Preparation of traditional Chinese medicine preparation for periodontal disease

Abstract

The invention discloses a preparation method and application of a traditional Chinese medicine compound preparation for treating periodontitis, and relates to the technical field of traditional Chinese medicine preparations. Comprising 11 kinds of coptis chinensis, scutellaria baicalensis, honeysuckle, andrographis paniculata, cimicifuga foetida, rehmannia, moutan bark, angelica sinensis, mangnolia officinalis, borneol and liquorice. The traditional Chinese medicine composition comprises the following components in parts by weight: 1-3 parts of coptis chinensis, 3-5 parts of scutellaria baicalensis, 5-7 parts of honeysuckle, 3-5 parts of andrographis paniculata, 3-5 parts of cimicifuga foetida, 5-7 parts of rehmannia, 4-6 parts of moutan bark, 3-5 parts of angelica sinensis, 3-5 parts of mangnolia officinalis, 0.1-0.3 part of borneol and 2-4 parts of liquorice. The traditional Chinese medicine compound preparation has the effects of clearing away heat and toxic materials, relieving swelling and pain and cooling blood for hemostasis. The traditional Chinese medicine composition is used for treating periodontitis, gingivitis, swelling and aching of gum, gingival leakage and gingival bleeding. The mouthwash has the advantages of being good in effect on periodontal diseases and safe and convenient to use.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine compound preparation for treating periodontal diseases. Background Art

[0002] Periodontal diseases specifically refer to a variety of diseases occurring in the periodontal tissues (gingiva, periodontal ligament, alveolar bone and cementum), mainly including periodontitis and gingivitis, etc. The clinical manifestations are gingival bleeding, periodontal pocket formation, tooth loosening, displacement, chewing weakness, tooth loss, accompanied by alveolar bone resorption, toothache, bad breath, etc. Periodontal diseases are mainly caused by oral pathogenic bacteria infection. Gingivitis is reversible, without attachment loss and alveolar bone resorption, while periodontitis has damage to the periodontal supporting tissues, and the disease generally progresses slowly. If not treated in time, it will continue to progress until the teeth become loose and fall out. Therefore, periodontitis is the leading cause of tooth loss in adults.

[0003] Data shows that nearly 90% of adults in China suffer from periodontal diseases, and the detection rate of dental calculus in residents aged 35 - 44 reaches 96.7%; the detection rate of gingival bleeding reaches 87.4%, which has increased by 10.1% compared with the third epidemiological survey; about 90% of adults over 30 years old suffer from periodontal diseases of different degrees, and the incidence rate remains high. Periodontal diseases are not only the main cause of tooth loss in adults, but also a large number of research reports [2] also confirm that periodontal diseases are closely related to some systemic diseases. In view of the importance of periodontal health, the Chinese Stomatological Association has set the theme of the annual meetings from 2018 to 2020 as "Healthy Oral Cavity, Protected by Periodontium".

[0004] At present, the treatment of periodontal diseases mainly involves removing plaque and dental calculus on the tooth surface through periodontal sequential treatment. However, the bacteria remaining in the periodontal pocket will reattach and reproduce on the root surface in a short time. Therefore, in addition to removing plaque through periodontal sequential treatment, patients need to frequently and thoroughly remove the dental plaque biofilm through self - plaque control. Good oral hygiene and compliance are the keys to effectively preventing the development and recurrence of periodontal diseases. Poor oral hygiene will lead to the recolonization of subgingival bacteria within 4 - 8 weeks, increasing bacterial reproduction and periodontal recurrence. For periodontal diseases, in addition to mechanical therapy, chemical therapy is also used. However, long - term application of chemical agents to control plaque will have adverse effects such as dysbacteriosis and increased drug resistance. In recent years, more and more research has turned to new therapies with little or no toxic and side effects, such as probiotics and traditional Chinese medicine. Therefore, giving full play to the advantages of traditional Chinese medicine and developing a mucosa - administered traditional Chinese medicine compound preparation with definite curative effect, safety and convenient use has become an urgent problem to be solved.

[0005] In view of this, the present application is specifically proposed. Summary of the Invention

[0006] Based on the above problems, the present invention provides a traditional Chinese medicine compound preparation for treating periodontal disease, which includes 11 kinds of traditional Chinese medicines, namely Coptis chinensis, Scutellaria baicalensis, honeysuckle flower, andrographis paniculata, cimicifuga foetida, rehmannia glutinosa, cortex moutan, angelica sinensis, magnolia officinalis, borneol, and liquorice. Among them, in terms of parts by weight, Coptis chinensis is 1 - 3 parts, Scutellaria baicalensis is 3 - 5 parts, honeysuckle flower is 5 - 7 parts, andrographis paniculata is 3 - 5 parts, cimicifuga foetida is 3 - 5 parts, rehmannia glutinosa is 5 - 7 parts, cortex moutan is 4 - 6 parts, angelica sinensis is 3 - 5 parts, magnolia officinalis is 3 - 5 parts, borneol is 0.1 - 0.3 parts, and liquorice is 2 - 4 parts.

[0007] In this traditional Chinese medicine compound preparation, Coptis chinensis and Scutellaria baicalensis are bitter and cold in nature, clearing the accumulated heat in the stomach, and serving as the monarch drugs. Honeysuckle flower, andrographis paniculata, and cimicifuga foetida clear heat and detoxify, and reduce swelling; rehmannia glutinosa and cortex moutan clear heat and cool blood to stop bleeding, jointly serving as the minister drugs. Angelica sinensis nourishes blood and harmonizes blood, magnolia officinalis regulates qi and dries dampness, and borneol clears heat and relieves pain. These three drugs together serve as the assistant drugs; liquorice clears heat and detoxifies, and harmonizes all the drugs, serving as the envoy drug. All the drugs work synergistically, having the effects of clearing heat and detoxifying, reducing swelling and relieving pain, and cooling blood to stop bleeding. It is used to treat periodontitis and gingivitis, with symptoms such as gingival swelling and pain, gingival bleeding, gingival recession, tooth loosening and displacement, chewing weakness, bad breath, etc. Made into a mouthwash, it has the advantages of good efficacy, safe use, and convenience for periodontal disease.

[0008] This preparation is developed by adding ingredients on the basis of Qingwei Powder recorded in "Secret Collection of the Orchid Chamber" by Li Dongyuan, a famous doctor in the Jin and Yuan Dynasties. Qingwei Powder is composed of five traditional Chinese medicines, namely Coptis chinensis, rehmannia glutinosa, cortex moutan, cimicifuga foetida, and angelica sinensis, with the efficacy of clearing the stomach and cooling blood, treating toothache, gingival ulceration, gingival bleeding, and foul breath caused by accumulated heat in the stomach. These symptoms are all typical symptoms of periodontal disease. Nowadays, this prescription has been widely favored by traditional Chinese medicine stomatologists in the treatment of periodontal disease, and relevant pharmacological effects, mechanisms, and clinical studies have been successively carried out.

[0009] Meng Ying, etc. [3] Using chromatography - mass spectrometry technology, 189 chemical components in Qingwei Powder were analyzed, 39 active components were screened, corresponding to 180 potential action targets related to periodontitis. Through enrichment analysis of the action targets of the active components, 92 KEGG pathways were obtained. The "compound - target - pathway" network involves a total of 20 KEGG pathways, 34 active components, and 99 targets. The results of molecular docking verify that the key compounds have good binding ability with the key targets. It is preliminarily proved that the classic famous prescription Qingwei Powder treats periodontitis through multiple components, multiple targets, and multiple pathways, reflecting the action characteristics of the complex system of traditional Chinese medicine.

[0010] Clinically, Wang Fen, etc. [4]To observe the efficacy of orally taking Qingwei Powder combined with gargling with the soaking solution of Flos Lonicerae in the treatment of plaque-induced gingivitis. 300 patients were randomly divided into a treatment group and a control group, with 150 cases in each group. Both groups of patients received systematic gingival treatment (including scaling, root planing, irrigation, polishing, irrigating the gingival sulcus with 1% - 3% hydrogen peroxide solution by volume, and applying iodine preparation in the sulcus). In addition to that, the treatment group took Qingwei Powder orally and gargled with the soaking solution of Flos Lonicerae. The control group was treated with 0.1% chlorhexidine gargle by volume. The efficacy was evaluated after 2 weeks of treatment, and a follow-up was conducted after half a year. As a result, the cure rate of the treatment group was 96.67%, and that of the control group was 94.67%. The difference was not statistically significant ( P > 0.05). After half a year of follow-up, the recurrence rate of the treatment group was 4.67%, and that of the control group was 12.0%. The difference was statistically significant ( P < 0.05). Conclusion: Orally taking Qingwei Powder combined with gargling with the soaking solution of Flos Lonicerae has a significant effect in the treatment of plaque-induced gingivitis and can delay or prevent the recurrence of gingivitis. Wang et al. [5] Randomly divided 90 patients with periodontitis into two groups, with 45 cases in each group. The course of treatment was 3 weeks. Both groups were given conventional western medicine treatment, and the observation group was treated with Qingwei Powder in combination. The results showed that the improvement rate of the disease in the observation group was higher than that in the control group ( P < 0.05); the symptom control time of periodontitis and the periodontal index in the observation group were better than those in the control group ( P < 0.05). Conclusion: Conventional western medicine combined with Qingwei Powder has a definite effect in the treatment of periodontitis, can effectively improve the symptoms of periodontitis, and is safe in medication. Wu et al. [6] Used the modified Qingwei Powder as an adjuvant treatment for the syndrome of excessive stomach fire in children with acute pulpitis, which could significantly relieve the pain of the children, accelerate the recovery time of chewing function, and inhibit the expression of inflammatory factor transmitters, with remarkable curative effects. Lu et al. [7] Used Qingwei Powder combined with acupuncture to intervene in the pain of pericoronitis of wisdom teeth. There were 30 cases in each of the two groups. The control group was treated with penicillin V potassium capsules and metronidazole tablets, and the observation group was treated with Qingwei Powder combined with acupuncture on this basis. The course of treatment was 1 week. As a result, the total effective rates of the observation group and the control group were 93.33% and 53.33% respectively, and the difference was statistically significant ( P < 0.05); the total score of traditional Chinese medicine symptoms and VAS score in the observation group were significantly lower than those before treatment ( P < 0.05). It was confirmed that Qingwei Powder combined with acupuncture had a significant clinical effect in the treatment of the pain of pericoronitis of wisdom teeth.

[0011] It can be seen that currently, Qingwei Powder is used alone, or with added ingredients, or in combination with western medicine, or in combination with internal and external treatments of traditional Chinese medicine, and has achieved relatively definite curative effects in the treatment of periodontal diseases (periodontitis, gingivitis, acute pulpitis, pericoronitis of wisdom teeth).

[0012] In the prescription of this agent, experimental studies on single drugs for intervening in periodontal diseases have also been widely carried out. Regarding Coptis chinensis [8], the minimum inhibitory concentrations (MIC) of berberine contained therein against Streptococcus mutans, Streptococcus sobrinus, and Actinomyces viscosus are 0.625, 0.625, and 1.25 g / L respectively -1 . Zhou et al. [9] compared the in vitro inhibitory effects of 20 traditional Chinese medicine decoctions on Porphyromonas gingivalis, with the inhibition zone diameter and MIC against Porphyromonas gingivalis as the evaluation indicators. The results showed that the MICs of Coptis chinensis, Scutellaria baicalensis, Prunus mume, Schisandra chinensis, and Chinese gallnut were 0.0488 - 1.5625 mg / ml. It was confirmed that Coptis chinensis, Scutellaria baicalensis, elsholtzia oil, Prunus mume, Schisandra chinensis, and Chinese gallnut had the highest antibacterial sensitivity among these herbs. It has been proven

[10] that berberine has obvious inhibitory effects on periodontal suspected pathogenic bacteria including Actinomyces naeslundii, Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaninogenica, and Aggregatibacter actinomycetemcomitans. Hu Yang et al.

[11] investigated the in vitro antibacterial effects of five traditional Chinese medicines such as Coptis chinensis, Magnolia officinalis, and Rheum palmatum on Streptococcus mutans and Actinomyces viscosus, common cariogenic bacteria. The results showed that Coptis chinensis, Magnolia officinalis, and Rheum palmatum had strong inhibitory effects on Streptococcus mutans and Actinomyces viscosus, and the extract of Magnolia officinalis had strong antibacterial effects on common cariogenic bacteria. Wu Song et al.

[12] investigated the therapeutic effect of berberine (i.e., berberine) on rats with periodontitis, as well as the effects of berberine on inflammatory cytokines, oxidative stress, and inflammatory osteolysis in the gingival tissues of rats with periodontitis. As a result, compared with the rats in the periodontitis model group, the gingival index and attachment level of the rats with periodontitis in the berberine group were significantly decreased ( P <0.05). After 8 weeks of berberine treatment, the levels of inflammatory cytokines such as PEG2, IL-1β, TNF-α, and IL-6 in the gingival tissues of the periodontitis rat model were significantly decreased ( P <0.05), the oxidative stress indexes MDA and LPO were significantly decreased ( P <0.05), and the content of the antioxidant stress index CAT was significantly increased ( P <0.05). In addition, berberine also significantly decreased the content of RANKL and the ratio of RANKL / OPG in the gingival tissues of rats with periodontitis ( P <0.05), and significantly increased the content of OPG in the gingival tissues of rats with periodontitis ( P <0.05). It was confirmed that berberine had a high therapeutic effect on rats with periodontitis, and its mechanism might be related to the fact that berberine treatment could reduce the content of inflammatory cytokines in the gingival tissues of rats with periodontitis, reduce the level of oxidative stress, and relieve inflammatory osteolysis. Zhang Xuan et al.

[13] studied the inhibitory effect and mechanism of berberine on Porphyromonas gingivalis ( Pg ). Berberine on the standard strain ( Pg ATCC33277), highly virulent strain ( PgThe MIC and minimum bactericidal concentration (MBC) of berberine against Porphyromonas gingivalis ATCC33277 and Tannerella forsythia W83 were 15.625 μg / ml. At this concentration, berberine significantly decreased the viability of Pg ATCC33277 bacteria ( P < 0.05), and the ALP activity decreased after 12 h ( P < 0.05). Observation under TEM and SEM showed that after treatment with 15.625 μg / ml berberine, the Pg cells of ATCC33277 became deformed and shrank, losing their normal bacterial morphology. Conclusion: Berberine has a significant inhibitory effect on Pg ATCC33277 and Pg W83, probably by damaging the cell wall and cell membrane to reduce bacterial viability.

[0013] Zeng Hui et al.

[14] studied the combined application of baicalin and recombinant human bone morphogenetic protein 2 (rhBMP-2) double sustained-release preparations on the regeneration of periodontal tissues in minipigs. The results confirmed that baicalin could significantly increase the alveolar bone density and promote the repair and regeneration of alveolar bone. Conclusion: The combined application of baicalin and rhBMP-2 can promote periodontal tissue regeneration, laying a foundation for the clinical application of the baicalin and rhBMP-2 double sustained-release system. Li et al.

[15] A rat periodontitis model was established by locally injecting lipopolysaccharide between the first and second maxillary molars on the right side of rats. In the experimental group, 0.2 ml of baicalin solution (concentrations of 0.01, 0.1, and 1.0 μg / ml) was injected into the gingival sulcus of the experimental teeth every day, and the periodontitis group was injected with an equal amount of normal saline for 3 consecutive days. Histological changes were observed under a light microscope. The results showed that the periodontal inflammation in the periodontitis group was significantly more severe than that in the experimental group, indicating that baicalin could inhibit the damage of lipopolysaccharide to rat periodontal tissues. Ou et al.

[16] Using baicalin extract to intervene in a rat gingivitis model and comparing it with the indomethacin tablet group and the blank control group, the results showed that the levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the baicalin group and the indomethacin tablet group were both decreased compared with the blank control group ( P < 0.5); the levels of AST and ALP in the gingival crevicular fluid of rats in the baicalin group were slightly higher than those in the indomethacin tablet group. Conclusion: Baicalin and indomethacin tablets both have therapeutic effects on experimental gingivitis in rats, but the effect of indomethacin tablets is better than that of baicalin. Teng Rui et al.

[17] Observed the effects of baicalin extract on IL-1β and alveolar bone density in an animal model of periodontitis in SD rats. After treating the model animals with 50 mg / L baicalin extract for 4 weeks, the IL-1β in the gingival crevicular fluid and saliva decreased significantly, and the alveolar bone density, height, etc. increased significantly. Conclusion: 50 mg / L baicalin extract can significantly improve the conditions of IL-1β and alveolar bone in rat periodontitis tissues, providing an experimental basis for the clinical prevention and treatment of periodontal diseases. Li Min et al.

[18] To investigate the effects of baicalin at different concentrations on the production of prostaglandin E2 (PGE2) by human periodontal ligament cells (PDLCs) stimulated with IL-1β. Research has shown that baicalin at 0.01 - 10 μg / ml significantly inhibits the synthesis and secretion of PGE2 by PDLCs stimulated with IL-1β. PGE2 is an important inflammatory mediator in the pathological process of periodontal disease, and its level increases significantly in inflamed gingival tissues and gingival crevicular fluid. It has a decalcifying effect similar to parathyroid hormone, is an effective stimulator of bone resorption, and is closely related to periodontal attachment loss. Baicalin indirectly inhibits the synthesis and secretion of PGE2 and plays a role in tooth protection.

[0014] Chang et al.

[19] Research has confirmed that prim-O-glucosylcimifugin has inhibitory effects on 11 fungi such as Candida albicans and Trichophyton mentagrophytes. The MIC for Microsporum ferrugineum is 300 μg / ml, and for the other 7 fungi it is 100 μg / ml, which is comparable to clotrimazole. It has a good therapeutic effect on guinea pig tinea corporis infected with Trichophyton mentagrophytes and has no irritation to the intact or damaged skin of rats. Liang Jie et al.

[20] Research has shown that the ethanol extract of Cimicifuga foetida has antibacterial effects on 4 streptococci, namely Streptococcus mutans, Streptococcus sanguinis, Streptococcus salivarius, and Streptococcus beta-hemolyticus, which cause dental plaque formation, and its MIC is 0.21 - 1.67 mg / ml. Among them, the inhibitory activities against Streptococcus mutans and Streptococcus salivarius are significantly stronger than those against Streptococcus beta-hemolyticus and Streptococcus sanguinis.

[0015] Studies on the ethanol extract of Angelica sinensis have shown that [21、22] it has strong inhibitory effects on Escherichia coli, Staphylococcus aureus, Aspergillus niger, and Penicillium. The MICs for these 4 bacteria are 1.0, 1.0, 0.50, and 1.0 mg / ml respectively -1 . The antibacterial effect is even better than that of chemical antibacterial / antiseptic agents. Conclusion: The ethanol extract of Angelica sinensis has certain inhibitory effects on bacteria, is non-toxic and non-irritating, and is a natural antibacterial agent.

[0016] Xiao Qian et al.

[23] To explore the inhibitory effects of Andrographis paniculata and Astragalus membranaceus on the biofilm of Pseudomonas aeruginosa (PA) and their synergistic effects when combined with the antimicrobial peptide LL-37. The effects of Andrographis paniculata at 20, 50, 100 g / L, Astragalus membranaceus at 20, 50, 100 g / L used alone or combined with 32, 64 μg / ml antimicrobial peptide LL-37 on the PAO1 biofilm were detected by ultraviolet spectrophotometry. The results showed that Andrographis paniculata and Astragalus membranaceus used alone both had inhibitory effects on the early formation of the PAO1 biofilm ( P < 0.05), showing a concentration-dependent manner. The combined use of Astragalus membranaceus / Andrographis paniculata and the antimicrobial peptide LL-37 had no obvious effect on the formation of the PAO1 biofilm and the clearance of the mature biofilm, and there was no synergistic effect. Mu et al.

[24] Through comprehensive evaluation of a large number of literature materials, it is confirmed that the combination of Andrographis paniculata and antibacterial drugs has good inhibitory effects on clinically common pathogenic bacteria such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, coagulase-negative staphylococci, Candida albicans, and streptococci. Its antibacterial mechanisms mainly include inhibiting the formation of bacterial biofilms, inhibiting the bacterial efflux pump system, inhibiting the activity of enzymes in bacteria, and changing the permeability of the bacterial cell membrane.

[0017] Shen Tao et al.

[25] To explore the in vitro antibacterial activity of paeonol against Porphyromonas gingivalis. When the concentrations of paeonol were 1.5, 3, 7.5, 15, and 20 mmol / L, the OD600 of Porphyromonas gingivalis decreased significantly, showing a concentration-dependent manner ( P < 0.05). When the concentrations of paeonol were 3, 7.5, 15, and 20 mmol / L, it had certain antibacterial effects on Porphyromonas gingivalis, showing a concentration-dependent manner ( P < 0.05). After treating the biofilm of Porphyromonas gingivalis with paeonol at four concentrations, the blank control group was mainly green fluorescence and the red fluorescence was not obvious, while the paeonol groups at each dose and the positive control group were mainly red fluorescence and the green fluorescence was weak, indicating that paeonol had a significant killing effect on the biofilm of Porphyromonas gingivalis, and with the concentration gradually increasing from 0 - 15 mmol / L, the killing effect on the biofilm of Porphyromonas gingivalis was stronger, and the differences among groups were significant ( P < 0.05); the killing effects of 15 mmol / L and 20 mmol / L of paeonol on the biofilm of Porphyromonas gingivalis were similar. Conclusion: Paeonol has good in vitro antibacterial effects on Porphyromonas gingivalis and can be used as one of the drug components for the treatment of chronic periodontitis.

[0018] Huang Shi et al.

[26] Research has shown that the MICs of the ethanol extract of Magnolia officinalis against the periodontal pathogens Porphyromonas gingivalis strain 33277 and Bacteroides forsythus strain 43037 are both 1.95 g / L of crude drug, showing strong inhibitory effects. Yin Shi et al.

[27] To investigate the effects of Magnolia officinalis extracts (magnolol and honokiol) on the growth and adhesion of common oral pathogenic bacteria Streptococcus mutans, Actinomyces viscosus, Porphyromonas gingivalis, and Fusobacterium nucleatum. Evaluating the MIC and MBC, the results showed that the ethanol extract of Magnolia officinalis had strong inhibitory effects on the growth of oral pathogenic bacteria, had a rapid bactericidal effect, and had an inhibitory and promoting disintegration effect on the adhesion of cariogenic bacteria. Yang Shi et al.

[28] Research has shown that the MBCs of magnolol against the halitosis pathogenic bacteria Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus sanguinis are 16, 63, and 125 mg / L respectively, while those of zinc ions are 313, 625, and 1250 mg / L respectively, and the combination of the two can produce a synergistic antibacterial effect. Numerous studies have shown

[29] , Magnolol and honokiol contained in Magnolia officinalis have broad-spectrum antifungal, anti-coccus and anti-bacillus effects. For oral infectious diseases, through topical use of Magnolia officinalis extract, magnolol and honokiol, antioxidant and anti-inflammatory effects can be produced, thereby protecting oral epithelial cells, inhibiting and killing oral pathogenic bacteria, preventing and treating the occurrence and development of dental caries and periodontitis, and blocking alveolar bone resorption to prevent tooth loosening.

[0019] Song Jin et al.

[30] Determined the MIC and MBC of extracts from 6 traditional Chinese medicines such as Lonicera japonica and Panax notoginseng against Streptococcus mutans and Porphyromonas gingivalis and the possible antibacterial components. The results showed that the extract of Lonicera japonica had good antibacterial effects against the two strains, and total flavonoids and organic acids were the main antibacterial components; after purification, the concentration of total saponins in the extract of Panax notoginseng increased by 1.7 times, and its antibacterial effect against Porphyromonas gingivalis changed from no antibacterial effect to antibacterial effect; there was no obvious change in the antibacterial effects of the other 4 traditional Chinese medicine extracts before and after purification. Therefore, total flavonoids and total organic acids of Lonicera japonica are considered to be the main antibacterial components; total saponins of Panax notoginseng are very likely to be the substances that inhibit the growth of Porphyromonas gingivalis. Zhang et al.

[31] Chewable tablets prepared with the extract of Lonicera japonica were used on the subjects, and the breath values were measured at 0 h and 1 h respectively. The results showed that the breath value was (8.48 ± 30.78) ppb at 0 h and (92.83 ± 34.78) ppb after 1 h, which was lower than 100 ppb. Furthermore, it shows that the extract of Lonicera japonica can significantly improve halitosis in adolescents, and the effect has a certain persistence.

[0020] Li et al.

[32] The roots, leaves and flowers of Rehmannia glutinosa were extracted with 80% ethanol to prepare an ethanol extract. Using the common pathogenic bacterium Staphylococcus aureus as the test strain, the OD values of the treated bacterial suspensions were measured, and the antibacterial rate was calculated. The results showed that the ethanol extracts from different parts of Rehmannia glutinosa all had inhibitory effects on Staphylococcus aureus, especially the ethanol extract from the leaves of Rehmannia glutinosa had the strongest antibacterial effect. When the concentration was 80 g / L, the antibacterial rate against Staphylococcus aureus reached 72.43%, the MIC was 5.0 g / L, and the EC50 value was 10.651 g / L. Its inhibitory effect on Staphylococcus aureus was positively correlated with the concentration of the extract.

[0021] Chen Qiao et al.

[33] Using four common periodontal pathogenic bacteria, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans, as the test bacteria, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of licorice extract against the four bacteria were investigated; the time-kill curves of licorice extract at different concentrations against the four periodontal pathogenic bacteria were plotted. Results: The MIC values of licorice extract against Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans were 1.50, 1.50, 0.75, and 1.50 mg / ml, respectively, and the MBC values were 6, 3, 3, and 3 mg / ml, respectively. When the licorice extract reached the MBC values for the four bacteria, bactericidal effects could be achieved after 2 h for Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, and after 4 h for Fusobacterium nucleatum. Conclusion: Licorice extract has good antibacterial and bactericidal effects against four common periodontal pathogenic bacteria.

[0022] Since the main component of natural borneol is borneol, and synthetic borneol contains a relatively large amount of isoborneol in addition to borneol, in order to clarify the antibacterial effects of the two types of borneol, Mou et al.

[34] Selected five strains of clinically common bacteria, Staphylococcus aureus, Streptococcus beta-hemolyticus, Streptococcus pneumoniae, Streptococcus viridans, and Escherichia coli, as the test bacteria, and determined the MIC, MBC, and fractional inhibitory concentration index of synthetic borneol, borneol, and isoborneol, respectively. The results showed that the antibacterial effects of borneol and isoborneol were consistent, suggesting that the two types of borneol have equivalent antibacterial effects. Huang et al.

[35] Compared the in vitro antibacterial activities of different dosage forms of Borneolum Syntheticum. The results showed that Borneolum Syntheticum had strong antibacterial effects against Staphylococcus aureus, drug-resistant Staphylococcus aureus, and Staphylococcus albus. Among them, the antibacterial activity of the oil preparation was the strongest, with an MIC of 0.625 mg / ml against the first two types of bacteria, followed by the powder preparation with an MIC of 1.25 mg / ml; for Staphylococcus albus, the MIC of the oil preparation was 0.3125 and that of the powder preparation was 0.625. Conclusion: The oil preparation and powder preparation of Borneolum Syntheticum have good in vitro anti-staphylococcal activities.

[0023] In summary, most of the herbs in the traditional Chinese medicine compound preparation of this patent have broad-spectrum antibacterial activities and have definite antibacterial effects on various oral pathogenic bacteria that cause periodontal diseases. In addition, Coptis chinensis, Scutellaria baicalensis, Lonicera japonica, Andrographis paniculata, Cimicifuga foetida, Rehmannia glutinosa, Paeonia suffruticosa, Magnolia officinalis, Angelica sinensis, Glycyrrhiza glabra, and Borneol all have pharmacological effects such as anti-inflammatory, analgesic, and hemostatic effects, which play an important auxiliary role in the treatment of periodontal diseases. The combination of these herbs in the treatment of periodontal diseases can produce a synergistic effect. Furthermore, it provides strong evidence for the research and development of this traditional Chinese medicine compound preparation.

[0024] As a further improvement of the present invention, in parts by weight, the traditional Chinese medicine compound preparation comprises 2 parts of Coptis chinensis, 4 parts of Scutellaria baicalensis, 6 parts of Lonicera japonica, 5 parts of Andrographis paniculata, 4 parts of Cimicifuga foetida, 6 parts of Rehmannia glutinosa, 5 parts of Paeonia suffruticosa, 4 parts of Angelica sinensis, 4 parts of Magnolia officinalis, 0.2 part of Borneol, and 4 parts of Glycyrrhiza glabra.

[0025] As a further improvement of the present invention, the traditional Chinese medicine compound preparation further comprises pharmaceutically acceptable excipients: chitosan, methylparaben, phenoxyethanol, sodium benzoate.

[0026] As a further improvement of the present invention, the excipients include one or more of glycerol, propylene glycol, sorbitol, polyethylene glycol, allantoin, chitosan, methylparaben, phenoxyethanol, sodium lauryl sulfate, fatty alcohol polyether, cocamidopropyl betaine, alkyl glycoside, cellulose and its derivatives, silicon dioxide, calcium carbonate, carbomer, acrylate / C10-30 alkanol acrylate cross-linked polymer, urea, butanediol, borneol, sodium benzoate, potassium sorbate, benzyl alcohol, potassium hydroxide, sodium hydroxide, polyvinylpyrrolidone, polyvinyl alcohol, sweetening agent, xanthan gum, guar gum, phosphate, citrate, titanium dioxide, sodium hyaluronate, essence.

[0027] As a further improvement of the present invention, the dosage form of the traditional Chinese medicine compound preparation is selected from: ointment, aqueous solution, film or gel.

[0028] As a further improvement of the present invention, the dosage form of the traditional Chinese medicine compound preparation is an aqueous solution.

[0029] The present invention also provides a preparation method of the traditional Chinese medicine compound preparation, comprising the following steps: pulverizing, soaking, heating Coptis chinensis, Scutellaria baicalensis, honeysuckle, andrographis paniculata, cimicifuga foetida, rehmannia glutinosa, moutan cortex, angelica sinensis, magnolia officinalis, liquorice, adding borneol dissolved in an appropriate amount of ethanol, followed by ultrasonic extraction, filtration, adding phenoxyethanol and sodium benzoate, sedimentation, suction filtration, centrifugation, concentration, decolorization and deodorization.

[0030] The preparation method of the traditional Chinese medicine compound preparation specifically comprises the following steps:.

[0031] Step 1: Select raw materials according to the weight ratio: Coptis chinensis, Scutellaria baicalensis, honeysuckle, andrographis paniculata, cimicifuga foetida, rehmannia glutinosa, moutan cortex, angelica sinensis, magnolia officinalis, liquorice.

[0032] Step 2: Pulverize Coptis chinensis, Scutellaria baicalensis, honeysuckle, andrographis paniculata, cimicifuga foetida, rehmannia glutinosa, moutan cortex, angelica sinensis, magnolia officinalis, liquorice. After pulverization, filter to obtain the coarsest powder (powder that can all pass through the No. 1 sieve but contains no more than 20% of the powder that can pass through the No. 3 sieve) of the drug powder.

[0033] Step 3: Add 5 times the amount of water to soak the drug powder for 8 - 12 h, and then add 0.2 parts of borneol dissolved in an appropriate amount of ethanol when heating to 50°C in an ultrasonic extraction tank, and perform ultrasonic extraction for 1 h.

[0034] Step 4: Filter the extracted medicinal liquid, then add phenoxyethanol and sodium benzoate, stir well, let stand for 24 h, and then perform suction filtration.

[0035] Step 5: The obtained liquid is centrifuged at 19,000 r / min for 30 minutes in a centrifuge, then concentrated 1.5 times or 4 times, and decolorized or deodorized in a decolorizing membrane to obtain a traditional Chinese medicine compound preparation for treating acne.

[0036] The present invention also provides an application of the traditional Chinese medicine compound preparation in the preparation of a drug for treating periodontal diseases (periodontitis, gingivitis).

[0037] As a further improvement of the present invention, there is provided an application of the traditional Chinese medicine compound preparation in the preparation of a drug for treating oral diseases (dental caries, periapical periodontitis, acute pulpitis, pericoronitis of wisdom teeth, stomatitis) related to oral pathogenic bacteria infection.

[0038] As a further improvement of the present invention, the traditional Chinese medicine compound preparation is an external disinfection and killing variety, and its usage method is as follows: use after rinsing the mouth with clean water. 10 - 15 ml each time, gargle for 3 minutes, 3 times a day. 2 weeks is one course of treatment.

[0039] Compared with the prior art, the present invention has the following advantages:

[0040] 1. The traditional Chinese medicine compound preparation is prepared by adding flavors on the basis of the traditional famous prescription Qingwei Powder, integrating traditional Chinese medicine clinical experience, traditional Chinese medicine theory and pharmacodynamic research results. The traditional Chinese medicine compound preparation has been preliminarily clinically verified and has good effectiveness and safety; currently, there are few disinfection and killing products for periodontal diseases developed from traditional Chinese medicine, which can make up for the deficiencies in this aspect.

[0041] 2. The preparation process selected for the traditional Chinese medicine compound preparation can ensure the relatively full extraction and utilization of active substances.

[0042] 3. The traditional Chinese medicine compound preparation is made into a gargle, which is convenient to carry; as an oral mucosal drug preparation, its usage method is convenient and easy to accept.

[0043] 4. The traditional Chinese medicine compound preparation has sufficient drug sources, all from domestic sources, and can meet the needs of large-scale production. Specific embodiments

[0044] The following will describe the implementation scheme of the present invention in detail in conjunction with embodiments. However, those skilled in the art will understand that the following embodiments are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. Those not specified in the embodiments are carried out according to conventional conditions or conditions recommended by the manufacturer.

[0045] Example 1. Preparation of the traditional Chinese medicine compound preparation.

[0046] Taking the traditional Chinese medicine compound medicine, 2 parts of Coptis chinensis, 4 parts of Scutellaria baicalensis, 6 parts of Lonicera japonica, 5 parts of Andrographis paniculata, 4 parts of Cimicifuga foetida, 6 parts of Rehmannia glutinosa, 5 parts of Paeonia suffruticosa, 4 parts of Angelica sinensis, 4 parts of Magnolia officinalis, 0.2 part of Borneol, and 4 parts of Glycyrrhiza uralensis by weight, pulverize them, filter after pulverization to obtain medicine powder, soak the powder for 8 - 12 h, add 0.2 part of Borneol dissolved in an appropriate amount of ethanol when heated to 50 °C, and then perform ultrasonic extraction for 1 h. Filter the extracted medicinal liquid, then add phenoxyethanol and sodium benzoate and stir well. After standing for 24 h, perform suction filtration. Then, perform centrifugation, concentration, decolorization or deodorization in sequence to obtain the traditional Chinese medicine compound preparation for treating acne.

[0047] Example 2. Research on the in vitro antibacterial, anti - inflammatory activities and cytotoxicity of the traditional Chinese medicine compound preparation.

[0048] 2.1.1 Detection results of the anti - Porphyromonas gingivalis activity of the traditional Chinese medicine compound preparation.

[0049] Experimental materials.

[0050] ① Test articles: Traditional Chinese medicine compound preparation (concentration 19.7 mg / ml), Baicalin (index component of the traditional Chinese medicine compound preparation; purity 98.03%; batch number 21121404; Chengdu Pufeide Biotechnology Co., Ltd.).

[0051] ② Experimental strains: Porphyromonas gingivalis (ATCC33277; Beijing Bena Biotechnology Co., Ltd.).

[0052] ③ Experimental reagents BHI medium: Beijing Aoboxing Biotechnology Co., Ltd. (100 g; batch number 20230530); Tryptone: Beijing Aoboxing Biotechnology Co., Ltd. (250 g; batch number 20220712); Yeast extract powder: Beijing Aoboxing Biotechnology Co., Ltd. (250 g; batch number 20220228); Agar powder: Tianjin Kemiou Chemical Reagent Co., Ltd. (250 g; batch number 20210117); L - Cysteine hydrochloride: Tianjin Bodi Chemical Industry Co., Ltd. (10 g; batch number 20150926); Hemin: Beijing Bio - Opto Technology Co., Ltd. (1 g; batch number 20221130); Menadione sodium bisulfite injection: Shanghai Quanyu Biotechnology (Zhumadian) Animal Pharmaceutical Co., Ltd. (1 ml × 10 pieces; batch number 220403); Sterile defibrinated sheep blood: Beijing Aoboxing Biotechnology Co., Ltd. (7 ml × 10 pieces; batch number 20230615); PBS: Dalian Meilun Biotechnology Co., Ltd. (500 ml; batch number MA0015 - May - 11).

[0053] Experimental methods.

[0054] ① Strain activation: Dissolve the freeze - dried bacteria powder with liquid medium, inoculate the bacterial suspension onto the solid medium plate at a volume of 200 μL / plate, and place the inoculated medium in an incubator at 37°C for cultivation. Bacteria grow within 2 - 5 days. Pick a single colony for sub - culture on the solid plate until the 3rd generation can be used for experiments.

[0055] ② MIC / MBC detection Take the strain cultured in the logarithmic growth phase, adjust the bacterial density to 5.5×105 CFU / ml with sterile water for standby. Dilute the stock solution with liquid medium to the highest drug concentration to be tested. Take a sterile 96 - well plate and serially dilute the drug to be tested by the two - fold dilution method. Set up a drug - free control and a bacteria - free control. Add an equal amount of the diluted bacterial suspension to each well with the drug at each concentration in turn, and place the 96 - well plate in a bacterial incubator at 37°C for cultivation. The lowest drug concentration without bacterial growth is the minimum inhibitory concentration (MIC) of the drug. Take the bacterial suspension without growth and streak - plate it on the solid medium. The minimum bactericidal concentration (MBC) of the drug is defined as no growth.

[0056] Experimental results Table 1 Minimum inhibitory / bactericidal concentrations (MIC / MBC) of traditional Chinese medicine compound preparations and baicalin against Porphyromonas gingivalis

[0057] 2.1.2 Detection results of the antibacterial activity of traditional Chinese medicine compound preparations against Staphylococcus aureus.

[0058] Experimental materials.

[0059] ① Test articles: Traditional Chinese medicine compound preparation (concentration 19.7 mg / ml), baicalin (index component of traditional Chinese medicine compound preparation; purity 98.03%; batch number 21121404; Chengdu Pufeide Biotechnology Co., Ltd.).

[0060] ② Experimental strain: Staphylococcus aureus (isolated from human fecal samples in the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine).

[0061] ③ Experimental reagents BHI medium: Beijing Aoboxing Biotechnology Co., Ltd. (100 g; batch number 20230530); Tryptone: Beijing Aoboxing Biotechnology Co., Ltd. (250 g; batch number 20220712); Yeast extract powder: Beijing Aoboxing Biotechnology Co., Ltd. (250 g; batch number 20220228); Agar powder: Tianjin Kemiou Chemical Reagent Co., Ltd. (250 g; batch number 20210117); L-cysteine hydrochloride: Tianjin Bodi Chemical Co., Ltd. (10 g; batch number 20150926); Hemin chloride: Beijing Bioleader Technology Co., Ltd. (1 g; batch number 20221130); Menadione sodium bisulfite injection: Shanghai Quanyu Biotechnology (Zhumadian) Animal Pharmaceutical Co., Ltd. (1 ml × 10 vials; batch number 220403); Sterile defibrinated sheep blood: Beijing Aoboxing Biotechnology Co., Ltd. (7 ml × 10 vials; batch number 20230615); PBS: Dalian Meilun Biotechnology Co., Ltd. (500 ml; batch number MA0015-May-11).

[0062] Experimental methods.

[0063] ① Strain activation: Dissolve the freeze-dried bacteria with liquid medium, inoculate the bacterial suspension onto the solid medium plate at a dose of 200 μL / plate, and place the inoculated medium in an incubator at 37°C for cultivation. Bacteria grow within 2 - 5 days. Pick a single colony for subculture on a solid plate until the 3rd generation can be used for experiments.

[0064] ② MIC / MBC detection: Take the strain cultured in the logarithmic growth phase, adjust the bacterial density to 5.5×105 CFU / ml with sterile water for standby. Dilute the stock solution with liquid medium to the highest drug concentration to be tested. Take a sterile 96-well plate and serially dilute the drug to be tested by the two-fold dilution method. Set up a drug-free control and a bacteria-free control. Add an equal amount of the diluted bacterial suspension to each drug well at each concentration in sequence, and place the 96-well plate in a bacterial incubator at 37°C for cultivation. The lowest drug concentration without bacterial growth is the MIC of the drug. Take the bacterial solution without growth and streak it on a solid medium, and no growth is the MBC of the drug.

[0065] Experimental results Table 2 Minimum inhibitory / bactericidal concentration (MIC / MBC) of traditional Chinese medicine compound preparation and baicalin against Staphylococcus aureus

[0066] 2.1.3 Detection results of the anti-Candida albicans activity of traditional Chinese medicine compound preparation.

[0067] Experimental materials.

[0068] ① Test articles: Traditional Chinese medicine compound preparation (concentration 19.7 mg / ml), baicalin (index component of traditional Chinese medicine compound preparation; purity 98.03%; batch number 21121404; Chengdu Pufeide Biotechnology Co., Ltd.).

[0069] ② Experimental strain: Candida albicans (isolated from human fecal samples in the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine).

[0070] ③ Experimental reagents BHI medium: Beijing Aoboxing Biotechnology Co., Ltd. (100 g; batch number 20230530); Tryptone: Beijing Aoboxing Biotechnology Co., Ltd. (250 g; batch number 20220712); Yeast extract powder: Beijing Aoboxing Biotechnology Co., Ltd. (250 g; batch number 20220228); Agar powder: Tianjin Kemiou Chemical Reagent Co., Ltd. (250 g; batch number 20210117); L-cysteine hydrochloride: Tianjin Bodi Chemical Industry Co., Ltd. (10 g; batch number 20150926); Hemin: Beijing Bioleader Technology Co., Ltd. (1 g; batch number 20221130); Menadione sodium bisulfite injection: Shanghai Quanyu Biotechnology (Zhumadian) Animal Pharmaceutical Co., Ltd. (1 ml × 10 vials; batch number 220403); Sterile defibrinated sheep blood: Beijing Aoboxing Biotechnology Co., Ltd. (7 ml × 10 vials; batch number 20230615); PBS: Dalian Meilun Biotechnology Co., Ltd. (500 ml; batch number MA0015-May-11).

[0071] Experimental methods.

[0072] ① Strain activation Dissolve the freeze-dried bacteria powder with liquid medium, inoculate the bacterial suspension onto the solid medium plate at a volume of 200 μL / plate, and place the inoculated medium in an incubator at 37°C for cultivation. Bacteria grow within 2 - 5 days of cultivation. Pick a single colony for subculture on the solid plate, and the bacteria after 3 subcultures can be used for the experiment.

[0073] ② MIC / MBC detection Take the strain cultured in the logarithmic growth phase, adjust the bacterial density to 5.5 × 105 CFU / ml with sterile water for standby. Dilute the stock solution with liquid medium to the highest concentration of the drug to be tested. Take a sterile 96-well plate and serially dilute the drug to be tested by the two-fold dilution method. Set up a drug-free control and a bacteria-free control. Add an equal amount of the diluted bacterial suspension to each well of the drug at each concentration in sequence, and place the 96-well plate in a bacterial incubator at 37°C for cultivation. The lowest drug concentration at which no bacteria grow is the MIC of the drug. Take the bacterial suspension without growth and streak it on the solid medium, and no growth is the MBC of the drug.

[0074] Experimental results Table 3 Minimum Inhibitory / Bactericidal Concentrations (MIC / MBC) of Traditional Chinese Medicine Compound Preparation and Baicalin against Candida albicans

[0075] Conclusion: The traditional Chinese medicine compound preparation has antibacterial and bactericidal activities against Porphyromonas gingivalis, with an MIC of 0.62 mg / ml and an MBC of 1.23 mg / ml; it has inhibitory activities against the growth of Staphylococcus aureus and Candida albicans, with an MIC of 9.85 mg / ml for both, and MBC > 9.85 mg / ml.

[0076] 2.1.4 Detection Report on Anti-inflammatory Activity of Traditional Chinese Medicine Compound Preparation.

[0077] Experimental Materials.

[0078] ① Test articles: Traditional Chinese medicine compound preparation samples (concentration 19.7 mg / ml), Baicalin (index component of traditional Chinese medicine compound preparation; purity 98.03%; batch number 21121404; Chengdu Pufeide Biotechnology Co., Ltd.).

[0079] ② Experimental cell lines and sources: RAW264.7 (mouse mononuclear macrophage leukemia cells; Dalian Meilun Biotechnology Co., Ltd.).

[0080] ③ Experimental reagents BHI medium: Beijing Aoboxing Biotechnology Co., Ltd. (100 g; batch number 20230530); Tryptone: Beijing Aoboxing Biotechnology Co., Ltd. (250 g; batch number 20220712); Yeast extract powder: Beijing Aoboxing Biotechnology Co., Ltd. (250 g; batch number 20220228); Agar powder: Tianjin Kemiou Chemical Reagent Co., Ltd. (250 g; batch number 20210117); L-Cysteine hydrochloride: Tianjin Bodi Chemical Industry Co., Ltd. (10 g; batch number 20150926); Hemin: Beijing Bio-ATech Co., Ltd. (1 g; batch number 20221130); Menadione sodium bisulfite injection: Shanghai Quanyu Biotechnology (Zhumadian) Animal Pharmaceutical Co., Ltd. (1 ml × 10 vials; batch number 220403); Sterile defibrinated sheep blood: Beijing Aoboxing Biotechnology Co., Ltd. (7 ml × 10 vials; batch number 20230615); PBS: Dalian Meilun Biotechnology Co., Ltd. (500 ml; batch number MA0015-May-11).

[0081] Experimental Methods.

[0082] ① Culture of mouse mononuclear macrophage leukemia cells: RAW264.7 cells were cultured in A - 10% DMEM high - glucose cell culture medium prepared based on FBS medium. The cells were cultured at a density of approximately 2.5×105 cells / ml in an incubator with 5% CO2 at 37 °C. By the 3rd day, the cells occupied about 80 - 90% of the bottom area of the culture flask. The cells were then digested by pipetting and passaged to another culture flask.

[0083] ② Detection of NO concentration by Griess method: RAW264.7 cells in the logarithmic growth phase were taken, and the cell density was adjusted to 2.5×105 cells / ml with A - 10% DMEM high - glucose medium. The cells were inoculated into 96 - well plates at 200 μL / well and cultured in an incubator with 5% CO2 at 37 °C. After the cells adhered and were cultured for 12 h, the medium was replaced with fresh medium, and at the same time, modeling (1 μg / ml LPS) and drug - adding treatments were carried out. Different doses of samples were set, and a blank control was also set. After the cells were treated with drugs and continued to be cultured for 24 h, 100 μL / well of cell supernatant was aspirated into a 96 - well plate, and 50 μL / well of Griess A (1% sulfanilamide) and Griess B (0.1% N - (1 - naphthyl)ethylenediamine dihydrochloride) were added respectively. Incubate at room temperature for 30 min, and measure the optical density OD value at 546 nm. Calculate the NO content in each sample according to the standard curve of NaNO2.

[0084] Experimental results Table 4 Effects of traditional Chinese medicine compound preparation and baicalin on NO release (μmol / L) of LPS - induced RAW264.7 cells (Mean±SEM)

[0085] Note: Comparison between the model group and the blank group ### P <0.001, comparison between the drug - administered group and the model group ns P >0.05, * P <0.05, ** P <0.01.

[0086] Conclusion: The traditional Chinese medicine compound preparation significantly inhibits the production of NO in LPS - induced RAW264.7 cells at 30 - 100 μg / ml, showing certain anti - inflammatory activity.

[0087] 2.1.4 Cytotoxicity detection report of this traditional Chinese medicine compound preparation.

[0088] Experimental materials.

[0089] ① Test articles: Test articles: Traditional Chinese medicine compound preparation (concentration 19.7 mg / ml), baicalin (index component of traditional Chinese medicine compound preparation; purity 98.03%; batch number 21121404; Chengdu Pufeide Biotechnology Co., Ltd.).

[0090] ② Experimental cell lines and sources HaCat: Human epidermal keratinocytes (Shanghai Aoyin Biotechnology Co., Ltd.); RAW264.7: Mouse monocyte macrophage leukemia cells (Dalian Meilun Biotechnology Co., Ltd.).

[0091] ③ Experimental reagents Fetal bovine serum (FBS): Animal Blood Ware (500 ml; lot number AB20214311); DMEM high-glucose medium: Shanghai Dartshire Biotechnology Co., Ltd. (500 ml; lot number 2310048); PBS: Dalian Meilun Biotechnology Co., Ltd. (500 ml; lot number MA0015-May-11); Trypsin containing EDTA: Gibco, USA (500 ml; lot number 2764713); Lipopolysaccharide (LPS): Sigma-Aldrich, USA (10 mg; lot number 0000189847); 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): Dalian Meilun Biotechnology Co., Ltd. (1 g; lot number A0428D).

[0092] Experimental methods.

[0093] ① Culture of human epidermal keratinocytes: Prepare A - 10% DMEM high-glucose cell culture medium based on FBS medium. The cells are cultured at a density of approximately 2.5×105 cells / ml in a 5% CO2, 37°C incubator. By the 3rd day, the adherent cells account for about 80 - 90% of the bottom area of the culture flask. Digest the adherent cells with trypsin and passage them to another culture flask.

[0094] ② Culture of mouse monocyte macrophage leukemia cells: Prepare - 10% DMEM high-glucose cell culture medium based on FBS medium. The cells are cultured at a density of approximately 2.5×105 cells / ml in a 5% CO2, 37°C incubator. By the third day, the adherent cells account for about 80 - 90% of the bottom area of the culture flask. Digest the adherent cells with trypsin and passage them to another culture flask.

[0095] ③ Detection of the effect of samples on cell viability by MTT method. Logarithmically growing HaCat / RAW264.7 cells were taken respectively, and the cell density was adjusted to 2.5×105 cells / ml with A-10% DMEM high-glucose medium, inoculated into 96-well plates, 100 μL / well, and cultured in an incubator at 37℃ and 5% CO2. After the cells adhered and were cultured for 12 h, the fresh culture medium was changed, and at the same time, drug treatment was carried out. Different doses of samples were set, and a blank control was set at the same time. After the cells were treated with drugs and continued to be cultured for 48 h, then MTT solution was added to the cell liquid, 50 μL / well, and the cells were co-incubated with 2 mg / ml MTT at 37℃ for 4 h. The culture medium was aspirated, and then 100 μL of DMSO solution was added to measure its optical density OD value. Calculate the average value of the OD values of 3 wells for each sample, and calculate the cell viability (cell viability, CV%) according to the following formula using the average value. Cell viability % = average value of the OD value of the sample group / average value of the OD value of the blank control group × 100%.

[0096] Experimental results Table 5 Effects of traditional Chinese medicine compound preparation and baicalin on the survival rate of HaCat cells (Mean±SEM)

[0097] Note: ns P >0.05, * P <0.05, ** P <0.01, *** P <0.001.

[0098] Experimental results Table 6 Effects of traditional Chinese medicine compound preparation and baicalin on the survival rate (%) of RAW264.7 cells (Mean±SEM)

[0099] Note: ns P >0.05, * P <0.05, ** P <0.01.

[0100] Experimental conclusion: When the traditional Chinese medicine compound preparation is at 10 - 100 μg / ml, the survival rates of RAW264.7 cells and HaCat cells after administration are both greater than 90%, and no cytotoxicity is shown.

[0101] Example 3. Study on the effectiveness of traditional Chinese medicine compound preparation in the treatment of periodontal disease.

[0102] Diagnostic Criteria (1) Western Medicine Diagnostic Criteria: Refer to the diagnostic criteria for aggressive periodontitis in "Periodontology" (edited by Cao Caifang. People's Medical Publishing House, 2001). ① Poor oral hygiene with a history of repeated attacks. ② Gingival pain, swelling, bleeding, atrophy, periodontal pocket formation, and tooth mobility. ③ X-ray shows alveolar bone resorption. In localized aggressive periodontitis, vertical bone resorption can be seen in the incisors and the first permanent molars on X-ray, and vertical bone resorption forms in the mesial, distal, and middle parts of the first molar; in generalized aggressive periodontitis, vertical bone resorption can be seen in the first molar on X-ray, and horizontal bone resorption in the incisors. (2) Traditional Chinese Medicine Diagnostic Criteria: Refer to the dialectical criteria for periodontitis of the syndrome of stomach fire flaring upward in "Diagnostic Criteria and Therapeutic Effects of Traditional Chinese Medicine Diseases and Syndromes" (issued by the State Administration of Traditional Chinese Medicine. Nanjing University Press, 1994: 128-129). Main symptoms: Gingival swelling, bleeding, tooth mobility or even tooth loss; secondary symptoms: Bad breath, restlessness and thirst, less body fluid, constipation, red urine; red tongue with yellow coating, rapid and forceful pulse.

[0103] Periodontitis Grading Criteria Mild: Gingiva has inflammation and bleeding on probing, periodontal pocket ≤ 4mm, attachment loss 1-2mm, and X-ray shows horizontal alveolar bone resorption not exceeding 1 / 3 of the root length; Moderate: Periodontal pocket ≤ 6mm, attachment loss 3-4mm, X-ray shows horizontal or angular alveolar bone resorption exceeding 1 / 3 of the root length but not exceeding 1 / 2 of the root length, and the teeth have mild mobility; Severe: Periodontal pocket > 6mm, attachment loss ≥ 5mm, X-ray shows alveolar bone resorption exceeding 1 / 2 of the root length, even up to 2 / 3 of the root length.

[0104] Inclusion Criteria for Cases (1) Meeting the above Western medicine diagnostic criteria for periodontitis, with mild and moderate conditions; (2) Meeting the diagnostic criteria for the syndrome of stomach fire flaring upward in traditional Chinese medicine; (2) Course of disease ≥ 2 months; (3) Age 18-50 years old; (4) Those who give informed consent to participate in this trial.

[0105] Exclusion Criteria for Cases (1) Complicated with diseases of organs such as the heart, liver, and kidneys and mental diseases; (2) Using antibiotics and other therapeutic drugs in the past month; (3) Having received periodontal treatment and irregular orthodontic treatment in the past 3 months; (4) Pregnant women, women preparing for pregnancy, and lactating women.

[0106] Clinical Observation and Evaluation Indicators Efficacy evaluation criteria for plaque index (PLI), sulcus bleeding index (SBI), probing depth (PD), and attachment loss (AL).

[0107] Plaque Index (PLI) Measurement Standard: Apply the plaque staining agent basic fuchsin solution to the tooth surface for 1 minute, then rinse with water and record.

[0108] 0 score = no dental plaque on tooth surface; 1 score = scattered spotty dental plaque on the tooth surface near the gingival margin at the tooth neck; 2 scores = continuous narrow band of dental plaque at the tooth neck with a width not exceeding 1 mm; 3 scores = the area of dental plaque coverage at the tooth neck exceeds 1 mm but is less than 1 / 3 of the tooth surface; 4 scores = the area of dental plaque coverage at the tooth neck accounts for at least 1 / 3 of the tooth surface but does not exceed 2 / 3; 5 scores = the area of dental plaque coverage at the tooth neck accounts for 2 / 3 or more of the tooth surface.

[0109] Gingival Bleeding Index (SBI) Measurement standard: Gently insert the periodontal probe about 1 mm below the gingival margin and slide it gently to observe the presence and degree of bleeding.

[0110] 0 score = normal gingiva, healthy appearance of the gingival margin and gingival papilla, no bleeding of the gingiva after probing; 1 score = mild inflammation of the gingival margin and gingival papilla, no bleeding when gently probing the gingival sulcus; 2 scores = mild gingival inflammation, change in gingival color, punctate bleeding after probing; 3 scores = moderate gingival inflammation, change in gingival color and mild edema, bleeding on the probe, blood spreading along the gingival sulcus; 4 scores = moderate gingival inflammation, bleeding after probing, blood overflowing from the gingival sulcus; 5 scores = change in gingival color, obvious swelling, sometimes ulcers, bleeding after probing or spontaneous bleeding.

[0111] Probing Depth (PD) Measurement standard: The distance from the bottom of the gingival sulcus to the gingival margin. The probing depth of healthy gingiva does not exceed 2 - 3 mm. However, when clinically using a periodontal probe to measure the gingival sulcus depth, the probe usually exceeds the histological bottom of the sulcus and enters the junctional epithelium, with the unit being mm.

[0112] Attachment Loss (AL) Measurement standard: When a periodontal pocket forms and the probing depth exceeds 3 mm, and the bottom of the pocket is located apical to the periodontal pocket, attachment loss occurs. Record the distance from the bottom of the gingival sulcus to the cementoenamel junction, with the unit being mm.

[0113] Treatment methods Both groups of patients received basic periodontal treatment, including supragingival scaling, subgingival scraping, and root planing. The experimental group used a mouthwash made of a Chinese medicine compound (produced by Dandong Xinshidai Biomedicine Technology Co., Ltd., production batch number DXY20220695) to rinse the periodontal pocket and rinse the mouth, 10 ml per time, 4 times / day, gargle for 2 minutes each time and spit out, while the control group used Longzhang oral solution (produced by Guiyang Xintian Pharmaceutical Co., Ltd., national medicine standard Z20025005; batch number: 220702) to rinse the mouth, 10 ml per time, 4 times a day, gargle for 2 minutes each time and spit out. Both groups were treated for 2 consecutive weeks.

[0114] General information of enrolled patients A total of 60 cases of dental outpatient clinics that met the inclusion criteria from July 2022 to October 2023 were selected. They were randomly divided into an experimental group and a control group according to the random number table, with 30 cases in each group. There were 17 males and 13 females in the experimental group; aged 33 to 42 years, with an average of 37.82±4.73 years; the course of disease was 8 months to 5 years, with an average of 3.43±1.44 years; 12 cases were mild and 18 cases were moderate. There were 16 males and 14 females in the control group; aged 34 to 44 years, with an average of 38.24±5.34 years; the course of disease was 6 months to 5 years, with an average of 3.28±1.76 years; 13 cases were mild and 17 cases were moderate. There was no statistically significant difference in the general information of the two groups of patients ( P >0.05), which is comparable (see Table 7 for details).

[0115] Table 7 Comparison of general conditions between the experimental group and the control group before enrollment

[0116] Comparison of various indicators between the experimental group and the control group before treatment Before periodontal basic treatment and periodontal pocket irrigation, the PLI, SBI, PD, AL and other related clinical indicators of the two groups of patients were detected and recorded. There was no statistically significant difference in these indicators between the two groups ( P >0.05), indicating that the experimental group and the control group were balanced and comparable (Tables 8 and 9).

[0117] Table 8 Clinical indicators before treatment ( ±s, n=60) Group PLI SBI PD AL Experimental group 3.32±0.92 3.70±0.45 3.21±0.78 3.75±0.54 Control group 3.29±0.57 3.74±0.21 3.13±0.83 3.41±0.97 Table 9 Main symptoms of the experimental group and the control group before treatment ( ±s, n=60)

[0118] Observation results Analysis of various indicators in the two groups after treatment After 2 weeks of periodontal system treatment and periodontal pocket irrigation treatment, the four indicators of periodontitis PLI, SBI, PD, and AL in the experimental group and the control group were significantly improved compared with those before treatment; when comparing between the two groups after treatment, the experimental group tended to be better than the control group, but the statistical difference was not significant ( P > 0.05) (see Tables 10 and 11).

[0119] Table 10 Clinical indicators after treatment ( ±s, n = 60) Note: Compared with the control group P > 0.05 Table 11 Chief complaints of the experimental group and the control group after treatment Note: Compared with the control group P > 0.05.

[0120] Conclusion: On the basis of basic treatment, irrigation of the periodontal pocket with the traditional Chinese medicine compound preparation can significantly improve the indicators of PLI, SBI, PD, and AL; and significantly improve the symptoms of gingival swelling and redness, toothache, gingival bleeding, and bad breath, demonstrating the effects of clearing heat and detoxifying, reducing swelling and relieving pain, and cooling blood and stopping bleeding. No adverse reactions were found during the observation period, and the oral gargle is highly safe.

[0121] The above is only the preferred embodiment of the present invention and is not used to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

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Claims

1. A traditional Chinese medicine compound preparation for treating periodontal disease, characterized by its prescription including 11 ingredients: Coptis chinensis, Scutellaria baicalensis, Lonicera japonica, Andrographis paniculata, Cimicifuga foetida, Rehmannia glutinosa, Paeonia suffruticosa, Angelica sinensis, Magnolia officinalis, Borneol, and Glycyrrhiza uralensis. Among them, By weight, 1 - 3 parts of Coptis chinensis, 3 - 5 parts of Scutellaria baicalensis, 5 - 7 parts of Lonicera japonica, 3 - 5 parts of Andrographis paniculata, 3 - 5 parts of Cimicifuga foetida, 5 - 7 parts of Rehmannia glutinosa, 4 - 6 parts of Paeonia suffruticosa, 3 - 5 parts of Angelica sinensis, 3 - 5 parts of Magnolia officinalis, 0.1 - 0.3 parts of Borneol, 2 - 4 parts of Glycyrrhiza uralensis.

2. The traditional Chinese medicine compound preparation according to claim 1, characterized in that By weight, the traditional Chinese medicine compound preparation comprises 2 parts of Coptis chinensis, 4 parts of Scutellaria baicalensis, 6 parts of Lonicera japonica, 5 parts of Andrographis paniculata, 4 parts of Cimicifuga foetida, 6 parts of Rehmannia glutinosa, 5 parts of Paeonia suffruticosa, 4 parts of Angelica sinensis, 4 parts of Magnolia officinalis, 0.2 parts of Borneol, 4 parts of Glycyrrhiza uralensis.

3. The traditional Chinese medicine compound preparation according to claim 1, characterized in that The traditional Chinese medicine compound preparation comprises a disinfection and sterilization product, a cosmetic or a pharmaceutically acceptable excipient.

4. The traditional Chinese medicine compound preparation according to claim 3, characterized in that The excipients include one or more of glycerol, propylene glycol, sorbitol, polyethylene glycol, allantoin, chitosan, methylparaben, phenoxyethanol, sodium lauryl sulfate, fatty alcohol polyether, cocamidopropyl betaine, alkyl glycoside, cellulose and its derivatives, silicon dioxide, calcium carbonate, carbomer, acrylate / C10 - 30 alkyl acrylate cross - polymer, urea, butanediol, borneol, sodium benzoate, potassium sorbate, benzyl alcohol, potassium hydroxide, sodium hydroxide, polyvinylpyrrolidone, polyvinyl alcohol, sweetening agent, xanthan gum, guar gum, phosphate, citrate, titanium dioxide, sodium hyaluronate, essence.

5. The traditional Chinese medicine compound preparation according to any one of claims 1 - 4, characterized in that The dosage form of the traditional Chinese medicine compound preparation is selected from ointment, aqueous solution, film or gel.

6. The traditional Chinese medicine compound preparation according to claim 5, characterized in that The dosage form of the traditional Chinese medicine compound preparation is aqueous solution.

7. A preparation method of the traditional Chinese medicine compound preparation according to any one of claims 1 - 4, characterized in that It includes the following steps: Step 1: Select raw materials according to the weight ratio: Coptis chinensis, Scutellaria baicalensis, Lonicera japonica, Andrographis paniculata, Cimicifuga foetida, Rehmannia glutinosa, Paeonia suffruticosa, Angelica sinensis, Magnolia officinalis, Glycyrrhiza uralensis; Step 2: Crush Coptis chinensis, Scutellaria baicalensis, Lonicera japonica, Andrographis paniculata, Cimicifuga foetida, Rehmannia glutinosa, Paeonia suffruticosa, Angelica sinensis, Magnolia officinalis, Glycyrrhiza uralensis, and filter after crushing to obtain the coarsest powder (powder that can all pass through No. 1 sieve but contains no more than 20% of the powder that can pass through No. 3 sieve) of the drug powder; Step 3: Add 5 times the amount of water to soak the drug powder for 8 - 12 h, then add 0.2 parts of borneol dissolved in appropriate ethanol when heating to 50 °C in an ultrasonic extraction tank, and carry out ultrasonic extraction for 1 h; Step 4: Filter the extracted medicinal liquid, then add phenoxyethanol and sodium benzoate and stir well, let it stand for 24 h, and then carry out suction filtration; Step 5: The obtained liquid is centrifuged, concentrated, decolorized or de - flavored in sequence to obtain the traditional Chinese medicine compound preparation for treating acne.

8. Use of the traditional Chinese medicine compound preparation according to any one of claims 1 - 4 in the preparation of a drug for treating periodontal disease.