Pharmaceutical composition containing three medicinal materials of dendrobium nobile and blumea balsamifera

Abstract

The invention discloses a pharmaceutical composition for preventing or treating influenza virus infection. The pharmaceutical composition provided by the invention is characterized by comprising the following components in parts by weight: 20-25 parts of dendrobium nobile, 10-20 parts of caulis sinomenii and 5-15 parts of blumea balsamifera, and the pharmaceutical composition provided by the invention is relatively safe, can be used as a preparation for preventing or treating influenza virus infection, and has a certain medicinal value.

Description

Technical Field

[0001] The invention relates to a pharmaceutical composition for treating or preventing influenza virus infection, and in particular to a pharmaceutical composition containing three Chinese medicinal materials, namely, Dendrobium nobile, Caulis dahuricae and Blumea balsamifera. The pharmaceutical composition has pharmacological activity against influenza virus and can be used for treating or preventing respiratory diseases such as pharyngitis, pneumonia, bronchitis and the like caused by influenza virus infection. Background Art

[0002] Influenza virus is called influenza virus for short. It is divided into three types: A, B, and C. Influenza viruses discovered in recent years are classified as D. Influenza virus can cause infection and disease in many animals such as humans, poultry, pigs, horses, bats, etc. It is the pathogen of human and animal diseases such as human influenza, avian influenza, swine influenza, and equine influenza. The typical clinical symptoms of these diseases are acute high fever, body pain, significant fatigue and respiratory symptoms. Influenza virus is mainly transmitted through droplets in the air, contact between susceptible and infected persons, or contact with contaminated objects. Generally, autumn and winter are its peak seasons. Human influenza is mainly caused by influenza A virus and influenza B virus. Influenza A virus often undergoes antigenic variation and can be further divided into subtypes such as H1N1, H3N2, H5N1, and H7N9 (where H and N represent two surface glycoproteins of influenza virus, respectively).

[0003] People are generally susceptible to influenza viruses, regardless of age, gender, occupation, etc. Antibodies appear one week after infection, peak in 2 to 3 weeks, begin to decline after 1 to 2 months, and drop to the lowest level in about one year. Antibodies are present in the blood and nasal secretions, but the antibodies in nasal secretions are only about 5% of those in the blood. There is no cross-immunity between the three types of influenza viruses, and immunity does not last long after infection. According to on-site observations, although antibodies are present in the blood 5 months after infection, the same type of virus can still be infected again. The respiratory tract produces secretory antibodies that can prevent the invasion of viruses, but when the local mucosal epithelial cells fall off, they lose their protective effect, so local antibodies are more important than antibodies in the blood.

[0004] If the patient's resistance is weak or there are signs of worsening of the disease, such as persistent fever or shortness of breath, he should seek medical attention as soon as possible. Antiviral agents such as amantadine can effectively fight influenza A, but they must be used with caution because amantadine can cause serious side effects, such as poor appetite, vomiting, insomnia, dizziness and hallucinations. As a treasure of the Chinese nation, traditional Chinese medicine has unique advantages in the prevention and treatment of influenza. By adjusting diet, exercising properly, and taking Chinese medicine for prevention, the risk of influenza infection can be effectively reduced and the body's resistance can be improved.

[0005] Dendrobium nobile Lindl is the stem of Dendrobium nobile Lindl, a plant of the genus Dendrobium in the Orchidaceae family. It has the effects of clearing away heat and nourishing yin, moistening the lungs and producing body fluid, benefiting the kidneys and nourishing the stomach, improving eyesight and strengthening the waist. It is mainly used to treat heat diseases that damage body fluids, dry mouth and thirst, dry coughs due to lung heat, insufficient stomach yin, calming the nerves and relieving convulsions, stomach pain and dry retching, etc.

[0006] Cocculus orbiculatus is the dried stem or root of Cocculus orbiculatus (L.) DC. of the Menispermaceae family. It tastes bitter, pungent and cold. It enters the lung, spleen, kidney and bladder meridians. It is used to treat rheumatic joint pain, intercostal neuralgia, acute nephritis, urinary tract infection, hypertension, rheumatic heart disease, edema, and can also treat snake bites.

[0007] Blumea balsamifera (L.) DC. is a plant of the genus Blumea in the Asteraceae family. It has the effects of dispelling wind and dampness, warming the middle and stopping diarrhea, promoting blood circulation and detoxifying. It is mainly used to treat colds; headaches; rheumatic arthralgia; cold and damp diarrhea; inchworm disease; snake bites; traumatic injuries; and ringworms.

[0008] Through the study of the formula and compatibility of three medicinal materials, Dendrobium nobile, Caulis dahurica and Blumea balsamifera, it was found that the combination of the three in a certain proportion has a good pharmacological activity in inhibiting influenza virus, and has medicinal value in treating or preventing influenza virus infection. Summary of the invention

[0009] One of the purposes of the present invention is to provide a pharmaceutical composition for treating or preventing influenza virus infection, thereby reducing the risks of current clinical medication for treating influenza virus infection and the problem of drug resistance.

[0010] The technical solution adopted to solve the above technical problems is a pharmaceutical composition for treating or preventing influenza virus infection, which contains 20-25 parts by weight of Dendrobium nobile, 10-20 parts of Rhizoma Cyperi, and 5-15 parts of Blumea balsamifera. It has good pharmacological activity of inhibiting influenza virus and is very suitable for industrial production.

[0011] Preferably, the composition contains 25 parts of Dendrobium nobile, 20 parts of Caulis dahuricae, and 15 parts of Blumea balsamifera by weight.

[0012] Preferably, the composition contains 20 parts of Dendrobium nobile, 10 parts of Caulis dahuricae, and 5 parts of Blumea balsamifera by weight.

[0013] The second object of the present invention is to provide a drug for preventing or treating influenza virus infection, comprising the above-mentioned composition and pharmaceutically acceptable excipients, such excipients (including but not limited to: starch, lactose, mannitol, sorbitol, microcrystalline cellulose, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, magnesium stearate, talc, micro-powdered silica gel, etc.

[0014] The preferred dosage forms are oral solid preparations and oral liquid preparations.

[0015] The composition of the present invention is prepared by mixing using conventional methods, and the pharmaceutical composition preparation is prepared using conventional preparation methods in the field of preparations.

[0016] Pharmacological experiments have shown that the above-mentioned pharmaceutical composition has pharmacological activity of inhibiting influenza virus and can be used to prevent or treat respiratory diseases such as pharyngitis and pneumonia caused by influenza virus infection.

[0017] The pharmaceutical composition provided by the present invention has clear active ingredients and strong therapeutic effects, is very suitable for industrial production, and will produce good social and economic benefits.

[0018] In order to better understand the essence of the present invention, the present invention is described in detail below by describing the preferred embodiments of the present invention but without limiting the present invention. DETAILED DESCRIPTION

[0019] The present invention is further described below in conjunction with the embodiments, but the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments, and the protection scope of the present invention is not limited thereto.

[0020] Example 1 Preparation of Chinese medicine composition 1-6

[0021] The Chinese medicine compositions 1-6 of the present invention adopt a uniform design experimental scheme: referring to the literature (Liang Maoxin, Li Dongan. Improved application of uniform design in the selection of small Chinese medicine compound prescriptions [J]. World Science and Technology - Modernization of Traditional Chinese Medicine, 2006, 8 (02): 53-56.), the uniform design scheme U6 (6 3 )(as shown in Table 1), the three Chinese medicinal materials of Dendrobium nobile, Caulis dahurica and Artemisia balsamifera were used as investigation factors, each factor took 6 levels (i.e. 6 different doses with increasing gradient), the investigation dose was between 0-25g, and each factor and level were arranged according to the uniform design table, and the prescription design was carried out, and a total of 6 groups of Chinese medicine compositions were constructed.

[0022] Table 1 Chinese medicine composition U6(6 3 )Uniform Design Table

[0023]

[0024]

[0025] Preparation of Chinese medicine composition 1-6 According to the amount of medicinal materials of composition 1-6 in Table 1, each medicinal material is weighed according to the prescription of each group, crushed into coarse powder, and mixed evenly. According to the total amount of medicinal materials in each group, 15 times the amount of purified water is added respectively, soaked for 1 hour, decocted for 1.5 hours, cooled, filtered, and the filtrate is collected. Add 10 times the amount of purified water of the original medicinal material to the residue, decoct again for 1 hour, cool, filter, combine the filtrates of the two decoctions, and concentrate to 2 times the volume of the original medicinal material (volume / mass ratio), let stand to 70°C, add 3 times the amount of 95% ethanol while hot, let stand for 4 hours, take the supernatant, reduce pressure to recover ethanol and concentrate, and reduce pressure and dry the concentrate at 60°C to obtain the extract of Chinese medicine composition 1-6.

[0026] Example 2 In vitro antiviral effect of the pharmaceutical composition

[0027] 1. Materials

[0028] 1.1 Influenza virus strains: H1N1, H3N2.

[0029] 1.2 Cell model: Vero monkey kidney cell line.

[0030] Culture conditions: DMEM + 10% fetal bovine serum, 37°C, 5% CO2.

[0031] 1.3 Test samples: Sample numbers and concentrations are shown in Table 1.

[0032] 2. Principles and methods

[0033] 2.1 Drug cytotoxicity testing

[0034] Vero cells were inoculated in a 96-well cell culture plate and the cells were attached to the wall for later use. The drug was diluted 3 times from a 200-fold starting concentration to 6 gradients with DMSO, and then diluted with cell maintenance medium (DMEM + 4% serum) to a culture medium containing the drug, and each concentration gradient was tested in a single well. After 72 hours of drug culture, the culture supernatant was discarded, and the culture medium containing alamarBlue was added, incubated at 37°C for 2 hours, and the reduction of alamarBlue was detected by fluorescence, with an excitation light of 570nm and an emission light of 595nm.

[0035] Cell activity (%) = (sample well - blank control) / (cell control - blank control) × 100%

[0036] 2.2 Inhibitory effects of drugs on H1N1 and H3N2 viruses

[0037] After H1N1 and H3N2 infect Vero cells, the infected cells will shrink, fuse with each other, and form grape-like or star-shaped lesions. The inhibition of drug on viral replication can be determined by observing CPE and detecting cell survival rate.

[0038] Vero cells were inoculated in a 96-well cell culture plate. After the cells grew into a monolayer, 100 μl of maintenance medium containing 2× drugs and 100 μl of virus solution diluted in DMEM were added and cultured at 37°C. The occurrence of specific CPE in cells was observed and recorded every day. After 72 hours of culture (100% lesions in the virus control well), the cell survival rate was detected.

[0039] The experiment set up a cell control group (no virus infection), a virus control group (wells without drug addition after virus infection), and a positive drug (oseltamivir) control well.

[0040] Inhibition rate (%) = (drug group - virus control group) / (cell control group - virus control group) × 100% 3. Test results of drug samples' toxicity to cells and their inhibitory activity to H1N1 and H3N2

[0041] The solvents used for dilution of drug samples, the highest solubility concentration, the highest tested concentration, CC50, EC50 and SI (selectivity index) are shown in Table 2.

[0042] Table 2 Experimental results of various composition samples

[0043]

[0044] “-”, no obvious cytotoxicity or influenza virus inhibition activity was detected, and its CC50 value was greater than the maximum tested concentration.

[0045] 4. Conclusion

[0046] All pharmaceutical compositions exhibited certain anti-H1N1 and H3N2 virus activity, especially combination 5 and combination 6, which had the strongest anti-H1N1 and H3N2 virus activity. The above experimental data indicate that combination 5 and combination 6 have application prospects in the preparation of drugs for preventing or treating influenza viruses.

[0047] Example 3 Syrup Preparation

[0048] 20 parts of Dendrobium nobile, 10 parts of Caulis dahuricae, and 5 parts of Blumea balsamifera in weight proportion are added with 15 times amount of purified water, soaked for 1 hour, boiled for 1.5 hours, cooled, filtered, and the filtrate is collected. 10 times amount of purified water of the original medicinal material is added to the medicinal residue, boiled again for 1 hour, cooled, filtered, the filtrates of the two decoctions are combined, and concentrated to 2 times volume of the original medicinal material (volume / mass ratio), allowed to stand at 70°C, 3 times amount of 95% ethanol is added while hot, allowed to stand for 4 hours, the supernatant is taken and decompressed to recover ethanol and concentrated to an appropriate amount, monosyrup, paraben, and benzoic acid are added, mixed and filled into a colored glass bottle, and the syrup of the present invention is obtained.

[0049] Example 4 Tablet Preparation

[0050] 25 parts of Dendrobium nobile, 20 parts of Caulis Agni and 15 parts of Blumea Balsamifera in weight proportion are added with 15 times amount of purified water, soaked for 1 hour, boiled for 1.5 hours, cooled, filtered and the filtrate is collected. 10 times amount of purified water of the original medicinal material is added to the medicinal residue, boiled again for 1 hour, cooled, filtered, the filtrates of the two decoctions are combined, and concentrated to 2 times volume of the original medicinal material (volume / mass ratio), allowed to stand at 70°C, 3 times amount of 95% ethanol is added while hot, allowed to stand for 4 hours, the supernatant is taken to recover ethanol under reduced pressure and concentrated, the concentrated solution is dried under reduced pressure at 60°C, one or more auxiliary materials such as starch, microcrystalline cellulose and lactose are added, mixed, granulated, dried, sieved and tableted to form the tablet of the present invention.

Claims

1. An anti-influenza virus pharmaceutical composition containing three medicinal materials: Dendrobium nobile, Rhizoma Cyperi, and Artemisia balsamifera, characterized in that: The invention contains 20-25 parts by weight of Dendrobium nobile, 10-20 parts by weight of Caulis dasyphyllae and 5-15 parts by weight of Blumea balsamifera.

2. The pharmaceutical composition according to claim 1, characterized in that: The invention contains 20 parts by weight of Dendrobium nobile, 10 parts by weight of Caulis dasyphyllae and 5 parts by weight of Blumea balsamifera.

3. The pharmaceutical composition according to claim 1, characterized in that: The invention contains 25 parts by weight of Dendrobium nobile, 20 parts by weight of Caulis dasyphyllae and 15 parts by weight of Blumea balsamifera.

4. Use of the pharmaceutical composition according to claims 1 to 3 in the preparation of a preparation for preventing or treating influenza virus infection.

5. A pharmaceutical composition for preventing or treating influenza virus infection, comprising the pharmaceutical composition according to claims 1 to 3 and a pharmaceutically acceptable excipient.

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