Application of traditional Chinese medicine composition in preparation of medicine for treating or preventing hand-foot-and-mouth disease

Abstract

The invention relates to application of a traditional Chinese medicine composition in a medicine for treating or preventing a hand-foot-and-mouth disease. The traditional Chinese medicine composition is prepared from 100 to 400 parts of honeysuckle flower, 75 to 300 parts of radix puerariae, 100 to 400 parts of fructus forsythiae, 60 to 240 parts of fructus arctii, 60 to 240 parts of herba menthae, 60 to 240 parts of radix isatidis, 75 to 300 parts of rhizoma anemarrhenae, 50 to 200 parts of rhizoma cimicifugae and 30 to 120 parts of cicada slough. The traditional Chinese medicine composition can significantly reduce the death rate of ICR suckling mice infected with hand-foot-mouth viruses, improve the death protection rate, prolong the average survival days of the suckling mice, improve and prolong the life rate, and relieve clinical disease symptoms after the suckling mice are infected.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, relates to a new use of a traditional Chinese medicine composition, and specifically relates to an application of a traditional Chinese medicine composition in preparing a medicine for treating or preventing hand, foot and mouth disease. Background Art

[0002] Hand, foot and mouth disease (HFMD) is a common infectious disease caused by enterovirus. The main clinical features of this disease are herpes on the hands, feet and mouth, so it is commonly known as HFMD. Most patients have mild symptoms, but a few patients may develop complications such as myocarditis, pulmonary edema, aseptic encephalitis, meningoencephalitis, etc. Some severely ill children progress rapidly and are prone to death. HFMD mainly occurs in children under 5 years old. The incubation period is usually 2 to 10 days, with an average of 3 to 5 days.

[0003] Acute onset, fever, mouth pain, anorexia, scattered herpes or ulcers on the oral mucosa, mostly located on the tongue, buccal mucosa and hard forehead, and may also affect the soft palate, gums, tonsils and pharynx. Maculopapular rashes appear on the hands, feet, buttocks, arms and legs, and then turn into herpes. There may be inflammatory redness around the herpes, and there is less fluid in the blisters. There are more on the hands and feet, and on the back of the palm. In a few cases (especially those under 3 years old), the disease progresses rapidly, and meningitis, encephalitis (brainstem encephalitis is the most dangerous), encephalomyelitis, pulmonary edema, circulatory disorders, etc. occur about 1 to 5 days after the onset of the disease. In very few cases, the condition is critical and can cause death, and surviving cases may have sequelae.

[0004] Treatment for hand, foot and mouth disease is aimed at relieving symptoms. Medications such as acetaminophen or ibuprofen can relieve pain and fever. Teeth should be brushed gently with a soft-bristled toothbrush and rinsed with salt water. Patients should eat a soft diet and avoid acidic or salty foods. Although mouth sores can be painful, it is important to drink enough fluids to avoid dehydration. Summary of the invention

[0005] To solve the above technical problems, the present invention provides an application of a Chinese medicine composition in the preparation of a medicine for treating or preventing hand, foot and mouth disease. The Chinese medicine composition comprises: 100-400 parts of honeysuckle, 75-300 parts of kudzu root, 100-400 parts of forsythia, 60-240 parts of burdock fruit, 60-240 parts of mint, 60-240 parts of isatis root, 75-300 parts of anemarrhena, 50-200 parts of cicada shell, and 30-120 parts of cicada shell.

[0006] Furthermore, the Chinese medicine composition includes: 200-240 parts of honeysuckle, 150-180 parts of kudzu root, 200-240 parts of forsythia, 120-150 parts of burdock fruit, 120-150 parts of mint, 120-150 parts of isatis root, 150-180 parts of anemarrhena, 100-120 parts of cicada shell, and 60-80 parts of cicada shell.

[0007] Preferably, the Chinese medicine composition comprises: 200 parts of honeysuckle, 150 parts of kudzu root, 200 parts of forsythia, 120 parts of burdock fruit, 120 parts of mint, 120 parts of isatis root, 150 parts of anemarrhena, 100 parts of cicada shell, and 60 parts of cicada shell. The present invention also provides a use of the Chinese medicine composition as described above in the preparation of a drug against coxsackie virus.

[0008] The above composition, if in grams, can be made into a preparation with a dosage of 50-1000 times. For example, as tablets, 1000 tablets can be made, and each dosage can be 1-20 tablets, which can be taken 50-1000 times in total. If as granules, 125 bags can be made, and 1-2 bags can be taken each time, which can be taken 62.5-125 times in total.

[0009] The above composition is based on weight proportions, and can be increased or decreased in corresponding proportions during production. For example, large-scale production can be measured in kilograms or tons, and small-scale production can also be measured in milligrams. The weight can be increased or decreased, but the weight ratio of the raw medicinal materials between the components remains unchanged.

[0010] The above weight ratios are obtained through scientific screening. For special patients, such as those with severe or mild illnesses, obese or thin patients, the ratio of the components can be adjusted accordingly, with an increase or decrease of no more than 100%, and the efficacy remains unchanged.

[0011] Specifically, the medicine for treating or preventing hand, foot and mouth disease includes pharmaceutically acceptable excipients or additives.

[0012] Specifically, the pharmaceutically acceptable excipients or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

[0013] Specifically, the dosage form of the drug includes an oral dosage form, an injection dosage form or an external dosage form.

[0014] The Chinese medicine preparation of the present invention can be any pharmaceutically acceptable dosage form, and these dosage forms include: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, lozenges, granules, electuary, pills, powders, pastes, pills, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, and patches. The preparation of the present invention is preferably an oral dosage form, such as: capsules, tablets, oral liquids, granules, pills, powders, pills, pastes, etc. Most preferably, tablets.

[0015] The preparation of the present invention is used in a dosage determined according to the patient's condition, and can be taken three times a day, 1-20 doses each time, such as 1-20 bags, granules or tablets.

[0016] The optional preparation method of the Chinese medicine preparation of the present invention is as follows:

[0017] Volatile oils of forsythia and mint are extracted by steam distillation, the obtained volatile oils are included in beta-cyclodextrin to obtain inclusion compounds, and the extract is filtered and set aside; after the oil is extracted, the residues are extracted with water, filtered, and the filtrate is combined with the steam distillation extract and set aside; the remaining seven ingredients are decocted with water, the extract is concentrated, cooled, ethanol is added, allowed to stand, filtered, the ethanol is recovered, dried, and dry powder is obtained, the volatile oil inclusion compound is added to obtain active pharmaceutical ingredients; the ingredients are prepared alone or mixed with pharmaceutically acceptable carriers to prepare the Chinese medicine preparation of the present invention according to conventional pharmaceutical preparation techniques.

[0018] For the preparation of tablets, the above active ingredients can be added with starch, sucrose, magnesium stearate and microcrystalline cellulose, mixed evenly, dry granulated, dried, granulated, tableted, film-coated and packaged.

[0019] Preferably, the preparation method of the traditional Chinese medicine composition comprises the following steps: adding 10 times the amount of water to two ingredients, Forsythia suspensa and mint, extracting volatile oil by steam distillation, the extraction time is 3.0 hours, filtering the extract and setting aside; the obtained volatile oil is included in 8 times the amount of β-cyclodextrin at 60°C for 3.0 hours to obtain an inclusion compound, which is set aside; adding 8 times the amount of water to the residue after oil extraction, extracting for 2.0 hours, filtering, combining the filtrate with the steam distillation liquid, and setting aside; adding water to seven ingredients including Pueraria lobata and boiling twice, each time for 2.0 hours, with 11 times the amount of water for the first time and 10 times the amount of water for the second time, boiling for 2.0 hours; The liquid is filtered, and the filtrates are combined and set aside; the above two filtrates are combined, concentrated under reduced pressure to a relative density of 1.07-1.09, cooled to room temperature, ethanol is slowly added to make the alcohol content reach 70%, fully stirred, allowed to stand for 18 hours, filtered, the filtrate is decompressed to recover ethanol until there is no alcohol taste, the drug solution is diluted with water to a relative density of 1.03-1.05, spray-dried to obtain dry powder, the above volatile oil inclusion compound, starch, sucrose, appropriate amount of magnesium stearate and microcrystalline cellulose are added, mixed, dry granulated, dried, granulated, tableted, film-coated, and packaged to obtain.

[0020] The composition of the present invention can significantly reduce the mortality rate of ICR suckling mice infected with hand, foot and mouth disease virus, improve the death protection rate, prolong the average survival days of suckling mice, improve the life extension rate, and alleviate the clinical symptoms of suckling mice after infection, indicating that the traditional Chinese medicine composition has a good therapeutic effect on hand, foot and mouth disease. DETAILED DESCRIPTION

[0021] As mentioned above, the present invention aims to provide a use of a Chinese medicine composition in the preparation of a drug for treating or preventing hand, foot and mouth disease. The following will be described in detail in conjunction with the content of a specific experiment.

[0022] The following experiments, if no specific conditions are specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The APIs or excipients, reagents or instruments used, if the manufacturer is not specified, are all conventional products that can be purchased commercially. Unless otherwise specified, all percentages, ratios, proportions or parts are by weight.

[0023] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention.

[0024] Example 1 Preparation of the Composition Tablets of the Present Invention

[0025] The Chinese medicine composition of this embodiment is prepared from the following raw materials: 200g of honeysuckle, 150g of kudzu root, 200g of forsythia, 120g of burdock fruit, 120g of mint, 120g of isatis root, 150g of anemarrhena, 100g of cicada shell, and 60g of cicada shell.

[0026] The Chinese medicine composition is prepared according to the following method:

[0027] The above nine herbs, forsythia and mint, are added with 10 times the amount of water, and the volatile oil is extracted by steam distillation for 3.0 hours. The extract is filtered and set aside; the obtained volatile oil is included with 8 times the amount of β-cyclodextrin at 60°C for 3.0 hours to obtain an inclusion compound, which is set aside; after oil extraction, the residue is added with 8 times the amount of water, extracted for 2.0 hours, filtered, and the filtrate is combined with the steam distillation liquid for use; the seven herbs including Pueraria root are decocted with water twice, each time for 2.0 hours, 11 times the amount of water for the first time and 10 times the amount of water for the second time, the decoction is filtered, the filtrates are combined and set aside; the above two filtrates are combined and concentrated under reduced pressure to a relative The density is 1.07-1.09 (60°C), cooled to room temperature, ethanol is slowly added to make the alcohol content reach 70%, fully stirred, allowed to stand for 18 hours, filtered, the filtrate is decompressed (-0.085Mpa, 70-80°C) to recover ethanol until there is no alcohol taste, the drug solution is diluted with water to a relative density of 1.03-1.05 (20°C), spray dried to obtain dry powder, the above-mentioned volatile oil inclusion compound is added to obtain a composite intermediate, starch, sucrose, an appropriate amount of magnesium stearate and microcrystalline cellulose are added, mixed, dry granulated, dried, granulated, tableted, film coated, packaged, and the product is obtained.

[0028] Pharmacological tests

[0029] Experimental Example 2 In vivo efficacy experiment of Chinese medicine composition against Coxsackie virus

[0030] 1. Experimental Materials

[0031] 1.1 Animals

[0032] SPF-grade ICR mice were selected, and the formal infection experiment used 13-14-day-old suckling mice, both male and female.

[0033] 1.2 Drugs

[0034] Chinese medicine composition: the intermediate prepared according to Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; ribavirin granules, Sichuan Baili Pharmaceutical Co., Ltd., batch number: 230318, specification: 50 mg / bag.

[0035] 2. Dosage design

[0036] The daily dosage of the Chinese medicine composition is 14.64g of crude drug / day. According to the body surface area conversion method, the equivalent dose for mice is about 3g of crude drug / kg (calculated as 14.64g of crude drug / 60kg*12.3). According to the 1 / 2:1:2 dose gradient, the low, medium and high doses are 1.5, 3 and 6g of crude drug / kg respectively.

[0037] The daily dosage of ribavirin granules is 450 mg / day. Based on the body surface area conversion method, the equivalent dose for mice is approximately 92 mg / kg (calculated as 450 mg / 60 kg*12.3).

[0038] 3. Experimental Methods

[0039] The suckling mice at 13-14 days old were randomly divided into a normal control group, a virus control group, a ribavirin granule group (92 mg / kg), and a low-, medium-, and high-dose group of the Chinese medicine composition (1.5, 3, and 6 g crude drug / kg), with 10 mice in each group.

[0040] CVA16-MA was diluted with PBS (CVA16-MA is a mouse-adapted strain obtained by adaptive passage of the shzh05-1 strain of Coxsackievirus A16 (from the Institute of Pathogenic Biology, Chinese Academy of Medical Sciences) in mice) and 200ul (equivalent to 3500 TCID 50 ) were infected with virus, and the normal control group was intraperitoneally injected with an equal volume of PBS.

[0041] The first administration was carried out 1 hour after virus infection, and the drug was administered by gavage once a day for 7 consecutive days. The normal control group and virus control group were gavaged with an equal volume of pure water.

[0042] The death protection rate, life extension rate, average survival days, and clinical symptom scores were used as observation indicators, and the death and clinical symptoms of the suckling mice were observed for 14 consecutive days. The scoring criteria for clinical symptoms of suckling mice are: normal is 0 points; reduced activity is 1 point; arched back and erect hair are 2 points; hind limb weakness is 3 points; hind limb paralysis is 4 points; death is 5 points. The calculation method of death protection rate and life extension rate is: death protection rate (%) = (mortality rate of virus control group-mortality rate of experimental group) / mortality rate of virus control group*100%; life extension rate (%) = (average survival days of experimental group-average survival days of virus control group) / average survival days of virus control group*100%.

[0043] 4. Experimental Results

[0044] After the CVA16 virus solution was injected intraperitoneally to create a model, all the suckling mice in the virus control group died 13 days after infection, with a mortality rate of 100% and an average survival of 9.1 days. Compared with the virus control group, by the end of the observation, 7 suckling mice in the low-dose group of the Chinese medicine composition died, with a death protection rate of 30%, an average survival of 10.4 days, and a life extension rate of 14.3%; 6 suckling mice in the medium-dose group of the Chinese medicine composition died, with a death protection rate of 40%, an average survival of 11.8 days, and a life extension rate of 29.7%; 4 suckling mice in the high-dose group of the Chinese medicine composition died, with a death protection rate of 60%, an average survival of 12.2 days, and a life extension rate of 34.1%. It shows that the Chinese medicine composition has a certain protective effect on the survival of suckling mice and can prolong the average survival of infected suckling mice. The results are shown in Table 1.

[0045] Table 1 Protective effect of the Chinese medicine composition of the present invention on suckling mice infected with CVA16

[0046]

[0047] After CVA16 virus infected 13-14 day old ICR suckling mice, the suckling mice in the virus control group became ill on the same day, died on the 6th day, and all died on the 13th day. Compared with the virus control group, the low, medium and high dose groups of the Chinese medicine composition all had a certain protective effect. Although some mice also showed reduced activity on the same day, the disease process was slower than that of the virus control group, and 3, 4 and 6 mice survived at the end of the observation, respectively, and the mouse disease score was always lower than that of the virus control group during the observation period. The results are shown in Table 2.

[0048] Table 2 Effect of the Chinese medicine composition of the present invention on clinical symptom scores of suckling mice infected with CVA16

[0049]

[0050] The Chinese medicinal composition proposed by the invention can significantly reduce the death caused by Coxsackie virus infection in ICR suckling mice, improve the death protection rate, prolong the average survival days, improve the life extension rate, and alleviate the clinical symptoms of suckling mice after infection.

[0051] The above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. Use of a Chinese medicine composition in preparing a drug for treating or preventing hand, foot and mouth disease, characterized in that: The Chinese medicine composition comprises, by weight, 100-400 parts of honeysuckle, 75-300 parts of kudzu root, 100-400 parts of forsythia, 60-240 parts of burdock fruit, 60-240 parts of mint, 60-240 parts of isatis root, 75-300 parts of anemarrhena, 50-200 parts of cicada shell, and 30-120 parts of cicada shell.

2. The use according to claim 1, characterized in that: The traditional Chinese medicine composition comprises: 200-240 parts of honeysuckle, 150-180 parts of kudzu root, 200-240 parts of forsythia, 120-150 parts of burdock fruit, 120-150 parts of mint, 120-150 parts of isatis root, 150-180 parts of anemarrhena, 100-120 parts of cicada shell, and 60-80 parts of cicada shell.

3. The use according to claim 1, characterized in that: The traditional Chinese medicine composition comprises: 200 parts of honeysuckle, 150 parts of kudzu root, 200 parts of forsythia, 120 parts of burdock fruit, 120 parts of mint, 120 parts of isatis root, 150 parts of anemarrhena, 100 parts of cicada shell, and 60 parts of cicada shell.

4. The use according to claims 1-3, characterized in that The medicine for treating or preventing hand, foot and mouth disease includes pharmaceutically acceptable excipients or additives.

5. The use according to claim 1, characterized in that: The medicine is selected from tablets, capsules, granules, pills, ointments, suspensions, solutions, suppositories or patches.

6. The use according to claim 1, characterized in that: The preparation method of the traditional Chinese medicine composition comprises the following steps: extracting volatile oil from two herbs, forsythia and mint, by steam distillation, encapsulating the obtained volatile oil with beta-cyclodextrin to obtain an inclusion compound, filtering the extract and setting aside; extracting the residues after oil extraction with water, filtering, combining the filtrate with the steam distillation extract and setting aside; decocting the remaining seven herbs with water, concentrating the extract, cooling, adding ethanol, standing, filtering, recovering ethanol, drying, obtaining dry powder, and adding the above-mentioned volatile oil inclusion compound.

7. The use according to claim 1, characterized in that: The preparation method of the Chinese medicine composition comprises the following steps: adding 10 times of water to two ingredients of forsythia and mint, extracting volatile oil by steam distillation, the extraction time is 3.0 hours, filtering the extract and setting aside; encapsulating the obtained volatile oil with 8 times of beta-cyclodextrin at 60°C for 3.0 hours to obtain an inclusion compound, which is set aside; adding 8 times of water to the residue after oil extraction, extracting for 2.0 hours, filtering, combining the filtrate with the steam distillation medicinal liquid and setting aside; adding water to the remaining seven ingredients and decocting them twice, each time for 2.0 hours, the first time with 11 times of water, the second time with 10 times of water, filtering the decoction, combining the filtrate and setting aside; combining the above two filtrates, concentrating under reduced pressure to a relative density of 1.07-1.09, cooling to room temperature, slowly adding ethanol to make the alcohol content reach 70%, fully stirring, standing for 18 hours, filtering, recovering ethanol from the filtrate under reduced pressure until there is no alcohol taste, diluting the medicinal liquid with water to a relative density of 1.03-1.05, spray drying to obtain dry powder, and adding the above volatile oil inclusion compound.

8. Use of a Chinese medicine composition in the preparation of a drug against Coxsackie virus, characterized in that: The Chinese medicine composition comprises, by weight, 100-400 parts of honeysuckle, 75-300 parts of kudzu root, 100-400 parts of forsythia, 60-240 parts of burdock fruit, 60-240 parts of mint, 60-240 parts of isatis root, 75-300 parts of anemarrhena, 50-200 parts of cicada shell, and 30-120 parts of cicada shell.

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