CN110302337B

CN110302337B - Pharmaceutical composition for treating periodontal and mucosal diseases, and preparation method and application thereof

Info

Publication number: CN110302337B
Application number: CN201910695832.2A
Authority: CN
Inventors: 金钊; 左渝陵; 严航; 郑涛; 艾黄萍
Original assignee: Chengdu University of Traditional Chinese Medicine
Current assignee: Chengdu University of Traditional Chinese Medicine
Priority date: 2019-07-30
Filing date: 2019-07-30
Publication date: 2021-10-29
Anticipated expiration: 2039-07-30
Also published as: CN110302337A

Abstract

The invention provides a pharmaceutical composition for treating periodontal and mucosal diseases of oral cavity, which is prepared from the following raw material medicines in parts by weight: 5-60 parts of turmeric, 3-30 parts of coptis root and 10-60 parts of angelica dahurica. The invention further discloses a preparation method and application of the pharmaceutical composition. The pharmaceutical composition has better therapeutic effect on periodontitis, oral speckle diseases, oral lichen planus and other oral periodontal and mucosal diseases. The pharmaceutical composition has the advantages of novel formula, simple composition, low cost, obvious curative effect, no toxic or side effect, difficult tolerance generation and the like, and provides a new medicine selection for clinically treating patients with periodontitis, oral speckle diseases, oral lichen planus and oral leukoplakia.

Description

Pharmaceutical composition for treating periodontal and mucosal diseases, and preparation method and application thereof

Technical Field

The invention relates to the field of traditional Chinese medicines, in particular to a pharmaceutical composition for treating oral periodontal and mucosal diseases, a preparation method and application thereof.

Background

Along with the improvement of life of people, the oral hygiene and the oral diseases are more and more important to be nursed, and the common oral periodontal diseases in clinic are periodontitis, gingivitis and the like; common oral mucosa diseases are oral lichen planus, oral mucosa leukoplakia and the like. Although various treatment means and medicines exist in clinic at present, good effects are not obtained.

Periodontal disease is a common disease frequently occurring in the oral cavity, and can cause gingival bleeding, periodontal pus discharge, tooth loosening and even tooth falling, and the chewing and digestion functions are seriously affected. Meanwhile, it is a high risk factor for cardiovascular diseases, diabetes, premature birth of newborn and the like. Regarding the etiology of periodontal disease, modern medicine considers plaque bacteria and their products as their initiating factors, and therefore focuses on treatment for bacterial etiology, but lacks effective measures in enhancing the body's systemic regulatory ability. Therefore, it is one of the research focuses in recent years to find new drugs for controlling periodontal disease plaque microorganisms among traditional Chinese medicines or natural substances.

Burning Mouth Syndrome (BMS) is a benign condition that manifests as burning pain in the oral mucosa, tongue, but is not accompanied by significant intraoral examination abnormalities, signs of clinical damage, and histological changes. About 2% to 3.7% of the population suffers from this disease, with the number of women being about 7 times that of men. Postmenopausal women are the vast majority, and certainly, premenopausal and perimenopausal women may also suffer from the disease. The burning sensation is also present in any part of the oral cavity, but for most patients, the burning sensation is usually located on the tip and side of the tongue, the back of the tongue, the palate, and the mucous membrane inside the lips. The patient may feel a hot sensation from hot food, and may experience a sour, bitter, or metallic taste. It also feels dry in mouth. Is usually progressive, with no known triggers or behaviors. The pathogenesis is complex, and the possible induction factors comprise local, systemic, mental and nervous factors and the like.

The oral speckle diseases are clinically common Oral Lichen Planus (OLP) and oral white speckle lesion, and are chronic superficial skin mucosa inflammation diseases. According to domestic and foreign literature, all human races have OLP, and the population with OLP is mainly adults over 40 years old, and young people and children account for about 2% -3% of the total number of patients. The prevalence of OLP in adults is about 0.51%. Epidemiological studies report that patients with oral lichen planus have a higher chance of becoming cancerous than normal. The degree of deterioration is reported to be 0.2% to 1.5% abroad. In the study of the correlation between the clinical morphology of oral lichen planus and canceration, many authors mention that atrophic, ulcerated and erosive forms of oral lichen planus are at greater risk of canceration. The site of the cancer is usually found in the tongue, and the gingival and buccal mucosa.

At present, glucocorticoid, immunopotentiator, vitamin and the like are mostly adopted for treating the diseases in western medicine, the curative effect is unclear, and the long-term administration can generate larger side effect. In recent years, Chinese medicine has achieved initial results in the research of oral diseases. Therefore, it is one of the research focuses in recent years to find new drugs for controlling periodontal disease plaque microorganisms among traditional Chinese medicines or natural substances.

Chinese patent 201711262589.2 discloses a Chinese medicinal composition for treating periodontitis, which comprises the following raw materials in parts by weight: 5-9 parts of red peony root, 2-5 parts of wooly datchmanspipe herb, 10-15 parts of blighted wheat, 12-15 parts of honeysuckle, 6-9 parts of coptis chinensis, 2-4 parts of white curculigo rhizome, 5-7 parts of barbed skullcap herb, 3-5 parts of diverse wormwood herb, 8-10 parts of paniculate swallowwort root, 6-8 parts of cooked rhubarb, 6-10 parts of baical skullcap root, 2-5 parts of salvia miltiorrhiza, 3-4 parts of rhizoma corydalis processed with vinegar, 8-10 parts of chastetree fruit, 6-8 parts of plantain seed, 2-4 parts of drynaria rhizome, 1-3 parts of plantain herb, 6-7 parts of cowherb seed, 2-4 parts of largetrifolioliolioliolioliolious bugbane rhizome, 4-6 parts of mussel leaf and 4-5 parts of tylophora; chinese patent 201510430158.7 discloses a Chinese medicinal composition for treating female climacteric, which is prepared from the following raw materials by oral administration: 10-20 parts of salvia miltiorrhiza, 10-20 parts of motherwort, 10-20 parts of astragalus membranaceus, 10-20 parts of rhizoma anemarrhenae, 10-20 parts of gypsum, 10-20 parts of polygala tenuifolia, 10-20 parts of bighead atractylodes rhizome, 10-20 parts of rhizoma cyperi, 10-20 parts of radix puerariae, 10-20 parts of scutellaria baicalensis, 10-20 parts of fructus forsythiae, 10-20 parts of fructus aurantii, 10-20 parts of fructus evodiae, 10-20 parts of radix paeoniae alba, 10-20 parts of pericarpium citri reticulatae, 10-20 parts of herba epimedii and 10-20 parts of lophatherum gracile; the external medicine comprises: 10-20 parts of indigo naturalis, 10-20 parts of radix rehmanniae, 10-20 parts of fructus forsythiae, 10-20 parts of herba artemisiae scopariae, 10-20 parts of mint, 10-20 parts of oldenlandia diffusa, 10-20 parts of radix angelicae and 10-20 parts of fructus evodiae; chinese patent 201210114967.3 discloses a compound preparation for treating oral mucosa lichen planus, the preparation is composed of 16-28 parts of lophatherum gracile, 16-28 parts of rhizoma cimicifugae, 16-28 parts of toad skin, 16-28 parts of coptis chinensis, 16-28 parts of rose root, 16-28 parts of symplocos chinensis, 12-25 parts of fructus amomi, 12-25 parts of trogopterus dung, 12-25 parts of elecampane, 12-25 parts of desmodium, 12-25 parts of hericium erinaceus, 12-25 parts of cantharis, 6-18 parts of panax notoginseng, 6-18 parts of lotus stamen, 6-18 parts of solanum melongena root, 6-18 parts of waxberry bark, 6-18 parts of artificial bezoar, 6-18 parts of vitamin C6, 1-12 parts of fructus choerospondiatis, 1-12 parts of saffron, 1-12 parts of ginseng flower, 1-12 parts of gleditsia sinensis fruit, 1-12 parts of loquat leaf and 1-12 parts of water chestnut. The above-mentioned patent has better clinical curative effect in treating periodontal disease and mucous membrane disease, but the above-mentioned patent has more medicinal herbs, higher production cost, and it is difficult to control the impurity content in the industrialized mass production, so a medicinal composition with less medicinal herbs and remarkable clinical curative effect is urgently needed in clinic. At present, no reports about treating oral inflammatory diseases by using turmeric, coptis chinensis and angelica dahurica are found.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide the pharmaceutical composition for treating the diseases of the periodontal and the mucous membrane of the oral cavity, which has simple composition, novel formula and definite curative effect and can be used for treating periodontitis, oral speckle diseases, oral lichen planus and oral leukoplakia. The pharmaceutical composition has the advantages of low cost, good curative effect, no toxic or side effect, difficult tolerance generation, convenient administration and carrying, and the like.

The invention aims to provide a pharmaceutical composition for treating periodontal and mucosal diseases in the oral cavity, and a preparation method and application thereof.

The invention provides a pharmaceutical composition for treating periodontal and mucosal diseases of oral cavity, which is prepared from the following raw material medicines in parts by weight: 5-60 parts of turmeric, 3-30 parts of coptis root and 10-60 parts of angelica dahurica.

Further, the pharmaceutical composition is prepared from the following raw materials in parts by weight: 5-30 parts of turmeric, 3-20 parts of coptis root and 10-30 parts of angelica dahurica.

Further, the pharmaceutical composition is prepared from the following raw materials in parts by weight: 5-20 parts of turmeric, 3-15 parts of coptis root and 10-20 parts of angelica dahurica.

Further, the pharmaceutical composition is prepared from the following raw materials in parts by weight: 5 parts of turmeric, 3 parts of coptis root and 10 parts of angelica dahurica.

Further, the pharmaceutical composition is prepared from the following raw materials in parts by weight: 10 parts of turmeric, 9 parts of coptis root and 15 parts of angelica dahurica.

Further, the pharmaceutical composition is prepared from the following raw materials in parts by weight: 25 parts of turmeric, 15 parts of coptis root and 30 parts of angelica dahurica.

Furthermore, the pharmaceutical composition is a preparation prepared by taking the medicinal powder of the raw material medicines, the water or organic solvent extract of the raw material medicines as active ingredients and adding pharmaceutically acceptable auxiliary materials according to the weight ratio.

Further, the preparation is an oral preparation, an inhalation preparation or an parenteral preparation.

Further, the oral preparation is tablets, capsules, pills, powder, granules, syrup, oral liquid and the like; the parenteral preparation is freeze-dried powder injection, injection and the like; preferably, the adjuvant of the preparation is filler, disintegrant, lubricant, suspending agent, adhesive, sweetener, flavoring agent, preservative, matrix, etc. The filler comprises: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; the disintegrating agent comprises: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crospolyvinylpyrrolidone, low-substituted hydroxypropylcellulose, croscarmellose sodium, etc.; the lubricant comprises: magnesium stearate, sodium lauryl sulfate, talc, silica, and the like; the suspending agent comprises: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, and the like; the adhesive comprises starch slurry, polyvinylpyrrolidone, hydroxypropyl methylcellulose, etc.; the sweetener comprises: saccharin sodium, aspartame, sucrose, sodium cyclamate, glycyrrhetinic acid, and the like; the flavoring agent comprises: sweeteners and various essences; the preservative comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroacetidine acetate, eucalyptus oil, etc.; the matrix comprises: PEG6000, PEG4000, insect wax, etc.

The invention also provides a method for preparing the pharmaceutical composition, which comprises the following steps:

a. weighing raw materials in each weight ratio;

b. pulverizing the raw materials directly, or extracting with water or organic solvent, and adding pharmaceutically acceptable adjuvants or auxiliary components.

The invention also provides application of the pharmaceutical composition in preparing a medicament for treating oral periodontal and mucosal diseases.

Further, the oral inflammatory diseases are periodontitis, oral speckle diseases, oral lichen planus and oral leukoplakia.

The invention is composed of three medicines of turmeric, coptis root and dahurian angelica root.

Turmeric (Latin's name: Curcuma longa L.) is also named as Yujin, Baoding Xiang, Happy, Huangjiang, etc. The plant height of a perennial herb plant of Curcuma of Zingiberaceae of order Curcuma, which belongs to the order Curcuma, is 1-1.5 m, the rhizome is developed, the root is thick and strong, and the tail end is expanded to form a root tuber; the blades are long round or oval, and the top ends of the blades are short and tapered; the bract is oval or oblong, light green, blunt at the top end, and the corolla is light yellow; the flowering phase is 8 months; turmeric root tuber can promote qi circulation, remove blood stasis, dredge meridians and alleviate pain. It can be used for treating abdominal distention and pain, shoulder pain, pain in arm, heart pain, puerperal blood pain, skin sore, tinea, menoxenia, amenorrhea, and traumatic injury. But also can extract yellow edible dye. Coptis chinensis, (scientific name: Coptis chinensis Franch.) is also called rhizoma coptidis, rhizoma coptidis and rhizoma coptidis which belong to Ranunculaceae and belong to perennial herb plants, leaves are base-shaped, hard and paper, the shape of an oval triangle is triangular, three cracks are completely formed, the shape of a central cracked oval diamond is deep-cracked, sharp sawteeth are arranged on the edge, and lateral cracked pieces are not deep-cracked by 2; the petiole is 5-12cm long. Wild or cultivated in valley cool and wet shading forest with elevation of 1000-1900 m. Has the effects of clearing heat, eliminating dampness, purging fire and removing toxicity. The taste is extremely bitter, and the common words of cloud that the Coptis is eaten by dumb people and the Coptis cannot be eaten by people are that the taste is achieved; coptis root, rhizoma Coptidis, being cold in nature and bitter in taste, has strong smell, can ascend and descend, enters the yin-middle-yang meridians as well as the hand-shaoyin meridians. It is used for purging heart fire, and also used for purging heart fire; removing damp-heat in middle energizer and removing damp-heat in middle energizer; all sores are essential, and the third is also; rheumatism and rheumatoid diseases are removed; acute contagious conjunctivitis, and acute contagious conjunctivitis; six also in stopping the middle part with blood. Zhang Zhongjing is used for treating diarrhea and heart diseases such as nine kinds of epigastric stuffiness and five kinds of diarrhea. Radix Angelicae Dahuricae (academic name: Angelica Dahurica) is a plant belonging to the family Umbelliferae, Angelica. Are distributed in northeast and northeast China of China, grow in areas with an altitude of 200-1,500 m, and generally grow under forests, forest borders, stream sides, shrubs and valley grasslands. The other names are dahurian angelica root (Chinese higher plant identification), pubescent angelica root (Beijing plant), Dahuo, Xiangdahuo, herba ramosensis, Maqinbei (northeast) and Langshan celery (Heilongjiang), and the dahurian angelica root is recorded in Shennong Bencao Jing of east Han, famous white and fragrant, and listed as a middle-quality product. Pungent in flavor and warm in nature, it is indicated for "red and white bleeding, blood blocking and swelling of yin, cold and heat, wind invading eyes and tear-out, growing skin, moistening and moistening as face fat for women. "famous physicians bibliography": the angelica dahurica is grown in the east of the river, the valley, the lower part of the valley, and the roots of February and August are dried suddenly. Its functions are dispelling wind-damp, promoting blood circulation, expelling pus, promoting granulation and relieving pain. It can be used for treating headache, toothache, nasosinusitis, hemorrhoid, leucorrhea with reddish discharge, carbuncle, cellulitis, pyocutaneous disease, and skin pruritus, mainly involving yangming, with the effects of inducing resuscitation, expelling pathogenic wind, and relieving pain. It is indicated for swelling and pain of gum, cheek and toothache.

The pharmaceutical composition is used for treating periodontal and mucosal diseases in the oral cavity, can be used for periodontitis, oral speckle diseases, oral lichen planus and oral leukoplakia, and has definite drug effect and excellent clinical application prospect.

Obviously, many modifications, substitutions, and variations are possible in light of the above teachings, without departing from the basic technical spirit of the present invention, as defined by the following claims.

The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.

Drawings

FIG. 1 the incremental effect of different concentrations of pharmaceutical compositions on hPDHF

Detailed Description

EXAMPLE 1 preparation of a pharmaceutical composition of the invention

(1) Raw materials: 5g of turmeric, 3g of coptis root and 10g of angelica dahurica.

(2) The preparation method comprises the following steps:

step 1: adding 6-8 times of water into the medicinal materials, soaking for 0.5-1 hour, then decocting for 0.5-1 hour, filtering to obtain a water decoction, and keeping the dregs for later use.

Step 2: and (3) adding water in an amount which is 6-8 times that of the medicinal materials into the medicinal residues in the step (1), decocting for 1-1.5 hours, filtering to obtain a water decoction, and discarding the medicinal residues.

And step 3: and (3) combining the water decoctions obtained in the step (1) and the step (2), concentrating the mixture into an extract, and then drying the extract in vacuum to obtain dry paste.

And 4, step 4: and (3) crushing the dry paste prepared in the step (3), adding 30g of starch serving as an auxiliary material, granulating, adding 2g of magnesium stearate, 20g of dextrin and 20g of microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.

EXAMPLE 2 preparation of pharmaceutical compositions of the invention

(1) Raw materials: 20g of turmeric, 9g of coptis root and 25g of angelica dahurica.

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed, added with 280g of starch as auxiliary materials for granulation, 20g of magnesium stearate, 100g of dextrin and 100g of microcrystalline cellulose, uniformly prepared into granules, and tabletted to obtain tablets.

EXAMPLE 3 preparation of a pharmaceutical composition of the invention

(1) Raw materials: 25g of turmeric, 12g of coptis root and 30g of angelica dahurica.

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed, and then 260g of starch, 20g of magnesium stearate, 100g of dextrin and 100g of microcrystalline cellulose which are auxiliary materials are added for granulation, and granules are uniformly prepared and are tabletted to obtain tablets.

EXAMPLE 4 preparation of a pharmaceutical composition of the invention

(1) Raw materials: 20g of turmeric, 6g of coptis root and 30g of angelica dahurica.

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed, and then 210g of starch, 20g of magnesium stearate, 100g of dextrin and 100g of microcrystalline cellulose which are auxiliary materials are added for granulation, and granules are uniformly prepared and are tabletted to obtain tablets.

EXAMPLE 5 preparation of a pharmaceutical composition of the invention

(1) Raw materials: 15g of turmeric, 6g of coptis root and 25g of angelica dahurica.

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed, and then added with 210g of starch as auxiliary materials for granulation, 16g of magnesium stearate, 80g of dextrin and 80g of microcrystalline cellulose, and the mixture is uniformly prepared into granules and tabletted to obtain tablets.

EXAMPLE 6 preparation of a pharmaceutical composition of the invention

(1) Raw materials: 10g of turmeric, 6g of coptis root and 20g of angelica dahurica.

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed, added with 160g of starch as auxiliary materials for granulation, 10g of magnesium stearate, 100g of dextrin and 100g of microcrystalline cellulose, uniformly prepared into granules, and filled into capsules to obtain capsules.

EXAMPLE 7 preparation of a pharmaceutical composition of the invention

(1) Raw materials: 15g of turmeric, 6g of coptis root and 20g of angelica dahurica.

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed and then added with pharmaceutically acceptable auxiliary materials to prepare the tablets commonly used in pharmacy.

EXAMPLE 8 preparation of a pharmaceutical composition of the invention

(1) Raw materials: 20g of turmeric, 6g of coptis root and 25g of angelica dahurica.

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed and added with pharmaceutically acceptable auxiliary materials to prepare a pharmaceutically common capsule.

EXAMPLE 9 preparation of a pharmaceutical composition of the invention

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed and then added with pharmaceutically acceptable auxiliary materials to prepare the granules commonly used in pharmacy.

EXAMPLE 10 preparation of a pharmaceutical composition of the invention

(1) Raw materials: 30g of turmeric, 10g of coptis root and 40g of angelica dahurica.

(2) The preparation method comprises the following steps: the dry paste obtained by the preparation method of the embodiment 1 is crushed and then added with pharmaceutically acceptable auxiliary materials to prepare the oral liquid commonly used in pharmacy.

EXAMPLE 11 preparation of a pharmaceutical composition of the invention

(2) The preparation method comprises the following steps: is prepared into decoction according to the conventional process.

EXAMPLE 12 preparation of a pharmaceutical composition of the invention

(2) The preparation method comprises the following steps: the water decoctions obtained in the step 1 and the step 2 of the embodiment 1 are combined and filtered, the filtrate is concentrated and added with polyvinyl alcohol-124, propylene glycol, azone and the like, and the gel is prepared according to the preparation method of the gel.

The beneficial effects of the invention are demonstrated by specific clinical tests and cytotoxicological experiments.

Test example 1 clinical efficacy of the pharmaceutical composition of the present invention on lichen planus

1. Case data

All cases were selected from patients treated by the outpatient department of the department of stomatology who met the diagnostic criteria for oral lichen planus. Dividing into two groups according to a random parallel control method, wherein the treatment groups comprise 30 cases, wherein 14 cases of men and 16 cases of women are aged 35-70 years; the control group comprises 30 cases, wherein 13 cases of men and 17 cases of women are aged 35-70 years. The differences in sex, age, course of disease, etc. of the two groups of patients are not statistically significant and are comparable.

1.1 diagnostic criteria

Diagnostic criteria: the method is drawn to the 3 rd edition of oral mucosa pathology in 2008 and the first edition of oral mucosa drug treatment essence edition in 2010. (1) Symptoms are: the oral mucosa is pearl white stripe, has smooth surface, and is interlaced into various shapes such as net, tree, ring, cord or spot. Erythema, congestion, erosion, atrophy, blisters, pigmentation, etc., can also occur simultaneously, and multiple disorders overlap and transform. The mucous membrane is soft and has unchanged elasticity. It usually occurs in the cheek, tongue, gum and palate, and is usually left-right symmetrical. (2) And (4) disease detection: during biopsy, the basal cells are liquefied and denatured under the microscope, and a large number of lymphocytes below the basal membrane infiltrate into a band shape. The epithelium and lamina propria are mostly gelatinous corpuscles. The epithelial nail is jagged, the spinous layer is thickened or atrophied, the granular layer is obviously hyperplastic, and the epithelium is hyperkeratotic or parakeratosis; the method is drawn up according to the 1984 edition of Chinese medicine diagnostics and the 2008 edition of Chinese and Western medicine combined mucosal pathology. (1) Systemic symptoms: sallow complexion, flushed cheeks, dry eyes and eyes, dry mouth and lips, dry mouth and throat, occasional parageusia, red lips, dry nails, dizziness and tinnitus, insomnia and dreamful sleep, irritability, tidal fever and night sweat, soreness and weakness of waist and knees, feverish palms and soles, menstrual disorder, small menstrual blood volume, spermatorrhea, dry stool and dark urine, thin tongue, reddish tongue with little saliva, smooth coating, dry and yellow tongue coating, and thready and rapid or deep thready and weak pulse. (2) Oral mucosa local symptoms and signs: the oral local mucosa is gray, striped or netted, has desquamation, incrustation and itching feeling, and is sometimes accompanied by hyperemia and erosion, burning pain or slight pain.

1.2 inclusion criteria

(1) Patients who meet the diagnostic criteria for western medicine oral lichen planus; (2) patients who accord with the diagnosis standard of the yin deficiency and fire excess syndrome of traditional Chinese medicine; (3) the age is 35-70 years old; (4) those within 3d of course; (5) informed consent, volunteers were tested. The process of obtaining informed consent complies with GCP regulations.

1.3 exclusion criteria

(1) Patients diagnosed with recurrent oral ulceration, oral leukoplakia, oral cancer; (2) those with allergic or anaphylactic constitution to known components of the test agent; (3) patients with serious diseases and mental diseases such as severe gravity, liver, kidney, hematopoietic system and immune system; (4) patients with serious infection, diabetic ketoacidosis and hyperkalemia are combined; (5) those with a history of allergy or allergic constitution such as drugs, food, pollen, etc.; (6) preparing a pregnant, pregnant or lactating woman; (7) other clinical trials were enrolled within the last 3 months.

1.4 criteria for shedding

All patients who filled out informed consent and screened for eligibility to enter the trial were withdrawn from the clinical trial.

Common causes are: an adverse event; lack of efficacy; back test protocol (including poor compliance); missed visits (including patient self-withdrawal); the patient withdraws informed consent; exfoliation due to other causes.

Statistical principles for cases of abscission: (1) taking adverse reaction statistics to calculate if the falling is caused by adverse reaction; (2) patients who fall off automatically due to ineffectiveness should be listed for statistics of therapeutic effect; (3) patients can be cured after less than 1 course of treatment, and no exfoliation cases are listed; (4) the treatment process is effective, but the whole treatment course cannot be completed, and patients with missed visits are not listed in treatment effect statistics. For the cases of exfoliation, intention analysis should be done.

2. Treatment regimens

Treatment groups: the preparation method of the pharmaceutical composition of the embodiment 6 of the invention is adopted to prepare 0.5 g/capsule according to the crude drug calculation. The taking method comprises the following steps: the preparation is administered 3 times a day, 3 granules each time.

Control group: the chloroquine phosphate tablet is orally taken at a dose of 0.125 g/time and 2 times/d. 1 month of treatment course, 2 courses of treatment were observed in both groups.

In the treatment period, the poor prosthesis and the filling body are removed from two groups of cases, local sharp tooth tips are removed, teeth are cleaned, diet is light, spicy food, tobacco, wine and the like are forbidden, sufficient sleep is kept, and psychotherapy is given.

3. Observation of therapeutic effects

The rate of reduction or disappearance of lesions in the oral mucosa; incidence of adverse outcome (proportion of oral cancer development). The evaluation was performed 1 time each at the end of the treatment and at the end of the follow-up visit. The traditional Chinese medicine syndrome curative effect is as follows: recording for 1 time every 3 months; and (3) quality of life investigation: carrying out quality of life investigation according to the SF-36 scale; relapse rate after drug withdrawal: the proportion of patients with symptoms and abnormalities after stopping taking the medicine; the evaluation of curative effect includes the near-term curative effect and the long-term curative effect, and the evaluation of the health economic index is carried out on all the treatment cases at the same time.

The evaluation standard of the curative effect is as follows: and (3) healing: the erosion is completely healed, white lines or gray lines are formed, congestion is relieved, and subjective symptoms disappear; the effect is shown: the erosion face is healed without congestion, white lines or gray lines are faded over 2/3, and the symptoms are obviously relieved; improvement: the white lines or gray lines of the oral cavity are reduced below 2/3, and the symptoms are partially relieved; and (4) invalidation: there was no change before and after treatment. The total effective rate is calculated according to the cure and obvious effect.

4. Safety observation index

Comprises routine examination of blood, urine and stool, renal function and electrocardiogram examination, and analysis of adverse reaction incidence, adverse reaction type and treatment.

5. Statistical method

Processing with SPSS20.0 software, and averaging the measured data

The representation shows that the counting data is relatively tested by chi-square by using t test, P is less than 0.05, and the statistical significance is achieved.

6. Results

6.1 Total effective rate comparison of two groups of patients

TABLE 1 comparison of the Total effective rates of two groups of patients

As a result: the treatment group had a clear advantage over the control group.

And (4) conclusion: compared with the conventional western medicines for treating oral lichen planus, the pharmaceutical composition has remarkable drug effect.

6.2 adverse reactions and safety indices

No serious adverse reaction occurs in both groups of patients; before and after the test, the general vital signs, the electrocardiogram, the liver and kidney functions and three major routine of the two groups of patients have no obvious abnormal changes.

Test example 2 cytotoxicity test study of pharmaceutical composition of the present invention

1. Experimental Material

Table 2 table of experimental materials

2. Experimental methods

Digesting human periodontic fibroblast (hPDLF) in logarithmic growth phase with 0.25% trypsin containing 0.02% EDTA, and blowing the bottom of a culture bottle with DMEM culture solution containing 10% newborn calf serum to prepare single cell suspension; trypan blue staining counting, the cell activity is more than or equal to 95 percent, and the cell concentration is adjusted to 1 multiplied by 10 by nutrient solution⁵Each well was inoculated with 100. mu.l of cell suspension per well in 96-well culture plates, and 200. mu.l was replenished with nutrient solution, resulting in three plates. 37 ℃ and 5% CO₂The culture was carried out overnight.

The next day, the cell plate is taken out, and cells are observed to be uniformly distributed at the bottom of the holes of the cell culture plate under an inverted microscope to reach about 50 percent of the bottom area. 100. mu.l of the culture supernatant was discarded from each well, and the CELL culture wells of three plates were filled with the CELL culture medium of example 11 of the present invention so that the dilutions were 1/25, 1/50, 1/100, 1/200 and 0(CELL), respectively. The liquid volume in each culture well was 200. mu.l, and each concentration well was triplicated. At 37 ℃ 5% CO₂Culturing under the condition. Taking out the culture plate 4-6 h before the culture time is over (24h, 48h and 72h), sequentially adding 10 mu l of MTT solution into each well, and continuously incubating until the culture is over. Measuring at 570nm wavelength selected by enzyme-linked immunosorbent assayThe absorbance (A value) of each well was determined. Relative cell proliferation rate (RGR) was calculated according to the formula, where RGR is a test group/a control group × 100%.

3. Results of the experiment

TABLE 3 Effect of the pharmaceutical compositions of the present invention on human gingival fibroblast proliferation

And (4) conclusion: the pharmaceutical composition provided by the invention has a promotion effect on the increment of hPDLF, which indicates that the drug is safe.

In conclusion, clinical tests and pharmacodynamic tests prove that the pharmaceutical composition can be used for treating periodontitis, oral speckle diseases, oral lichen planus, oral leukoplakia and other oral periodontal and mucosal diseases, and has safe use and definite drug effect.

The pharmaceutical composition is prepared by combining turmeric, coptis root and angelica dahurica according to a certain dosage ratio, and the dosage ratio among the drugs is the dosage range which is finally determined through a plurality of different experimental screens. Compared with the common western medicines, the pharmaceutical composition has more remarkable drug effect, and compared with the traditional Chinese medicines in the prior art, the pharmaceutical composition has the advantages of reduced number of medicinal ingredients and reduced dosage of the medicines, and experiments prove that the clinical curative effect is not weakened, but the total effective rate is improved, so the pharmaceutical composition has unexpected technical effects compared with the prior art. The pharmaceutical composition has simple composition and novel formula, and the raw material medicines have lower prices, so compared with the prior art, the pharmaceutical cost is lower.

Claims

1. A pharmaceutical composition for treating oral lichen planus, comprising: the traditional Chinese medicine is prepared from the following raw materials in parts by weight: 5-20 parts of turmeric, 3-15 parts of coptis root and 10-20 parts of angelica dahurica.

2. The pharmaceutical composition of claim 1, wherein: the traditional Chinese medicine is prepared from the following raw materials in parts by weight: 5 parts of turmeric, 3 parts of coptis and 10 parts of angelica dahurica.

3. The pharmaceutical composition of claim 1, wherein: the traditional Chinese medicine is prepared from the following raw materials in parts by weight: 10 parts of turmeric, 9 parts of coptis and 15 parts of angelica dahurica.

4. The pharmaceutical composition of claim 1, wherein: the traditional Chinese medicine is prepared from the following raw materials in parts by weight: 25 parts of turmeric, 15 parts of coptis and 30 parts of angelica dahurica.

5. The pharmaceutical composition according to claims 1 to 4, wherein: the preparation is prepared by taking the medicinal powder of the raw material medicines or the water extract of the raw material medicines in the weight ratio as active ingredients and adding pharmaceutically acceptable auxiliary materials.

6. The pharmaceutical composition of claim 5, wherein: the preparation is an oral preparation, an inhalation preparation or an external administration preparation.

7. The pharmaceutical composition of claim 6, wherein: the oral preparation is tablets, capsules, pills, powder, granules, syrup or oral liquid; the external administration preparation is gel.

8. The pharmaceutical composition of claim 5, wherein: the adjuvants of the preparation are bulking agent, disintegrating agent, lubricant, suspending agent, binder, sweetener, correctant, antiseptic or matrix; the fillers are: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose or sucrose; the disintegrating agent is: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crospolyvinylpyrrolidone, low-substituted hydroxypropylcellulose or croscarmellose sodium; the lubricant is: magnesium stearate, sodium lauryl sulfate, talc or silica; the suspending agent is: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, or hydroxypropyl methylcellulose; the adhesive is: starch slurry, polyvinylpyrrolidone or hydroxypropyl methylcellulose; the sweetener is: saccharin sodium, aspartame, sucrose, sodium cyclamate, or glycyrrhetinic acid; the flavoring agent is: sweeteners and flavors; the preservative is: parabens, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroacetidine acetate or eucalyptus oil; the matrix is: PEG6000, PEG4000 or insect wax.

9. A process for preparing a pharmaceutical composition according to any one of claims 1 to 8, characterized in that: it comprises the following steps:

a. weighing raw materials in each weight ratio;

b. pulverizing the raw materials into powder, or extracting with water, and adding pharmaceutically acceptable adjuvants or adjuvant ingredients.

10. Use of a pharmaceutical composition according to any one of claims 1 to 8 in the manufacture of a medicament for the treatment of oral lichen planus.