CN113288943A - Application of traditional Chinese medicine composition in preparation of medicine for treating or preventing coronavirus infection - Google Patents
Application of traditional Chinese medicine composition in preparation of medicine for treating or preventing coronavirus infection Download PDFInfo
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
- A61K36/355—Lonicera (honeysuckle)
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/744—Gardenia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Abstract
The invention discloses application of a traditional Chinese medicine composition in preparing a medicine for treating or preventing coronavirus infection, which is characterized in that the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5-30 parts of sweet wormwood, 3-20 parts of honeysuckle and 2-15 parts of gardenia. The traditional Chinese medicine composition can show strong protection effect on VeroE6 cells infected by 2019-nCoV under dilution concentrations of 1:5000, 1:10000 and 1:20000 times, the infected cells can not be diseased due to the three concentrations, and the 2019-nCoV can be inhibited from being replicated in the cells, so that the traditional Chinese medicine composition has a good effect of treating or preventing coronavirus infection.
Description
Technical Field
The invention relates to the field of disease treatment medicines, in particular to application of a traditional Chinese medicine composition in preparing a medicine for treating or preventing coronavirus infection.
Background
2019-nCoV belongs to a novel coronavirus of beta genus, has an envelope, is round or oval in particle shape, is usually polymorphic, and has a diameter of 60-140 nm. The gene characteristics of the mutant are obviously different from those of SARSr-CoV and MERSR-CoV. The present research shows that the homology with bat SARS-like coronavirus (bat-SL-CoVZC45) reaches more than 85%. Droplet and intimate contact transmission are the major transmission pathways, and aerosol transmission is possible with prolonged exposure to high concentrations of viral aerosols in a relatively closed environment. The patients mainly show fever, hypodynamia and dry cough, and few patients have symptoms such as nasal obstruction, watery nasal discharge, diarrhea and the like. In severe cases, dyspnea occurs after one week, and severe cases rapidly progress to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, and hemorrhagic clotting dysfunction.
The injection is prepared by refining three traditional Chinese medicines of honeysuckle, gardenia and sweet wormwood, has the effects of clearing heat, dispelling wind and detoxifying, is mainly used for treating symptoms such as cold, cough, upper respiratory infection, acute bronchitis and the like caused by wind heat, and has definite curative effect and obvious effect. Whether it can be effective in preventing and treating coronavirus-related diseases, particularly COVID-19, requires scientific research.
Disclosure of Invention
In view of the above, the present invention provides an application of a Chinese medicinal composition in preparing a medicament for treating or preventing coronavirus infection, wherein the Chinese medicinal composition comprises the following raw material medicines: 5-30 parts of sweet wormwood, 3-20 parts of honeysuckle and 2-15 parts of gardenia.
Further, the coronavirus infectious disease comprises COVID-19.
Preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 5-25 parts of sweet wormwood, 3-15 parts of honeysuckle and 2-12 parts of gardenia.
More preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 10-25 parts of sweet wormwood, 6-15 parts of honeysuckle and 4-12 parts of gardenia.
More preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 20-25 parts of sweet wormwood, 12-15 parts of honeysuckle and 10-12 parts of gardenia.
More preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 11 parts of sweet wormwood, 8 parts of honeysuckle and 7 parts of gardenia.
More preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 15 parts of sweet wormwood, 11 parts of honeysuckle and 10 parts of cape jasmine.
More preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 25 parts of sweet wormwood, 15 parts of honeysuckle and 12 parts of cape jasmine.
The Chinese medicinal composition can be added with pharmaceutically acceptable adjuvants to make into various dosage forms, such as decoction, granule, capsule, tablet, oral liquid, pill, tincture, syrup, suppository, gel, spray, injection, etc. Wherein, the raw material medicine can be directly ground into powder, or can be extract prepared by the conventional means in the field, etc.; the composition can be prepared by directly grinding several compositions into powder by conventional method, or by conventional method to obtain extract.
The invention also provides an optional preparation method of the traditional Chinese medicine composition for preventing or treating coronavirus infection, which is characterized by comprising the following steps of:
soaking flos Lonicerae and herba Artemisiae Annuae in water, heating, decocting, distilling, and collecting volatile oil. Mixing decoctions, concentrating, and drying to obtain flos Lonicerae and herba Artemisiae Annuae dry extract powder. Pulverizing fructus Gardeniae into coarse powder, heating and refluxing with ethanol solution, filtering, recovering ethanol from filtrate, concentrating, adjusting to acidity with hydrochloric acid, heating for 0.5-1.5 hr, refrigerating for 10-14 hr, filtering, concentrating the filtrate, and drying to obtain fructus Gardeniae dry extract powder. Coating the volatile oil with adjuvant, or directly collecting volatile oil, and mixing with the above dry extract powder. Finally, the clinically acceptable preparation formulation is prepared directly or by adding pharmaceutically acceptable excipients through the conventional process.
The traditional Chinese medicine composition disclosed by the invention can show a good protection effect on VeroE6 cells infected by 2019-nCoV virus under the dilution concentration of 1:5000, 1:10000 and 1:20000 times of stock solution of a Reduining injection, so that the infected cells are free from pathological changes, and the 2019-nCoV can be inhibited from being replicated in the cells, thereby showing that the traditional Chinese medicine composition disclosed by the invention has a good effect of treating or preventing related diseases of coronavirus.
Detailed Description
The invention provides the application of the traditional Chinese medicine composition, and the technical personnel in the field can use the contents for reference and properly improve the process parameters for realization. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.
Unless otherwise specified, the drugs, biological materials or instruments used in the present invention are commercially available and are commercially available.
The invention is further illustrated by the following examples:
example 1
Sweet wormwood 1250g honeysuckle flower 750g cape jasmine 600g
Soaking flos Lonicerae and herba Artemisiae Annuae in 13-18 times of water for 3 hr, heating, decocting, distilling for 2 times, each time for 2 hr, and collecting volatile oil. Mixing decoctions, concentrating under reduced pressure to relative density of 1.03-1.08, centrifuging at high speed (20000 rpm) to obtain supernatant, performing fractional ultrafiltration, concentrating ultrafiltrate under reduced pressure to relative density of 1.10-1.12 at 50 deg.C, and vacuum drying to obtain dry extract powder of flos Lonicerae and herba Artemisiae Annuae. Pulverizing fructus Gardeniae into coarse powder, heating and refluxing with 6 times of 80% ethanol for 1-3 times, each for 1 hr, mixing the medicinal liquids, filtering, recovering ethanol from the filtrate, concentrating to 1:1, adjusting pH to 4.0 with hydrochloric acid, heating at 100 deg.C for 1 hr, refrigerating for 12 hr, filtering, concentrating the filtrate to relative density of 1.10-1.12 at 50 deg.C, and vacuum drying to obtain fructus Gardeniae dry extract powder. Adding 6g poloxamer 108 into the volatile oil, grinding, mixing, adding 900ml water for injection, stirring to clarify, adding the above dried extract powder, stirring to dissolve, adjusting pH to 7.5-8.0 with sodium hydroxide solution, and adding water for injection to 1000 ml. Filtered through a G4 sintered funnel, filled in a 10ml ampoule and sterilized by flowing steam at 100 ℃. Each 10ml is equivalent to 26 g of crude drug, the injection is instilled into the vein, 10-20ml of the product is injected, and 500ml of 5% grape liquid or 0.9% sodium chloride injection 250-.
Example 2
Sweet wormwood 1100g honeysuckle flower 800g cape jasmine 700g
Soaking flos Lonicerae and herba Artemisiae Annuae in 13-18 times of water for 3 hr, heating, decocting, distilling for 2 times, each time for 2 hr, and collecting volatile oil. Mixing decoctions, concentrating under reduced pressure to relative density of 1.03-1.08, centrifuging at high speed (20000 rpm) to obtain supernatant, concentrating under reduced pressure to relative density of 1.10-1.12 at 50 deg.C, and vacuum drying to obtain flos Lonicerae and herba Artemisiae Annuae dry extract powder. Pulverizing fructus Gardeniae into coarse powder, heating and refluxing with 6 times of 80% ethanol for 1-3 times, each for 1 hr, mixing the medicinal liquids, filtering, recovering ethanol from the filtrate, concentrating to 1:1, adjusting pH to 4.0 with hydrochloric acid, heating at 100 deg.C for 1 hr, refrigerating for 12 hr, filtering, concentrating the filtrate to relative density of 1.10-1.12 at 50 deg.C, and vacuum drying to obtain fructus Gardeniae dry extract powder. Mixing the above volatile oil and dry extract powder, adding 0.5-1.5 times of edible vegetable oil, grinding, and making into soft capsule 1000 granules by conventional process to obtain soft capsule of composition, wherein each granule contains 0.55g, which is equivalent to 2.6g of raw medicinal materials.
Examples of drug efficacy test
1. Experimental Material
The tested drugs are: the invention example 1 prepared drug.
VeroE6 cells: preserved by the pathogenic center of the institute of medical laboratory animals of Chinese academy of medical science.
2019-nCoV Virus: titer 105TCID50Perml, animal tested by the Chinese academy of medical sciencesThe pathogenic center of the research institute is stored at-80 ℃. Using a Virus titre of 100TCID50。
2. Experimental methods
Sterile 96-well culture plate, 200. mu.l of 5X 10 concentration per well4cell/ml Vero E6 cells, 5% CO at 37 ℃2Culturing for 24 hours; diluting the tested medicine into 3 concentrations (1:5000, 1:10000, 1:20000), each concentration is 5 multiple wells, each well has 100 μ l, then adding 100 volume of TCID50 virus into each well, and acting for 1 h; after 1h, removing the cell culture solution in the 96-well culture plate, and adding the mixed solution; simultaneously setting a cell control, a blank control (solvent control) and a virus control (negative control); cells at 37 ℃ and 5% CO2Incubating in an incubator for 4-5 days; cytopathic effects (CPE) were observed under light microscopy, with complete lesions recorded as "++++", 75% lesions recorded as "++++", 50% lesions recorded as "+++", 25% lesions recorded as "+", and no lesions recorded as "-".
3. The experimental conditions are as follows: the above experimental operations are all completed in a BSL-3 laboratory.
4. And (5) judging a result: the absence of CPE in the cells is the concentration effective to inhibit the virus and the presence of CPE is ineffective.
5. The experimental results are as follows:
the drug group of the invention is set to 3 concentrations, and can effectively inhibit 2019-nCoV replication on cells. The results are shown in Table 1.
TABLE 1 anti-2019-nCoV effect of drugs
Remarking: "-" is not diseased; "+ ++" indicates that the cells were completely diseased.
6. And (4) conclusion:
according to the screening results at the cellular level, the samples prepared according to the invention in example 1 can inhibit the 2019-nCoV from replicating in cells under the dilution concentration of 1:5000, 1:10000 and 1:20000 times, which indicates that the Gangdu injection has the activity of resisting the 2019-nCoV in vitro.
Claims (10)
1. The application of a traditional Chinese medicine composition in preparing a medicine for treating or preventing coronavirus infection is characterized in that the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5-30 parts of sweet wormwood, 3-20 parts of honeysuckle and 2-15 parts of gardenia.
2. The use according to claim 1, wherein the coronavirus infection comprises COVID-19.
3. The application of claim 1, wherein the Chinese medicinal composition comprises the following raw material medicaments in part by weight: 5-25 parts of sweet wormwood, 3-15 parts of honeysuckle and 2-12 parts of gardenia.
4. The application of claim 1, wherein the Chinese medicinal composition comprises the following raw material medicaments in part by weight: 10-25 parts of sweet wormwood, 6-15 parts of honeysuckle and 4-12 parts of gardenia.
5. The application of the traditional Chinese medicine composition as claimed in claim 1, wherein the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 11 parts of sweet wormwood, 8 parts of honeysuckle and 7 parts of gardenia.
6. The application of the traditional Chinese medicine composition as claimed in claim 1, wherein the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 15 parts of sweet wormwood, 11 parts of honeysuckle and 10 parts of cape jasmine.
7. The application of the traditional Chinese medicine composition as claimed in claim 1, wherein the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 25 parts of sweet wormwood, 15 parts of honeysuckle and 12 parts of cape jasmine.
8. The use according to any one of claims 1 to 7, characterized in that the medicament for the treatment or prevention of coronavirus infections comprises a decoction, granules, capsules, tablets, oral liquids, pills, tinctures, syrups, suppositories, gels, sprays, injections.
9. The use according to any one of claims 1 to 7, wherein the preparation method of the Chinese medicinal composition comprises the following steps:
step A, soaking honeysuckle and sweet wormwood in water, heating, decocting and distilling, collecting volatile oil for later use, merging decoction, concentrating and drying to obtain honeysuckle and sweet wormwood dry extract powder;
pulverizing fructus Gardeniae into coarse powder, heating and refluxing with ethanol solution, filtering, recovering ethanol from filtrate, concentrating, adjusting acidity with hydrochloric acid, heating for 0.5-1.5 hr, refrigerating for 10-14 hr, filtering, concentrating the filtrate, and drying to obtain fructus Gardeniae dry extract powder;
and step C, coating the volatile oil by using auxiliary materials conventionally or uniformly mixing the volatile oil with the honeysuckle, the sweet wormwood dry extract powder and the gardenia dry extract powder.
10. The use according to claim 9, wherein the medicament for the treatment or prevention of coronavirus infection comprises an oral administration form, an injection form, a nebulization form or an external preparation.
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| CN1813983A (en) * | 2004-12-17 | 2006-08-09 | 江苏康缘药业股份有限公司 | Method for identifying finger print atlas of injecta |
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| CN104415130A (en) * | 2013-09-10 | 2015-03-18 | 成都力思特制药股份有限公司 | Reduning injection and preparation method thereof |
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