Application of traditional Chinese medicine composition in preparation of influenza A (H1N1)

Abstract

The invention relates to an application of a traditional Chinese medicine composition in preparation of a medicament for influenza A (H1N1), which is characterized in that the traditional Chinese medicine composition is prepared from radix aconiti carmichaeli, rhizoma zingiberis, liquorice, honeysuckle, spina gleditsiae, humulus scandens, pogostemon cablin and pericarpium citri reticulatae. The composition disclosed by the invention can be used for remarkably reducing the lung index and reducing the content of cell factors IL-4 and IL-33 in lung tissues of infected mice, and has a relatively good treatment effect on influenza A (H1N1).

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 the use of a traditional Chinese medicine composition in preparing a medicine for influenza A (H1N1). Background Art

[0002] Influenza A (H1N1) is an acute respiratory infectious disease caused by influenza A (H1N1) virus infection. Initially, the World Health Organization (WHO) called this type of influenza "human swine flu", and later renamed it "influenza A (H1N1)". The general population is susceptible, and often manifests flu-like symptoms such as fever, sore throat, cough, sputum, runny nose, nasal congestion, headache, body aches, fatigue, etc. Most patients with mild symptoms can be cured after active and effective treatment, but patients with severe symptoms progress rapidly, may develop viral pneumonia, combined with respiratory failure, multiple organ damage, and even death, and the prognosis is poor. Influenza A (H1N1) is mainly transmitted through droplets such as sneezing and coughing, and can also be transmitted through direct or indirect contact with mucous membranes such as the mouth, nose, and eyes. It can also be infected by contact with objects contaminated by the virus. The overall mortality rate of patients is 2 / 10000 to 9 / 1000. In recent years, traditional Chinese medicine has unique advantages and development prospects in the prevention and treatment of influenza virus pneumonia, especially in the regulation of immune function. Summary of the invention

[0003] According to one aspect of the present invention, there is provided a use of a traditional Chinese medicine composition in the preparation of a drug for influenza A (H1N1), which comprises the following components in parts by mass: 10-30 parts of aconite root, 5-15 parts of dried ginger, 20-30 parts of liquorice, 10-20 parts of honeysuckle, 10-30 parts of Gleditsia sinensis thorns, 20-45 parts of Ipomoea australis, 10-15 parts of patchouli, and 5-15 parts of tangerine peel.

[0004] In the prescription, aconite, dried ginger and liquorice are the main drugs, honeysuckle, honeysuckle thorn and five-clawed dragon are the assistant drugs, patchouli is the adjuvant drug, and tangerine peel is the guiding drug. Specifically:

[0005] Aconite, dried ginger, and a large amount of licorice are the main drugs, warming the lower abdomen. Wuzhaolong, also known as Nanqi, nourishes the middle and replenishes qi, and is the minister drug. Together with the three main drugs, they support the positive energy; a large amount of licorice and Wuzhaolong strengthen the spleen and replenish qi, and are used together with the adjuvant drugs Patchouli and Tangerine Peel to aromaticize the evil of dampness and turbidity; honeysuckle clears heat and detoxifies, and expel evil. Wu Jutong "treats the upper Jiao like feathers, and it will not rise unless it is light", so only 10-20 parts of honeysuckle are used; honeysuckle and Gleditsia sinensis are both minister drugs. Wuzhaolong (Nanqi) and Gleditsia sinensis are the main components of Tounong Powder. Gleditsia sinensis and honeysuckle are used together to increase the function of clearing away epidemic toxins and draining pus.

[0006] In some embodiments, the following components are included by mass: 10-20 parts of aconite, 10-15 parts of dried ginger, 20-25 parts of licorice, 10-15 parts of honeysuckle, 10-20 parts of Gleditsia sinensis, 20-30 parts of Ipomoea australis, 10-12 parts of patchouli, and 5-10 parts of tangerine peel.

[0007] In some embodiments, the following components are included in parts by mass: 10-12 parts of aconite, 12-15 parts of dried ginger, 20-22 parts of licorice, 10-12 parts of honeysuckle, 10-12 parts of Gleditsia sinensis, 20-22 parts of Ipomoea australis, 10-12 parts of patchouli, and 5-6 parts of tangerine peel.

[0008] In some embodiments, the following components are included by mass: 10 parts of aconite, 15 parts of dried ginger, 20 parts of licorice, 10 parts of honeysuckle, 10 parts of Gleditsia sinensis, 20 parts of Ipomoea australis, 10 parts of patchouli, and 5 parts of tangerine peel.

[0009] In some embodiments, the drug further comprises pharmaceutically acceptable adjuvants or additives. Specifically, the pharmaceutically acceptable adjuvants or additives include fillers, disintegrants, lubricants, suspending agents, adhesives, sweeteners, flavoring agents, preservatives, matrices, including but not limited to starch, lactose, glucose, sodium carboxymethyl cellulose, ethyl cellulose and methyl cellulose, malt, gelatin, polyols (such as propylene glycol, glycerol, mannitol), compressed tablets, etc., to help improve the stability of the pharmaceutical composition or increase the activity, or produce an acceptable taste or smell in the case of oral administration.

[0010] In some embodiments, the aforementioned composition can be prepared into granules, tablets, capsules, pills, oral solutions, oral suspensions or oral emulsions using existing traditional Chinese medicine preparation methods, thereby facilitating clinical administration.

[0011] The preparation method of the traditional Chinese medicine composition comprises the following steps: taking aconite root, dried ginger, liquorice, honeysuckle, thorn of Gleditsia sinensis, five-clawed dragon, patchouli, and tangerine peel, adding 8 to 12 times of water equivalent to the total mass of the raw materials, heating to boiling, maintaining a slight boiling for 1 to 2 hours, and obtaining a first decoction and medicinal residues after separation; a second time, taking the medicinal residues obtained after the first decoction, adding 6 to 10 times of water equivalent to the total mass of the raw materials, heating to boiling, maintaining a slight boiling for 1 to 2 hours, and obtaining a second decoction and medicinal residues after separation; combining the first decoction and the second decoction to prepare a decoction, and reducing the pressure on the decoction filtrate to concentrate to obtain a clear paste, and crushing it.

[0012] According to another aspect of the present invention, there is provided a use of any of the aforementioned Chinese medicine compositions in the preparation of a medicament for treating influenza A (H1N1) pneumonia.

[0013] When the present invention is used as a drug for treating influenza A (H1N1), an oral solution can be used. Severe patients can be given one dose per day, divided into 2-3 oral or nasogastric administrations, once every 6-8 hours; critical patients can be given two doses per day, divided into two oral or nasogastric administrations in the morning and evening, once every 8-12 hours; mild patients can be given one dose per day, orally or nasogastric administration. Each dose is 150-250 ml.

[0014] When the medicine of the present invention is in the form of granules or tablets, the dosage is converted into a decoction piece dosage and then taken orally.

[0015] The composition of the present invention can significantly reduce the lung index, reduce the content of cytokines IL-4 and IL-33 in the lung tissue of infected mice, and has a good therapeutic effect on influenza A (H1N1). DETAILED DESCRIPTION

[0016] As mentioned above, the present invention aims to provide a use of a Chinese medicine composition in the preparation of a drug for influenza A (H1N1). The following will be described in detail in conjunction with the content of a specific experiment.

[0017] The following experiments, if no specific conditions are specified, are conducted under conventional conditions or conditions recommended by the manufacturer. The raw materials or excipients used, as well as the 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. Unless otherwise specified, the medicinal materials of the present invention can be raw products or processed products thereof without significantly affecting the overall effect of the prescription.

[0018] 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.

[0019] Example 1 Preparation of Chinese medicine composition

[0020] Take 10 parts of cooked aconite, 15 parts of dried ginger, 20 parts of roasted licorice, 10 parts of honeysuckle, 10 parts of Gleditsia sinensis, 20 parts of Ipomoea australis, 10 parts of Patchouli, and 5 parts of dried tangerine peel, add 8 times the total mass of water of the raw material, heat to boiling, keep slightly boiling for 1 hour, and separate to obtain the first decoction and medicinal residue; for the second time, take the medicinal residue obtained after the first decoction, add 8 times the total mass of water of the raw material, heat to boiling, keep slightly boiling for 1 hour, and separate to obtain the second decoction and medicinal residue; combine the first decoction and the second decoction to obtain a decoction, reduce the pressure and concentrate the decoction filtrate to obtain a clear paste, grind it into fine powder to obtain a traditional Chinese medicine composition, add an appropriate amount of maltodextrin, mix well, and granulate to obtain 1000g of granules, that is, to obtain traditional Chinese medicine composition granules.

[0021] Experimental Example 2 Therapeutic Effect of Chinese Medicine Composition on Pneumonia Model of Mice Infected with H1N1 Strain of Influenza Virus 1. Experimental Materials

[0022] 1.1 Animals

[0023] ICR mice, SPF grade, 70 mice, weighing 9-11 g, half male and half female.

[0024] Rearing environment: room temperature 22±1℃, humidity 40-50%. Males and females were reared in separate cages, 5 per cage / sex / group.

[0025] 1.2 Drugs

[0026] The Chinese medicine composition prepared in Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; Oseltamivir phosphate granules (Yichang East Sunshine Changjiang Pharmaceutical Co., Ltd., batch number 0651912300); Lianhua Qingwen granules (Beijing Yiling Pharmaceutical Co., Ltd., batch number 2012075); Isoflurane (Shanghai Yuyan Scientific Instrument Co., Ltd., batch number S200106); IL-4 (Shanghai ELISA Biological Co., Ltd., batch number ml063156); IL-4 (Thermo Fisher, batch number 230852-006).

[0027] 1.3 Instruments

[0028] Electronic balance (Shanghai Yueping Scientific Instrument Co., Ltd., model YP1002 MAX100g); electronic analytical balance (Mettler-Toledo Instrument Co., Ltd., model AL204 MAX210g); tissue homogenizer (MP Company, USA, model FastPre-24TM); low-temperature high-speed centrifuge (eppendorf company, Germany, model Eppendorf-5810R); multi-function microplate reader (PerkinElmer company, Germany, model Enspire).

[0029] 2. Dosage design

[0030] The daily dosage of the Chinese medicine composition is 100g of crude drug / day, and the clinical dosage is 1.67g of crude drug / kg. According to the body surface area conversion method, the equivalent dose for mice is 18.37g of crude drug / kg. According to the 1 / 4:1 / 2:1 dosing method, the low dose is 4.59g of crude drug / kg and the medium dose is 9.18g of crude drug.

[0031] The daily dose of oseltamivir phosphate granules is 150 mg, and the clinical dose is 2.5 mg / kg. According to the body surface area conversion method, the equivalent dose for mice is 27.5 mg / kg.

[0032] The daily dosage of Lianhua Qingwen Granules is 18g, and the clinical dosage is 0.3g / kg. According to the body surface area conversion method, the equivalent dose for mice is 3.3g / kg.

[0033] 3. Experimental Methods

[0034] 70 ICR mice of appropriate weight were randomly divided into 7 groups according to weight level, namely normal control group, model control group, oseltamivir phosphate granules group, Lianhua Qingwen granules group, and high, medium and low dose groups of Chinese medicine combination, with 10 mice in each group. Except for the normal control group, the mice were lightly anesthetized with isoflurane and 15 LD 50 Influenza virus liquid (H1N1 strain) was dripped into the nose for infection, 35 μL per mouse. The drug was administered on the day of infection, 0.2 mL / 10 g was gavaged once a day for 4 consecutive days. The normal control group and the model control group were gavaged with distilled water under the same conditions. On the 5th day, the mice in each group were weighed; the lungs were dissected and weighed, and the lung index and lung index inhibition rate were calculated; the lung tissues in the same part were taken, ground, centrifuged at 4000g for 15 minutes at 4°C, and the supernatant was taken for the detection of inflammatory factors IL-4 and IL-33.

[0035] Lung index (%) = lung wet weight (g) / body weight (g) × 100;

[0036] Lung index inhibition rate (%) = (mean lung index of model control group - mean lung index of drug group) / (mean lung index of model control group - mean lung index of normal control group) × 100.

[0037] 4. Statistical methods

[0038] The results were statistically analyzed using t-test.

[0039] 5. Experimental Results

[0040] 5.1 Effect on lung index

[0041] After mice were infected with influenza A (H1N1) virus (FM1 strain virus), the lung index of mice in the model control group was significantly increased, which was significantly different from that in the normal control group (P<0.01); the Chinese medicine composition was given for 4 days starting from the day of infection, and the lung index of the medium-dose group of the Chinese medicine composition was significantly reduced, which was significantly different from that in the model control group (P<0.05). The lung index inhibition rate of the medium-dose group of the Chinese medicine composition was %. See Table 1.

[0042] Table 1: Effects on lung index

[0043]

[0044]

[0045] Note: Compared with the normal control group, ## P<0.001; compared with the model control group, **P<0.01.

[0046] 5.2 Effects on cytokine levels in lung tissue

[0047] After mice were infected with influenza A (H1N1) virus (FM1 strain), the levels of IL-4 and IL-33 in the lung tissue of mice were significantly increased compared with the normal control group, with statistical differences (P<0.01); after 4 days of treatment with the Chinese medicine composition starting from the day of infection, the levels of IL-4 and IL-33 in high, medium and low doses were significantly reduced compared with the model control group, with statistical differences (P<0.01, P<0.05). See Table 2.

[0048] Table 2: Effects on cytokine levels in lung tissue

[0049]

[0050] 6. Experimental conclusion

[0051] The Chinese medicine composition can significantly inhibit the increase of lung index in infected mice and reduce the content of inflammatory factors IL-4 and IL-33 in lung tissue, indicating that the Chinese medicine composition has a good therapeutic effect on influenza A (H1N1).

[0052] 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 the preparation of a drug for influenza A (H1N1), characterized in that: The traditional Chinese medicine composition is prepared from the following components: 10-30 parts of aconite root, 5-15 parts of dried ginger, 20-30 parts of liquorice, 10-20 parts of honeysuckle, 10-30 parts of Gleditsia sinensis, 20-45 parts of Ipomoea australis, 10-15 parts of patchouli, and 5-15 parts of tangerine peel.

2. The use according to claim 1, characterized in that: The invention is prepared from the following raw material components by weight: 10-20 parts of aconite root, 10-15 parts of dried ginger, 20-25 parts of liquorice, 10-15 parts of honeysuckle, 10-20 parts of gleditsia thorn, 20-30 parts of cinnamon bark, 10-12 parts of patchouli and 5-10 parts of tangerine peel.

3. The use according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following components by weight: 10-12 parts of aconite root, 12-15 parts of dried ginger, 20-22 parts of liquorice, 10-12 parts of honeysuckle, 10-12 parts of Gleditsia sinensis, 20-22 parts of Ipomoea australis, 10-12 parts of patchouli, and 5-6 parts of tangerine peel.

4. The use according to claim 1, characterized in that: The invention is prepared from the following raw material components by mass: 10 parts of aconite root, 15 parts of dried ginger, 20 parts of liquorice, 10 parts of honeysuckle, 10 parts of gleditsia thorn, 20 parts of cinnamon bark, 10 parts of patchouli, and 5 parts of tangerine peel.

5. The use according to any one of claims 1 to 4, characterized in that: The medicine also includes pharmaceutically acceptable excipients or additives.

6. The use according to claim 5, characterized in that The pharmaceutically acceptable adjuvants or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

7. The application according to claim 6, characterized in that: The dosage form for the drug includes an oral dosage form, an injection dosage form or an external dosage form.

8. The use according to claim 4, characterized in that: The medicine is in the form of granules, tablets, capsules, pills, oral solutions, oral suspensions or oral emulsions.

9. The use according to claims 1-4, characterized in that: The preparation method of the traditional Chinese medicine composition comprises the following steps: taking aconite root, dried ginger, liquorice, honeysuckle, thorn of Gleditsia sinensis, five-clawed dragon, patchouli, and tangerine peel, adding 8 to 12 times of water equivalent to the total mass of the raw materials, heating to boiling, maintaining a slight boiling for 1 to 2 hours, and obtaining a first decoction and medicinal residues after separation; a second time, taking the medicinal residues obtained after the first decoction, adding 6 to 10 times of water equivalent to the total mass of the raw materials, heating to boiling, maintaining a slight boiling for 1 to 2 hours, and obtaining a second decoction and medicinal residues after separation; combining the first decoction and the second decoction to prepare a decoction, and reducing the pressure on the decoction filtrate to concentrate to obtain a clear paste, and crushing it.

10. Use of a Chinese medicine composition in the preparation of a drug for treating influenza A (H1N1) pneumonia, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 10-30 parts of aconite root, 5-15 parts of dried ginger, 20-30 parts of liquorice, 10-20 parts of honeysuckle, 10-30 parts of Gleditsia sinensis, 20-45 parts of Ipomoea australis, 10-15 parts of patchouli, and 5-15 parts of tangerine peel.

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