute hydrochloric acid, and the excess solvent is removed by vacuum distillation, and recrystallization is purified to finally obtain 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide (HMPA) as a white solid.
[0034] Xylitol: 8 parts, plays a dual role as a sweetener and a moisturizer, improving the taste of the mouthwash, preventing water from evaporating too quickly, maintaining the moist state of the mouthwash, and facilitating long-term storage.
[0035] Tocopherol acetate (vitamin E): 2 parts, with its powerful antioxidant properties, it resists the damage of free radicals to oral cells and accelerates the repair and regeneration of damaged mucosa and gingival tissues.
[0036] Polysorbate 80: 1 part, as a surfactant, reduces the surface tension of the mouthwash, promotes the rapid spreading of the mouthwash in the mouth, and ensures that all ingredients act evenly on the oral tissue.
[0037] Sodium benzoate: 0.5 parts, acts as a preservative, inhibits the growth of microorganisms, extends the shelf life of the mouthwash, and maintains the safety of product use.
[0038] Sodium citrate: 0.5 parts, precisely regulates the pH value of the mouthwash to 5.5-6.5, which fits the oral physiological environment and stabilizes the oral microecology.
[0039] Preparation method: Carefully prepare small molecule peptides from honeysuckle, perilla, and patchouli extracts, as well as synthesized HMPA, and set them aside. Add purified water to the mixing kettle, heat it to 40-50°C, add xylitol and tocopherol acetate in sequence, and continue stirring until completely dissolved to obtain a basic solution. Slowly add polysorbate-80, stir for 10-15 minutes, then add the three small molecule peptides and HMPA, and continue stirring for 30-45 minutes to ensure sufficient mixing. Use sodium citrate to accurately adjust the pH value, then add sodium benzoate and stir for 15-20 minutes to stabilize the system. Finally, filter and sterilize through a 0.22μm microporous filter membrane, fill into sterile packaging bottles, and make the finished product.
[0040] Formula: Prepare the raw materials according to the above weight. Preparation and trial: Strictly follow the above process to make a mouthwash, select 50 patients with oral ulcers, aged 20-45 years old, half male and half female, and the ulcer area is 3-5mm 2 Patients were instructed to use the mouthwash for 3-5 minutes every day after meals and before bedtime for 2 weeks. Trial results: After 1 week of use, 80% of patients reported that their ulcer pain was significantly relieved; after 2 weeks, examinations found that 95% of patients had completely healed ulcer surfaces, their oral mucosa was smooth again, and inflammation completely subsided, fully demonstrating the excellent repair effect of the mouthwash.
[0041] Example 2
[0042] Formula: 82 parts of purified water, 6 parts of small molecule peptides from honeysuckle extract, 4 parts of small molecule peptides from perilla extract, 3 parts of small molecule peptides from patches of grass extract, 4 parts of HMPA, 6 parts of xylitol, 3 parts of tocopheryl acetate, 1.2 parts of polysorbate-80, 0.4 parts of sodium benzoate, and 0.4 parts of sodium citrate.
[0043] Preparation and trial: Following the process of Example 1, 50 patients with mild gingival atrophy and inflammation were selected for a 2-week trial, requiring them to rinse their teeth in the morning and evening.
[0044] Trial effect: Within 1 week, 70% of the patients had significantly reduced gum redness and swelling. After 2 weeks, it was found through testing that 92% of the patients' gum atrophy trend was curbed and inflammation was greatly reduced, indicating that the formula has a good effect on gum repair.
[0045] Comparative Example
[0046] Comparative Example 1 Formula 1 (traditional chemical gargle): mainly contains chlorhexidine, alcohol, and water, and is prepared according to the proportion of conventional commercial gargles. This type of gargle inhibits bacteria through chemical bactericides and is a common type in the market.
[0047] Comparative Example 2 Formula 2 (common Chinese medicine gargle): contains common honeysuckle and chrysanthemum extracts, combined with basic moisturizing and preservative ingredients, to simulate some existing gargles containing Chinese medicine ingredients.
[0048] Comparative Example 3 Formula 3 (the present invention removes the key innovative ingredients): 80 parts of purified water, 5 parts of honeysuckle extract, 3 parts of perilla extract, 2 parts of patchouli extract, 8 parts of xylitol, 2 parts of tocopheryl acetate, 1 part of polysorbate-80, 0.5 parts of sodium benzoate, 0.5 parts of sodium citrate, does not contain small molecule peptides and HMPA.
[0049] Preparation and trial: Three comparative gargles were prepared according to their respective conventional processes, and 50 patients with oral ulcers were selected from each group. The age and condition of the patients matched those in Example 1, and the patients were also required to gargle for 3-5 minutes after meals and before going to bed every day for 2 weeks.
[0050] Comparison of trial effects: Formula 1: After 2 weeks, only 30% of patients had a reduction in ulcer surface, and the pain relief was not obvious. Most patients reported dry mouth and affected taste, because chemical disinfectants have a greater irritation to the oral mucosa, destroying the microecology and not conducive to repair. Formula 2: Within 2 weeks, 45% of patients had some improvement in ulcers and slightly reduced pain, but the healing was slow, indicating that under the ordinary Chinese medicine extraction process, the effective ingredients are insufficient and the repair power is lacking. Formula 3: After 2 weeks, 50% of patients had limited reduction in ulcer surface and incomplete inflammation, highlighting the key role of small molecule peptides and HMPA in improving the repair effect of mouthwash.
[0051] Example 3
[0052] Key formula and components: Purified water: 85 parts, as a solvent, to ensure uniform dispersion of each component, maintain the stable texture of the gargle, and facilitate storage and daily use. Centella asiatica extract small molecule peptide: the sequence is glycine-serine-proline-arginine-leucine-histidine-aspartic acid (GSPRLHD), 4 parts. During extraction, take the whole plant of dried Centella asiatica and crush it to 30-50 mesh, add 75% ethanol at 1:12 (g / mL), ultrasonic extraction at 55℃ for 40 minutes, ultrasonic power 250W, repeat 2 times, combine and concentrate to obtain crude extract. Prepare a 12% solution, adjust pH7, add substrate 2% chymosin, enzymatic hydrolysis at 40℃ for 4.5 hours, inactivate the enzyme at 90℃ for 10 minutes, centrifuge through 8kDa and 3kDa ultrafiltration membranes, collect 3-8kDa peptides, and freeze-dry. Sequencing was performed by capillary electrophoresis-mass spectrometry (CE-MS), first re-dissolved to 0.7 mg / mL, added with methanol to precipitate the protein, centrifuged, and the supernatant was freeze-dried before sequencing. This small molecule peptide can promote collagen synthesis and accelerate the repair of damaged oral mucosa.
[0053] Small molecule peptide from peppermint extract: The sequence is valine-alanine-tyrosine-lysine-isoleucine-threonine-phenylalanine (VAYKITF), 3 parts. Wash and dry the fresh peppermint leaves, crush them to 25-40 mesh, add 80% ethanol at 1:10 (g / mL), soak at 40℃ for 3 hours, filter and repeat twice, combine and concentrate. The crude extract is prepared with 10% solution, adjusted to pH 6.5, added with 3% pepsin, hydrolyzed at 38℃ for 5 hours, inactivated at 95℃ for 15 minutes, and lyophilized with 4-10kDa peptides through 10kDa and 4kDa ultrafiltration membranes, and sequenced with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). It can cool, soothe, and resist bacteria, and help relieve oral discomfort.
[0054] Small molecule peptides from Callicarpa oleracea leaf extract: The sequence is lysine-glutamic acid-cysteine-arginine-glycine-methionine-leucine (KECRGLM), 2 parts. Callicarpa oleracea leaf was crushed into 40-60 mesh, added with 65% ethanol at 1:15 (g / mL), refluxed at 60℃ for 2.5 hours, filtered and concentrated. A 15% solution was made, pH was adjusted to 8.5, 2.5% alkaline protease was added, enzymolysis was performed at 42℃ for 3.5 hours, enzyme was inactivated at 100℃ for 10 minutes, passed through 15kDa and 6kDa ultrafiltration membranes, 6-15kDa peptides were collected and freeze-dried, and sequenced by Edman degradation method. It has astringent hemostasis, antibacterial and anti-inflammatory effects, and is beneficial to the healing of oral injuries.
[0055] New organic compound (4-(3-hydroxypropoxy)-N-(3-methylbutyl) benzamide, referred to as HMBA): 3 parts. The design principle is that the hydroxyl group is antioxidant and antibacterial, the propoxy group provides stability and fat solubility, the amide group helps adhesion, and the butyl group adjusts the hydrophilicity and hydrophobicity of the molecule. During the synthesis, first add p-hydroxybenzoic acid (1.0 mol), 3-chloro-1-propanol (1.2 mol) and an appropriate amount of potassium hydroxide to a three-necked flask, use tetrahydrofuran as a solvent, stir at 70-80°C for 5-7 hours, filter and distill to obtain the intermediate product; then mix it with 3-methyl-1-butylamine (1.0 mol) and sodium carbonate in a flask, add toluene, reflux at 100-110°C for 4-6 hours, and post-treat to obtain the product. Sorbitol: 6 parts, moisturizing, preventing the loss of water in the gargle, and keeping it moist. Vitamin C: 2 parts, antioxidant, helps to scavenge free radicals and promote tissue repair. Tween-20: 1 part, surfactant, reduces surface tension and allows the mouthwash to spread better. Potassium benzoate: 0.4 part, preservative, extends shelf life. Citric acid: 0.4 part, adjusts pH to 5-6 to adapt to the oral environment.
[0056] Preparation method: Prepare three small molecule peptides and HMBA separately and set aside. Add purified water into the mixing kettle and heat it to 45-55°C. Add sorbitol and vitamin C in turn, stir and dissolve, and set aside for use. Add Tween-20 and stir for 10-15 minutes, then add small molecule peptides and HMBA, and continue stirring for 30-45 minutes. Adjust the pH with citric acid, add potassium benzoate, stir for 15-20 minutes, filter and sterilize through a 0.22μm microporous filter membrane, and fill. Recipe: Prepare the raw materials according to the above weight portions.
[0057] Preparation and trial: After the mouthwash was prepared, 50 patients with oral mucosa damaged due to friction of dentures were selected, aged 30-60 years old, half male and half female, and were asked to rinse for 3-5 minutes after three meals a day for 2 weeks.
[0058] Trial effect: After 1 week, mucosal pain and redness and swelling were relieved in 75% of patients; after 2 weeks, mucosal injuries in 90% of patients were basically healed and friction discomfort was significantly relieved, proving that it has a good repair effect on this type of injury.
[0059] Example 4
[0060] Key formula and components: Purified water: 83 parts, providing a uniform dispersion medium. Astragalus extract small molecule peptide: the sequence is phenylalanine-lysine-histidine-valine-arginine-threonine-glycine (FKHVRTS), 5 parts. Wash and dry the root of Astragalus, crush it to 40 mesh, add 85% ethanol at 1:8 (g / mL), reflux at 70℃ for 3 hours, extract twice and combine and concentrate. Prepare 18% solution, adjust pH8, add substrate 2.5% trypsin, enzymolysis at 45℃ for 3 hours, inactivate the enzyme at 100℃ for 10 minutes, centrifuge through 20kDa and 10kDa ultrafiltration membranes, and take 10-20kDa peptide segments and freeze-dry. Sequencing by liquid chromatography-tandem mass spectrometry (LC-MS / MS), re-dissolve to 0.8mg / mL, add acetone to precipitate protein, centrifuge and freeze-dry the supernatant for sequencing, which can enhance the body's immunity and help oral anti-inflammatory repair. Small molecule peptides from Phellodendron amurense extract: The sequence is aspartic acid-tyrosine-leucine-arginine-proline-serine-isoleucine (DYLRPSI), 3 copies. Phellodendron amurense bark is crushed to 30-50 mesh, added with 70% ethanol at 1:10 (g / mL), extracted at 60℃ for 2.5 hours, filtered and concentrated. A 14% solution is made, pH is adjusted to 6, 3% papain is added, enzymatic hydrolysis is carried out at 37℃ for 4.5 hours, enzyme is inactivated at 95℃ for 15 minutes, 8-15kDa peptides are taken through 15kDa and 8kDa ultrafiltration membranes and freeze-dried, and sequenced by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), which has antibacterial, heat-clearing and dampness-drying effects. Small molecule peptides from Bletilla striata extract: The sequence is arginine-glycine-cysteine-glutamic acid-leucine-methionine-tyrosine (RGCELMY), 2 copies. The tubers of Bletilla striata were crushed into 30-40 mesh, and 60% ethanol was added at a ratio of 1:12 (g / mL), and ultrasonicated at 55℃ for 30 minutes. The extracts were combined and concentrated twice. A 16% solution was prepared, and the pH was adjusted to 7.5. 2% alkaline protease was added, and the solution was hydrolyzed at 40℃ for 4 hours, and the enzyme was inactivated at 90℃ for 10 minutes. The solution was filtered through 10kDa and 5kDa ultrafiltration membranes, and the 5-10kDa peptides were collected and freeze-dried. The peptides were sequenced by Edman degradation method, which can astringe and stop bleeding and promote mucosal repair.
[0061] New organic compound (3-(2-methoxyethoxy)-N-(2-hydroxypropyl) benzenesulfonamide, referred to as MEMB): 4 parts. The oxygen group in the molecule helps dissolution and improves stability, the sulfonamide group is affinity with mucous membranes, and the methoxy group enhances antibacterial synergy. During the synthesis, p-hydroxybenzenesulfonic acid (1.0 mol) and 2-chloroethanol (1.2 mol) and potassium carbonate are reacted at 85-95°C for 4-6 hours with N,N-dimethylformamide as solvent to obtain an intermediate product; then, it is stirred with 2-amino-1-propanol (1.0 mol) and sodium hydroxide at 65-75°C for 3-5 hours to obtain the product. Xylitol: 5 parts, moisturizing and sweetening agent. Tocopherol: 2 parts, antioxidant and cell protection.
[0062] Polyoxyethylene sorbitan fatty acid ester (Span-80): 1.2 parts, to reduce surface tension. Methylparaben: 0.3 parts, for preservation. Disodium hydrogen phosphate: 0.3 parts, to adjust pH to 6-7. Preparation method: After preparing each small molecule peptide and MEMB, add purified water into the kettle and heat it to 42-52°C. First add xylitol and tocopherol and stir to dissolve. Add Span-80 and stir for 10-15 minutes, then add small molecule peptide and MEMB, and stir for 30-45 minutes. Adjust pH with disodium hydrogen phosphate, add methylparaben, stir for 15-20 minutes, filter, sterilize and fill. Formula: Prepare materials according to weight. Preparation and trial: Select 50 patients with periodontitis after surgery, aged 25-55 years old, half male and half female, rinse for 3-5 minutes every morning and evening for 2 weeks. Trial effect: After 1 week, the redness, swelling and pain in the surgical area were relieved in 68% of the patients; after 2 weeks, the periodontal pockets became shallower and the wound healing was accelerated in 88% of the patients, indicating a positive effect on postoperative periodontal repair.
[0063] Example 5
[0064] Key formula and components: Purified water: 81 parts, as the basic solvent of the entire gargle system, to ensure that the components are evenly dispersed, maintain good fluidity and stability, and facilitate storage and use. Small molecule peptides from witch hazel extract: the sequence is histidine-tryptophan-arginine-glutamic acid-leucine-alanine-serine (HWRELAS), 4 parts. First, crush the dried witch hazel leaves to 20-30 mesh, add 70% ethanol according to the solid-liquid ratio of 1:14 (g / mL), perform ultrasonic-assisted extraction at 50°C for 35 minutes, ultrasonic power 280W, repeat the extraction twice, combine the extracts, concentrate under reduced pressure to recover ethanol, and obtain a crude extract. Prepare the crude extract into a 10% solution, adjust the pH to 7.2, add chymosin according to 2.5% of the substrate protein mass, enzymolysis at 42°C for 4 hours, and heat to 92°C to inactivate the enzyme for 12 minutes after the enzymolysis. Cool and centrifuge, take the supernatant and grade it with 8kDa and 4kDa ultrafiltration membranes in turn, collect 4-8kDa peptides, and then purify them by ion exchange chromatography and freeze-dry to obtain small molecule peptides. Sequencing uses liquid chromatography tandem mass spectrometry (LC-MS / MS), first re-dissolve the freeze-dried peptide to 0.9mg / mL, add acetonitrile to precipitate the protein, and then detect on the machine to determine the sequence after treatment. The peptide has astringent and anti-inflammatory effects and helps to reduce oral redness and swelling. Small molecule peptides from Xiqing fruit extract: the sequence is lysine-phenylalanine-tyrosine-histidine-glycine-threonine-valine (KFYHGTV), 3 parts. Take the dried fruit of Xiqing fruit and crush it to 30-40 mesh, add 65% ethanol at a solid-liquid ratio of 1:10 (g / mL), reflux extract at 65℃ for 2.5 hours, filter, extract the residue again, and combine the filtrate to concentrate the crude extract. The crude extract was prepared into a 13% solution, adjusted to pH 6.8, and 3% papain was added as substrate. The solution was enzymatically hydrolyzed at 36°C for 5 hours, and the enzyme was inactivated at 94°C for 14 minutes. After centrifugation, the 6-12kDa peptide was obtained through 12kDa and 6kDa ultrafiltration membranes and freeze-dried. Sequencing was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), which helps regulate oral flora and refresh breath. Small molecule peptides from seabuckthorn extract: The sequence is glycine-arginine-asparagine-leucine-alanine-methionine-isoleucine (GRNALMI), 2 parts. The seabuckthorn pomace was crushed to 40-50 mesh, and 80% ethanol was added at 1:13 (g / mL), and the mixture was soaked and extracted at 55°C for 3 hours, filtered and concentrated several times. A 16% solution was made, the pH was adjusted to 8.2, 2% alkaline protease was added as substrate, enzymatic hydrolysis was carried out at 41°C for 3.5 hours, the enzyme was inactivated at 100°C for 10 minutes, the solution was filtered through 18kDa and 9kDa ultrafiltration membranes, the 9-18kDa peptide segments were collected and freeze-dried, and sequenced using the Edman degradation method. The solution is rich in nutrients and can promote the regeneration of mucosal cells.
[0065] New organic compound (5-(2-hydroxyethoxy)-N-(4-ethylbenzyl) benzamide, referred to as HEEB): 3 parts. In terms of molecular design, hydroxyl group is antioxidant and antibacterial, ethoxy group improves stability and solubility, benzyl group and ethyl group adjust lipophilicity and hydrophilicity and molecular spatial structure, which helps the ingredients to be compatible with oral tissues. During the synthesis, p-hydroxybenzoic acid (1.0 mol), 2-chloroethanol (1.2 mol) and an appropriate amount of potassium hydroxide were added to a three-necked flask as a catalyst, dimethyl sulfoxide was used as a solvent, and the reaction was stirred at 80-90°C for 6 hours. The intermediate product was filtered to remove impurities and distilled under reduced pressure; then it was mixed with 4-ethylbenzylamine (1.0 mol) and an appropriate amount of sodium carbonate in a toluene solvent, refluxed at 110-120°C for 5 hours, and then treated to obtain white solid HEEB. Trehalose: 7 parts, an excellent moisturizer, prevents the mouthwash from drying, maintains a suitable humidity, and protects oral cells from drying damage.
[0066] Vitamin D3: 1 part, promotes the absorption and utilization of calcium by oral mucosal cells, strengthens cell structure, and assists in the repair of damaged tissues. Polyethylene glycol-400: 1 part, surfactant, reduces the surface tension of the mouthwash, promotes its rapid spread in the mouth, and makes the effective ingredients evenly cover all parts of the mouth. Potassium sorbate: 0.4 part, preservative, inhibits the growth of microorganisms and prolongs the shelf life of the mouthwash. Potassium citrate: 0.4 part, accurately adjusts the pH value of the mouthwash to 5.8-6.2, and stabilizes the oral microecology.
[0067] Preparation method: First, prepare three small molecule peptides and HEEB for use. Add purified water to the mixing kettle, heat to 43-53°C, add trehalose and vitamin D3 in turn, and stir until completely dissolved to form a basic solution. Slowly add polyethylene glycol-400, stir for 10-15 minutes, then add small molecule peptides and HEEB, and continue stirring for 30-45 minutes. Adjust the pH with potassium citrate, add potassium sorbate, stir for 15-20 minutes, filter and sterilize through a 0.22μm microporous filter membrane, and fill into the finished product.
[0068] Recipe: Prepare the raw materials according to the above weight portions.
[0069] Preparation and trial: After the gargle solution was prepared, 50 patients with oral mucosal burning pain caused by eating spicy food were selected, aged 22-48 years old, half of them were male and half were female. They were required to gargle for 3-5 minutes after meals and before going to bed every day for 2 weeks.
[0070] Trial effect: After 1 week of use, 78% of patients had significantly reduced oral burning pain; after 2 weeks, 93% of patients' oral mucosa returned to normal without obvious discomfort, indicating that it is effective in repairing this type of mucosal damage.
[0071] Example 6
[0072] Key formula and components: Purified water: 84 parts, to ensure the stability of the gargle system and to allow the various ingredients to blend evenly. Rose extract small molecule peptide: the sequence is phenylalanine-tryptophan-valine-lysine-arginine-glycine-proline (FTVKRGP), 5 parts. Take dried rose petals and crush them to 30-50 mesh, add 75% ethanol according to the material-liquid ratio of 1:11 (g / mL), ultrasonic extraction at 58℃ for 30 minutes, ultrasonic power 300W, extract twice and combine and concentrate. Prepare 11% solution, adjust pH7.8, add substrate 2% trypsin, enzymatic hydrolysis at 44℃ for 3.5 hours, inactivate the enzyme at 98℃ for 10 minutes, centrifuge through 10kDa and 5kDa ultrafiltration membranes to obtain 5-10kDa peptide segments, and freeze-dry. Use capillary electrophoresis-mass spectrometry (CE-MS) sequencing, first re-dissolve to 0.6mg / mL, add methanol to precipitate protein, centrifuge and freeze-dry the supernatant for sequencing, which can soothe emotions, antibacterial and anti-inflammatory, and improve oral discomfort. Osmanthus extract small molecule peptide: the sequence is methionine-tyrosine-leucine-histidine-alanine-serine-threonine (MYLHAST), 3 parts. Osmanthus dried flowers are crushed to 25-40 mesh, 60% ethanol is added at 1:9 (g / mL), refluxed at 68℃ for 2 hours, and filtered and concentrated. A 14% solution is made, the pH is adjusted to 6.5, 3% pepsin is added, enzymatic hydrolysis is carried out at 39℃ for 4.5 hours, the enzyme is inactivated at 96℃ for 15 minutes, and the 7-14kDa peptide segment is obtained by passing through 14kDa and 7kDa ultrafiltration membranes, freeze-dried, and sequenced by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to add fragrance and assist in regulating oral microecology. Clove extract small molecule peptide: the sequence is lysine-cysteine-arginine-glutamic acid-glycine-asparagine-leucine (KCREGANL), 2 parts. Clove dried buds were crushed into 40-60 mesh, and 85% ethanol was added at 1:13 (g / mL), and soaked at 52℃ for 3 hours, filtered, combined and concentrated. Prepared into a 17% solution, adjusted to pH 8.5, added with substrate 2.5% alkaline protease, enzymatically hydrolyzed at 43℃ for 3 hours, inactivated at 100℃ for 10 minutes, passed through 16kDa and 8kDa ultrafiltration membranes, and 8-16kDa peptides were collected and freeze-dried, sequenced by Edman degradation method, and had antibacterial and analgesic effects, relieving oral pain. New organic compound (4-(3-methoxypropoxy)-N-(2-methyl-2-hydroxyethyl) benzenesulfonamide, referred to as MMPB): 4 parts. The molecule contains methoxy to enhance antibacterial, propoxy to improve stability, sulfonamide to help adhesion, and hydroxyethyl to moisturize and be skin-friendly. Synthesis: p-Hydroxybenzenesulfonic acid (1.0 mol), 3-chloro-1-propanol (1.2 mol) and potassium carbonate, with N,N-dimethylformamide as solvent, react at 90-100℃ for 5 hours to obtain the intermediate product; stir with 2-amino-2-methyl-1-propanol (1.0 mol) and sodium hydroxide at 70-80℃ for 4 hours, and post-treat to obtain the product. Erythritol: 6 parts, sweetener and moisturizer, improves the mouthwash taste and locks in moisture. Vitamin B12: 1 part, participates in cell metabolism, helps repair and regenerate oral mucosal cells.Laureth-23: 1.2 parts, surfactant, reduces surface tension and helps spread the rinse. Sodium benzoate: 0.3 parts, preservative, ensures product quality. Sodium dihydrogen phosphate: 0.3 parts, adjusts pH to 5.6-6.0.
[0073] Preparation method: After preparing the small molecule peptide and MMPB, add purified water to the kettle and heat it to 46-56°C, add erythritol and vitamin B12, stir and dissolve, and place. Add laureth-23 and stir for 10-15 minutes, then add the small molecule peptide and MMPB and stir for 30-45 minutes. Adjust the pH with sodium dihydrogen phosphate, add sodium benzoate, stir for 15-20 minutes, filter, sterilize and fill.
[0074] Formula: Prepare the raw materials according to weight. Preparation and trial: Select 50 patients with bad breath and mild mucosal damage caused by long-term smoking, aged 30-55 years old, half male and half female, and rinse for 3-5 minutes every morning and evening for 2 weeks. Trial effect: Within 1 week, 72% of the patients had reduced bad breath and relieved pain of mucosal damage; after 2 weeks, 89% of the patients had repaired oral mucosal damage and fresh breath, indicating that it is effective in repairing oral problems caused by smoking.
[0075] Example 7
[0076] Key formula and components: Purified water: 80 parts, to provide a uniform medium for the gargle and ensure the dispersion of ingredients. Small molecule peptides from Gynostemma pentaphyllum extract: The sequence is arginine-tyrosine-histidine-leucine-glycine-phenylalanine-threonine (RYHLGPT), 4 parts. Gynostemma pentaphyllum whole plant is crushed to 20-40 mesh, 70% ethanol is added at 1:12 (g / mL), ultrasonic extraction is performed at 55°C for 40 minutes, the ultrasonic power is 260W, and the extraction is combined and concentrated twice. Prepare a 12% solution, adjust the pH to 7.4, add 2.5% chymosin as the substrate, enzymolysis at 43°C for 4 hours, inactivate the enzyme at 95°C for 10 minutes, centrifuge through 9kDa and 4kDa ultrafiltration membranes, collect 4-9kDa peptides, and freeze-dry. Sequencing is performed using liquid chromatography-tandem mass spectrometry (LC-MS / MS), re-dissolved to 0.8mg / mL, acetonitrile is added to precipitate the protein, centrifuged and the supernatant is freeze-dried and sequenced, which can enhance immunity, anti-inflammatory, and help oral tissue health. Rosemary extract small molecule peptide: the sequence is lysine-tryptophan-valine-arginine-alanine-serine-isoleucine (KWVRASI), 3 parts. Rosemary dried leaves were crushed to 30-50 mesh, and 65% ethanol was added at a solid-liquid ratio of 1:10 (g / mL), refluxed at 62°C for 2.5 hours, and concentrated by suction. A 15% solution was made, the pH was adjusted to 6.6, and the substrate 3% papain was added, enzymatically hydrolyzed at 38°C for 5 hours, and the enzyme was inactivated at 93°C for 15 minutes. The 7-13kDa peptide segment was obtained through 13kDa and 7kDa ultrafiltration membranes, freeze-dried, and sequenced by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), which is antioxidant, antibacterial, and optimizes the oral environment. Licorice extract small molecule peptide: the sequence is glycine-alanine-cysteine-arginine-leucine-methionine-tyrosine (GACRLMY), 2 parts. Grind the licorice root into 40-60 mesh, add 80% ethanol at 1:14 (g / mL), soak at 58℃ for 3 hours, filter, combine and concentrate. Prepare 18% solution, adjust pH to 8, add substrate 2% alkaline protease, enzymolysis at 40℃ for 3.5 hours, inactivate enzyme at 100℃ for 10 minutes, pass through 17kDa and 9kDa ultrafiltration membranes, collect 9-17kDa peptides and freeze-dry, sequence by Edman degradation method, have anti-inflammatory and soothing effects, and reduce oral inflammation. New organic compound (3-(2-hydroxypropoxy)-N-(3-isopropylbenzyl) benzamide, referred to as HPIB): 3 parts. Molecular design uses hydroxyl, propoxy, benzyl and isopropyl to achieve antioxidant, antibacterial, adhesion and hydrophilicity adjustment. Synthesis: p-Hydroxybenzoic acid (1.0 mol), 2-chloropropanol (1.2 mol) and appropriate amount of potassium hydroxide, with tetrahydrofuran as solvent, stirred at 75-85℃ for 6 hours to obtain the intermediate product; with 3-isopropylbenzylamine (1.0 mol) and sodium carbonate, refluxed at 115-125℃ for 4 hours in toluene, and post-treated to obtain the product. Xylitol: 8 parts, moisturizing and sweet, maintains the moistness and taste of the mouthwash. Vitamin E acetate: 2 parts, anti-oxidation, resists free radicals, and accelerates oral tissue repair.Polysorbate-60: 1 part, surfactant, reduces surface tension and helps spread the rinse. Ethylparaben: 0.4 part, preservative, extends shelf life. Trisodium citrate: 0.4 part, adjusts pH to 5.5-6.5.
[0077] Preparation method: After preparing small molecule peptides and HPIB, add purified water into the mixing kettle and heat it to 40-50°C. First, add xylitol and vitamin E acetate and stir to dissolve. Add polysorbate-60 and stir for 10-15 minutes, then add small molecule peptides and HPIB and stir for 30-45 minutes. Adjust the pH with trisodium citrate, add ethylparaben, stir for 15-20 minutes, filter and sterilize through a 0.22μm microporous filter membrane, and fill. Formula: Prepare the raw materials according to the above weight portions. Preparation and trial: Select 50 patients with oral mucosal friction damage and mild inflammation caused by wearing braces, aged 18-40 years old, half male and half female, rinse for 3-5 minutes after three meals a day for 2 weeks. Trial effect: After 1 week, 76% of patients had reduced mucosal friction pain and relieved inflammation; after 2 weeks, 94% of patients had basically healed mucosal damage and disappeared inflammation, which had a good repair effect on this type of oral injury.
Claims
1. A tissue repair Chinese medicine oral rinse, characterized in that: It includes plant extracts, tocopherol acetate, xylitol, polysorbate, preservatives, sodium citrate, purified water and the organic compound 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide; the plant extract is a plant extract small molecule peptide; the plants are honeysuckle, perilla and patchouli.
2. The tissue repair Chinese medicine oral rinse according to claim 1, characterized in that: The amino acid sequence of the small molecule peptide from the honeysuckle extract is tryptophan-cysteine-valine-arginine-leucine-glycine-proline; the amino acid sequence of the small molecule peptide from the perilla extract is methionine-phenylalanine-histidine-tyrosine-isoleucine-serine-threonine; the amino acid sequence of the small molecule peptide from the patchouli extract is lysine-arginine-glutamic acid-alanine-glycine-asparagine-leucine.
3. The tissue repair Chinese medicine oral rinse according to claim 1 or 2, characterized in that: The gargle specifically comprises: 80-82 parts of purified water, 3-6 parts of honeysuckle flower extract, 2-4 parts of perilla extract, 2-3 parts of patchouli extract, 6-8 parts of xylitol, 3-4 parts of organic compound 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide, 2-3 parts of tocopherol acetate, 1-1.2 parts of polysorbate 80, and the preservatives are 0.4-0.5 parts of sodium benzoate or methyl paraben and 0.4-0.5 parts of sodium citrate.
4. The tissue repair Chinese medicine oral rinse according to claim 1 or 2, characterized in that: The plant may also be Centella asiatica, mint and perilla, or Astragalus, Phellodendron bark and Bletilla tuber; or Hamamelis virginiana, Osmanthus fragrans and Seabuckthorn, or Rose, Osmanthus fragrans and Clove; or Licorice, Gynostemma pentaphyllum and Rosemary.
5. The method for preparing the tissue repair Chinese medicine oral rinse according to any one of claims 1 to 4, characterized in that: The method comprises the following steps: (1) preparing plant extract small molecule peptides and synthesizing the organic compound 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide respectively for use; (2) adding xylitol and tocopherol acetate to purified water at 40-50° C. and stirring until dissolved to obtain a base solution; (3) adding polysorbate 80, stirring, and adding plant extract small molecule peptides and 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide, and continuing stirring; (4) The pH value is adjusted to 5.5-6.5, a preservative is added, the mixture is stirred and sterilized by filtering with a microporous membrane to obtain a tissue repair Chinese medicine oral rinse.
6. The method for preparing the tissue repair Chinese medicine oral rinse according to claim 5, characterized in that: The method for preparing the plant-derived small molecule peptide comprises the following steps: crushing the plant, ultrasonically extracting the crude extract with an ethanol-water mixture, hydrolyzing the crude extract with protease, inactivating the enzyme, and then ultrafiltration, ion exchange chromatography, and drying to obtain the target extract small molecule peptide.
7. The method for preparing the tissue repair Chinese medicine oral rinse according to claim 6, characterized in that: The mass volume ratio of the crushed plant to the ethanol-water mixture is 1:10-15, the concentration of ethanol in the ethanol-water mixture system is 60-85%; the extraction temperature is 45-70°C, and the extraction time is 30min-4h.
8. The method for preparing the tissue repair Chinese medicine oral rinse according to claim 6, characterized in that: The concentration of the crude extract is 10-20wt%; the protease is trypsin, papain or alkaline protease; the amount of the protease is 2-3wt% of the crude extract; the enzymolysis temperature is 37-45°C, and the time is 4-5h.
9. The method for preparing the tissue repair Chinese medicine oral rinse according to claim 5, characterized in that: The preparation steps of the organic compound 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide are as follows: 1) mixing hydroxyanisole, epichlorohydrin, anhydrous carbonic acid as a catalyst and toluene as a solvent, heating the mixture under reflux for reaction, filtering, and removing the solvent by distillation under reduced pressure to obtain an intermediate product, 4-(chloropropoxy)-2-methoxyphenol; 2) stirring the intermediate product and ethanolamine to react in a system with a pH value of 9-10; then neutralizing, distilling under reduced pressure to remove the solvent, and purifying by recrystallization to obtain the product 3-(4-hydroxy-3-methoxyphenoxy)-N-(2-hydroxyethyl) propionamide.
10. The method for preparing the tissue repair Chinese medicine oral rinse according to claim 5, characterized in that: In the step 1), the molar ratio of p-hydroxyanisole to epichlorohydrin is 1:1.2; the heating reflux reaction time is 6-8 hours; in the step 2), the molar ratio of the intermediate product to ethanolamine is 0.8:1; the heating reaction temperature is 60-70°C and the time is 4-6 hours.