CN1109546C - Compound antimalarial medicine containing artemisine medicines and malaridine - Google Patents
Compound antimalarial medicine containing artemisine medicines and malaridine Download PDFInfo
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- CN1109546C CN1109546C CN98115332A CN98115332A CN1109546C CN 1109546 C CN1109546 C CN 1109546C CN 98115332 A CN98115332 A CN 98115332A CN 98115332 A CN98115332 A CN 98115332A CN 1109546 C CN1109546 C CN 1109546C
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- malaridine
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- arteannuin
- artemether
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The present invention belongs to antimalarial medicine which is mainly compounded by medicine in the class of arteannuin and malaridine. Medicine in the class of arteannuin has the advantages of short half-life period and high afterburning rate. A product of the present invention essentially contains 35 to 80 weight portions of medicine in the class of artemisinin and 2 to 10 weight portions of malaridine and contains general pharmaceutic adjuvant at the same time. The medicine in the class of arteannuin comprises arteannuin, dihydroarteannuin, artemether, arteether, artesunate, arteether phosphoric acid, etc. The antimalarial preparation obtained by the substances has the advantages of small toxicity, high stability and improvement in a treating effect, medicine in the class of arteannuin and malaridine are compounded according to the proportion, and obtained medicine has the functions of obviously increasing effect and reducing the afterburning rate.
Description
Technical field
The invention belongs to a kind of is the antimalarial agent that main compound recipe forms by artemisinin-based drug and malaridine.
Background technology
Artemisinin-based drug is the arteannuin that extracts from Chinese medicine Herba Artemisiae Annuae, Herba Artemisiae annuae, Yunnan Artemisia annua L. F. Macrocephala Pamp and the semi-synthetic derivant thereof of China's invention, is representative with the Artemether, is a class new high-efficiency anti-malarial agents.Cross resistance with existing antimalarial does not appear so far as yet.This class medicine has been applied to subtertian malaria in global malaria district treatment has obtained tangible economic benefit and social benefit.This class medicine half-life is short, and recrudescence rate is high slightly, also might bring out the generation drug resistance.There is the recrudescence rate of report arteannuin very high, do not use clinically in fact substantially.Also there is similar problem in other artemisinin derivatives.
Summary of the invention
The objective of the invention is to overcome the above-mentioned shortcoming of artemisinin-based drug, a kind of high curative effect is provided, the antimalarial agent of low recrudescence rate.
The present invention is according to world's antimalarial research and development trend, and the effect characteristics of artemisinin-based drug, by secular repetition test, contrast, analysis and screening, itself and long lasting antimalarial agent malaridine is got compound preparation through scientific composition.Malaridine is also efficient for a class of China invention, the novel antimalarial of low toxicity, its long half time, behind the two recurrence due to taking drug sides of setting up jointly, can complementary potentiation to improve curative effect, reduction recrudescence rate, suspension of pesticide resistance generation.
Product of the present invention contains 35～80 parts of (weight ratio) artemisinin-based drugs in essence, and malaridine 2-10 part is also contained conventional pharmaceutic adjuvant simultaneously.Product of the present invention preferably contains the 35-80mg artemisinin-based drug by every dosage and the 2-10mg malaridine is made oral formulations.
Said artemisinin-based drug comprises: arteannuin, dihydroarteannuin, Artemether, arteether, artesunate, the acid of Artemisia ether woods etc.
The malaria preparation of above-mentioned formation gained, little, the good stability of toxicity, curative effect improves, and two medicines have made up obvious synergistic effect according to the above ratio and have reduced the recrudescence rate effect.This can be confirmed by following experimental result: one, Artemether and malaridine list are used the inhibiting observation of Mus malaria erythrocytic stage
Method: adopt four days inhibition methods, i.e. rbc is infected in mice do inoculation p.berghei ANKA strain, and every Mus is the first agent medicine of ig after 5,000,000,4 hours, and successive administration 4 days is had a blood test, and asks the parasitemia negative conversion rate.All with the preparation of 1% tragakanta, the result is as follows for medicine:
Artemether is to the inhibitory action of Mus malaria
| Dosage (mg/kg * 4) | Number of animals | The Mus number of turning out cloudy |
| 3.89 | 10 | 0 |
| 4.86 | 10 | 1 |
| 6.08 | 10 | 3 |
| 7.6 | 10 | 6 |
| 9.5 | 10 | 7 |
| ED 50 | 7.38(6.16-8.85) | |
| ED 95 | 14.81(10.48-19.95) |
Malaridine is to the inhibitory action of Mus malaria
Two, Artemether and malaridine share Mus malaria erythrocytic stage inhibitory action
| Dosage (mg/kg * 4) | Number of animals | The Mus number of turning out cloudy |
| 0.63 | 10 | 0 |
| 0.84 | 10 | 2 |
| 1.13 | 10 | 8 |
| 1.5 | 10 | 10 |
| ED 50 | 0.97(0.88-1.08) | |
| ED 95 | 1.27(1.07-1.52) |
Experimental technique is the same.The ED95 of each medicine when asking Artemether and malaridine compatibility to use respectively, and make isoboles, the model of action of learning drug combination is addition.Three, Artemether and malaridine merge the experimental therapy of using infection Bai Shi plasmodium mice
Method: Kunming mouse d
0Rbc, every Mus 5,000,000, d are infected in abdominal cavity inoculation p.berghei ANKA strain
3Treat that parasitemia reached behind the 5-10% successive administration 3 days, have a blood test, ask the parasitemia negative conversion rate.All with the preparation of 1% tragakanta, malaridine and Artemether are made into mixture by 1 to 15 to medicine.The result is as follows: drug dose (mg/kg * 3) the number of animals Mus of turning out cloudy is counted Artemether 36.9 10 2
46.1 10 5
57.6 10 5
72.0 10 5
90.0 10 6
ED
95376.8 (187.5-786.6) malaridine 1.2 10 0
1.5 10 2
1.9 10 5
2.3 10 5
2.9 10 7
ED
954.3 (2.7-6.8) Artemether and malaridine 10.8 90 (15: 1) 14.4 10 1
19.2 10 6
25.6 9 7
ED
95 30.1(22.5-40.3)
The amalgamation mode of mixture is calculated by equation, and formula is as follows: the expection ED of 1/ mixture
95The ED of=a/A chemical compound
95The ED of+b/BA chemical compound
95(a, b are respectively A, B chemical compound shared ratio in mixture, a+b=1)
Experimental result is calculated expection ED for the above-mentioned formula of people
95=58.7.
According to keplinger, ML etc., expection ED
95With actual measurement ED
95Ratio be antagonism less than 0.75,0.75-1.75 is a summation action, greater than 1.75 for potentiation.
This experiment actual measurement ED
95Be 30.1, expection ED
95/ actual measurement ED
95=1.95 (＞1.75), so the drug combination model of action is judged to potentiation.Four, Artemether and malaridine share infecting the influence of Bai Shi plasmodium mice resume combustion at a specified future date
Artemether merges to use with malaridine to be compared with independent application, no matter the plasmodium ANKA strain mice of infection medicine sensitivity or the former Tubifex disease of Bai Shi plasmodium RL NAKA strain mice of chloroquine resistance is turned out cloudy soon, and resume combustion at a specified future date is slower, and recrudescence rate is low
Compare with prior art, the advantage of product of the present invention is the drug effect height, and recrudescence rate is low.
The specific embodiment
Embodiment 1:
With Artemether 50g, malaridine 3g, carboxymethyl starch sodium 15.6g, microcrystalline Cellulose 15g, medical starch 180g, tween 80 1g, magnesium stearate 4g, be that 1000, packing form Coartem malaridine tablet by granulating, pressing.This product is taken a slice at every turn, every day three times, five days one courses of treatment.
Embodiment 2:
With Artemether 40g, malaridine 3.5g, carboxymethyl starch sodium 12.48g, low-substituted hydroxypropyl cellulose 7 grams, medical starch 250g, tween 80 0.8g, magnesium stearate 3.2g, by granulate, dry, capsule subpackage is that 1000, packing form Coartem malaridine capsule.Each one of this product, every day three times, five days one courses of treatment.
Above embodiment is only for the present invention is further illustrated, and scope of invention is not subjected to the limitation of illustrated embodiment.
Claims (2)
1, the compound preparation antimalarial agent of a kind of artemisinin-based drug and malaridine is characterized in that containing in essence by weight being 35～80 parts of Artemether, and malaridine 2-10 part is also contained conventional pharmaceutic adjuvant simultaneously.
2,, it is characterized in that containing the 35-80mg Artemether and the 2-10mg malaridine is made oral formulations by every dosage as the said antimalarial agent of claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98115332A CN1109546C (en) | 1998-06-17 | 1998-06-17 | Compound antimalarial medicine containing artemisine medicines and malaridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98115332A CN1109546C (en) | 1998-06-17 | 1998-06-17 | Compound antimalarial medicine containing artemisine medicines and malaridine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1238950A CN1238950A (en) | 1999-12-22 |
| CN1109546C true CN1109546C (en) | 2003-05-28 |
Family
ID=5224514
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98115332A Expired - Lifetime CN1109546C (en) | 1998-06-17 | 1998-06-17 | Compound antimalarial medicine containing artemisine medicines and malaridine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1109546C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101544638B (en) * | 2009-05-12 | 2012-05-30 | 重庆通天药业有限公司 | Lact-pyrondridin and its pharmaceutical composition |
| CN113350334A (en) * | 2021-02-05 | 2021-09-07 | 中国中医科学院中药研究所 | Antimalarial drug containing dihydroartemisinin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1041694A (en) * | 1988-10-07 | 1990-05-02 | 赫彻斯特股份公司 | The anti-malaria composition of quinidine, arteannuin and derivant thereof and Therapeutic Method |
| CN1075254A (en) * | 1992-02-07 | 1993-08-18 | 希巴-盖吉股份公司 | Compound with cooperation of anti-malaria |
-
1998
- 1998-06-17 CN CN98115332A patent/CN1109546C/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1041694A (en) * | 1988-10-07 | 1990-05-02 | 赫彻斯特股份公司 | The anti-malaria composition of quinidine, arteannuin and derivant thereof and Therapeutic Method |
| CN1075254A (en) * | 1992-02-07 | 1993-08-18 | 希巴-盖吉股份公司 | Compound with cooperation of anti-malaria |
Non-Patent Citations (1)
| Title |
|---|
| CHEMICAL,ABSTRACT VOL.126,NO.324959,1997 1997-06-23 peters.et al."chemotherapy of radent malaria iv.interaction between pyronaridine and artemisinin" * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1238950A (en) | 1999-12-22 |
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| 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 | ||
| C56 | Change in the name or address of the patentee | ||
| CP03 | Change of name, title or address |
Address after: 200025 Luwan District Road, Ruijin, No. two, No. 207, Shanghai Patentee after: Prevention & Control Station of Parasitic Disease, China Diseases Prevention & C Patentee after: Kun Yao Group Plc Address before: 200025 No. two, 207, Ruijin, Shanghai Patentee before: Inst. of Parasitic Diseases Prevention & Control, Chinese Center of Diseases Pre Patentee before: Kunming Pharmaceutical Industry Group Corp., Ltd. |
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| CX01 | Expiry of patent term |
Granted publication date: 20030528 |
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| CX01 | Expiry of patent term |