CN116077494A - Pharmaceutical composition for treating respiratory syncytial virus and preparation method thereof - Google Patents
Pharmaceutical composition for treating respiratory syncytial virus and preparation method thereof Download PDFInfo
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- CN116077494A CN116077494A CN202310038720.6A CN202310038720A CN116077494A CN 116077494 A CN116077494 A CN 116077494A CN 202310038720 A CN202310038720 A CN 202310038720A CN 116077494 A CN116077494 A CN 116077494A
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- deoxynojirimycin
- pharmaceutical composition
- benzimidazole compound
- respiratory syncytial
- syncytial virus
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- 241000725643 Respiratory syncytial virus Species 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
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- LXBIFEVIBLOUGU-UHFFFAOYSA-N Deoxymannojirimycin Natural products OCC1NCC(O)C(O)C1O LXBIFEVIBLOUGU-UHFFFAOYSA-N 0.000 claims abstract description 70
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- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 2
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Animal Behavior & Ethology (AREA)
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- Pulmonology (AREA)
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Abstract
The invention relates to a pharmaceutical composition for treating respiratory syncytial virus and a preparation method thereof, which comprises 1-deoxynojirimycin, benzimidazole compound and pharmaceutically acceptable carrier, wherein the 1-deoxynojirimycin and the benzimidazole compound are combined to prepare an inhalation preparation, and the treatment effect of the respiratory syncytial virus of the pharmaceutical composition comprising the 1-deoxynojirimycin is obviously improved through the screening optimization of drug administration route, benzimidazole compound type and dosage, and the dosage of the 1-deoxynojirimycin is successfully reduced, thereby being beneficial to reducing the toxic and side effects of the 1-deoxynojirimycin and expanding the application field of the 1-deoxynojirimycin.
Description
Technical Field
The invention belongs to the field of medicines, and in particular relates to a pharmaceutical composition for treating respiratory syncytial virus and a preparation method thereof.
Background
Viruses are a class of microorganisms that do not have cellular structures and have vital signs of inheritance, replication, etc. Viruses are the main cause of infectious diseases, and have extremely high hazard and wide influence. Many diseases known at present for human beings are caused by virus infection, the virus infection and transmission are all the important health problems threatening the world, the spanish influenza in 1918 causes 5000 thousands of deaths worldwide, and the number of deaths is counted as ten thousands in China ancient times. Of the major epidemic diseases at present, diseases caused by viral infection account for more than half. Viruses have been found throughout the world in excess of 3600 and new viruses are continually being discovered, which has been one of the biggest confusion faced by the human health care industry. In recent years, due to the random spread of viruses, antiviral drugs have developed faster, and become important varieties of anti-infective drugs, and most antiviral drugs have certain toxicity to host cells, and the antiviral drugs have narrow antiviral spectrum and limited clinical curative effects, so that the application range is limited. Antiviral drugs must have high selectivity to intracellular viruses, but have no obvious toxicity to host cells, so that they have practical clinical value, have high selectivity, act on cellular virus metabolism, and have no obvious damage to hosts, and are still the key point of current research.
Respiratory syncytial virus (Respiratory Syncytial Virus, RSV) was isolated in 1956 from chimpanzees with mild upper respiratory symptoms, and fused into multinucleated megacytes, and was therefore known as respiratory syncytial virus. RSV infection is highly sporadic and highly endemic, and is affected by all stages of life, with the most dangerous being the major cause of bronchiolitis and pneumonia in infants, children, and the suffering of immunocompromised persons and the elderly. WHO data showed that there were approximately 6400 tens of thousands of respiratory syncytial virus infected persons worldwide and 16 tens of thousands of deaths.
1-deoxynojirimycin (1-deoxynojirimycin, 1-DNJ) is a piperidine alkaloid, has a similar structure to oligosaccharides, is very soluble in water, is prepared from natural products such as mulberry leaves, white mulberry root barks, mulberry twigs, mulberry, silkworm excrement and silkworm body, has the highest content in mulberry leaves except silkworms, can reach 0.05-0.2%, and is originally found in natural plants by nojirimers of Japanese students, so the nojirimycin is named nojirimycin. Modern pharmacological studies have shown that 1-DNJ is an alpha-glucosidase inhibitor, and that 1-deoxynojirimycin, after oral administration into the gastrointestinal tract, competitively binds to carbohydrate binding sites on various glucosidases present on the microvilli of the brush border cells of the small intestine, rendering the oligosaccharides non-hydrolyzable to monosaccharides by the glucosidases, preventing their absorption and thus exerting a hypoglycemic effect. European patent EPO282618A1 in 1987 published anti-HIV effect of 1-deoxynojirimotoxin and did not show human cytotoxicity. Subsequently, the derivative zidovudine (3 '-azido-3' -deoxyhypodine, AZT) of 1-deoxynojirimycin was marketed as an anti-aids drug in 1987, but the adverse reaction was large. At present, 1-deoxynojirimycin is a new focus of research, and the in vitro antiviral test results of 1-Deoxynojirimycin (DNJ) or derivatives thereof, which appear continuously at home and abroad, show that the 1-deoxynojirimycin not only has good effects on DNA viruses and RNA viruses, but also has inhibiting effects on the transmission and replication processes of a plurality of viruses such as non-nucleic acid small molecule non-immunity hydrophobic proteins, i.e. prion, and the like, such as Human Immunodeficiency Virus (HIV), hepatitis B Virus (HBV), coronavirus (SARS related virus), herpes virus, influenza virus, japanese encephalitis virus and the like.
Although 1-deoxynojirimycin shows excellent broad-spectrum antiviral effect in vitro antiviral test, 1-deoxynojirimycin can be competitively combined with various glucosidases on small intestinal brush border cell microvilli when being administrated through oral gastrointestinal tract due to the unique chemical structure of the 1-deoxynojirimycin, and the large quantity of the glucosidases tend to be saturated when being used in a common dosage, so that the 1-deoxynojirimycin can not be absorbed into blood almost when being administrated through oral gastrointestinal tract, and can not exert good antiviral effect in human body, thereby limiting the application of the 1-deoxynojirimycin in antiviral field.
The invention aims to provide an antiviral pharmaceutical composition containing 1-deoxynojirimycin with obviously improved therapeutic effect.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for treating respiratory syncytial virus and a preparation method thereof.
In one aspect, the invention provides a pharmaceutical composition for treating respiratory syncytial virus, which comprises 1-deoxynojirimycin, benzimidazole compound and a pharmaceutically acceptable carrier.
Preferably, the pharmaceutical composition for treating respiratory syncytial virus uses 1-deoxynojirimycin and benzimidazole compound as the only active ingredients.
Preferably, the weight ratio of the 1-deoxynojirimycin to the benzimidazole compound is as follows: 3-8:1-5; more preferably, the weight ratio of the 1-deoxynojirimycin to the benzimidazole compound is as follows: 4-6:2-4; most preferably, the weight ratio of the 1-deoxynojirimycin to the benzimidazole compound is as follows: 5:3;
preferably, the benzimidazole compound is selected from the group consisting of compounds of formula I or formula II:
more preferably, the benzimidazole compound is a compound of formula II:
the pharmaceutical composition for treating respiratory syncytial virus of the invention can be administered orally, by injection or by inhalation; preferably, the pharmaceutical composition for the treatment of respiratory syncytial virus according to the invention is administered by inhalation in a pharmaceutical dosage form selected from the group consisting of: aerosol, spray, or dry powder inhalants, and the like;
preferably, the sum of the contents of the 1-deoxynojirimycin and the benzimidazole compound in the pharmaceutical composition for treating respiratory syncytial virus accounts for 1-50% of the total weight of the pharmaceutical composition; more preferably, the method further comprises the steps of,
the sum of the contents of the 1-deoxynojirimycin and the benzimidazole compound in the pharmaceutical composition for treating the respiratory syncytial virus accounts for 3-30% of the total weight of the pharmaceutical composition, and most preferably, the sum of the contents of the 1-deoxynojirimycin and the benzimidazole compound in the pharmaceutical composition for treating the respiratory syncytial virus accounts for 10% of the total weight of the pharmaceutical composition.
It is still another object of the present invention to provide the use of a combination of 1-deoxynojirimycin and benzimidazole compound in the preparation of a pharmaceutical composition for respiratory syncytial virus;
preferably, the weight ratio of the 1-deoxynojirimycin to the benzimidazole compound is as follows: 3-8:1-5; more preferably, the weight ratio of the 1-deoxynojirimycin to the benzimidazole compound is as follows: 4-6:2-4; most preferably, the weight ratio of the 1-deoxynojirimycin to the benzimidazole compound is as follows: 5:3;
preferably, the benzimidazole compound is selected from:
more preferably, the benzimidazole compound is a compound of formula II:
it is still another object of the present invention to provide a method for preparing a pharmaceutical composition for treating respiratory syncytial virus, comprising the steps of:
(1) Weighing 1-deoxynojirimycin, benzimidazole compound and lactose 2-20 times of the total weight of 1-deoxynojirimycin and benzimidazole compound according to the weight, respectively pulverizing to D 90 3-5 mu m of particles for standby;
(2) Uniformly mixing the particles obtained in the step (1) to obtain mixture particles;
(3) And (3) packaging the mixture particles obtained in the step (2) into a dry powder inhaler.
The invention has the beneficial effects that
The invention combines the 1-deoxynojirimycin with the benzimidazole compound to prepare the inhalation preparation, and obviously improves the treatment effect of respiratory syncytial virus of the pharmaceutical composition containing the 1-deoxynojirimycin by optimizing the drug administration route, the type and the dosage of the benzimidazole compound and the screening of dry powder inhalant parameters, and successfully reduces the dosage of the 1-deoxynojirimycin, thereby being beneficial to reducing the toxic and side effects of the 1-deoxynojirimycin and expanding the application field of the 1-deoxynojirimycin.
Detailed Description
The present invention is described in more detail below to facilitate an understanding of the present invention.
Example 1: pharmaceutical composition for treating respiratory syncytial virus
10g of 1-deoxynojirimycin, 6g of a compound of the formula II and 144g of lactose, and is prepared according to the following steps:
(1) Weighing 1-deoxynojirimycin, compound of formula II and lactose according to the amount, and pulverizing to obtain powder D 90 Spare 3 μm particles;
(2) Uniformly mixing the particles obtained in the step (1) to obtain mixture particles;
(3) And (3) packaging the mixed particles obtained in the step (2) into a dry powder inhaler to obtain the pharmaceutical composition for treating respiratory syncytial virus.
Example 2: pharmaceutical composition for treating respiratory syncytial virus
12g of 1-deoxynojirimycin, 4g of a compound of the formula II and 144g of lactose are prepared according to the procedure of the example 1.
Example 3: pharmaceutical composition for treating respiratory syncytial virus
12g of 1-deoxynojirimycin, 6g of a compound shown in a formula I and 162g of lactose are prepared according to the steps of the example 1.
Example 4: pharmaceutical composition for treating respiratory syncytial virus
6g of 1-deoxynojirimycin, 10g of a compound shown in the formula I and 144g of lactose are prepared according to the steps of the example 1.
Effect example 1: therapeutic effects of the pharmaceutical composition of the invention on respiratory syncytial virus
1.1 Experimental drugs
(1) 1-deoxynojirimycin; (2) a compound of formula I; (3) a compound of formula II; (4) 1-deoxynojirimycin: compound of formula I = 1:3, a step of; (5) 1-deoxynojirimycin: compound of formula I = 5:3, a step of; (6) 1-deoxynojirimycin: compound of formula I = 10:1, a step of; (7) 1-deoxynojirimycin: compound of formula II = 1:3, a step of; (8) 1-deoxynojirimycin: compound of formula II = 5:3, a step of; (9) 1-deoxynojirimycin: compound of formula II = 10:1, a step of; (10) ribavirin; the drug (1) - (10) groups were prepared as mixture particles according to the steps (1) - (2) of example 1;
1.2 Experimental methods
65 mice, weighing 18-20g, were randomized into a blank group, model group, drug 1-10 groups, and orally administered group, 5 mice per group, wherein the blank group was isolated from the other mice in each group to avoid infection. After 1d of adaptive feeding of each group of mice, the mice outside the blank group were anesthetized and then were nasal-dropped into human respiratory syncytial virus Long strain suspension (8×10) 5 TCID 50 ) After mice in the blank group are dripped into an equal volume of normal saline and are continuously fed for 3 days, corresponding mixture particles are applied to the mice in the 1-10 groups by using a mouse tracheal administration device, the administration dose is 40mg/kg (the mixed drugs are the sum of the active ingredient doses), the lactose particles in the blank group and the model group are equal, and 1-deoxynojirimycin is administrated by the drug (11) group by stomach irrigation: compound of formula II = 5:3, the administration dose was also 40mg/kg (sum of the doses of 1-deoxynojirimycin and the compound of formula II), and the continuous administration was recorded for 10 daysMice survived. After the last administration for 2 hours, the mice were sacrificed after neck breakage, lung tissues were aseptically taken, homogenized, centrifuged and diluted, inoculated into normal cultured Hela cells, virus titer was measured by cytopathic inhibition, and virus inhibition rates of each group were calculated. Experiments were performed on an ultra clean bench and the isolation of mice from the blank group was noted to avoid infection.
1.3 experimental results
TABLE 1 therapeutic Effect of the pharmaceutical compositions of the invention on respiratory syncytial Virus
| Group of | Sample size (only) | Death count | Virus inhibition ratio (%) |
| Blank group | 5 | 0 | - |
| Model group | 5 | 2 | 0 |
| Drug 1 group | 5 | 1 | 32.16 |
| Drug group 2 | 5 | 1 | 45.67 |
| Drug 3 group | 5 | 1 | 55.84 |
| Medicine 4 group | 5 | 0 | 39.64 |
| Drug 5 group | 5 | 0 | 68.52 |
| Drug 6 group | 5 | 1 | 30.59 |
| Drug 7 group | 5 | 0 | 43.66 |
| Medicine 8 group | 5 | 0 | 79.17 |
| Medicine 9 group | 5 | 0 | 29.03 |
| Medicament 10 group | 5 | 1 | 53.64 |
| Drug 11 group | 5 | 1 | 25.51 |
The experimental results in table 1 show that two mice die in the model group mice in the experimental process, and the number of the mice die in each drug group is lower than that of the model group, and the experimental results show that the experimental drugs all show a certain treatment effect of respiratory syncytial virus infection.
The experimental results of each administration group show that although oral administration and respiratory administration show a certain respiratory syncytial virus inhibition effect, the respiratory administration shows a remarkably better respiratory syncytial virus inhibition effect under the condition that the drug types and the administration doses are identical.
Although 1-deoxynojirimycin, the compound of formula I, the compound of formula II and ribavirin Lin Jun exhibit a certain respiratory syncytial virus inhibition effect for the drug class, a mixture of 1-deoxynojirimycin and the compound of formula I or the compound of formula II in a specific ratio exhibits a significantly improved respiratory syncytial virus inhibition effect, wherein 1-deoxynojirimycin is used in particular: compound of formula II = 5:3 and 1-deoxynojirimycin: compound of formula I = 5:3, the inhibition effect is most excellent, and on the basis of obviously reducing the dosage of the 1-deoxynojirimycin, the inhibition effect of the respiratory syncytial virus is still obviously improved. In addition, partial mixtures also have lower inhibitory effects than the individual drugs, especially in group 6 and 9, which is probably because the use of too little compounds of formula I and II results in an ineffective anti-respiratory syncytial virus effect.
The foregoing describes preferred embodiments of the present invention, but is not intended to limit the invention thereto. Modifications and variations to the embodiments disclosed herein may be made by those skilled in the art without departing from the scope and spirit of the invention.
Claims (10)
1. A pharmaceutical composition for treating respiratory syncytial virus, which is characterized by comprising 1-deoxynojirimycin, benzimidazole compound and pharmaceutically acceptable carrier.
2. The pharmaceutical composition for treating respiratory syncytial virus according to claim 1, wherein the pharmaceutical composition comprises 1-deoxynojirimycin and benzimidazole compound as the only active ingredients.
3. The pharmaceutical composition for treating respiratory syncytial virus according to any one of claims 1-2, wherein the weight ratio of 1-deoxynojirimycin to benzimidazole compound is: 3-8:1-5; preferably, the weight ratio of the 1-deoxynojirimycin to the benzimidazole compound is as follows: 4-6:2-4; more preferably, the weight ratio of the 1-deoxynojirimycin to the benzimidazole compound is as follows: 5:3.
4. A pharmaceutical composition for the treatment of respiratory syncytial virus according to claim 3, wherein the benzimidazole compound is selected from the group consisting of compounds of formula I or formula II:
5. the pharmaceutical composition for the treatment of respiratory syncytial virus according to any one of claims 1-4, wherein the pharmaceutical composition is administered orally, by injection or by inhalation; preferably, the pharmaceutical dosage form for administration by inhalation is selected from the group consisting of: aerosol, spray or dry powder inhalants.
6. The pharmaceutical composition for treating respiratory syncytial virus according to any one of claims 1-5, wherein the sum of the contents of 1-deoxynojirimycin and benzimidazole compound is 1-50% of the total weight of the pharmaceutical composition; preferably, the sum of the contents of the 1-deoxynojirimycin and the benzimidazole compound accounts for 3-30% of the total weight of the pharmaceutical composition, and more preferably, the sum of the contents of the 1-deoxynojirimycin and the benzimidazole compound accounts for 10% of the total weight of the pharmaceutical composition.
7. A method of preparing a pharmaceutical composition for the treatment of respiratory syncytial virus according to any one of claims 1-6, comprising the steps of:
(1) Weighing 1-deoxynojirimycin, benzimidazole compound and lactose 2-20 times of the total weight of 1-deoxynojirimycin and benzimidazole compound according to the weight, respectively pulverizing to D 90 3-5 mu m of particles for standby;
(2) Uniformly mixing the particles obtained in the step (1) to obtain mixture particles;
(3) And (3) packaging the mixture particles obtained in the step (2) into a dry powder inhaler.
Use of a combination of 1-deoxynojirimycin and a benzimidazole compound for the preparation of a pharmaceutical composition of respiratory syncytial virus.
9. The use according to claim 8, wherein the benzimidazole compound is selected from the group consisting of:
10. the use according to any one of claims 8 to 9, wherein the pharmaceutical composition comprises 1-deoxynojirimycin and benzimidazole compound as the only active ingredients.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5622972A (en) * | 1994-02-25 | 1997-04-22 | G. D. Searle & Co. | Method for treating a mammal infected with respiratory syncytial virus |
| CN107108557A (en) * | 2014-10-07 | 2017-08-29 | 瑞威有限公司 | Loop coil dihydroindolines for treating and preventing respiratory syncytial virus (RSV) (RSV) infection |
| CN108601774A (en) * | 2016-02-03 | 2018-09-28 | 爱尔兰詹森科学公司 | Combination product for treating RSV |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5622972A (en) * | 1994-02-25 | 1997-04-22 | G. D. Searle & Co. | Method for treating a mammal infected with respiratory syncytial virus |
| CN107108557A (en) * | 2014-10-07 | 2017-08-29 | 瑞威有限公司 | Loop coil dihydroindolines for treating and preventing respiratory syncytial virus (RSV) (RSV) infection |
| CN108601774A (en) * | 2016-02-03 | 2018-09-28 | 爱尔兰詹森科学公司 | Combination product for treating RSV |
Non-Patent Citations (1)
| Title |
|---|
| 李春花等: "《经典名方传承与现代制剂开发》", vol. 1, 31 August 2020, 中国医药科技出版社, pages: 202 - 203 * |
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