CN1265796C - SARS preventing medicine - Google Patents
SARS preventing medicine Download PDFInfo
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- CN1265796C CN1265796C CN 200310103718 CN200310103718A CN1265796C CN 1265796 C CN1265796 C CN 1265796C CN 200310103718 CN200310103718 CN 200310103718 CN 200310103718 A CN200310103718 A CN 200310103718A CN 1265796 C CN1265796 C CN 1265796C
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- Prior art keywords
- medicine
- concentration
- atypical pneumonia
- coronavirus
- cell
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- 239000003814 drug Substances 0.000 title claims abstract description 70
- 206010003757 Atypical pneumonia Diseases 0.000 claims abstract description 22
- 230000002265 prevention Effects 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 5
- 241000315672 SARS coronavirus Species 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 230000003449 preventive effect Effects 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 2
- 239000000178 monomer Substances 0.000 abstract description 2
- YURJSTAIMNSZAE-UHFFFAOYSA-N UNPD89172 Natural products C1CC(C2(CC(C3C(C)(C)C(O)CCC3(C)C2CC2O)OC3C(C(O)C(O)C(CO)O3)O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O YURJSTAIMNSZAE-UHFFFAOYSA-N 0.000 abstract 1
- YURJSTAIMNSZAE-HHNZYBFYSA-N ginsenoside Rg1 Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YURJSTAIMNSZAE-HHNZYBFYSA-N 0.000 abstract 1
- CBEHEBUBNAGGKC-UHFFFAOYSA-N ginsenoside Rg1 Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5CC(OC6OC(CO)C(O)C(O)C6O)C34C)C CBEHEBUBNAGGKC-UHFFFAOYSA-N 0.000 abstract 1
- 239000012567 medical material Substances 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 22
- 241000711573 Coronaviridae Species 0.000 description 20
- 231100001274 therapeutic index Toxicity 0.000 description 16
- 229940079593 drug Drugs 0.000 description 14
- 238000004113 cell culture Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 241000700605 Viruses Species 0.000 description 8
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 8
- 229960002963 ganciclovir Drugs 0.000 description 8
- 239000013641 positive control Substances 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 231100000028 nontoxic concentration Toxicity 0.000 description 6
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 230000029052 metamorphosis Effects 0.000 description 5
- 231100000645 Reed–Muench method Toxicity 0.000 description 4
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 4
- 231100001134 median toxic concentration Toxicity 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012531 culture fluid Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 231100000820 toxicity test Toxicity 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 1
- 101000612134 Homo sapiens Procollagen C-endopeptidase enhancer 1 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
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- 102100041026 Procollagen C-endopeptidase enhancer 1 Human genes 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
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- 239000000969 carrier Substances 0.000 description 1
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- 238000003113 dilution method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a medicine with a preventive effect on atypical pneumonia, which is prepared by using monomer components extracted from natural vegetation medical materials as effective medical components. The medicine for preventing atypical pneumonia of the present invention is composed of the following components according to a weight percentage: 50 to 99% of ginsenoside Rg1 and medical auxiliary material as the rest. The medicine of the present invention is mainly used for preventing the atypical pneumonia.
Description
Technical field
The present invention relates to a kind of by the monomer composition that extracts in the natural plant crude drugs be effective medicinal ingredient make atypical pneumonia is had the medicine of preventive effect.
Background technology
Atypical pneumonia is a kind of infectious disease that is caused by coronavirus, and its harm to the mankind is well-known.For the treatment of atypical pneumonia and the research of prophylactic agent is this field problem demanding prompt solution.
Summary of the invention
Purpose of the present invention aims to provide a kind of atypical pneumonia prophylactic agent that can be used in prevention of atypical pneumonia.
Panaxoside Rg
1Application in preparation prevention of atypical pneumonia medicine, described atypical pneumonia is the atypical pneumonia that is caused by sars coronavirus.By percentage by weight is the panaxoside Rg of 50-99%
1With the application of compositions in preparation prevention of atypical pneumonia medicine that the surplus pharmaceutic adjuvant is formed, described atypical pneumonia is the atypical pneumonia that is caused by sars coronavirus.
Above-mentioned panaxoside Rg
1Content range also can be 60-99%, Rg
1Purity be more than 90%.
Medicine of the present invention contains the panaxoside Rg of medicinal effective dose
1Be active component, and contain one or more pharmaceutically acceptable carriers.
Above-mentioned pharmaceutically acceptable carrier is meant the pharmaceutical carrier of pharmaceutical field routine.
Oral tablet, soft capsule, hard capsule, granule or preparations such as oral liquid, enteric coatel tablets that medicine of the present invention can be made by known method.Active component is mixed with one or more carriers, be made into required dosage form then.
The amount of application of medicine of the present invention can be according to variations such as the type of route of administration, patient's age, body weight, the disease of being treated and the orders of severity, and its daily dose can be 50-500mg.
Medicine of the present invention is mainly used in the prevention of atypical pneumonia.
The animal acute experiment of medicine of the present invention:
Mice gastric infusion 3 times in 24 hours, (120ml/ 7200mg/kg), according to the weight, is equivalent to 4800 times of human dosage (90mg/60kg every day), non-toxic reaction to each 0.8ml/20g.Mice intraperitoneal injection 3 times in 24 hours, (60ml/kg, 3600mg/kg according to the weight, are equivalent to 2400 times of human dosage (90mg/60kg every day) r, non-toxic reaction to each 0.4ml/20g.
Medicine of the present invention is for the preventive effect of coronavirus:
One, test objective
Detect the external prevention of this medicine and suppress the effect of coronavirus No. 04,, provide test basis for accelerating the screening progress of medicine.
Two, test material
1, checking medicine: this medicine is provided by Daphne Pharmaceutical (Group) Co., Ltd.Yunnan.
2, positive control medicine: injection ganciclovir lot number: 020802 is provided by Hubei KeYi Pharmacentic Co., Ltd..
3, cell: tumor mould stricture of vagina flesh passage cell (RD cell) is provided by this chamber.
4, virus: coronavirus No. 04 (the SARS patients serum separates No. 04) provides by estimating peace hospital.
5, CO
2Incubator NUAIR US AUTO FLOW provides.
6, (XSZ-D2) produced by the optical instrument factory, Chongqing.
7, other reagent, equipment etc. provide by this chamber.
Three, test method
Pilot study:
1, this medicine is to the toxicity test of RD cell
The RD cell is inoculated 96 well culture plates with 400,000/ml concentration, 37 ℃, 5%CO
2Cultivated 24 hours, and added the checking medicine, verify that this medicine doubling dilution is 6000ug/ml～11.7ug/ml, the dilution of positive control medicine ganciclovir is 6000ug/ml～11.7ug/ml, and every concentration is inoculated 3 holes, every hole 100 μ l, establish the normal cell contrast simultaneously, 37 ℃ of 5%CO
2Incubator was cultivated 6 days, every day is observation of cell metamorphosis (CPE) under inverted microscope, with 25% following metamorphosis is "+", 26%～50% metamorphosis is " ++ ", 51%～75% metamorphosis is " +++", 76%～100% metamorphosis is " ++ ++ ", uses the Reed-Muench method, calculates medicine median toxic concentration (TD
50) and maximal non-toxic concentration (TD
0).
2, in the RD cell culture to the separation of coronavirus No. 04 and the mensuration of virulence
The separation that coronavirus is No. 04 (SARS patients serum separation):
The RD cell is with every milliliter 400,000 concentration inoculation test tube, 37 ℃ of 5%CO
2Cultivated 24 hours, and discarded culture fluid, every pipe adds SARS patients serum 0.2ml, and 33 ℃ of rotary drums were cultivated 5～7 days.After the CPE variation appears in cell, adopt the method for PCR to detect coronavirus, No. 04 specimen PCR positive is defined as the coronavirus separated strain.With whole last dilution method purified virus 2 times.It is still positive that PCR detects coronavirus, through immunofluorescence assay double SARS patients serum, and the IgM positive, IgG4 doubly raises, and is defined as coronavirus.Adopting viral CPE method to measure it tires.
Virus CPE method:
The RD cell is inoculated 96 well culture plates with every milliliter 400,000 concentration, 37 ℃ of 5%CO
2Cultivated 24 hours, and added viral liquid, viral dilution 10
-1～10
-6, 6 concentration, every concentration 3 holes, every hole 100 μ l establish the normal cell contrast, 37 ℃ of 5%CO
2Cultivated 5～7 days, observed and recorded cellular morphology variation (CPE) under inverted microscope in per 24 hours: to be changed to "+" below 25%, 26%～50% is changed to " ++ ", 51%～75% be " +++", 76%～100% be changed to " ++ ++ ", use the Reed-Muench method, calculate viral half and infect concentration TCID
50
Formal test
This medicine in the RD cell culture to the inhibitory action of coronavirus No. 04
Test objective:
To the inhibitory action of coronavirus No. 04, virocyte PCPE is adopted in test to this medicine of observing variable concentrations in the RD cell culture) method, calculate the medium effective concentration (IC of medicine
50) and minimum effective drug concentration (MIC) and therapeutic index TI, judge drug effect.
The RD cell is inoculated 96 well culture plates with 40/ml concentration, 37 ℃ of 5%CO
2Incubator was cultivated 24 hours, and cell culture discards culture fluid to single room, added 100TCID
50Coronavirus liquid, establish normal cell contrast and virus control simultaneously, put 37 ℃ of 5%CO
2Adsorb after 2 hours, discard viral liquid, add seven of variable concentrations and give birth to power sheet medicinal liquid, the maximal non-toxic concentration (TD of choice of drug pair cell
0) the i.e. 750 μ g/ml～1.46 μ g/ml of 10 concentration of 2 times of dilutions, positive control medicine ganciclovir is that 10 concentration of 2 times of dilutions are 6000ug/ml～11.7ug/ml, and the medicine that dilutes is added in the cell hole every concentration 3 holes respectively, establish normal cell contrast and virus control simultaneously, put 37 ℃ of 5%CO
2Incubator was cultivated 5～7 days, observed viral CPE day by day under inverted microscope, occurred with virus control +++---++ ++ in time, finish to test, and uses the Reed-Muench method, calculates the medium effective concentration (IC of medicine
50) and minimum effective drug concentration (MIC) and therapeutic index (TI) judgement drug effect, the test triplicate.
Four, result of the test
The pilot study result:
This medicine in the RD cell culture to the preventive effect of coronavirus No. 04
Test objective:
To the preventive effect of coronavirus No. 04, virocyte (CPE) method is adopted in test to this medicine of observing variable concentrations, calculates the medium effective concentration (IC of medicine in the RD cell culture
50) and minimum effective drug concentration (MIC) and therapeutic index TI, judge drug effect.
The RD cell is inoculated 96 well culture plates with 40/ml concentration, 37 ℃ of 5%CO
2Incubator was cultivated 24 hours, and cell culture discards culture fluid to single room, added this medicine medicinal liquid of variable concentrations, the maximal non-toxic concentration (TD of choice of drug pair cell
0) the i.e. 750 μ g/ml～1.46 μ g/ml of 10 concentration of 2 times of dilutions, positive control medicine ganciclovir is that 10 concentration of 2 times of dilutions are 6000ug/ml～11.7ug/ml, 37 ℃ of 5%CO are put in every concentration 3 holes
2Adsorbed 2.5 hours, and added 100TCID
50No. 04 liquid of coronavirus, establish normal cell contrast and virus control simultaneously, put 37 ℃ of 5%CO
2Incubator was cultivated 5～7 days, observed viral CPE day by day under inverted microscope, occurred with virus control +++--++ ++ in time, finish to test, and uses the Reed-Muench method, calculates the medium effective concentration (IC of medicine
50) and minimum effective drug concentration (MIC) and therapeutic index (TI) judgement medicine, the test triplicate.
Toxic action to the RD cell:
This medicine that is provided by Daphne Pharmaceutical (Group) Co., Ltd.Yunnan and positive control medicine injection ganciclovir adopt cellular morphology to change (CPE) method in the RD cell culture.Calculate medicine maximal non-toxic concentration (TD
0) and median toxic concentration (TD
50), following result of the test is the average of three result of the tests.
1, this medicine is to the toxicity test result of RD cell
The checking medicine:
This medicine: maximal non-toxic concentration (TD
0) be 750 ± 0 μ g/ml, median toxic concentration (TD
50) be 1500 ± 0 μ g/ml.
The positive control medicine:
Injection ganciclovir: maximal non-toxic concentration (TD
0) be＞6000 ± 0 μ g/ml, median toxic concentration (TD
50) be＞6000 ± 0 μ g/ml.
1, in the RD cell culture to No. 04 toxicity test result of coronavirus (TCID
50)
Coronavirus No. 04: median infective dose (TCID
50) be 10
-3
The formal test result
This medicine in the RD cell culture to the preventive effect (following test data is the average of three result of the tests) of coronavirus No. 04.
The checking medicine:
This medicine: CPE method, medicine medium effective concentration (IC
50) be 93.75 ± 0 μ g/ml, minimum effective drug concentration (MIC) is 46.8 ± 0 μ g/ml, therapeutic index (TI) is 16.
The positive control medicine:
Injection ganciclovir: CPE method, medicine medium effective concentration (IC
50) be 46.8 μ g/ml ± 0, minimum effective drug concentration (MIC) is 23.44 μ g/ml ± 0, therapeutic index (TI) is 256.
This medicine in the RD cell culture to the inhibitory action (following test data is the average of three result of the tests) of coronavirus No. 04.
The checking medicine:
This medicine: CPE method, medicine medium effective concentration (IC
50) be 375 ± 0 μ g/ml, minimum effective drug concentration (MIC) is 187.5 ± 0 μ g/ml, therapeutic index (TI) is 4.
The positive control medicine:
Injection has ganciclovir: CPE method, medicine medium effective concentration IC
50) be 46.8 μ g/ml ± 0, minimum effective drug concentration (MIC) is 23.44 μ g/ml ± 0, therapeutic index (TI) is 256.
Five, sum up
This medicine by Daphne Pharmaceutical (Group) Co., Ltd.Yunnan provides in the RD cell culture, adopts viral CPE method, and result of the test shows that this medicine has certain preventive effect to coronavirus, suppresses DeGrain.
The specific embodiment
Embodiment 1:
Get percentage by weight and be 90%, purity is 90% panaxoside Rg
1With the pharmaceutic adjuvant of surplus, make panaxoside Rg according to conventional enteric coatel tablets manufacturing process
1Enteric coated tablet.
Embodiment 2:
Get percentage by weight and be 70%, purity is 90% panaxoside Rg
1With the pharmaceutic adjuvant of surplus, make panaxoside Rg according to conventional capsule manufacturing process
1Capsule.
Claims (2)
1, panaxoside Rg
1Application in preparation prevention of atypical pneumonia medicine, described atypical pneumonia is the atypical pneumonia that is caused by sars coronavirus.
2, by percentage by weight be the panaxoside Rg of 50-99%
1With the application of compositions in preparation prevention of atypical pneumonia medicine that the surplus pharmaceutic adjuvant is formed, described atypical pneumonia is the atypical pneumonia that is caused by sars coronavirus.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310103718 CN1265796C (en) | 2003-10-24 | 2003-10-24 | SARS preventing medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310103718 CN1265796C (en) | 2003-10-24 | 2003-10-24 | SARS preventing medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1608627A CN1608627A (en) | 2005-04-27 |
| CN1265796C true CN1265796C (en) | 2006-07-26 |
Family
ID=34756767
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200310103718 Expired - Lifetime CN1265796C (en) | 2003-10-24 | 2003-10-24 | SARS preventing medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1265796C (en) |
-
2003
- 2003-10-24 CN CN 200310103718 patent/CN1265796C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CN1608627A (en) | 2005-04-27 |
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| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: DAPHNE PHARMACEUTICAL (GROUP) CO.,LTD. YUNNAN Assignor: Tang Xiuwen Contract fulfillment period: 2009.10.10 to 2015.10.9 Contract record no.: 2009530000040 Denomination of invention: SARS preventing medicine Granted publication date: 20060726 License type: Exclusive license Record date: 20091013 |
|
| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.10.10 TO 2015.10.9; CHANGE OF CONTRACT Name of requester: DAPHNE PHARMACEUTICAL (GROUP) CO., LTD.YUNNAN Effective date: 20091013 |
|
| ASS | Succession or assignment of patent right |
Owner name: YUNNAN DAPHNE PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: TANG XIUWEN Effective date: 20140416 |
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| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 650236 YUXI, YUNNAN PROVINCE TO: 663000 YUXI, YUNNAN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20140416 Address after: 663000 37 pharmaceutical industry park, Yunnan, Wenshan Patentee after: DAPHNE PHARMACEUTICAL (GROUP) CO.,LTD. YUNNAN Address before: Panzhihua 650236, Yunnan province Wenshan County Township Gordon pharmaceutical factory Patentee before: Tang Xiuwen |
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| CX01 | Expiry of patent term |
Granted publication date: 20060726 |
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| CX01 | Expiry of patent term |