A Chinese medicine composition for treating recurrent oral ulcers, a Chinese medicine preparation and a preparation method thereof

Abstract

The present invention proposes a Chinese medicine composition, a Chinese medicine preparation and a preparation method thereof for treating recurrent oral ulcers, and belongs to the technical field of Chinese medicine. Aiming at the problem that oral ulcer drugs in the prior art cannot relieve the pain of oral ulcers or the pain effect is not ideal, the Chinese medicine composition of the present invention includes Indigo Naturalis, Phellodendron Amurense, Toad Venom, Aconite, Galla Chinensis, Catechu, Borneol, Amber, Dragon Bone, and Licorice. By adding heat-clearing and fire-purging ingredients such as Indigo Naturalis and Phellodendron Amurense, the root causes of the symptoms of heat accumulation in the spleen and stomach, blazing heart fire, and yin deficiency and fire are effectively removed, and the repair of ulcer mucosa is promoted; by adding swelling and analgesic ingredients such as Toad Venom and Aconite, the pain of the affected part is quickly relieved; by adding sedative and tranquilizing ingredients such as amber and dragon bone, the irritability and insomnia caused by oral ulcers are effectively relieved. The present invention utilizes the synergistic effect and compatibility mechanism between various Chinese medicinal materials to prepare a Chinese medicine composition with the dual effects of promoting ulcer healing and rapid analgesia, which can achieve both symptomatic and root treatment, good therapeutic effect and low recurrence rate.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition and a traditional Chinese medicine preparation for treating recurrent oral ulcers and a preparation method thereof. Background Art

[0002] Recurrent oral ulcers (RAU) are the most common oral mucosal diseases in clinical practice, with a prevalence rate of up to 20% in the general population. The main manifestations are the recurrence of isolated, round or oval ulcers on the oral mucosa. The ulcers are shallow, light yellow or white, with neat edges and surrounded by a red halo. They can be single or multiple. The onset is not limited by age, mostly in young people, slightly more in women than in men. It can occur all year round, but more in winter and spring. It has the characteristics of self-healing, high incidence, and high recurrence rate. The burning pain is unbearable when it occurs, which seriously affects the patient's daily life. Long-term repeated attacks will directly affect the body's immune function and may also induce the risk of cancer.

[0003] At present, the etiology and pathogenesis of RAU are still unclear, and there is no specific treatment. Glucocorticoids are often used in clinical treatment, but these drugs have no obvious direct effect on ulcer repair, and long-term use has significant side effects. For severe RAU, local injection of adrenocortical hormones is often used for treatment, which has significant efficacy, but this method is prone to damage to local surrounding tissues. Patients have a fear of local injection of hormones, which is easy to cause psychological burden. It is difficult to follow up with remote patients, and its application is limited.

[0004] The use of Chinese herbal medicine and its prescriptions to treat recurrent oral ulcers is mainly to improve microcirculation, supplement trace elements or regulate the body's immune function to achieve the purpose of treatment. However, the Chinese herbal preparations currently on the market generally have defects such as inadequate indicators and long treatment time. In addition, although drugs such as Xigua Shuang and Bingpeng San have a certain analgesic effect, they are often accompanied by a burning sensation for dozens of seconds when applied to the ulcer mucosa, and the pain can only be relieved briefly after the burning pain.

[0005] In recent years, there are more and more prescriptions for treating oral ulcers with Chinese medicinal materials, such as the Chinese invention patent with patent number CN109620923B, entitled a Chinese medicinal composition for treating recurrent oral ulcers and its application, which discloses a Chinese medicinal composition made of raw astragalus, gypsum, rhizoma anemarrhenae, radix rehmanniae, rhizoma smilax, rhizoma chinensis, rhizoma picrorhizoma, folium lanospermi, rhizoma schizonepetae, rhizoma schizonepetae, rhizoma schizonepetae, rhizoma schizonepetae, rhizoma moutan, and jasper powder. The raw materials in this prior art have a wide range of sources, and the preparation method is simple and low in cost. However, the above-mentioned prior art prescriptions do not focus on relieving the pain caused by oral ulcers or the pain effect is not ideal. Therefore, it is particularly necessary to develop a new Chinese medicinal preparation that has the dual effects of promoting ulcer healing and rapid analgesia to solve the existing problems. Summary of the invention

[0006] The purpose of the present invention is to overcome the deficiencies and defects of the therapeutic drugs for oral ulcers in the prior art, and to provide a Chinese medicine composition with simple compatibility, dual effects of promoting ulcer healing and rapid analgesia, so as to solve the technical problems existing in the above-mentioned prior art.

[0007] In order to achieve the above object, the present invention is implemented by the following technical solutions:

[0008] The Chinese medicine composition of the present invention is prepared by referring to the clinical experience prescription of the traditional Chinese medicine system, and is mainly composed of two medicinal materials, Indigo and Phellodendron, recorded in Qianjin Yaofang·Koutou.

[0009] Indigo: salty, cold, enters the liver, lung, and stomach meridians, has the effects of clearing away heat and detoxifying, cooling blood and dispersing swelling, etc. It is clinically used for macules and vomiting, convulsions, coughing and hemoptysis, itchy cheek swelling and pain, etc.

[0010] Phellodendron chinense: bitter, cold, enters the kidney meridian. It has the effects of clearing away heat and dampness, purging fire and removing steam, detoxifying and curing sores.

[0011] Toad venom: pungent, warm, enters the heart meridian. Mainly used for carbuncle, furuncle, swelling and pain relief.

[0012] Aconitum: pungent, bitter, hot, enters the heart, liver, kidney, spleen meridians. It has the effects of dispelling wind and dampness, warming the meridians and relieving pain, and can be used for pain caused by cold hernia and anesthesia.

[0013] Gallnut: sour, astringent, and cold, it enters the lung, large intestine, and kidney meridians. It is mainly used to absorb moisture, heal sores, relieve pain, and stop bleeding.

[0014] Catechu: bitter, astringent, slightly cold, enters the lung and heart meridians. It has the effects of stopping bleeding, promoting tissue regeneration, absorbing moisture and healing sores, reducing swelling and relieving pain, and can be used for traumatic bleeding, sores that do not heal, eczema, wet sores, and lung heat cough.

[0015] Borneol: pungent, bitter, slightly cold, enters the heart, spleen, and lung meridians. It can clear away heat and relieve pain, prevent decay and promote tissue regeneration.

[0016] Amber: sweet, neutral, enters the heart, liver, spleen, lung, and bladder meridians. It has the effects of calming the nerves, dispersing blood stasis and stopping bleeding, and can be used for symptoms such as carbuncle, sore, and trauma.

[0017] Dragon bone: sweet, astringent, neutral, enters the heart, liver, and kidney meridians. It can calm the mind, astringe and consolidate, promote tissue regeneration, heal sores, and stop bleeding.

[0018] Licorice: sweet, neutral, enters the heart, lung, spleen, and stomach meridians. It has the effects of tonifying the spleen and replenishing qi, clearing away heat and detoxifying, removing phlegm and relieving cough, relieving pain, and harmonizing various medicines.

[0019] Indigo clears heat and detoxifies, while Phellodendron chinense clears heat and dries dampness. The two medicines are used together as the monarch, and their synergistic effect can clear the root causes of symptoms such as spleen and stomach heat accumulation, blazing heart fire, and yin deficiency and hyperactivity of fire, calm fire and generate yin, and repair mucosa; toad venom reduces swelling and relieves pain, Aconitum carmichaelii warms the meridians and relieves pain, Galla chinensis stops bleeding and regenerates tissue, Catechu absorbs dampness and heals sores, and Borneol clears heat and relieves pain. The five medicines are used together as the ministers, and they can assist the monarch medicine in relieving inflammation and relieving pain, clearing fire and removing steaming; at the same time, amber and dragon bone are used as adjuvants to calm the nerves, disperse blood stasis and kill bacteria; licorice is used to harmonize the medicines and eliminate the symptoms of oral ulcers. The combination of the medicines can achieve the therapeutic goals of relieving pain, reducing inflammation, inhibiting bacteria, stopping bleeding and promoting ulcer healing.

[0020] Based on the medicinal properties and mechanisms of the above Chinese medicinal materials, one aspect disclosed in the present invention is to provide a Chinese medicine composition for treating recurrent oral ulcers, which is composed of the following Chinese medicinal materials in parts by weight: 20-40 parts of Indigo Naturalis, 2-15 parts of Phellodendron Amurense, 15-35 parts of Toad Venom, 15-35 parts of Aconitum Kusnezoffii, 15-35 parts of Galla Chinensis, 5-25 parts of Catechu, 5-25 parts of Borneol, 5-25 parts of Amber, 5-25 parts of Dragon Bone, and 2-15 parts of Licorice.

[0021] Preferably, the Chinese medicine composition is composed of the following Chinese medicinal materials in parts by weight: 25-35 parts of Indigo, 5-12 parts of Phellodendron, 20-30 parts of Toad Venom, 20-30 parts of Aconitum, 20-30 parts of Gallnut, 10-20 parts of Catechu, 10-20 parts of Borneol, 10-20 parts of Amber, 10-20 parts of Dragon Bone, and 5-12 parts of Licorice.

[0022] Preferably, the Chinese medicine composition is composed of the following Chinese medicinal materials in parts by weight: 32 parts of Indigo Naturalis, 8 parts of Phellodendron Amurense, 24 parts of Toad Venom, 24 parts of Aconitum Kusnezoffii, 24 parts of Galla Chinensis, 16 parts of Catechu, 16 parts of Borneol, 16 parts of Amber, 16 parts of Dragon Bone, and 8 parts of Licorice.

[0023] Preferably, the particle size of the traditional Chinese medicine composition is ≤150 μm.

[0024] Another aspect of the present invention is to provide a Chinese medicine preparation for treating recurrent oral ulcers. The Chinese medicine preparation is prepared from the above Chinese medicine composition, or is prepared by adding pharmaceutically acceptable excipients to the above Chinese medicine composition.

[0025] The Chinese medicine composition of the present invention can be added with some pharmaceutically acceptable excipients as needed, and the Chinese medicine preparations, including external dosage forms and internal dosage forms, are prepared by conventional pharmaceutical techniques. Various conventional excipients such as thickeners, humectants, film-forming agents, such as glycerol, liquid paraffin, carbomer, polyvinyl alcohol, etc. are added to the raw materials to prepare external preparations such as powders, sprays, ointments, gels, films, tinctures, mouthwashes, mouthwash tablets, etc.; various conventional excipients such as diluents, disintegrants, lubricants, such as microcrystalline cellulose, lactose, cross-linked polyvinylpyrrolidone, magnesium stearate, etc. can also be added to the raw materials to prepare internal preparations such as oral liquids, decoctions, capsules, granules, granules, tablets, pills, etc.

[0026] Preferably, in order to make the raw materials of the drug better exert their efficacy and reduce toxic and side effects, the raw materials are made into powders or sprays for external use, but these cannot be used to limit the scope of protection of the present invention.

[0027] Another aspect disclosed in the present invention is to provide a method for preparing a Chinese medicine preparation for treating recurrent oral ulcers. The active pharmaceutical ingredient of each Chinese medicine composition is processed by traditional pharmaceutical technology, such as the following processing method:

[0028] S1: Weigh indigo, phellodendron, toad venom, aconite, gallnut, catechu, borneol, amber, dragon bone, and liquorice respectively by weight, crush them, and pass through a No. 6 sieve to obtain fine powder of each Chinese medicinal ingredient;

[0029] S2: The above-mentioned fine powders are mixed thoroughly in equal increments;

[0030] S3: Pass the mixed powder through a No. 5 sieve five times, shake and mix to obtain Chinese medicine powder.

[0031] When necessary, the above-mentioned auxiliary materials are added and the Chinese medicine dosage form is prepared according to conventional pharmacy techniques.

[0032] Or the following method:

[0033] S1: Weigh indigo naturalis, phellodendron amurense, toad venom, aconite, gallnut, catechu, borneol, amber, dragon bone, and liquorice respectively by weight and place them in a container;

[0034] S2: Add 3-8 times the weight of water to the container and boil for 3 times, each time for 2 hours, to obtain an extract;

[0035] S3: filtering the extract and concentrating it into an extract;

[0036] The extract is used as the active ingredient, and the auxiliary materials are added when necessary to prepare a Chinese medicine dosage form according to conventional pharmacy techniques.

[0037] Or the following method:

[0038] S1: Weigh indigo naturalis, phellodendron amurense, toad venom, aconite, gallnut, catechu, borneol, amber, dragon bone, and liquorice respectively by weight and place them in a container;

[0039] S2: Add 3-8 times the weight of ethanol to the container and reflux and extract for 3 times, each time for 1 hour, and separate the extract;

[0040] S3: filtering the extract, distilling the ethanol from the solution, and concentrating it into an extract;

[0041] The extract is used as the active ingredient, and the auxiliary materials are added when necessary to prepare a Chinese medicine dosage form according to conventional pharmacy techniques.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] 1. By adding functional ingredients such as Indigo and Phellodendron, which can clear away heat and purge fire, it can effectively remove the root causes of spleen and stomach heat, blazing heart fire, yin deficiency and hyperactivity of fire, and promote the repair of ulcer mucosa; by adding functional ingredients such as Toad Venom and Aconitum, which can reduce swelling and relieve pain, it can quickly relieve pain in the affected area; by adding functional ingredients such as Amber and Dragon Bone, which can calm and soothe the nerves, it can effectively relieve the irritability, insomnia and other adverse feelings caused by oral ulcers.

[0044] 2. The aconite in the Chinese medicine composition of the present invention has a surface anesthetic effect, which can quickly block the pain transmission of nerve endings, and can effectively solve the problem that the analgesic effect of existing oral ulcer treatment drugs is not ideal. Experiments have confirmed that the analgesic effect of the Chinese medicine composition of the present invention is better than that of watermelon frost, and after the patient uses the Chinese medicine composition, the pain peculiar to oral ulcers disappears after about 5 seconds. Compared with the short-term burning pain caused by the existing commercially available drugs watermelon frost and ice pen powder when they come into contact with the ulcer surface, the Chinese medicine composition of the present invention does not cause any discomfort during use, and the pain relief rate is as high as 100%, so it can significantly improve the quality of life of patients.

[0045] 3. The Chinese medicinal materials of the present invention are widely available, low in price, and simple in compatibility and preparation process, which solves the problem of complex compatibility and unsatisfactory therapeutic effect of existing similar drugs; at the same time, the Chinese medicine composition is dialectically accurate and complete, and the various components act synergistically to treat both the symptoms and the root causes. The Chinese medicine preparation of the present invention has a good therapeutic effect on recurrent oral ulcers and a low recurrence rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below.

[0047] Figure 1 is the weight change of rats in each group of the present invention (x±s, n=6);

[0048] Figure 2Observation of the healing of oral ulcers in rats of each group of the present invention;

[0049] Figure 3 This is the histopathological observation of oral ulcers in rats of each group of the present invention (×100);

[0050] Figure 4 The content changes of bFGF, IL-2, IL-6 and TNF-α in oral ulcer tissues of rats in each group of the present invention (x±s, n=3; compared with the normal group, *P<0.05; compared with the model group, #P<0.05);

[0051] Figure 5 The content of IL-2 in oral ulcer tissue of each group of rats in the present invention is changed (x±s, n=3; compared with the normal group, *P<0.05; compared with the model group, #P<0.05);

[0052] Figure 6 The content changes of IL-6 in oral ulcer tissues of rats in each group of the present invention (x±s, n=3; compared with the normal group, *P<0.05; compared with the model group, #P<0.05);

[0053] Figure 7 The content changes of TNF-α in oral ulcer tissues of rats in each group of the present invention (x±s, n=3; compared with the normal group, *P<0.05; compared with the model group, #P<0.05);

[0054] Figure 8 This is a picture of the rat ring-piercing and mouth-opening behavior training of the present invention;

[0055] Fig. 9 The pain thresholds caused by mechanical stimulation in rats of each group of the present invention (x±s, n=3; compared with the normal group, *P<0.05; compared with the model group, #P<0.05). DETAILED DESCRIPTION

[0056] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments.

[0057] Reference Figure 1-9 The present invention provides a Chinese medicine composition and a Chinese medicine preparation for treating recurrent oral ulcers and a preparation method thereof.

[0058] The Chinese medicine composition is composed of the following Chinese medicinal materials in parts by weight: 20-40 parts of Indigo, 2-15 parts of Phellodendron, 15-35 parts of Toad Venom, 15-35 parts of Aconitum, 15-35 parts of Galla Chinensis, 5-25 parts of Catechu, 5-25 parts of Borneol, 5-25 parts of Amber, 5-25 parts of Dragon Bone and 2-15 parts of Licorice.

[0059] Preferably, the Chinese medicine composition is composed of the following Chinese medicinal materials in parts by weight: 25-35 parts of Indigo, 5-12 parts of Phellodendron, 20-30 parts of Toad Venom, 20-30 parts of Aconitum, 20-30 parts of Gallnut, 10-20 parts of Catechu, 10-20 parts of Borneol, 10-20 parts of Amber, 10-20 parts of Dragon Bone, and 5-12 parts of Licorice.

[0060] Preferably, the Chinese medicine composition is composed of the following Chinese medicinal materials in parts by weight: 32 parts of Indigo Naturalis, 8 parts of Phellodendron Amurense, 24 parts of Toad Venom, 24 parts of Aconitum Kusnezoffii, 24 parts of Galla Chinensis, 16 parts of Catechu, 16 parts of Borneol, 16 parts of Amber, 16 parts of Dragon Bone, and 8 parts of Licorice.

[0061] Preferably, the particle size of the traditional Chinese medicine composition is ≤150 μm.

[0062] Another aspect of the present invention is to provide a Chinese medicine preparation for treating recurrent oral ulcers. The Chinese medicine preparation is prepared from the above Chinese medicine composition, or is prepared by adding pharmaceutically acceptable excipients to the above Chinese medicine composition.

[0063] The Chinese medicine composition of the present invention can be added with some pharmaceutically acceptable excipients as needed, and the Chinese medicine preparation is prepared by conventional pharmaceutical technology. The Chinese medicine preparation includes external dosage forms and internal dosage forms. Various conventional excipients such as thickeners, moisturizers, film-forming agents, such as glycerol, liquid paraffin, carbomer, polyvinyl alcohol, etc. are added to the raw materials to prepare external preparations such as powders, sprays, ointments, gels, films, tinctures, mouthwashes, mouthwash tablets, etc.; various conventional excipients such as diluents, disintegrants, lubricants, such as microcrystalline cellulose, lactose, cross-linked polyvinylpyrrolidone, magnesium stearate, etc. can also be added to the raw materials to prepare internal preparations such as oral liquids, decoctions, capsules, granules, granules, tablets, pills, etc.

[0064] Preferably, in order to make the raw materials of the drug better exert their efficacy and reduce toxic and side effects, the raw materials are made into powders or sprays for external use, but these cannot be used to limit the scope of protection of the present invention.

[0065] Another aspect disclosed in the present invention is to provide a method for preparing a Chinese medicine preparation for treating recurrent oral ulcers. The active pharmaceutical ingredient of each Chinese medicine composition is processed by traditional pharmaceutical technology, such as the following processing method:

[0066] S1: grind each of the above Chinese medicinal materials respectively and pass through a No. 6 sieve to obtain fine powder of each Chinese medicinal material;

[0067] S2: Mix thoroughly according to the weight ratio and the equal-increment method;

[0068] S3: Pass the mixed powder through a No. 5 sieve five times and shake to mix well.

[0069] Or the following method:

[0070] S1: Weigh each of the above Chinese medicinal materials and place them in a container;

[0071] S2: Add 3-8 times the weight of water to the container and boil for 3 times, each time for 2 hours, to obtain an extract;

[0072] S3: Filter and concentrate into extract;

[0073] S4: Using the above extract as the active ingredient, adding the above auxiliary materials when necessary, and preparing a Chinese medicine preparation according to conventional pharmacy techniques.

[0074] Or the following method:

[0075] S1: Weigh each of the above Chinese medicinal materials and place them in a container;

[0076] S2: Add 3-8 times the weight of ethanol to the container and reflux and extract for 3 times, each time for 1 hour, and separate the extract;

[0077] S3: Filtration, filtration, distillation of ethanol from the solution, and concentration into an extract;

[0078] S4: Using the above extract as the active ingredient, adding the above auxiliary materials when necessary, and preparing a Chinese medicine preparation according to conventional pharmacy techniques.

[0079] Specifically, the technical solution of the present invention is described in detail through the following embodiments, but the following embodiments should not be understood as limiting the scope of protection of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the following descriptions and ideas. It is not necessary and impossible to list all the implementation methods here.

[0080] Example 1: Preparation of powder

[0081] By weight, the ingredients include 32 parts of Indigo, 8 parts of Phellodendron, 24 parts of Toad Venom, 24 parts of Aconitum, 24 parts of Gallnut, 16 parts of Catechu, 16 parts of Borneol, 16 parts of Amber, 16 parts of Dragon Bone and 8 parts of Licorice. Grind each Chinese herbal medicine separately and pass it through a No. 6 sieve to obtain fine powder of each Chinese herbal medicine, mix them thoroughly according to the equal incremental method according to the weight ratio, pass the mixed powder through a No. 5 sieve five times, shake and mix well to obtain a powder.

[0082] Example 2: Preparation of tablets

[0083] By weight, 30 parts of Indigo, 10 parts of Phellodendron, 22 parts of Toad Venom, 26 parts of Aconitum, 22 parts of Galla Chinensis, 18 parts of Catechu, 14 parts of Borneol, 18 parts of Amber, 14 parts of Dragon Bone and 10 parts of Licorice; grind each Chinese medicinal material separately and pass through No. 6 sieve to obtain fine powder of each Chinese medicinal material, mix them thoroughly according to the equal incremental method according to the weight proportion, add excipients microcrystalline cellulose, cross-linked polyvinylpyrrolidone and magnesium stearate, mix well, and make mouthwash tablets by direct powder tableting method.

[0084] Example 3: Preparation of ointment

[0085] By weight, 35 parts of Indigo, 5 parts of Phellodendron, 28 parts of Toad Venom, 20 parts of Aconite, 28 parts of Galla Chinensis, 12 parts of Catechu, 20 parts of Borneolum, 12 parts of Amber, 18 parts of Dragon Bone, and 6 parts of Licorice. Add 3-8 times the weight of ethanol and reflux and extract for 3 times, each time for 1 hour, take the extract, filter, distill the ethanol from the solution, concentrate it into an extract, add excipient Vaseline, stir evenly to make an ointment, and pack it.

[0086] Example 4: Preparation of granules

[0087] By weight, 28 parts of Indigo, 12 parts of Phellodendron, 20 parts of Toad Venom, 28 parts of Aconite, 20 parts of Galla Chinensis, 20 parts of Catechu, 12 parts of Borneolum, 20 parts of Amber, 12 parts of Dragon Bone, and 12 parts of Licorice. Take each Chinese herbal medicine, add 3-8 times the weight of water and decoct for 3 times, each time for 2 hours, to obtain an extract, filter, concentrate into an extract, add an appropriate amount of excipient dextrin, mix well, make granules, and package to obtain.

[0088] Example 5: Preparation of pills

[0089] By weight, 24 parts of Indigo, 12 parts of Phellodendron, 26 parts of Toad Venom, 22 parts of Aconite, 26 parts of Galla Chinensis, 14 parts of Catechu, 18 parts of Borneolum, 14 parts of Amber, 18 parts of Dragon Bone, and 10 parts of Licorice. Take each Chinese herbal medicine, add 3-8 times the weight of water and decoct for 3 times, each time for 2 hours, to obtain an extract, filter, concentrate into an extract, add excipient starch, stir evenly to make pills, and pack them.

[0090] Example 6: Experimental verification

[0091] Example 1 was used as the test drug for pharmacodynamics test verification, and the commercially available watermelon frost was selected as the positive control. The test results are as follows:

[0092] 1. Experimental verification of the healing effect of oral ulcers in rats

[0093] 1.1 Establishment of oral ulcer model

[0094] 108 healthy male SD rats were selected and randomly divided into 6 groups, namely normal group, model group, positive drug Guilin Xiguashuang group, low, medium and high dose groups of the tested drug, with 18 rats in each group. The rats were placed in a room with alternating day and night, temperature and humidity (24±2℃ and 40-70%) for three days of adaptive feeding and normal diet. They were anesthetized by intraperitoneal injection of Shutai 50 (0.75g / kg) and xylazine hydrochloride (0.01g / kg). A 5mm diameter absorbent cotton ball soaked in 50% glacial acetic acid was placed close to the mucosa of the lower lip corner of the rat. After continuous pressing for 60s, the cotton ball was quickly removed and rinsed with 5mL of normal saline to establish an oral ulcer model (normal saline was used instead of glacial acetic acid in the normal group, and other operation steps were the same). After 24h, the inflammation of the local mucosa was observed. If a red and swollen pseudomembrane was observed, it indicated that an ulcer had formed.

[0095] 1.2 Administration

[0096] The drug was administered on the day of successful modeling. The positive group was administered by sprinkling twice a day (equivalent to 0.50 g / kg), and the low, medium, and high dose groups were administered by sprinkling 1, 2, and 3 times a day (equivalent to 0.25, 0.50, and 0.75 g / kg), respectively, for 4 consecutive days. The normal group and the model group did not receive any treatment. No food or water was allowed within 2 hours after medication, and food and water were allowed freely at other times.

[0097] 1.3 General Observation

[0098] After the model was successfully established, the changes in the appearance, spirit and general condition of the animals were observed. The results showed that the rats in the normal group were sensitive, with shiny back hair, normal bowel movements and activities; the rats in the model group were slow to react, with wet lips, drooling, rough and forked hair, and loose stools; the rats in the positive group and the test drug group were sensitive to reaction, shiny back hair, and normal activities.

[0099] 1.4 Changes in body mass

[0100] After the model was successfully established, the changes in the rats’ body weight were recorded. Figure 1 .

[0101] On the second day of the experiment, compared with the normal group, the body weight changes of the model group, the positive group and the test drug groups were significantly decreased (P < 0.05), indicating that the glacial acetic acid treatment caused pain and discomfort in the rats, resulting in a decrease in the body weight of the rats;

[0102] On the third day of the experiment, compared with the model group, the changes in body weight in the positive group and each dose group of the test drug were significantly increased (P < 0.05), indicating that the administration of appropriate drug treatment can relieve oral discomfort in rats and reduce the weight loss of rats;

[0103] On the fifth day of the experiment, compared with the model group, the body weight of rats in the high-dose group was significantly increased (P < 0.05), but there was no statistically significant difference compared with the normal group.

[0104] On the 7th day of the experiment, compared with the model group, the body weight of rats in the medium-dose group was significantly increased (P < 0.05), but there was no statistically significant difference compared with the normal group.

[0105] The results suggested that the test drug treatment could accelerate the recovery of body weight in rats.

[0106] 1.5 Observation of ulcer wound healing

[0107] After the model was successfully established, the healing of the ulcer wounds in the rats was observed. Figure 2 .

[0108] The oral mucosal surface of rats in the normal group was smooth at each time point, without edema or congestion ( Figure 2 A, B, C).

[0109] On the third day of the experiment, the model group, positive group and each dose group of the tested drug had edema in the modeling area, forming a yellow-white pseudomembrane ( Figure 2 D, G, J, M, P);

[0110] On the 6th day of the experiment, the yellow-white pseudomembrane in the model group had not yet fallen off, and local congestion was severe ( Figure 2 E); The yellow-white pseudomembrane in the positive group and the low- and medium-dose groups of the test drug became thinner and partially fell off ( Figure 2 H, K, N); The yellow-white pseudomembrane in the high-dose group of the test drug has completely fallen off, the swelling has been reduced, and the congestion around the tissue has been reduced ( Figure 2 Q);

[0111] On the 9th day of the experiment, the yellow-white pseudomembrane in the model group had not completely fallen off, which was significantly improved compared with the 6th day ( Figure 2 F); The pseudomembrane in the positive group and the test drug dose groups completely fell off, the ulcer was basically healed, the swelling disappeared, the surrounding tissue congestion disappeared, and the appearance was no significantly different from the normal group ( Figure 2 I, L, O, R).

[0112] The results showed that the test drug treatment could significantly accelerate the healing of oral ulcers and verify that oral ulcers have self-healing properties.

[0113] 1.6 Histopathological observation of ulcer

[0114] Three rats were randomly selected from each group on the 3rd, 6th, and 9th day after the start of the experiment, and mucosal specimens were obtained. The mucosal specimens were rinsed with physiological saline and immediately fixed in 4% paraformaldehyde solution. After the tissues were embedded in paraffin, they were sliced ​​into 5 μm sections, stained with HE, and then observed and analyzed under an optical microscope. The results are shown in the figure. Figure 3 The oral mucosal epithelium of rats in the normal group was intact and continuous, and there was no pathological change such as vascular congestion and a large number of inflammatory cell infiltration in the lamina propria ( Figure 3 A, B, C).

[0115] On the third day of the experiment, the epithelial structure of the mucosa in the model group, positive group and each dose group of the test drug was destroyed and disappeared, with fibrous exudation on the surface, vacuolar degeneration of cells, and dense inflammatory cell infiltration in the ulcer site, mainly neutrophils and lymphocytes ( Figure 3 D, G, J, M, P).

[0116] On the sixth day of the experiment, the epithelium in the model group showed a repair response, but inflammatory cell infiltration was obvious, mostly lymphocytes ( Figure 3 E); New granulation tissue was produced in the positive group and the low and medium dose groups of the test drug, and the epithelial cell layer increased, but inflammatory cells were still infiltrated ( Figure 3 H, K); The basal layer of the high-dose group was gradually repaired, the infiltration of inflammatory cells was significantly reduced, and the mucosal tissue structure tended to be intact ( Figure 3 N).

[0117] On the 9th day of the experiment, the mucosal epithelium in the model group was initially repaired, but the thickness was uneven and the layers were disordered ( Figure 3 F); The mucosal epithelium of the positive group and the test drug groups was completely healed, with uniform thickness and clear layers, and there was no significant difference from the normal group ( Figure 3 I, L, O, R).

[0118] The results showed that the test drug treatment could significantly accelerate the healing of oral ulcers and verify that oral ulcers have self-healing properties.

[0119] 1.7 Determination of the levels of inflammatory factors bFGF, IL-2, IL-6 and TNF-α in local ulcer tissue

[0120] Three animals were randomly selected from each group and killed on the 3rd, 6th, and 9th day after the start of the experiment. Normal mucosa was cut from the normal group, and ulcer tissue mucosa was cut from the other groups. The tissue was rinsed with pre-cooled saline to remove residual blood, and the mucosa was cut into pieces with small ophthalmic scissors. The operation should be performed in an ice water bath. After being placed in an EP tube and weighed, NP-40 lysis solution was added with a pipette. The volume of the lysis solution was 10 times the weight of the mucosa. The EP tube was placed in a beaker filled with ice water, and the mucosa was fully crushed with a cell ultrafine grinder. The crushed tissue homogenate was placed in a high-speed centrifuge, centrifuged at 4°C and 5000r / min for 20 minutes, and then the supernatant was removed with a pipette and stored in a -20°C refrigerator for later use. The contents of bFGF, IL-2, IL-6 and TNF-α in the supernatant were determined according to the instructions of the ELISA kit. The results are as follows. Figure 4-7 .

[0121] On the third day of the experiment, compared with the normal group, the levels of bFGF and IL-2 in oral ulcer tissues of the model group, positive group and each dose group of the test drug were significantly decreased (P < 0.05), and the levels of IL-6 and TNF-α were significantly increased (P < 0.05), indicating that the model was successfully established.

[0122] On the 6th day of the experiment, compared with the model group, the levels of bFGF and IL-2 in the positive group and each dose group of the test drug increased significantly (P < 0.05), and the levels of IL-6 and TNF-α decreased significantly (P < 0.05).

[0123] On the 9th day of the experiment, compared with the normal group, there were no significant differences in the levels of bFGF, IL-2, IL-6 and TNF-α in oral ulcer tissues between the positive group and each dose group of the test drug. Compared with the model group, the levels of bFGF and IL-2 were still significantly increased (P < 0.05), and the levels of IL-6 and TNF-α were still significantly decreased (P < 0.05).

[0124] 2. Experimental verification of the analgesic effect on oral ulcers in rats

[0125] 2.1 Establishment of a model for measuring pain threshold using mechanical stimulation

[0126] Eighteen healthy male SD rats were selected and randomly divided into six groups, namely, a normal group, a model group, a positive drug Guilin Xiguashuang group, and a low-, medium-, and high-dose group of the test drug, with three rats in each group. The rats were placed in a room with alternating day and night, and the temperature and humidity were (24±2°C and 40-70%) for three days of adaptive feeding and a normal diet. In order to stably expose the fornix area of ​​the oral mucosa of the rats, they were anesthetized by intraperitoneal injection of Shutai 50 (0.75g / kg) and xylazine hydrochloride (0.01g / kg), and then the rats were pierced with a ring. After the ring was pierced, the rats were first adapted for one week. After the behavior was stable for one week, a 6g weight was added to enable the mucosa to be stably exposed. The rats were placed in a handmade black plastic box for 10 minutes a day. After two weeks of continuous training, the oral ulcer modeling and medication were carried out according to the above-mentioned "1.1" and "1.2" methods. The ring piercing and opening behavior training are shown in the figure. Figure 8 .

[0127] 2.2 Determination of pain threshold in rats by Von Frey method

[0128] A group of VonFrey wires (0.02, 0.04, 0.07, 0.16, 0.4, 0.6, 1, 2, 4 and 6g) were used to stimulate the oral mucosa to measure the pain threshold. In order to prevent damage to the mucosa, a maximum of 6g of VonFrey wire was used for measurement. The measurements were performed on the first day of the experiment, which was the day of modeling, and after the last administration on the second, fifth and ninth days of the experiment. Before the test, the rats were placed in a homemade plastic box for 10 minutes. After the rats' behavior stabilized, VonFrey wires were used to stimulate the mucosa of the stably exposed oral ulcer area, and the behavior of the rats struggling and attempting to escape was defined as a positive reaction. When positive behavior was found, a smaller needle was used to try again. The mechanical threshold was defined as 3 positive behaviors after 5 measurements. Each measurement was separated by at least 30s. The results are shown in the figure. Fig. 9 On the 2nd, 5th and 9th days of the experiment, compared with the normal group and the model group, the pain threshold caused by mechanical stimulation in each dose group of the test drug was significantly increased (P < 0.05), and was better than the positive group. This shows that the appropriate amount of the test drug treatment can significantly relieve the pain in the oral ulcer area of ​​rats induced by glacial acetic acid.

[0129] The above test results show that the Chinese medicine composition of the present invention can significantly accelerate the healing of oral ulcers in rats, reduce inflammatory reactions and relieve pain, and compared with the positive drug watermelon frost, the Chinese medicine composition of the present invention has a better analgesic effect.

[0130] The above is only a preferred embodiment of the present invention. It should be pointed out that, for ordinary technicians in this field, several improvements, modifications and substitutions can be made without departing from the principles of the present invention and without creative work. These improvements, modifications and substitutions are also included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating recurrent oral ulcers, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicines in parts by weight: 32 parts of Indigo Naturalis, 8 parts of Phellodendron Amurense, 24 parts of Toad Venom, 24 parts of Aconitum Kusnezoffii, 24 parts of Galla Chinensis, 16 parts of Catechu, 16 parts of Borneol, 16 parts of Amber, 16 parts of Dragon Bone and 8 parts of Licorice.

2. A Chinese medicine composition for treating recurrent oral ulcers according to claim 1, characterized in that: The particle size of the Chinese medicine composition is ≤150 μm.

3. A Chinese medicine preparation for treating recurrent oral ulcers prepared from the Chinese medicine composition according to claim 1 or a Chinese medicine composition with pharmaceutically acceptable excipients added thereto.

4. A Chinese medicine preparation for treating recurrent oral ulcers according to claim 3, characterized in that: Chinese medicine preparations are in the form of external or internal dosage forms, including: The external dosage form is one of powder, spray, ointment, gel, film, tincture, mouthwash, and mouthwash tablets; The oral dosage form is one of oral liquid, decoction, capsule, granule, tablet and pill.

5. A Chinese medicine preparation for treating recurrent oral ulcers according to claim 3, characterized in that: Pharmaceutically acceptable excipients include one or more of thickeners, humectants, film formers, diluents, disintegrants, lubricants, colorants, sweeteners, binders, or antioxidants.

6. A method for preparing a Chinese medicine powder for treating recurrent oral ulcers, characterized in that: At least the following steps are included: S1: Weigh indigo, phellodendron, toad venom, aconite, gallnut, catechu, borneol, amber, dragon bone, and liquorice respectively according to the weight proportions described in claim 1, crush them and pass through a No. 6 sieve to obtain fine powder of each Chinese medicinal ingredient; S2: The above-mentioned fine powders are mixed thoroughly in equal increments; S3: Pass the mixed powder through a No. 5 sieve five times and shake to mix well.

7. A method for preparing a Chinese medicine extract for treating recurrent oral ulcers, characterized in that: At least the following steps are included: S1: Weigh indigo naturalis, phellodendron amurense, toad venom, aconite, gallnut, catechu, borneol, amber, dragon bone, and liquorice in proportions according to claim 1, and place in a container; S2: Add 3-8 times the weight of water to the container and boil for 3 times, each time for 2 hours, to obtain an extract; S3: Filter the extract and concentrate it into an extract.

8. A method for preparing a Chinese medicine extract for treating recurrent oral ulcers, characterized in that: At least the following steps are included: S1: Weigh indigo naturalis, phellodendron amurense, toad venom, aconite, gallnut, catechu, borneol, amber, dragon bone, and liquorice in proportions according to claim 1, and place in a container; S2: Add 3-8 times the weight of ethanol to the container and reflux and extract for 3 times, each time for 1 hour, and separate the extract; S3: Filter the extract, distill out the ethanol from the solution and concentrate it into an extract.

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