阅读说明：本技术 治疗牙周炎的中药组合物 (Traditional Chinese medicine composition for treating periodontitis ) 是由 李艳冰 于 2021-10-13 设计创作，主要内容包括：本发明公开了一种治疗牙周炎的中药组合物,以两面针、丝瓜络、山楂、三七、忍冬藤、石膏、槐花蕾、葛根行气止痛、活血化瘀,辅以夏枯草、连翘、薄荷散结消肿、清热解毒,主臣合用,散瘀止血、疏风通络,补中有降,以奏消肿定痛、宣散风热之效。本发明治疗牙周炎的中药组合物配伍科学,用材合理,协同增效以治疗牙周炎。以本发明治疗牙周炎的中药组合物制备而成的口腔贴片具有见效快、药效久、药物成分释放均匀的特点,对引起牙周炎的致病菌,如牙龈卟啉单胞菌、伴放线放线杆菌有抗菌效果,可以大大缓解牙周炎对人造成的痛苦,标本兼治。(The invention discloses a traditional Chinese medicine composition for treating periodontitis, which is prepared from radix zanthoxyli, loofah sponge, hawthorn, pseudo-ginseng, honeysuckle stem, gypsum, sophora flower bud and kudzuvine root, wherein the honeysuckle stem, the gypsum, the sophora flower bud and the kudzuvine root are used for promoting qi circulation and relieving pain and activating blood and dissolving stasis, and selfheal, weeping forsythia and mint are used for dispersing accumulation of pathogen and reducing swelling and clearing away heat and toxic materials. The traditional Chinese medicine composition for treating periodontitis is scientific in compatibility, reasonable in material consumption and synergistic in synergism to treat periodontitis. The oral patch prepared from the traditional Chinese medicine composition for treating periodontitis has the characteristics of quick response, long drug effect and uniform release of drug ingredients, has an antibacterial effect on pathogenic bacteria causing periodontitis, such as porphyromonas gingivalis and actinobacillus actinomycetemcomitans, can greatly relieve the pain of periodontitis to people, and treats both principal and secondary aspects of diseases.)

1. A preparation method of a traditional Chinese medicine composition for treating periodontitis is characterized by comprising the following steps:

s1, weighing 15-20 parts of Zanthoxylum nitidum, 12-18 parts of loofah sponge, 8-16 parts of hawthorn, 4-8 parts of pseudo-ginseng, 10-16 parts of honeysuckle stem, 15-35 parts of gypsum, 12-18 parts of sophora flower bud, 20-25 parts of kudzu root, 9-15 parts of selfheal, 6-9 parts of fructus forsythiae and 3-6 parts of mint according to the parts by weight, cleaning to remove dust and impurities on the surface of the raw material, drying at normal temperature for 4-6 hours, and sterilizing to obtain a clean raw material; mixing, crushing and sieving clean raw materials to obtain raw material medicinal powder for later use;

s2, mixing the raw material powder obtained in the step S1 with 115-375 parts of ethanol in parts by weight, sealing and standing for 2-4 hours to obtain wet powder; filling the wet medicinal powder into a percolation device, adding ethanol, exhausting, and soaking for 24-36 h to obtain soaked medicinal powder for later use;

s3, percolating the immersed medicinal powder obtained in the step S2 in parts by weight, adding 475-1500 parts of ethanol for percolation at one time, adopting a warm leaching method, controlling the extraction temperature to be 45-50 ℃, controlling the percolation rate to be 1.5-2.5 mL of percolate flowing out every 1kg of medicinal materials per minute, stopping percolation when the collected percolate reaches 75-80% of the mass of the ethanol for percolation, collecting and squeezing the residual medicinal powder, and combining the squeezed liquid and the percolate to obtain a percolation product for later use;

s4, distilling the diacolation product obtained in the step S3 under reduced pressure to recover ethanol, wherein the pressure is 12.31kPa, and the temperature is 55-60 ℃, so that the residual extracting solution is obtained, and the residual extracting solution is the traditional Chinese medicine composition for treating periodontitis.

2. The preparation method of the traditional Chinese medicine composition for treating periodontitis according to claim 1, wherein the preparation method comprises the following steps: the powder grade of the raw material medicinal powder in the step S1 is medium powder or coarse powder.

3. A Chinese medicinal composition for treating periodontitis, prepared by the method of any one of claims 1-2.

4. The use of the traditional Chinese medicine composition for treating periodontitis according to claim 3 in an oral cavity external product.

5. Use according to claim 4, characterized in that: the oral cavity external product is one of ointment, oral cavity patch, collutory, toothpaste and oral cavity spray.

6. Use according to claim 4, characterized in that: the traditional Chinese medicine composition for treating periodontitis, according to claim 3, is added in an amount of 0.1-8 wt% in the product for oral external use.

7. The preparation method of the oral patch for treating periodontitis is characterized by comprising the following steps of:

a1, dissolving 1-2 parts by weight of the traditional Chinese medicine composition for treating periodontitis according to claim 3 in 1-2 parts by weight of ethanol, then continuously stirring and mixing with 6-8 parts by weight of water, 15-25 parts by weight of carbomer, 20-30 parts by weight of dextrin, 30-50 parts by weight of starch and 0.2-0.4 part by weight of magnesium stearate uniformly, granulating and drying to obtain traditional Chinese medicine granules for later use;

a2 pressing the Chinese medicinal granules obtained in step A1 to obtain Chinese medicinal tablet, i.e. adhesive layer;

a3 spraying the protective layer spray solution on one side of the Chinese medicinal tablet obtained in step A2, and drying to obtain a double-layer Chinese medicinal tablet;

a4 spraying the controlled release layer spray solution on one side of the double-layer Chinese medicinal tablet obtained in step A3, and drying to obtain the oral patch for treating periodontitis; the oral patch is of a sandwich structure, and the protective layer and the controlled release layer are respectively arranged on two sides of the traditional Chinese medicine tablet; the controlled release layer spraying liquid consists of 3-5 wt% of a composite controlled release agent, 2-4 wt% of bocam and the balance of water.

8. The method for preparing an oral patch for treating periodontitis according to claim 7, wherein: in the step A1, the fineness of the traditional Chinese medicine particles is 30-50 meshes, and the water content is 3-5 wt%; the diameter of the traditional Chinese medicine tablet in the step A2 is 4-6 mm; the thickness of the protective layer of the double-layer traditional Chinese medicine tablet in the step A3 is 0.2-0.4 mm, and the thickness of the controlled release layer of the oral patch for treating periodontitis in the step A4 is 0.1-0.2 mm.

9. The method for preparing an oral patch for treating periodontitis according to claim 7, wherein: the protective layer spraying liquid in the step A3 is a mixture obtained by mixing 2-4 wt% of acrylic resin, 2-3 wt% of riboflavin, 1.5-2 wt% of titanium dioxide, 0.1-0.3 wt% of dioctyl phthalate and the balance of water.

10. The method for preparing an oral patch for treating periodontitis according to claim 7, wherein: the composite controlled release agent in the step A4 is a synthetic controlled release agent, polyethylene glycol and triglyceride in a mass ratio of (5-8): (1-3): 1; the synthesized controlled release agent is any one of diosmetin controlled release agent and anti-coagulation hydroxypropyl methylcellulose controlled release agent.

Technical Field

The invention relates to the technical field of preparation or treatment of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating periodontitis.

Background

The teeth are the most rigid organs of the human body and are the only exposed bones. During daily eating, food residues remaining in the teeth provide nutrients for the proliferation of microorganisms. The mass propagation of microorganisms further causes periodontitis, teeth have abundant blood vessels and nerves, and the periodontitis is difficult to endure when patients suffer from diseases and sleep day and night, so that the daily life of people is seriously influenced. Periodontitis is severe, and can damage teeth and gums, cause bleeding and ulceration, and bring great pain to people. The traditional Chinese medicine has natural advantages in the aspect of treating periodontitis, the traditional Chinese medicine emphasizes treating both principal and secondary aspects of diseases, natural components in the traditional Chinese medicine have small damage to human bodies and small toxic and side effects, and the traditional Chinese medicine can be applied according to symptoms, so that the symptoms of periodontitis are relieved.

Patent CN 104623483A provides a traditional Chinese medicine decoction for treating periodontitis and a preparation method thereof, the traditional Chinese medicine decoction is obtained by decocting and concentrating a traditional Chinese medicine composition, and the problems of insufficient decoction and difficult purification of fat-soluble substances exist in actual production and use; the patent CN 104688998A discloses a traditional Chinese medicine tablet for treating periodontitis and a preparation method thereof, wherein traditional Chinese medicine extracts are uniformly mixed and then tabletted by a tabletting machine to prepare the traditional Chinese medicine tablet for treating periodontitis, but the traditional Chinese medicine tablet has the defect of slow effect due to the fact that the traditional Chinese medicine tablet needs to be digested and absorbed after being taken.

Disclosure of Invention

In view of the above-mentioned defects of the prior art, the technical problems solved by the present invention are: (1) the traditional Chinese medicine composition for treating periodontitis is provided, and has a good effect of treating periodontitis; (2) the traditional Chinese medicine composition oral patch for treating periodontitis, which is prepared by taking the traditional Chinese medicine composition for treating periodontitis as a raw material, has a good controlled release effect on medicines and prolongs the medicine effect duration.

Modern Chinese medicine holds that periodontitis has various causes, and is mostly caused by stomach fire steaming upwards, deficiency of qi and blood, essence and qi deficiency, and immunity decline, so that pathogenic microorganisms invade teeth to form diseases. Periodontitis often causes gingival atrophy, tooth root is revealed, bleeding and pus are oozed, and chewing pain is weak, so that the patient suffers from pain and short breath.

The traditional Chinese medicine composition for treating periodontitis is self-composing, scientific in compatibility, reasonable in material consumption, and synergistic to achieve the effect of treating periodontitis. The invention uses radix zanthoxyli, loofah sponge, hawthorn, pseudo-ginseng, honeysuckle stem, gypsum, sophora flower bud and kudzu-vine root to promote qi circulation and relieve pain, and promote blood circulation and remove blood stasis, and uses selfheal, forsythia and mint to dissipate stagnation and reduce swelling, clear away heat and toxic material as auxiliary materials, and the invention has the effects of dissipating blood stasis and stopping bleeding, dispelling wind and dredging collaterals, and descending in tonifying center to play the effects of reducing swelling and relieving pain and dispersing wind and heat. The radix zanthoxyli in the traditional Chinese medicine composition has the effects of promoting qi circulation, relieving pain, promoting blood circulation, removing blood stasis, dispelling wind and dredging collaterals; the loofah sponge has the effects of promoting blood circulation and removing meridian obstruction; the hawthorn can promote digestion, invigorate spleen, promote qi circulation and remove blood stasis; notoginseng radix has effects in dispelling blood stasis, stopping bleeding, relieving swelling, and relieving pain; honeysuckle stem has the effects of clearing away heat and toxic materials, dispelling wind and dredging collaterals; gypsum Fibrosum has effects of clearing heat, lowering fire, relieving restlessness, and quenching thirst; flos Sophorae bud has effects of cooling blood, stopping bleeding, clearing liver-fire; radix Puerariae has effects of expelling pathogenic factors from muscles, relieving fever, promoting fluid production, and promoting eruption; adjuvant drugs of common selfheal fruit-spike, weeping forsythia and peppermint are added, and bitter cold of common selfheal fruit-spike is used for dissipating stagnation and reducing swelling; fructus forsythiae clears away heat and toxic materials; the pungent and cool property of Bo He can disperse wind-heat and clear head to promote eruption. The traditional Chinese medicine has the advantages of combining the medicines, benefiting the mind of yin and yang, nourishing yin and suppressing yang, treating both symptoms and root causes, and having good effect of treating periodontitis.

The invention provides a preparation method of a traditional Chinese medicine composition for treating periodontitis, which comprises the following steps:

s1, weighing 15-20 parts of Zanthoxylum nitidum, 12-18 parts of loofah sponge, 8-16 parts of hawthorn, 4-8 parts of pseudo-ginseng, 10-16 parts of honeysuckle stem, 15-35 parts of gypsum, 12-18 parts of sophora flower bud, 20-25 parts of kudzu root, 9-15 parts of selfheal, 6-9 parts of fructus forsythiae and 3-6 parts of mint according to the parts by weight, cleaning to remove dust and impurities on the surface of the raw material, drying at normal temperature for 4-6 hours, and sterilizing to obtain a clean raw material; mixing, crushing and sieving clean raw materials to obtain raw material medicinal powder for later use;

s2, mixing the raw material powder obtained in the step S1 with 115-375 parts of ethanol in parts by weight, sealing and standing for 2-4 hours to obtain wet powder; filling the wet medicinal powder into a percolation device, adding ethanol, exhausting, and soaking for 24-36 h to obtain soaked medicinal powder for later use;

s3, percolating the immersed medicinal powder obtained in the step S2 in parts by weight, adding 475-1500 parts of ethanol for percolation at one time, adopting a warm leaching method, controlling the extraction temperature to be 45-50 ℃, controlling the percolation rate to be 1.5-2.5 mL of percolate flowing out every 1kg of medicinal materials per minute, stopping percolation when the collected percolate reaches 75-80% of the mass of the ethanol for percolation, collecting and squeezing the residual medicinal powder, and combining the squeezed liquid and the percolate to obtain a percolation product for later use;

s4, distilling the diacolation product obtained in the step S3 under reduced pressure to recover ethanol, wherein the pressure is 12.31kPa, and the temperature is 55-60 ℃, so that the residual extracting solution is obtained, and the residual extracting solution is the traditional Chinese medicine composition for treating periodontitis.

Preferably, the powder grade of the raw material powder in step S1 is medium powder or coarse powder specified in chinese pharmacopoeia (2015 edition).

The invention also protects the application of the traditional Chinese medicine composition for treating periodontitis in preparing an oral cavity external product for treating periodontitis, wherein the oral cavity external product for treating periodontitis is one of ointment, oral cavity patch, mouthwash, toothpaste and oral cavity spray for treating periodontitis; when the traditional Chinese medicine composition is used for preparing an oral external product for treating periodontitis, the addition amount of the traditional Chinese medicine composition for treating periodontitis is 0.1-8 wt%.

The oral patch is used as a product form of an oral medicament, and has the characteristics of convenient use and quick response after being directly contacted with an inflammation part. In long-term production practice, the inventors found that an oral patch for treating periodontitis has a technical problem that the release of a pharmaceutically active ingredient is unstable, although having the above advantages. The oral patch is used as a carrier of the medicine and is contacted with an affected part through the attaching layer, the medicine is released from the patch due to concentration difference, but the release rate of the medicine is not constant, the release rate of the medicine is increased and then decreased along with the progress of diffusion, proper concentration is needed for the active ingredients of the medicine to exert the efficacy, the persistence of the medicine is poor due to the waste of the active ingredients when the concentration is too high, and the expected therapeutic effect is difficult to achieve when the concentration is too low.

In view of the technical problems encountered, the inventors have found that, by introducing a controlled-release layer containing a controlled-release component in the preparation of an oral patch, a drug can be quantitatively and uniformly released to the affected part, and the drug concentration can be maintained in a relatively constant range.

The invention provides a preparation method of a traditional Chinese medicine composition oral patch for treating periodontitis, the traditional Chinese medicine composition oral patch for treating periodontitis comprises a protective layer, an adhesive layer and a controlled release layer, and the traditional Chinese medicine composition oral patch for treating periodontitis is prepared by taking the traditional Chinese medicine composition as a raw material, and comprises the following steps:

a1 is prepared by dissolving 1-2 parts by weight of a traditional Chinese medicine composition for treating periodontitis in 1-2 parts by weight of ethanol, and then continuously stirring and mixing with 6-8 parts by weight of water, 15-25 parts by weight of carbomer, 20-30 parts by weight of dextrin, 30-50 parts by weight of starch and 0.2-0.4 part by weight of magnesium stearate, granulating and drying to obtain traditional Chinese medicine granules for later use;

a2 pressing the Chinese medicinal granules obtained in step A1 to obtain Chinese medicinal tablet, i.e. adhesive layer;

a3 spraying the protective layer spray solution on one side of the Chinese medicinal tablet obtained in step A2, and drying to obtain a double-layer Chinese medicinal tablet;

a4 spraying the controlled release layer spray solution on one side of the double-layer Chinese medicinal tablet obtained in step A3, and drying to obtain the oral patch for treating periodontitis; the oral patch is of a sandwich structure, and the protective layer and the controlled release layer are respectively arranged on two sides of the traditional Chinese medicine tablet; the controlled release layer spraying liquid consists of 3-5 wt% of a composite controlled release agent, 2-4 wt% of bocam and the balance of water.

Preferably, the fineness of the traditional Chinese medicine particles in the step A1 is 30-50 meshes, and the water content is 3-5 wt%.

Preferably, the diameter of the traditional Chinese medicine tablet in the step A2 is 4-6 mm.

Preferably, the protective layer spraying liquid in the step a3 is a mixture obtained by mixing 2-4 wt% of acrylic resin, 2-3 wt% of riboflavin, 1.5-2 wt% of titanium dioxide, 0.1-0.3 wt% of dioctyl phthalate and the balance of water.

Preferably, the thickness of the protective layer of the double-layer traditional Chinese medicine tablet in the step A3 is 0.2-0.4 mm, and the thickness of the controlled release layer of the traditional Chinese medicine composition oral patch for treating periodontitis in the step A4 is 0.1-0.2 mm.

Preferably, the composite controlled release agent in the step A4 is a synthetic controlled release agent, polyethylene glycol and triglyceride in a mass ratio of (5-8): (1-3): 1 of the mixture formed.

Preferably, the synthetic controlled-release agent is any one of a diosmetin controlled-release agent and an anticoagulation hydroxypropyl methylcellulose controlled-release agent.

The inventor finds that the composition formed by the diosmetin and the polycaprolactone grafted polyetherimide has a controlled release effect, long molecular chains of the polymer can slow down the short-time release of drug molecules, and the concentration is controlled so that the drug concentration does not suddenly rise; the active ingredients in the medicine are slowly released along with diosmetin through polymer-induced degradation and hydrolysis, and the concentration can be kept constant for a long time, so that the medicine effect is prolonged.

The preparation method of the diosmetin controlled release agent comprises the following steps:

x1 is characterized in that 10-20 parts by weight of polyethylene glycol monomethyl ether, 120-180 parts by weight of epsilon-caprolactone and 0.01-0.05 part by weight of stannous octoate are added into a reaction container, the mixture is stirred at the speed of 240-480 rpm for 2-4 hours at the protection of nitrogen at the temperature of 110-130 ℃ to react to obtain a reaction product A, the reaction product A is dissolved in 150-200 parts by weight of chloroform and then poured into 180-240 parts by weight of 0-4 ℃ n-hexane for precipitation, filtration and drying to obtain a copolymer I for later use;

x2, dissolving the copolymer I obtained in the step X1 in 75-150 parts of dichloromethane, adding 0.02-0.10 part of triethylamine and 120-180 parts of acryloyl chloride, reacting for 6-12 hours at the stirring speed of 120-240 rpm under the protection of nitrogen at 40-50 ℃ to obtain a reaction product B, dissolving the reaction product B in 150-200 parts of chloroform, adding 50-75 parts of polyetherimide, reacting for 18-36 hours at the stirring speed of 120-240 rpm under the protection of nitrogen at 40-50 ℃, cooling, pouring 120-180 parts of petroleum ether, precipitating, filtering and drying to obtain a copolymer II for later use;

x3 dissolving the copolymer II obtained in the step X2 and 8-12 parts of diosmetin in 80-120 parts of acetone, carrying out ultrasonic treatment for 5-15 min at the power of 550-850W to obtain a mixture A, placing the mixture in a vacuum drying device, carrying out vacuum drying for 2-4 h at the temperature of 55-65 ℃ to obtain a dried product, blending the dried product and 100-120 parts of water at the stirring speed of 30-60 rpm for 1-2 h to obtain a mixture B, pre-freezing the mixture B at the temperature of-10 to-20 ℃ for 0.5-1 h, then carrying out freeze drying at the temperature of-60 to-80 ℃ for 6-12 h to obtain a freeze-dried product A, and crushing and sieving the freeze-dried product A to obtain the diosmetin controlled release agent.

The inventor finds that the hydroxypropyl methyl cellulose can form gel after meeting water, the release speed of the medicine depends on the speed of penetrating through a gel layer, the hydroxypropyl methyl cellulose is gradually dissolved, the medicine is released, and the controlled release effect is good; in addition, the hydroxypropyl methyl cellulose can be used as a supporting structure of the controlled release layer, so that the stability of the controlled release layer is improved.

In practical use, when the oral patch is stuck to an affected part, blood platelets in blood can adhere to the surface of the controlled release layer and coagulate, and the aggregation of the blood platelets can reduce the rate of the drug penetrating through the controlled release layer, so that the drug is not uniformly released, and the controlled release effect is influenced. The inventor makes an improvement on the technology, and introduces polytrimethylene carbonate into the controlled release layer to reduce the adhesion of platelets, thereby solving the problem of uneven release of the controlled release layer.

The preparation method of the anticoagulant hydroxypropyl methylcellulose controlled release agent comprises the following steps:

y1 is calculated by weight, 10-20 parts of polyethylene glycol monomethyl ether, 120-180 parts of epsilon-caprolactone and 0.01-0.05 part of stannous octoate are added into a reaction container, the mixture is stirred at the speed of 240-480 rpm for 2-4 hours under the protection of nitrogen at the temperature of 110-130 ℃ to react to obtain a reaction product A, the reaction product A is dissolved in 150-200 parts of chloroform and then poured into 180-240 parts of 0-4 ℃ n-hexane, and the mixture is precipitated, filtered and dried to obtain a copolymer I for later use;

y2, dissolving the copolymer I obtained in the step Y1 in 75-150 parts of dichloromethane, adding 0.02-0.10 part of triethylamine and 120-180 parts of acryloyl chloride, reacting for 6-12 hours at the stirring speed of 120-240 rpm under the protection of nitrogen at 40-50 ℃ to obtain a reaction product B, dissolving the reaction product B in 150-200 parts of chloroform, adding 50-75 parts of polyetherimide, reacting for 18-36 hours at the stirring speed of 120-240 rpm under the protection of nitrogen at 40-50 ℃, cooling, pouring 120-180 parts of petroleum ether, precipitating, filtering and drying to obtain a copolymer II for later use;

y3, dissolving the copolymer II obtained in the step Y2 and 8-12 parts of diosmetin in 80-120 parts of acetone, carrying out ultrasonic treatment for 5-15 min at the power of 550-850W to obtain a mixture A, placing the mixture in a vacuum drying device, carrying out vacuum drying for 2-4 h at the temperature of 55-65 ℃ to obtain a dried product, blending the dried product and 100-120 parts of water at the stirring speed of 30-60 rpm for 1-2 h to obtain a mixture B, pre-freezing the mixture B at the temperature of-10 to-20 ℃ for 0.5-1 h, then carrying out freeze drying at the temperature of-60 to-80 ℃ for 6-12 h to obtain a freeze-dried product A, and crushing and sieving the freeze-dried product A to obtain a diosmetin controlled release agent for later use;

y4 dissolving 15-20 parts of xanthan gum in 800-1200 parts of water at 55-70 ℃, mixing at a stirring speed of 360-480 rpm for 1-2 h, adding 1.2-1.5 parts of sodium orthoperiodate into the xanthan gum mixed solution, adjusting the pH of the xanthan gum mixed solution to 5-6 with 1-2 mol/L sulfuric acid aqueous solution, reacting at a stirring speed of 180-360 rpm at 40-50 ℃ for 2-4 h, stopping the reaction, pre-freezing at-10-20 ℃ for 0.5-1 h, and freeze-drying at-60-80 ℃ for 6-12 h to obtain a freeze-dried product B for later use;

y5, dissolving 15-20 parts of hydroxypropyl methyl cellulose in a phosphate buffer salt solution with the pH value of 5.5, mixing for 0.5-1 h at a stirring speed of 120-180 rpm, adding 2.5-7.5 parts of polytrimethylene carbonate, carrying out ultrasonic treatment for 10-15 min at a power of 550-850W, adding the freeze-dried product B obtained in the step Y4 and the diosmetin controlled release agent obtained in the step Y3 after the ultrasonic treatment is finished, continuously mixing for 2-4 h at a stirring speed of 120-180 rpm, adjusting the pH value to 9-10 with 1-2 mol/L of sodium hydroxide aqueous solution after the mixing is finished, washing for 3-5 times, carrying out pre-freezing for 0.5-1 h at-10-20 ℃, carrying out freeze drying for 6-12 h at-60-80 ℃, crushing and sieving to obtain the hydroxypropyl anticoagulant methyl cellulose controlled release agent.

The introduction and the function of each raw material in the formula of the invention are as follows:

two-side needle: the plants are also named as shanshan tiger, shinyleaf pricklyash root, bilateral needle, and root of Zanthoxylum nitidum (Roxb.) DC. Mild in nature, bitter and pungent in flavor. Has little toxicity. It enters stomach meridian and liver meridian. Promoting qi circulation, relieving pain, promoting blood circulation, removing blood stasis, dispelling pathogenic wind, and dredging collaterals. Contains alkaloids such as nitidine, chelerythrine, isophythradine, xanthophylline, nitidine chloride, xanthophylline chloride, and nitidine oxide.

Loofah sponge: also called as vascular bundles of mature fruits of Luffa cylindrica roem, Luffa stem, Luffa mesh, Luffa pulp, Luffa cloth, Luffa thread, Luffa stem, and huperzia serrata (L.) serrata. Mild in nature and sweet in taste. It enters lung meridian, stomach meridian and liver meridian. Promoting blood circulation, dredging collaterals, and dispelling pathogenic wind. Contains cellulose, xylan, mannan, galactan, and lignin.

Hawthorn fruit: also called Crataegus pinnatifida, Crataegus cuneata, Liangmei, Crataegus pinnatifida Bge, var majorn, E.Br. Slightly warm in nature, sour and sweet in taste. It enters spleen, stomach and liver meridians. Mainly contains organic acid and flavonoid compounds. And further contains L-epicatechin, quercetin, beta-sitosterol, citric acid, ursolic acid, linolenic acid, linoleic acid, gallic acid, protocatechuic acid, etc.

Pseudo-ginseng: root and rhizome of Panax notoginseng, radix Stephaniae Sinicae, Panax pseudoginseng, and Lacca sinica exsiccata, Panax notoginseng (Burk.) F.H.Chen. Warm in nature, sweet and slightly bitter in taste. It enters liver meridian and stomach meridian. Mainly contains 12 monomer saponins such as ginsenoside, quercetin, acetic acid, caryophyllene, leucine, beta-sitosterol-D-glucoside, panaxytriol, notoginsenoside and the like, and a hemostatic component of pseudo-ginseng acid. And volatile oil and multiple trace elements.

Honeysuckle stem: the Japanese honeysuckle stem is prepared from stems and branches of Lonicera japonica Thunb of Caprifoliaceae. Cold in nature and sweet in taste. It enters lung and stomach meridians.

Gypsum: soft gypsum, fine marble, white tiger, gypsum rubrum, white tiger, jade boulder, and ice stone. The sulfate mineral anhydrite Gypsum ore. Big and cold in nature, sweet and pungent in flavor. It enters lung and stomach meridians. The gypsum contains predominantly hydrous calcium sulfate.

And (3) bud of the sophora japonica: flower buds of Sophora japonica L, a plant belonging to the family of plants, namely Sophora japonica bud and Sophora japonica bud. Slightly cold in nature and bitter in taste. It enters liver meridian and large intestine meridian. Contains rutin with highest content in flower bud and reduced content after blooming. In addition, the composition contains triterpene saponin, glucose, glucuronic acid, rhamnose, isorhamnetin-3-rutinoside, kaempferol-3-rutinoside, quercetin, semen Phaseoli saponin, Sophora Japonica flower diol, etc.

Kudzu root: also called as root of Pueraria lobata (Ohwi), Pueraria thomsonii, and Pueraria lobata (Willd.) Ohwi. Cool in nature, sweet and pungent in flavor. It enters spleen and stomach meridians. Mainly contains daidzein, daidzin and puerarin. The HPLC method is used for measuring the content of total flavone, daidzein, daidzin and puerarin in Pueraria mirifica and roots of the same genus, and the content of the total flavone of Pueraria mirifica is highest. And contains biochanin, puerarin A, puerarin B, daucosterol, p-sitosterol, etc.

Selfheal: other names are selfheal, club grass, oldenlandia, Tiexiakusu, Tiessen grass, Langerhans, club grass, and ears of Prunella vulgaris L. Cold in nature, pungent and bitter in flavor. It enters liver meridian and gallbladder meridian. The ears in different growth periods all contain ursolic acid, oleanolic acid, caffeic acid, gallic acid, Prunella vulgaris saponin A, Prunella vulgaris saponin B, umbelliferone, oleic acid, etc.

Fructus forsythiae: also called Luupi, Huanghua stripe, Huanglianhua, fruit of Vahl, Forsythia suspensa (Thunb.) of Oleaceae. Slightly cold in nature and bitter in taste. It enters lung meridian, heart meridian and small intestine meridian. Contains lignans, flavonoids, volatile components, phenethyl, ethyl cyclohexanol, triterpenes, coumarin, etc. Also comprises betulinic acid, phillyrin, arctiin, matairesinol, pinoresinol, phillyrin C, phillyrin D, etc.

Mint: it is also named as Ipomoea batatas, Su mint, JISU, \ 34082, Hehe, night killer, herba Leonuri, herba Pileae Scriptae, herba Menthae, and is cool and pungent in taste. It enters lung and liver meridians. The herba Menthae mainly contains volatile oil, and also contains levomenthol, isomenthone, pulegone, menthyl acetate, isorifolium, peppermint isoflavide extract, rosmarinic acid, etc.

On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.

The invention has the beneficial effects that:

compared with the prior art, the invention uses radix zanthoxyli, loofah sponge, hawthorn, pseudo-ginseng, honeysuckle stem, gypsum, sophora flower bud and kudzuvine root to promote qi circulation and relieve pain, activate blood and remove blood stasis, and uses prunella vulgaris, forsythia and mint to dissipate stagnation and reduce swelling and clear away heat and toxic material, and the main and minister drugs are combined together to dissipate blood stasis and stop bleeding, dispel wind and dredge collaterals, and the middle warmer is lowered to play the effects of reducing swelling and relieving pain and dispersing wind heat.

Compared with the prior art, the traditional Chinese medicine composition has the advantages of simple extraction process and convenient operation.

Compared with the prior art, the oral patch prepared from the traditional Chinese medicine composition for treating periodontitis has a good controlled-release effect on medicines, and can maintain the medicine concentration for a long time and prolong the medicine effect.

Detailed Description

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.

Some raw material parameters in the comparative examples and examples of the invention are as follows:

radix zanthoxyli, full dry sheet, producing area: guangxi Liuzhou city;

loofah sponge, full dry net shape, producing area: guangxi river pool city;

hawthorn, whole dry slices, origin: shandong Qingzhou city;

pseudo-ginseng, whole dry block, origin: yunnan Wenshan city;

honeysuckle stem, full dry strip, production area: mountain city, Pingtai Henan;

sophora flower bud, full dry and granular, producing area: handan market in Hebei province;

kudzu root, whole dry block, origin: shisha city, Hubei;

selfheal, full-dry rod-shaped, production area: changde city of Hunan;

forsythia, whole dry granules, origin: jiangsu Shuyang city;

mint, whole dry flakes, origin: anhui Fuyang City;

polyethylene glycol monomethyl ether, seaan petrochemical plant of Jiangsu province, CAS number: 9004-74-4;

epsilon-caprolactone, Jiangsu Minglin chemical science and technology Co., Ltd, CAS No.: 502-44-3;

polytrimethylene carbonate, wuhan kamick technologies ltd, CAS No.: 24937-78-8.

Example 1

A traditional Chinese medicine composition oral patch for treating periodontitis is composed of a protective layer, an adhesive layer and a controlled release layer and is prepared by the following steps:

a1 dissolving 1.8kg of the Chinese medicinal composition for treating periodontitis in 2kg of ethanol, mixing with 8kg of water, 20kg of bocam, 25kg of dextrin, 40kg of starch and 0.2kg of magnesium stearate in a granulator, granulating, and drying to obtain Chinese medicinal granules with fineness of 40 meshes and water content of 3 wt%;

a2 pressing the Chinese medicinal granules obtained in step A1 with a tablet press to obtain Chinese medicinal tablets with diameter of 5mm, i.e. adhesive layer;

a3 preparation of the protective layer adopts a spraying process, wherein the protective layer spraying liquid is sprayed on one surface of the Chinese medicinal tablet obtained in the step A2, and the Chinese medicinal composition oral patch for treating periodontitis is obtained after drying, wherein the thickness of the protective layer is 0.2 mm.

The preparation method of the traditional Chinese medicine composition for treating periodontitis in the step A1 comprises the following steps:

s1 weighing 150g of radix zanthoxyli, 140g of loofah sponge, 90g of hawthorn, 50g of pseudo-ginseng, 120g of honeysuckle stem, 150g of gypsum, 150g of sophora flower bud, 200g of kudzuvine root, 90g of selfheal and 60g of weeping forsythia, cleaning to remove dust and impurities on the surface of the raw materials, drying at normal temperature for 6h, and sterilizing to obtain clean raw materials; mixing, crushing and sieving clean raw materials to obtain raw material powder, wherein the grade of the raw material powder is medium powder for later use;

s2, mixing the raw material powder obtained in the step S1 with 1.8kg of ethanol, sealing and standing for 4 hours to obtain wet medicinal powder; filling the wet medicinal powder into a percolation device, adding ethanol, exhausting, and soaking for 24 hr to obtain soaked medicinal powder;

s3, percolating the immersed medicinal powder obtained in the step S2, adding 7.5kg of ethanol for percolation at one time, adopting a warm-leaching method, controlling the extraction temperature to be 45 ℃, controlling the percolation rate to be 1.5mL per 1kg of medicinal material per minute, stopping percolation when the collected percolation liquid reaches 80% of the mass of the ethanol for percolation, collecting and squeezing the residual medicinal powder, and combining the squeezed liquid and the percolation liquid to obtain a percolation product for later use;

s4, distilling the diacolation product obtained in the step S3 under reduced pressure to recover ethanol, wherein the pressure is 12.31kPa, and the temperature is 55 ℃, so as to obtain the residual extracting solution, namely the traditional Chinese medicine composition for treating periodontitis.

The protective layer spray coating liquid in the step A3 is a mixture obtained by mixing 3 wt% of acrylic resin, 2 wt% of riboflavin, 1.5 wt% of titanium dioxide, 0.1 wt% of dioctyl phthalate and the balance of water.

Example 2

Basically in accordance with example 1, the difference is only that in step S1, the raw materials are: 150g of radix zanthoxyli, 140g of loofah sponge, 90g of hawthorn, 50g of pseudo-ginseng, 120g of honeysuckle stem, 150g of gypsum, 150g of sophora flower bud, 200g of kudzuvine root, 90g of selfheal and 30g of mint.

Example 3

Basically in accordance with example 1, the difference is only that in step S1, the raw materials are: 150g of radix zanthoxyli, 140g of loofah sponge, 90g of hawthorn, 50g of pseudo-ginseng, 120g of honeysuckle stem, 150g of gypsum, 150g of sophora flower bud, 200g of kudzuvine root, 60g of weeping forsythia capsule and 30g of mint.

Example 4

Basically in accordance with example 1, the difference is only that in step S1, the raw materials are: 150g of radix zanthoxyli, 140g of loofah sponge, 90g of hawthorn, 50g of pseudo-ginseng, 120g of honeysuckle stem, 150g of gypsum, 150g of sophora flower bud, 200g of kudzuvine root, 90g of selfheal, 60g of weeping forsythia and 30g of mint.

Example 5

An oral patch for treating periodontitis is composed of a protective layer, an adhesive layer and a controlled release layer, and is prepared by the following steps:

a1 dissolving 1.8kg of the Chinese medicinal composition for treating periodontitis in 2kg of ethanol, mixing with 8kg of water, 20kg of bocam, 25kg of dextrin, 40kg of starch and 0.2kg of magnesium stearate in a granulator, granulating, and drying to obtain Chinese medicinal granules with fineness of 40 meshes and water content of 3 wt%;

a2 pressing the Chinese medicinal granules obtained in step A1 with a tablet press to obtain Chinese medicinal tablets with diameter of 5mm, i.e. adhesive layer;

a3 preparation of the protective layer adopts a spraying process, the protective layer spraying liquid is sprayed on one side of the Chinese medicinal tablet obtained in the step A2, and the Chinese medicinal tablet is dried, wherein the thickness of the protective layer is 0.2mm, and a double-layer Chinese medicinal tablet is obtained for later use;

a4 spraying the controlled release layer spray solution on one side of the double-layer Chinese medicinal tablet obtained in step A3, and drying to obtain the oral patch for treating periodontitis; the oral patch is of a sandwich structure, and the protective layer and the controlled release layer are respectively arranged on two sides of the traditional Chinese medicine tablet; the spraying liquid of the controlled release layer consists of 4 wt% of composite controlled release agent, 2 wt% of bocam and the balance of water; the thickness of the controlled release layer is 0.1 mm.

The preparation method of the traditional Chinese medicine composition for treating periodontitis in the step A1 comprises the following steps:

s1 weighing 150g of radix zanthoxyli, 140g of loofah sponge, 90g of hawthorn, 50g of pseudo-ginseng, 120g of honeysuckle stem, 150g of gypsum, 150g of sophora flower bud, 200g of kudzuvine root, 90g of selfheal, 60g of weeping forsythia capsule and 30g of mint, cleaning to remove dust and impurities on the surface of the raw materials, drying at normal temperature for 6h, and sterilizing to obtain clean raw materials; mixing, crushing and sieving clean raw materials to obtain raw material powder, wherein the grade of the raw material powder is medium powder for later use;

s2, mixing the raw material powder obtained in the step S1 with 1.8kg of ethanol, sealing and standing for 4 hours to obtain wet medicinal powder; filling the wet medicinal powder into a percolation device, adding ethanol, exhausting, and soaking for 24 hr to obtain soaked medicinal powder;

s3, percolating the immersed medicinal powder obtained in the step S2, adding 7.5kg of ethanol for percolation at one time, adopting a warm-leaching method, controlling the extraction temperature to be 45 ℃, controlling the percolation rate to be 1.5mL per 1kg of medicinal material per minute, stopping percolation when the collected percolation liquid reaches 80% of the mass of the ethanol for percolation, collecting and squeezing the residual medicinal powder, and combining the squeezed liquid and the percolation liquid to obtain a percolation product for later use;

s4, distilling the diacolation product obtained in the step S3 under reduced pressure to recover ethanol, wherein the pressure is 12.31kPa, and the temperature is 55 ℃, so as to obtain the residual extracting solution, namely the traditional Chinese medicine composition for treating periodontitis.

The protective layer spray coating liquid in the step A3 is a mixture obtained by mixing 3 wt% of acrylic resin, 2 wt% of riboflavin, 1.5 wt% of titanium dioxide, 0.1 wt% of dioctyl phthalate and the balance of water.

The compound controlled release agent in the step A4 is polyethylene glycol and triglyceride, and the mass ratio of the polyethylene glycol to the triglyceride is 2: 1 of the mixture formed.

Example 6

An oral patch for treating periodontitis is composed of a protective layer, an adhesive layer and a controlled release layer, and is prepared by the following steps:

a1 dissolving 1.8kg of the Chinese medicinal composition for treating periodontitis in 2kg of ethanol, mixing with 8kg of water, 20kg of bocam, 25kg of dextrin, 40kg of starch and 0.2kg of magnesium stearate in a granulator, granulating, and drying to obtain Chinese medicinal granules with fineness of 40 meshes and water content of 3 wt%;

a2 pressing the Chinese medicinal granules obtained in step A1 with a tablet press to obtain Chinese medicinal tablets with diameter of 5mm, i.e. adhesive layer;

a3 preparation of the protective layer adopts a spraying process, the protective layer spraying liquid is sprayed on one side of the Chinese medicinal tablet obtained in the step A2, and the Chinese medicinal tablet is dried, wherein the thickness of the protective layer is 0.2mm, and a double-layer Chinese medicinal tablet is obtained for later use;

a4 spraying the controlled release layer spray solution on one side of the double-layer Chinese medicinal tablet obtained in step A3, and drying to obtain the oral patch for treating periodontitis; the oral patch is of a sandwich structure, and the protective layer and the controlled release layer are respectively arranged on two sides of the traditional Chinese medicine tablet; the spraying liquid of the controlled release layer consists of 4 wt% of composite controlled release agent, 2 wt% of bocam and the balance of water; the thickness of the controlled release layer is 0.1 mm.

The preparation method of the traditional Chinese medicine composition for treating periodontitis in the step A1 comprises the following steps:

s1 weighing 150g of radix zanthoxyli, 140g of loofah sponge, 90g of hawthorn, 50g of pseudo-ginseng, 120g of honeysuckle stem, 150g of gypsum, 150g of sophora flower bud, 200g of kudzuvine root, 90g of selfheal, 60g of weeping forsythia capsule and 30g of mint, cleaning to remove dust and impurities on the surface of the raw materials, drying at normal temperature for 6h, and sterilizing to obtain clean raw materials; mixing, crushing and sieving clean raw materials to obtain raw material powder, wherein the grade of the raw material powder is medium powder for later use;

s2, mixing the raw material powder obtained in the step S1 with 1.8kg of ethanol, sealing and standing for 4 hours to obtain wet medicinal powder; filling the wet medicinal powder into a percolation device, adding ethanol, exhausting, and soaking for 24 hr to obtain soaked medicinal powder;

s3, percolating the immersed medicinal powder obtained in the step S2, adding 7.5kg of ethanol for percolation at one time, adopting a warm-leaching method, controlling the extraction temperature to be 45 ℃, controlling the percolation rate to be 1.5mL per 1kg of medicinal material per minute, stopping percolation when the collected percolation liquid reaches 80% of the mass of the ethanol for percolation, collecting and squeezing the residual medicinal powder, and combining the squeezed liquid and the percolation liquid to obtain a percolation product for later use;

s4, distilling the diacolation product obtained in the step S3 under reduced pressure to recover ethanol, wherein the pressure is 12.31kPa, and the temperature is 55 ℃, so as to obtain the residual extracting solution, namely the traditional Chinese medicine composition for treating periodontitis.

The protective layer spray coating liquid in the step A3 is a mixture obtained by mixing 3 wt% of acrylic resin, 2 wt% of riboflavin, 1.5 wt% of titanium dioxide, 0.1 wt% of dioctyl phthalate and the balance of water.

The compound controlled release agent in the step A4 is diosmetin controlled release agent and polyethylene glycol according to the mass ratio of 7: 2, and (c) 2.

The preparation method of the diosmetin controlled release agent comprises the following steps:

adding 15g of polyethylene glycol monomethyl ether, 140g of epsilon-caprolactone and 0.03g of stannous octoate into a reaction container by weight part X1, reacting for 3 hours at the stirring speed of 480rpm under the protection of nitrogen at 120 ℃ to obtain a reaction product A, dissolving the reaction product A in 180g of chloroform, pouring the solution into 200g of n-hexane at 0 ℃, precipitating, filtering and drying to obtain a copolymer I for later use;

x2, dissolving the copolymer I obtained in the step X1 in 125g of dichloromethane, adding 0.06g of triethylamine and 140g of acryloyl chloride, reacting for 8 hours at 45 ℃ under the protection of nitrogen and at a stirring speed of 240rpm to obtain a reaction product B, dissolving the reaction product B in 200g of chloroform, adding 75g of polyetherimide, reacting for 24 hours at 45 ℃ under the protection of nitrogen and at a stirring speed of 240rpm, cooling, pouring 180g of petroleum ether, precipitating, filtering and drying to obtain a copolymer II for later use;

x3 dissolving the copolymer II obtained in the step X2 and 10g of diosmetin in 120g of acetone, carrying out ultrasonic treatment for 8min at the power of 550W to obtain a mixture A, placing the mixture in a vacuum drying device, carrying out vacuum drying for 2h at 55 ℃ to obtain a dried product, blending the dried product and 100g of water at the stirring speed of 60rpm for 1h to obtain a mixture B, pre-freezing the mixture B at-20 ℃ for 1h, and then carrying out freeze drying at-80 ℃ for 8h to obtain a freeze-dried product A, and crushing and sieving the freeze-dried product A to obtain the diosmetin controlled release agent.

Example 7

An oral patch for treating periodontitis, which is substantially identical to the preparation method of example 6 except that the composite controlled-release agent in step a4 is a diosmetin controlled-release agent, and triglyceride is added in a mass ratio of 7: 1 of the mixture formed.

Example 8

An oral patch for treating periodontitis, which is substantially identical to the preparation method of example 6 except that the composite controlled-release agent in the step a4 is diosmetin controlled-release agent, polyethylene glycol and triglyceride in a mass ratio of 7: 2: 1 of the mixture formed.

Example 9

An oral patch for treating periodontitis, which is substantially identical to the preparation method of example 6 except that the composite type controlled-release agent in step a4 is an anti-coagulant hydroxypropyl methylcellulose controlled-release agent, polyethylene glycol, and triglyceride in a mass ratio of 7: 2: 1 of the mixture formed.

The preparation method of the anticoagulant hydroxypropyl methylcellulose controlled release agent comprises the following steps:

y1 is calculated by weight, 15g of polyethylene glycol monomethyl ether, 140g of epsilon-caprolactone and 0.03g of stannous octoate are added into a reaction container, the mixture is stirred at 480rpm and reacted for 3 hours under the protection of nitrogen at 120 ℃ to obtain a reaction product A, the reaction product A is dissolved in 180g of chloroform and poured into 200g of normal hexane at 0 ℃, and the mixture is precipitated, filtered and dried to obtain a copolymer I for later use;

y2, dissolving the copolymer I obtained in the step Y1 in 125g of dichloromethane, adding 0.06g of triethylamine and 140g of acryloyl chloride, reacting for 8 hours at 45 ℃ under the protection of nitrogen and at a stirring speed of 240rpm to obtain a reaction product B, dissolving the reaction product B in 200g of chloroform, adding 75g of polyetherimide, reacting for 24 hours at 45 ℃ under the protection of nitrogen and at a stirring speed of 240rpm, cooling, pouring 180g of petroleum ether, precipitating, filtering and drying to obtain a copolymer II for later use;

y3, dissolving the copolymer II obtained in the step Y2 and 10g of diosmetin in 120g of acetone, carrying out ultrasonic treatment for 8min at the power of 550W to obtain a mixture A, placing the mixture in a vacuum drying device, carrying out vacuum drying for 2h at 55 ℃ to obtain a dried product, blending the dried product and 100g of water at the stirring speed of 60rpm for 1h to obtain a mixture B, pre-freezing the mixture B at-20 ℃ for 1h, and then carrying out freeze drying at-80 ℃ for 8h to obtain a freeze-dried product A, and crushing and sieving the freeze-dried product A to obtain a diosmetin controlled release agent for later use;

y4 is prepared by dissolving 18g xanthan gum in 800g water at 55 deg.C, mixing at 480rpm for 1h, adding 1.2g sodium ortho-periodate into the xanthan gum mixture, adjusting pH of the xanthan gum mixture to 5.5 with 1mol/L sulfuric acid water solution, reacting at 40 deg.C at 360rpm for 3h, stopping reaction, pre-freezing at-20 deg.C for 0.5, and freeze-drying at-80 deg.C for 8h to obtain lyophilized product B;

y5 is prepared by dissolving 15-20 parts of hydroxypropyl methyl cellulose in phosphate buffer salt solution with pH of 5.5, mixing at a stirring speed of 180rpm for 0.5h, adding 5g of polytrimethylene carbonate, carrying out ultrasonic treatment at a power of 550W for 15min, adding the freeze-dried product B obtained in the step Y4 and the diosmetin controlled release agent obtained in the step Y3 after the ultrasonic treatment is finished, continuously mixing at a stirring speed of 180rpm for 3h, adjusting the pH to 10 by using 1mol/L sodium hydroxide aqueous solution after the mixing is finished, washing for 3 times, pre-freezing at-20 ℃ for 0.5h, then freeze-drying at-80 ℃ for 8h, crushing and sieving to obtain the anti-coagulation hydroxypropyl methyl cellulose controlled release agent.

Comparative example 1

An oral patch for treating periodontitis, which is substantially identical to the preparation method of example 1 except that the raw materials in step S1 are: 150g of radix zanthoxyli, 140g of loofah sponge, 90g of hawthorn, 50g of pseudo-ginseng, 120g of honeysuckle stem, 150g of gypsum, 150g of sophora flower bud and 200g of kudzu root.

Test example 1

The invention tests the antibacterial effect of the pathogenic bacteria of periodontitis by referring to the specific requirements of WS/T650 and 2019 antibacterial and bacteriostatic effect evaluation method 5.2 antibacterial effect. The carrier soaking quantitative sterilization test is adopted, and according to the types of common pathogenic bacteria causing periodontitis, the experimental strains for the test are selected from Porphyromonas gingivalis ATCC 33277 (Shanghai Shanzhu Zheng biological science Co., Ltd.) and Actinobacillus actinomycetemcomitans ATCC 43717 (Shanghai Fu Xiang biological science Co., Ltd.). The experimental strain was cultured for 72h, the experiment was repeated 3 times, and the results were averaged. The results of the antibacterial effect test of the periodontitis pathogenic bacteria are shown in table 1.

Table 1: results of the test of the antibacterial effect of the pathogenic bacteria of periodontitis

According to the specification in the 5.2.2.7 result judgment in WS/T650-plus 2019 antibacterial and bacteriostatic effect evaluation method 5.2 antibacterial effect, the bactericidal rate is more than or equal to 90 percent, and the antibacterial effect is judged; the sterilization rate in the time specified in the specification is more than or equal to 99 percent, and the antibacterial effect is judged to be stronger. It can be seen from comparison between the examples and the comparative examples that the main drug and the three ministerial drugs are matched to play a role in synergy, and the example 5 has an antibacterial effect on porphyromonas gingivalis and actinobacillus actinoplanes and can eliminate pathogenic bacteria of periodontitis. The reason for this may be that the traditional Chinese medicine composition for treating periodontitis contains bactericidal active ingredients, and the combined use can increase bactericidal effect.

Test example 2

The dissolution of the invention is measured according to the specific requirements of the dissolution and release determination method of the general rules of the pharmacopoeia of the people's republic of China (2015), the first method (basket method) is adopted for the determination, the test temperature is 37 ℃, 6 samples are tested in each group, and the results are averaged. The dissolution test results are shown in table 2.

Table 2: dissolution test results table

The dissolution rate can reflect the release rate and the drug effect duration of the drug, and the difference of the dissolution rates can influence the bioavailability and the curative effect of the drug. Depending on the field of application of the present invention, it is desirable that the drug is released over a prolonged period of time and that the release rate remains relatively constant, as evidenced by a linear increase in dissolution rate over time. It can be seen from the comparison of the examples that the dissolution rate of example 9 meets the requirement along with the change of time, and the controlled release layer of the invention can play a good controlled release effect, probably because the long molecular chain of the polymer can slow down the short-time release of the drug molecules, and the concentration is controlled so that the drug concentration does not suddenly rise; the active ingredients in the medicine are slowly released along with diosmetin through polymer-induced degradation and hydrolysis, so that the concentration can be kept constant for a long time, and the medicine effect is further prolonged; the hydroxypropyl methyl cellulose can form gel after meeting water, the release speed of the medicine depends on the speed of penetrating through the gel layer, the hydroxypropyl methyl cellulose is gradually dissolved, the medicine is released, and the controlled release effect is good; in addition, the hydroxypropyl methyl cellulose can be used as a supporting structure of the controlled release layer, so that the stability of the controlled release layer is improved.

Test example 3

The platelet adhesion test of the controlled release layer coating of the present invention was carried out with reference to the specific method in "platelet adhesion test (glass bead column method) normal values and clinical case observation" (second department of medical and military university, proceedings, 1982, 4 th), and platelet-rich plasma used for the test was provided by Shanghai pure Biotechnology Co., Ltd. The controlled release layer spraying solution used in examples 8 to 9 was sprayed on glass beads using common glass beads as a control group to prepare a controlled release layer having a thickness of 0.1mm as a corresponding test group. The glass beads were 0.6mm in diameter and the test was repeated 4 times per group and the results averaged. The results of the platelet adhesion test of the controlled release layer coating are shown in table 3.

Table 3: table of platelet adhesion test results of controlled release layer coating

Group of	Platelet adhesion rate (%)
		Control group	37.7
Example 8	42.9
		Example 9	24.4

The controlled-release effect of the controlled-release layer is hindered by the adhesion and coagulation of platelets to the surface of the controlled-release layer, and thus the lower the corresponding platelet adhesion rate, the better the effect. The comparison between the examples and the control group shows that the controlled release layer prepared from the anticoagulation hydroxypropyl methylcellulose controlled release agent can reduce the adhesion rate of surface platelets, reduce the coagulation of the platelets on the surface, and further facilitate the improvement of the stability of the controlled release layer.