Traditional Chinese medicine composition, preparation and mouthwash for treating periodontitis as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition, a preparation and mouth wash for treating periodontitis as well as a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following medicinal materials in parts by weight: 10 to 20 parts of rhizoma coptidis, 20 to 40 parts of gypsum, 5 to 15 parts of rhizoma cimicifugae, 10 to 30 parts of radix astragali seu hedysari, 10 to 30 parts of rhizoma drynariae, 10 to 30 parts of herba agrimoniae, 10 to 20 parts of radix cynanchi paniculati, 10 to 15 parts of radix angelicae sinensis, 10 to 20 parts of rhizoma dioscoreae and 5 to 15 parts of radix glycyrrhizae. The traditional Chinese medicine mouthwash comprises 10-30 parts of traditional Chinese medicine fluid extract prepared from the traditional Chinese medicine composition, 20-50 parts of an osmotic pressure regulator, 1-10 parts of a mucous membrane protective agent, 0.1-0.5 part of a freshener and 20-70 parts of water. The preparation method comprises the following steps: preparing the traditional Chinese medicine composition into traditional Chinese medicine fluid extract; preheating the obtained traditional Chinese medicine fluid extract, sequentially adding an osmotic pressure regulator, a mucous membrane protective agent and a freshener, finally adding water, and uniformly stirring to obtain the traditional Chinese medicine mouthwash. The traditional Chinese medicine mouthwash provided by the invention has an obvious treatment effect on periodontitis.

Description

Technical fields:

[0001] This invention belongs to the field of traditional Chinese medicine composition technology, specifically relating to a traditional Chinese medicine composition, preparation, mouthwash for treating periodontitis, its preparation method and application. Background technology:

[0002] Periodontitis is an inflammatory and destructive disease characterized by the destruction of periodontal soft tissues and alveolar bone resorption. Activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune responses are considered important factors contributing to the destruction of periodontal tissue structure. Its occurrence and development are closely related to chronic inflammatory diseases such as cardiovascular disease, neurodegenerative diseases, and autoimmune diseases. Periodontitis is the sixth most common human disease, and current treatments cannot completely solve the problem of periodontal tissue regeneration and repair. How to promote the repair and regeneration of damaged periodontal tissues remains a pressing scientific question in the field of periodontitis research. The pathogenesis of periodontitis is very complex. Traditional research has focused on plaque microorganisms, believing that plaque microorganisms are the initiating factor of periodontitis, inducing infection, triggering inflammation, driving the occurrence and development of periodontitis, and ultimately destroying periodontal tissue structure. Currently, the treatment of periodontitis mainly involves basic periodontal therapy to remove local irritants, while oral antibiotics and other drugs are used to reduce the number and types of suspected pathogenic bacteria, thereby delaying the degree of tissue damage. In recent years, traditional Chinese medicine treatment of periodontitis has gradually become a research hotspot in my country. Chinese medicine is widely used to treat periodontitis due to its advantages such as low toxicity and adverse reactions, low production cost, and long-term use.

[0003] Traditional Chinese medicine (TCM) considers periodontitis to be related to the health of various systems throughout the body, classifying it under the categories of "tooth decay" and "dietary disease." TCM emphasizes comprehensive treatment based on syndrome differentiation, focusing on the overall health and stability of the body, rather than merely eliminating local symptoms. Besides being used as an adjunct treatment for periodontitis, TCM aims to improve the stability of the internal environment and enhance the function of the entire body. TCM believes that the occurrence of periodontitis is mainly related to the following factors: 1. Stomach fire rising upwards: Excessive consumption of spicy and fatty foods, or excessive alcohol consumption, leads to heat accumulation in the stomach, which then rises along the Stomach Meridian of Foot Yangming, scorching the gum tissue and blood vessels. 2. Kidney yin deficiency, with deficiency fire rising upwards: Old age, weakness, prolonged illness damaging the kidneys, or excessive sexual activity can lead to kidney yin deficiency, generating internal deficiency fire that rises to the gums, causing teeth to lose nourishment. 3. Insufficient qi and blood, resulting in malnourishment of the gum tissue: Weakness of the spleen and stomach leads to insufficient production of qi and blood, or prolonged illness depletes qi and blood, causing the gums to lose nourishment and become atrophied and unstable. Blood stasis: Regardless of whether it's excess heat, deficiency heat, or qi deficiency, it can all lead to poor local blood circulation, blood stasis, and aggravated swelling, pain, and bleeding. Furthermore, modern pharmacological research has revealed the multifaceted effects of traditional Chinese medicine (TCM) compound formulas in treating periodontitis, including significant antibacterial and bacteriostatic effects: many compound formulas and their core ingredients, such as Coptis chinensis, Scutellaria baicalensis, Lonicera japonica, Taraxacum mongolicum, and Cimicifuga foetida, have significant inhibitory and bactericidal effects on the main pathogenic bacteria of periodontitis. TCM compound formulas can also effectively reduce the level of pro-inflammatory cytokines in periodontal tissues and inhibit the excessive activation of inflammatory signaling pathways, alleviating inflammatory symptoms such as gingival redness, swelling, bleeding, and pain. Simultaneously, they can clear excess oxygen free radicals in periodontal tissues, increase the activity of antioxidant enzymes, and reduce oxidative stress damage to periodontal tissues.

[0004] Several classic ancient formulas have been used for reference and research in treating periodontitis. For example, the *Lan Shi Mi Cang* mentions Qingwei San (Coptis chinensis, Cimicifuga foetida, Rehmannia glutinosa, Angelica sinensis, and Paeonia suffruticosa) as a representative formula for treating periodontitis of the stomach-fire type. Numerous studies have shown that it can effectively improve gingival redness, swelling, bleeding, and purulent discharge, reduce pain, and lower clinical indicators such as gingival index, gingival sulcus bleeding index, and plaque index. Mechanistic studies have confirmed its significant antibacterial, anti-inflammatory, and immunomodulatory effects. The *Jing Yue Quan Shu* mentions Yunu Jian (Gypsum, Rehmannia glutinosa, Ophiopogon japonicus, Anemarrhena asphodeloides, and Achyranthes bidentata) as a treatment for periodontitis of the yin deficiency and stomach-heat type. Studies show that it can improve gingival swelling and pain, tooth loosening, and reduce the level of inflammatory factors in gingival crevicular fluid, with mechanisms involving anti-inflammation and bone metabolism regulation. Furthermore, Liuwei Dihuang Wan and its modified formulas are often used for periodontitis of the kidney yin deficiency type, especially those accompanied by tooth loosening. Studies have shown that it can improve clinical indicators, reduce inflammatory factors, inhibit alveolar bone resorption, and promote osteogenic activity. Based on clinical experience and modern research findings, researchers often modify or create new formulas based on classic prescriptions to target different syndrome types. However, there are still very few Chinese herbal compound prescriptions available for reference for complex syndrome types. Therefore, it is still necessary to develop new Chinese herbal compound prescriptions that can be used for clinical reference. Summary of the Invention:

[0005] To address the shortcomings of existing technologies, this invention provides a self-formulated traditional Chinese medicine compound preparation for treating periodontitis. This compound preparation targets the primary symptom of excessive stomach fire, accompanied by complex syndromes such as spleen and kidney deficiency (qi and blood deficiency, kidney qi deficiency), and has multiple effects. The entire formula primarily clears stomach fire, detoxifies, and reduces swelling; it is supplemented by tonifying qi and strengthening the exterior, and tonifying the kidneys and strengthening bones; it is further aided by astringent and hemostatic agents, wind-dispelling and pain-relieving agents, blood-nourishing and blood-activating agents, and spleen-strengthening agents. All the herbs in the formula work synergistically and are indispensable, ultimately achieving the therapeutic goal for complex syndromes of periodontitis.

[0006] Specifically, the first aspect of this invention provides a traditional Chinese medicine composition for treating periodontitis, which comprises the following medicinal materials: Coptis chinensis, gypsum, Cimicifuga foetida, Astragalus membranaceus, Drynaria fortunei, Agrimonia pilosa, Cynanchum paniculatum, Angelica sinensis, Dioscorea opposita, and Glycyrrhiza uralensis. In this formula, Coptis chinensis and gypsum are the principal herbs. Coptis chinensis clears stomach heat, dries dampness, and detoxifies, while gypsum clears excess heat in the stomach meridian, relieves irritability and thirst, and assists Coptis chinensis in clearing heat, detoxifying, and reducing swelling. Together, they form the core of the formula's expelling pathogenic factors, effectively eliminating symptoms of excessive stomach heat. Cimicifuga, Astragalus, Drynaria, and Agrimonia are used as adjuvant herbs. Cimicifuga assists the principal herb in clearing stomach toxicity, and its ascending and dispersing properties can guide the medicinal power to the head, face, and oral cavity. Astragalus, while clearing away fire toxins as the principal and assistant herbs, can also replenish qi, strengthen the exterior, support the body's defenses against toxins, prevent the pathogens from penetrating deeper, and restrain the damage caused by cold and dampness. Drynaria can stabilize the tooth roots, promote alveolar bone repair, and relieve tooth loosening and pain. Agrimonia can effectively stop bleeding, and its tonifying effect matches the chronic wasting characteristics of periodontal disease, while its detoxifying and swelling-reducing properties assist the principal herb. The adjuvant herbs are Cynanchum paniculatum, Angelica sinensis, and Dioscorea opposita, with Dioscorea opposita being the key adjuvant. On one hand, it works synergistically with Astragalus membranaceus to tonify Qi and strengthen the spleen, protecting the middle Jiao and preventing coldness from harming the stomach. On the other hand, it works synergistically with Drynaria fortunei to tonify the kidneys and strengthen the foundation. Its Yin-nourishing and astringent properties complement Agrimonia pilosa's hemostatic and exterior-strengthening and detoxifying effects, further helping to control bleeding and exudation and strengthen teeth. The blood-activating effects of Cynanchum paniculatum and Angelica sinensis, combined with the astringent and consolidating effects of Agrimonia pilosa and Dioscorea opposita, form a harmonious combination that promotes local blood circulation without aggravating bleeding, under the premise of controlling inflammatory bleeding, thus facilitating inflammation resolution and tissue repair. The guiding herb is Glycyrrhiza uralensis, which harmonizes the cold, hot, warm, and cool properties of the other herbs. Its heat-clearing, detoxifying, pain-relieving, spleen-tonifying, and Qi-boosting effects further assist the entire formula.

[0007] In addition, from a pharmacological perspective, the ingredients in the formula, including Coptis chinensis (berberine), gypsum, Cimicifuga foetida (ferulic acid), and Cynanchum paniculatum (paeonol), can synergistically eliminate pathogenic bacteria and biofilms; Coptis chinensis (berberine), Cimicifuga foetida (ferulic acid), Glycyrrhiza uralensis (glycyrrhizic acid), and Astragalus membranaceus (astragaloside A, Astragalus polysaccharide) can inhibit inflammation and regulate immunity at multiple targets; Agrimonia pilosa (agrimonin, tannins), Angelica sinensis (ferulic acid), and Cynanchum paniculatum (paeonol) can synergistically stop bleeding, relieve pain, and improve microcirculation; Drynaria fortunei (total flavonoids of Drynaria fortunei), Astragalus membranaceus (astragaloside A), and Angelica sinensis (Angelica polysaccharide) can inhibit bone resorption and promote the regeneration of soft and hard tissues; while Dioscorea opposita (Dioscorea opposita polysaccharide), Astragalus membranaceus (astragalus polysaccharide), and Glycyrrhiza uralensis (glycyrrhizic acid) can protect the stomach and strengthen the body, maintaining long-term efficacy. The traditional Chinese medicine composition provided in this formula fully embodies the synergy between local pathological intervention and overall functional regulation, thus demonstrating the advantages of traditional Chinese medicine in addressing both the root cause and symptoms and providing multi-target treatment. It can effectively control the progression of periodontitis and promote periodontal tissue regeneration. Specifically:

[0008] Coptis chinensis: The dried rhizome of Coptis chinensis, Coptis triangularis, or Coptis yunnanensis, all belonging to the Ranunculaceae family. Properties and Channels Entered: Bitter, cold. Enters the Heart, Spleen, Stomach, Liver, Gallbladder, and Large Intestine channels. Functions: Clears heat and dries dampness, drains fire and detoxifies. Pharmacological Actions: Antibacterial and Anti-inflammatory: Contains alkaloids such as berberine, which significantly inhibits periodontal pathogens such as Porphyromonas gingivalis and Prevotella intermedius, while also inhibiting the release of inflammatory factors. Immunomodulatory Effects: Regulates macrophage function and reduces local inflammatory responses.

[0009] Gypsum: A sulfate mineral belonging to the anhydrite group, primarily containing hydrated calcium sulfate (CaSO4·2H2O). Properties and Channels Entered: Pungent, sweet, very cold. Enters the Lung and Stomach channels. Functions: Clears heat and drains fire, promotes fluid production and quenches thirst. Pharmacological Actions: Antipyretic and anti-inflammatory: Inhibits the thermoregulatory center, lowers the temperature of inflamed areas, and relieves periodontal redness, swelling, heat, and pain; enhances the phagocytic function of macrophages. Promotes Repair: Calcium ions participate in periodontal tissue mineralization and assist in alveolar bone repair.

[0010] Cimicifuga rhizome: The dried rhizome of Cimicifuga foetida, Cimicifuga dahurica, or Cimicifuga foetida, all belonging to the Ranunculaceae family. Properties and Channels Entered: Pungent, slightly sweet, slightly cold. Enters the Lung, Spleen, Stomach, and Large Intestine channels. Functions: Releases exterior pathogens and promotes rash eruption, clears heat and detoxifies, and raises Yang Qi. Pharmacological Actions: Anti-inflammatory and analgesic: Contains cimicifugin, isoflavonic acid, etc., which inhibit cyclooxygenase activity, reduce prostaglandin synthesis, and relieve periodontal pain; it also has inhibitory effects on Staphylococcus aureus and other bacteria. Immune Enhancement: Enhances the body's non-specific immunity and promotes mucosal barrier repair.

[0011] Astragalus: The dried root of *Astragalus mongholicus* or *Astragalus membranaceus*, both belonging to the Fabaceae family. Properties and Channels Entered: Sweet, slightly warm. Enters the Spleen and Lung channels. Functions: Tonifies Qi and raises Yang, consolidates the exterior and stops sweating, promotes diuresis and reduces swelling, generates fluids and nourishes blood, promotes circulation and relieves pain, promotes pus drainage and detoxification, and promotes tissue regeneration and wound healing. Pharmacological Actions: Immunomodulation: Enhances T-cell and B-cell function, improves local periodontal immunity, and reduces pathogenic bacterial colonization; promotes the secretion of anti-inflammatory factors such as IL-10. Tissue Repair: Promotes fibroblast proliferation and collagen synthesis, accelerating the repair of the periodontal ligament and alveolar bone.

[0012] Drynaria fortunei, the dried rhizome of *Drynaria fortunei*, a plant in the Polypodiaceae family. Properties and Channels: Bitter, warm. Enters the Liver and Kidney channels. Functions: Tonifies the kidneys and strengthens bones, promotes healing of injuries and relieves pain. Pharmacological Actions: Promotes bone repair: Contains total flavonoids from Drynaria fortunei, which stimulate osteoblast activity, inhibit osteoclasts, increase bone density, and delay alveolar bone resorption. Anti-inflammatory and Antibacterial: Inhibits periodontal pathogens and reduces the damage of inflammation to periodontal supporting tissues.

[0013] Agrimony: The dried aerial parts of Agrimony, a plant in the Rosaceae family. Properties and Channels Entered: Bitter, astringent, neutral. Enters the Heart and Liver channels. Functions: Astringent and hemostatic, antimalarial, antidysentery, detoxifying, and tonifying. Pharmacological Actions: Hemostatic and anti-inflammatory: Contains agrimonin, which promotes platelet aggregation, shortens clotting time, and relieves periodontal bleeding; inhibits inflammatory cell infiltration and reduces gingival edema. Antibacterial and tonifying: Has inhibitory effects on Escherichia coli, Streptococcus, etc., while improving the body's weak state.

[0014] Xu Changqing: The dried root and rhizome of *Cynanchum paniculatum*, a plant in the Asclepiadaceae family. Properties and Channels Entered: Pungent, warm. Enters the Liver and Stomach channels. Functions: Dispels wind and relieves pain, invigorates blood circulation and unblocks channels, relieves itching. Pharmacological Actions: Analgesic and Anti-inflammatory: Contains paeonol, which blocks pain signal transmission, relieving dull periodontal pain; inhibits the release of inflammatory mediators, reducing local swelling. Improves Circulation: Dilates blood vessels, promotes local blood circulation in the periodontal area, and accelerates the excretion of inflammatory products.

[0015] Angelica sinensis: The dried root of Angelica sinensis, a plant in the Apiaceae family. Properties and Channels: Sweet, pungent, warm. Enters the Liver, Heart, and Spleen channels. Functions: Nourishes and invigorates blood, regulates menstruation and relieves pain, moistens the intestines and promotes bowel movements. Pharmacological Actions: Improves microcirculation: Contains ferulic acid, inhibits platelet aggregation, reduces blood viscosity, increases blood flow to periodontal tissues, and promotes inflammation resolution and nutrient supply. Anti-inflammatory and Repairing: Inhibits the NF-κB pathway, reduces inflammatory factors, and simultaneously promotes fibroblast proliferation, repairing periodontal soft tissues.

[0016] Yam: The dried rhizome of Dioscorea opposita, a plant in the Dioscoreaceae family. Properties and Channels Entered: Sweet, neutral. Enters the Spleen, Lung, and Kidney channels. Functions: Tonifies Qi and Yin, strengthens the Spleen, Lung, and Kidney, consolidates essence and stops leukorrhea. Pharmacological Actions: Immune Enhancement: Contains yam polysaccharides, which increase the level of immunoglobulins in the body, enhance mucosal immune function, and reduce recurrent periodontal infections. Metabolic Regulation: Improves spleen deficiency, promotes nutrient absorption, and provides a material basis for periodontal tissue repair.

[0017] Raw licorice: The dried root and rhizome of the legume plant *Glycyrrhiza uralensis*. Properties and Channels Entered: Sweet, neutral. Enters the Heart, Lung, Spleen, and Stomach channels. Functions: Tonifies the spleen and replenishes qi, clears heat and detoxifies, resolves phlegm and relieves cough, alleviates spasms and pain, and harmonizes other herbs. Pharmacological Actions: Anti-inflammatory and detoxifying: Contains glycyrrhizic acid, which inhibits inflammatory responses and reduces gingival congestion; enhances the efficacy of heat-clearing and detoxifying herbs such as *Coptis chinensis* and gypsum, and reduces drug toxicity.

[0018] As a further explanation of the present invention, the composition consists of the following medicinal materials in parts by weight: 10-20 parts Coptis chinensis, 20-40 parts gypsum, 5-15 parts Cimicifuga foetida, 10-30 parts Astragalus membranaceus, 10-30 parts Drynaria fortunei, 10-30 parts Agrimonia pilosa, 10-20 parts Cynanchum paniculatum, 10-15 parts Angelica sinensis, 10-20 parts Dioscorea opposita, and 5-15 parts Glycyrrhiza uralensis.

[0019] As a further explanation of the present invention, the composition consists of the following medicinal materials in parts by weight: 15 parts Coptis chinensis, 30 parts gypsum, 10 parts Cimicifuga foetida, 20 parts Astragalus membranaceus, 20 parts Drynaria fortunei, 20 parts Agrimonia pilosa, 15 parts Cynanchum paniculatum, 12 parts Angelica sinensis, 15 parts Dioscorea opposita, and 10 parts Glycyrrhiza uralensis.

[0020] The second aspect of the present invention provides a traditional Chinese medicine mouthwash for treating periodontitis, comprising 10-30 parts of a traditional Chinese medicine fluid extract made from the traditional Chinese medicine composition described in any one of the above-mentioned methods, 20-50 parts of an osmotic pressure regulator, 1-10 parts of a mucosal protectant, 0.1-0.5 parts of a cooling agent, and 20-70 parts of water.

[0021] As a further explanation of the present invention, the osmotic pressure regulator is one or more of the following: 70% sorbitol solution, 50% xylitol solution, 20% trehalose solution, and 0.9% sodium chloride solution; the mucosal protectant is one or more of the following: glycerin, betaine, and aloe polysaccharide gel; and the cooling agent is one or more of the following: menthol, WS-3 mentholamide, eucalyptol, and L-carvone.

[0022] The aforementioned osmotic pressure regulators precisely adjust the osmotic pressure of the mouthwash to near that of saliva, preventing dehydration of the oral mucosa caused by hypertonic solutions or tissue edema caused by hypotonic solutions. They also provide moisturizing and flavor-correcting effects. The aforementioned mucosal protectants moisturize and form a protective film on the mucosa, thus preventing damage from the mouthwash. The aforementioned cooling agents not only provide a cooling sensation to the mouthwash but also have a certain antibacterial effect.

[0023] A third aspect of the present invention provides a traditional Chinese medicine preparation for treating periodontitis, wherein the traditional Chinese medicine preparation is made from the traditional Chinese medicine composition described in any one of the above-mentioned methods using conventional preparation methods.

[0024] As a further explanation of the present invention, the traditional Chinese medicine preparation is any one of decoction, powder, pill, granule, capsule, tablet, drop pill, or oral liquid.

[0025] The fourth aspect of this invention provides a method for preparing a traditional Chinese medicine mouthwash for treating periodontitis, comprising the following steps:

[0026] S1: Prepare a traditional Chinese medicine fluid extract from the traditional Chinese medicine composition described in any one of the above-mentioned methods for later use;

[0027] S2: After preheating the herbal extract obtained in step S1, add the osmotic pressure regulator, mucosal protectant and cooling agent in sequence, and finally add water and stir well to obtain the herbal mouthwash.

[0028] As a further explanation of the present invention, in S1, the traditional Chinese medicine fluid extract is prepared by any one of the following methods: decoction concentration method, percolation method, maceration concentration method, and reflux extraction concentration method.

[0029] The fifth aspect of the present invention provides the use of the traditional Chinese medicine composition described in any one of the above-mentioned methods, or the traditional Chinese medicine mouthwash described in any one of the above-mentioned methods, or the traditional Chinese medicine mouthwash prepared by any one of the above-mentioned methods, in the preparation of a medicament for treating periodontitis.

[0030] Compared with the prior art, the present invention has the following beneficial technical effects:

[0031] This invention provides a self-formulated traditional Chinese medicine compound preparation for treating periodontitis. This compound preparation targets the main symptom of excessive stomach fire, accompanied by complex syndromes such as deficiency of both spleen and kidney, and deficiency of qi and blood and deficiency of kidney qi. It has multiple effects. The whole formula mainly clears stomach fire, detoxifies and reduces swelling; it is supplemented by tonifying qi and consolidating the exterior, and tonifying the kidney and strengthening bones; it is also supplemented by astringent hemostasis, wind-dispelling and pain-relieving, blood-nourishing and blood-activating, and spleen-strengthening and foundation-consolidating.

[0032] The present invention provides a Chinese herbal mouthwash in which the herbal combinations have significant synergistic effects among the herbal pairs. Each herbal pair in the formula is indispensable, and ultimately achieves a significant therapeutic effect on periodontitis. Attached image description:

[0033] Figure 1 The results of HE staining of some rat gingival tissue are shown. Figure 1 (a)-(d) show the HE staining results of rat gingival tissue from the sham-operated group, model group, positive control group, and Example 1 group, respectively.

[0034] Figure 2 The results of periodontal index testing for rats in each group are shown.

[0035] Figure 3 The results show the content of pro-inflammatory factors in the gingival tissue of rats in each group. Detailed implementation method:

[0036] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] Example 1

[0038] This embodiment provides a traditional Chinese medicine composition for treating periodontitis, which consists of the following medicinal materials in parts by weight: 15 parts Coptis chinensis, 30 parts gypsum, 10 parts Cimicifuga foetida, 20 parts Astragalus membranaceus, 20 parts Drynaria fortunei, 20 parts Agrimonia pilosa, 15 parts Cynanchum paniculatum, 12 parts Angelica sinensis, 15 parts Dioscorea opposita, and 10 parts Glycyrrhiza uralensis.

[0039] Example 2

[0040] This embodiment provides a traditional Chinese medicine composition for treating periodontitis, which consists of the following medicinal materials in parts by weight: 10 parts Coptis chinensis, 20 parts gypsum, 5 parts Cimicifuga foetida, 10 parts Astragalus membranaceus, 10 parts Drynaria fortunei, 10 parts Agrimonia pilosa, 10 parts Cynanchum paniculatum, 10 parts Angelica sinensis, 10 parts Dioscorea opposita, and 5 parts Glycyrrhiza uralensis.

[0041] Example 3

[0042] This embodiment provides a traditional Chinese medicine composition for treating periodontitis, which consists of the following medicinal materials in parts by weight: 20 parts Coptis chinensis, 40 parts gypsum, 15 parts Cimicifuga foetida, 30 parts Astragalus membranaceus, 30 parts Drynaria fortunei, 30 parts Agrimonia pilosa, 20 parts Cynanchum paniculatum, 15 parts Angelica sinensis, 20 parts Dioscorea opposita, and 15 parts Glycyrrhiza uralensis.

[0043] Comparative Example 1:

[0044] This comparative example provides a traditional Chinese medicine composition for treating periodontitis. The difference between this composition and Example 1 is that Coptis chinensis and gypsum are removed from the formula.

[0045] Comparative Example 2:

[0046] This comparative example provides a traditional Chinese medicine composition for treating periodontitis. The difference between this composition and Example 1 is that the ingredients Cimicifuga rhizome, Astragalus membranaceus, and Drynaria fortunei are removed from the formula.

[0047] Comparative Example 3:

[0048] This comparative example provides a traditional Chinese medicine composition for treating periodontitis. The difference between this composition and Example 1 is that Agrimonia pilosa and Dioscorea opposita are removed from the composition.

[0049] Comparative Example 4:

[0050] This comparative example provides a traditional Chinese medicine composition for treating periodontitis. The difference between this composition and Example 1 is that Xu Changqing and Danggui are removed from the formula.

[0051] The following animal experiments were used to verify the efficacy of the traditional Chinese medicine compositions provided in the embodiments and comparative examples of the present invention on an experimental rat model of periodontitis.

[0052] 1. Experimental materials:

[0053] 1.1 Laboratory Animals

[0054] Male SD rats, 6-8 weeks old, with an average weight of (200g±20g), were purchased from the Animal Experiment Center of the Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine. After purchase, they were acclimatized under standard laboratory conditions for 1 week before subsequent experiments were conducted.

[0055] 1.2 Experimental drugs:

[0056] Positive control mouthwash: Compound chlorhexidine mouthwash, specification: 10mL*15 vials / box, approval number: National Drug Approval Number H20064218, manufacturer: Jinzhou Bentian Pharmaceutical Co., Ltd.

[0057] The traditional Chinese medicine mouthwashes prepared from the above-described embodiments and comparative examples specifically include the following steps:

[0058] Step 1: Weigh the medicinal materials in the traditional Chinese medicine compositions provided in the above examples and comparative examples according to the specified proportions, and then prepare a fluid extract by decoction and concentration. The specific process includes the following steps:

[0059] Step 101: Wash, dry and pulverize all the medicinal materials (calcined gypsum should be used). Gypsum should be pulverized into 100-120 mesh fine powder, and the other medicinal materials should be pulverized into 10-20 mesh coarse powder for later use.

[0060] Step 102: Weigh the powdered medicinal materials according to the weight fraction of each medicinal material in the traditional Chinese medicine composition provided in the above embodiments and comparative examples. Place the powdered medicinal materials other than Xu Changqing in a traditional Chinese medicine extraction tank, add 8 times the amount of purified water, soak for 40 minutes, then heat to a gentle boil and decoct for 1 hour (add Xu Changqing 10-15 minutes before the end of decoction), filter, and collect the first filtrate.

[0061] Step 103: Add 6 times the weight of the dregs obtained in Step 102 of purified water, heat to a boil, maintain a gentle boil for 40 minutes, filter, and collect the second filtrate.

[0062] Step 104: Combine the first and second filtrates and filter them again with gauze. Concentrate the resulting fine filtrate under reduced pressure (maintain a negative pressure of -0.05 to -0.08 MPa, and note that the pressure reduction temperature is around 70℃) until the relative density of the extract is about 1.20, thus obtaining the Chinese herbal fluid extract.

[0063] Step 2: After preheating the herbal extract obtained in Step 1, add the osmotic pressure regulator, mucosal protectant, and cooling agent in sequence. Finally, add water and stir well to obtain the herbal mouthwash. The specific process includes the following steps:

[0064] Step 201: Prepare the raw materials according to the following weight ratio for the Chinese herbal mouthwash: 15 parts Chinese herbal fluid extract, 30 parts 70% sorbitol solution, 5 parts glycerin, 0.2 parts menthol, and 50 parts purified water. Then dissolve the menthol in a small amount of ethanol and set aside.

[0065] Step 202: Preheat the herbal extract to 40°C, add 70% sorbitol solution and glycerin in sequence, stir well and cool to room temperature, then add menthol ethanol solution, and finally add purified water and stir well to obtain the final herbal mouthwash.

[0066] The negative control mouthwash is prepared as follows:

[0067] Step 301: Prepare the ingredients according to the weight ratio of 30 parts of 70% sorbitol solution, 5 parts of glycerin, 0.2 parts of menthol, and 50 parts of purified water in the mouthwash. Then dissolve the menthol in a small amount of ethanol and set aside.

[0068] Step 302: Stir the above 70% sorbitol solution and glycerin at 40°C until homogeneous, then cool to room temperature. Add menthol ethanol solution, and finally add purified water and stir until homogeneous to obtain the final negative control mouthwash.

[0069] 2. Experimental methods:

[0070] 2.1 Animal model establishment, grouping, and drug administration

[0071] A periodontitis model was constructed using the ligation method. The specific modeling process was as follows: Rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital (40g / kg). The rats were then fixed to an operating table, their mouths kept open by an oral gag, and 4-0 silk thread was wrapped around the neck of the maxillary first molar and tied. In the sham-operated group, only anesthesia and mouth opening were performed; no ligation wire was placed. Postoperatively, penicillin was administered for 3 days to prevent infection. Three weeks after ligation, plaque accumulated on the ligation wire, causing typical periodontitis pathological changes such as local gingival redness and swelling, and alveolar bone resorption, thus indicating successful modeling.

[0072] Grouping: Three weeks after modeling, the successfully modeled rats were randomly divided into 8 groups of 10 rats each: model group, positive control group, negative control group, Example 1 group, comparative example 1 group, comparative example 2 group, comparative example 3 group, and comparative example 4 group. Ten rats from the sham-operated group were used as blank controls.

[0073] Administration: After successful modeling, all ligatures on the modeling rats were removed before administration. Rats in Example 1 group were treated with a mouthwash made from the herbal composition provided in Example 1, applied to the gingival margin of the maxillary first molar; rats in Comparative Examples 1-4 were treated with the same mouthwash; rats in the negative control group were treated with the aforementioned negative control mouthwash; rats in the positive control group were treated with the aforementioned compound chlorhexidine mouthwash; and rats in the model group and sham-operated group were treated with sterile water. The dosage was 20 μL each time, applied three times daily for four consecutive weeks.

[0074] 2.2 Observation Indicators and Methods

[0075] 2.2.1 Periodontal index detection

[0076] Four weeks after administration, a periodontal probe was gently inserted into the gingival sulcus to assess gingival bleeding and inflammation (Sulcus Bleeding Index (SBI)). The specific criteria were as follows: 0 points: pink gingiva, normal shape, no bleeding upon probing; 1 point: slight color change and mild edema of the gingiva, but no bleeding upon probing; 2 points: mild inflammation, swollen gums, and punctate bleeding visible upon probing; 3 points: moderate inflammation, moderate swelling of the gums, bleeding upon probing, and bleeding spreading in the gingival sulcus; 4 points: significant inflammation of the gingiva, tendency to bleed upon probing, and bleeding from the gingival sulcus; 5 points: significant swelling and severe ulceration of the gingiva, with spontaneous bleeding.

[0077] Periodontal pocket probing depth (PD): A miniature periodontal probe with a marked scale is gently inserted into three sites on the buccal mesial (MB), buccal central (B), and buccal distal (DB) sides of the rat's maxillary first molar. The probe tip is kept stable at the bottom of the pocket, and the distance from the gingival margin to the probe tip is read. The average of the measurements at the three sites (MB, B, and DB) is taken as the periodontal pocket depth (PD), in mm.

[0078] 2.2.2 Detection of pro-inflammatory factors

[0079] Four weeks after administration, rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital (40 / kg), and then sacrificed. Gingival tissue around the first maxillary molar of the rats was quickly removed, homogenized and lysed with PBS buffer, and the supernatant was collected by centrifugation. The concentration levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the gingival tissue of each group of rats were detected using an ELISA kit according to the instructions of the test kit.

[0080] 2.2.3 Pathological tissue observation

[0081] The separated jawbone tissue was fixed in 4% paraformaldehyde solution. Following the standard method for preparing pathological mountings using HE staining, the jawbone tissue was sequentially dehydrated with graded ethanol, embedded in paraffin, sectioned at 4μm, stained with HE, and mounted with neutral resin. Finally, neutral resin mountings were prepared for pathological observation of gingival tissue around the jawbone, and the gingival tissue samples were observed under a microscope.

[0082] 3. Statistical Analysis

[0083] Quantitative data are expressed as mean ± standard deviation (x ± s). Statistical analysis was performed using SPSS 25.0 software. The t-test for two independent samples was used to compare the two groups. All tests were considered to be statistically significant with P < 0.05 or P < 0.01.

[0084] 4. Experimental Results

[0085] 4.1 Results of periodontal index detection in each group of rats.

[0086] Table 1 shows the results of periodontal index detection in each group of rats.

[0087]

[0088] Note: ## P < 0.01 compared with the sham surgery group; ** P < 0.01 compared with the model group; ▽ P > 0.05 compared with the model group; Δ P < 0.05 compared with Example 1 group; ΔΔ P < 0.01 compared with Example 1 group; n = 10.

[0089] From Table 1 and Figure 2 It can be seen that the SBI and PD of the model group rats were significantly higher than those of the sham-operated group, and the inter-group comparison P<0.01, which is statistically significant. Compared with the model group rats, the SBI and PD of the rats in Example 1 group and the positive control group rats were significantly reduced, and the inter-group comparison P<0.01, which is statistically significant. However, the negative control group rats showed little difference, indicating that the herbal mouthwash provided by this invention has a certain degree of improvement on gingival sulcus bleeding and gingival inflammation in rats with periodontitis. Compared with the rats in Example 1 group, the SBI and PD of the rats in Comparative Examples 1-4 were all increased to varying degrees, and the inter-group comparison P<0.05, which is statistically significant. This indicates that the absence of certain herbal pairs in the herbal composition of this invention will significantly affect the improvement effect of the herbal mouthwash on gingival sulcus bleeding and gingival inflammation in rats with periodontitis. It also shows that there is a significant synergistic effect among the herbal pairs in the herbal composition provided by this invention, and each herbal pair in the formula is indispensable.

[0090] 4.2 Results of pro-inflammatory factor detection in each group of rats.

[0091] Table 2 shows the results of pro-inflammatory factor content detection in each group of rats.

[0092]

[0093] Note: ## P < 0.01 compared with the sham surgery group; ** P < 0.01 compared with the model group; Δ P < 0.05 compared with Example 1 group; ΔΔ P < 0.01 compared with Example 1 group, n = 10.

[0094] From Table 2 and Figure 3 It can be seen that the levels of TNF-α and IL-6 in the gingival tissue of the model group rats were significantly higher than those in the sham-operated group, and the inter-group comparison P<0.01, indicating statistical significance. Compared with the model group rats, the levels of TNF-α and IL-6 in the gingival tissue of the rats in Example 1 group and the positive control group rats were significantly reduced, and the inter-group comparison P<0.01, indicating statistical difference. The difference in the negative control group rats was smaller, indicating that the herbal mouthwash provided by this invention has a certain degree of improvement on the inflammation problem in the gingival tissue of rats with periodontitis. Compared with the rats in Example 1 group, the levels of TNF-α and IL-6 in the gingival tissue of rats in Comparative Examples 1-4 were all increased to varying degrees, and the inter-group comparison P<0.05, indicating statistical difference. This indicates that the absence of certain herbal pairs in the herbal composition of this invention will significantly affect the improvement effect of the herbal mouthwash on the inflammation problem in the gingival tissue of rats with periodontitis. It also shows that there is a significant synergistic effect among the herbal pairs in the herbal composition provided by this invention, and each herbal pair in the formula is indispensable.

[0095] 4.3 Observation results of some rat pathological tissues

[0096] Figure 1 The results of HE staining of some rat gingival tissue are shown. Figure 1 (a)-(d) show the HE staining results of gingival tissue from rats in the sham-operated group, model group, positive control group, and Example 1 group, respectively. The figures show that the gingiva of rats in the sham-operated group was intact and continuous, with uniform cell distribution, no obvious inflammatory cell infiltration, and no significant alveolar bone resorption. In the model group, the integrity of the gingival epithelium was disrupted, with abundant inflammatory cell infiltration in the gingival tissue, disordered connective tissue arrangement, and visible alveolar bone resorption. The gingival tissue of rats in the positive control group and Example 1 group showed significant improvement compared to the model group, for example, the degree of inflammatory cell infiltration and alveolar bone height were significantly improved, thus demonstrating that the herbal mouthwash provided by this invention has a significant improving effect on the gingival tissue of rats with periodontitis.

[0097] In summary, the above animal experiments demonstrate that the herbal mouthwash provided by this invention has a significant improving effect on rats with periodontitis. Furthermore, the herbal composition used in the herbal mouthwash provided by this invention exhibits a significant synergistic effect among the herbal pairs, and each herbal pair is indispensable in the formula.

[0098] It should be noted that, in this document, terms such as “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0099] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for treating periodontitis, characterized in that, The composition consists of the following medicinal materials: Coptis chinensis, gypsum, Cimicifuga foetida, Astragalus membranaceus, Drynaria fortunei, Agrimonia pilosa, Cynanchum paniculatum, Angelica sinensis, Dioscorea opposita, and Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition for treating periodontitis as described in claim 1, characterized in that, The composition consists of the following medicinal materials in parts by weight: 10-20 parts Coptis chinensis, 20-40 parts gypsum, 5-15 parts Cimicifuga foetida, 10-30 parts Astragalus membranaceus, 10-30 parts Drynaria fortunei, 10-30 parts Agrimonia pilosa, 10-20 parts Cynanchum paniculatum, 10-15 parts Angelica sinensis, 10-20 parts Dioscorea opposita, and 5-15 parts Glycyrrhiza uralensis.

3. The traditional Chinese medicine composition for treating periodontitis as described in claim 1, characterized in that, The composition consists of the following medicinal materials in parts by weight: 15 parts Coptis chinensis, 30 parts gypsum, 10 parts Cimicifuga foetida, 20 parts Astragalus membranaceus, 20 parts Drynaria fortunei, 20 parts Agrimonia pilosa, 15 parts Cynanchum paniculatum, 12 parts Angelica sinensis, 15 parts Dioscorea opposita, and 10 parts Glycyrrhiza uralensis.

4. A traditional Chinese medicine mouthwash for treating periodontitis, characterized in that, The herbal fluid extract comprising any one of the herbal compositions according to claims 1-3 consists of 10-30 parts of herbal fluid extract, 20-50 parts of osmotic pressure regulator, 1-10 parts of mucosal protectant, 0.1-0.5 parts of cooling agent, and 20-70 parts of water.

5. The herbal mouthwash for treating periodontitis as described in claim 4, characterized in that, The osmotic pressure regulator is one or more of the following: 70% sorbitol solution, 50% xylitol solution, 20% trehalose solution, and 0.9% sodium chloride solution; the mucosal protectant is one or more of the following: glycerin, betaine, and aloe polysaccharide gel; and the cooling agent is one or more of the following: menthol, WS-3 mentholamide, eucalyptol, and L-carvone.

6. A traditional Chinese medicine preparation for treating periodontitis, characterized in that, The traditional Chinese medicine preparation is made from the traditional Chinese medicine composition of any one of claims 1-3 using conventional preparation methods.

7. The traditional Chinese medicine preparation for treating periodontitis as described in claim 6, characterized in that, The traditional Chinese medicine preparation is any one of the following: decoction, powder, pill, granule, capsule, tablet, drop pill, or oral liquid.

8. A method for preparing a traditional Chinese medicine mouthwash for treating periodontitis, characterized in that, Includes the following steps: S1: Prepare a traditional Chinese medicine fluid extract from the traditional Chinese medicine composition according to any one of claims 1-3 for later use; S2: After preheating the herbal extract obtained in step S1, add the osmotic pressure regulator, mucosal protectant and cooling agent in sequence, and finally add water and stir well to obtain the herbal mouthwash.

9. The method for preparing the traditional Chinese medicine mouthwash for treating periodontitis as described in claim 8, characterized in that, S1 is prepared into a traditional Chinese medicine fluid extract using any one of the following methods: decoction concentration, percolation, maceration concentration, or reflux extraction concentration.

10. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3, or the traditional Chinese medicine mouthwash according to any one of claims 4 to 5, or the traditional Chinese medicine mouthwash obtained by the preparation method according to any one of claims 8 to 9, in the preparation of a medicament for treating periodontitis.

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