CN1520823A - Novel compound antineoplastic drug preparing process - Google Patents
Novel compound antineoplastic drug preparing process Download PDFInfo
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- CN1520823A CN1520823A CNA031023843A CN03102384A CN1520823A CN 1520823 A CN1520823 A CN 1520823A CN A031023843 A CNA031023843 A CN A031023843A CN 03102384 A CN03102384 A CN 03102384A CN 1520823 A CN1520823 A CN 1520823A
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- cantharidin
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Abstract
The compound antitumor medicine consists of cantharidin derivative, artemisinin derivative and metal ion as antitumor promoter in the ratio of 1 to 1-1000 to 0.1-1000 and medicinal supplementary material. The present invention has lowered medicinal toxicity and raised treating effect on several kinds of malignant tumor.
Description
The present invention relates to a kind of preparation method with synergism and attenuation antitumor drug compound recipe.This compound recipe is (to comprise Cantharidin Cantharidin by the Cantharidin analog derivative, norcantharidin Norcantharidinum, Cantharidin sodium Sodium Cantharidinate, hydroxycantharidimide N-Hydroxycantharidin, Methyl cantharidinimide Methyleantharidinimide Methylcantharidimide N-Methylcantharidimide) (I) form with attenuation synergistic dosage with artemisinin derivatives (II) (comprising dihydroarteannuin, artesunate, sodium artesunate, Artemether, arteether).
Cantharidin class medicine is a kind of antitumor drug since the clinical use eighties, is one group of derivant by the Cantharidin that extracts in the big speckle insect destructive of the roots of seedlings in south and the yellow black stigma insect destructive of the roots of seedlings body.Its main anticancer mechanism is: anticancer DNA and proteinic synthetic; Influence cancerous cell mitochondria respiratoring control rate and enzymatic activity; The mitosis process of interfere with cancer cells; Increase body's immunity; Leukocyte increasing quantity.Its main advantage is: toxic and side effects is very little; Can under the prerequisite that suppresses tumor, increase the immunity of body comprehensively; Leucocytes reduction after the chemicotherapy is eased and recovers.Its major defect is: not to be very high increase consumption if improve suppression ratio to the antitumor suppression ratio causes bigger toxic and side effects easily; Be suitable for being difficult to as medicine use separately as auxiliary medicaments.
Artemisinin derivative (comprising dihydroarteannuin, artesunate, sodium artesunate, Artemether, arteether) is the chemical compound for having half times of terpene structure of peroxy-radical (I).Artemisinin-based drug has used as antimalarial since coming out always.Up to the nineties, people find its antitumor action first.At present, known artemisinin derivatives antitumor spectra comprises malignant tumor such as hepatocarcinoma, pulmonary carcinoma, gastric cancer, breast carcinoma, osteocarcinoma, leukemia, colon cancer, melanoma, fibroma.Its advantage is: the antitumor spectrum is wider; Antitumor action is obvious; Metabolism is not easy rapidly to develop immunity to drugs; Under relatively low dosage, use toxic and side effects minimum.Its major defect is: use must reach higher amounts and just can reach antitumor action separately; And toxicity is comparatively obvious under this drug dose, and outstanding behaviours is a neurotoxicity etc.
The present invention is the compound preparation of being made up of the Cantharidin analog derivative and the artemisinin derivatives of potentiation mutually experimental results demonstrate.
In view of the Cantharidin analog derivative has that toxic and side effects is less, the anticancer mitosis, can the human body immunity improving ability etc. advantage; And quick-acting, the broad-spectrum anti-tumor of artemisinin derivatives, be difficult for producing the advantage of resistance.Our developing thought be performance its separately advantage, sublate it separately on the basis of shortcoming, find two groups of medicine suitable proportioning, add a certain amount of metal ion simultaneously to reach the effect that promotes drug effect.
, the tumor-bearing mice animal model shows that the potentiation dosage of this compound recipe is at Cantharidin analog derivative (I) and artemisinin derivatives (II) and promote that the ratio of the metal ion consumption of antitumous effect is I: II: in the scope of metal ion=1: 1～1000: 0.1～1000 by being tested.Toxicity test shows that this compound recipe toxicity is than using Cantharidin analog derivative (I) and the artemisinin derivatives (II) of the same course of treatment that bigger reduction is all arranged separately.The inhibition test that bearing mouse model is carried out shows, this compound recipe improves 70% to the suppression ratio of malignant tumor tumors such as hepatocarcinoma, pulmonary carcinoma, gastric cancer, breast carcinoma, osteocarcinoma, leukemia, colon cancer, melanoma, fibroma than the independent Cantharidin analog derivative (I) that uses, and improves 30% than independent use artemisinin derivatives (II).Medication to tumor-bearing mice studies show that, this compound recipe to above each tumor control rate generally all more than 50%, the highest can reaching more than 70%.
Embodiment one: to ascites hepatocarcinoma H
22Research in the body of tumor-bearing mice
Use continuous 14 days intraperitoneal administrations of this compound preparation 10mg/kg, the mice time-to-live did not all have ascites and produces greater than 50 days; And continuous 14 days intraperitoneal administrations of the cyclophosphamide 10mg/kg of matched group, the mice time-to-live be 14.4 soil 1.9 days, and the Total Test mice within 30 days because of ascites death.Blank group Total Test mice also within 30 days because of ascites death.This effect that in vivo test of this medicine is described is better than antineoplastic agent---cyclophosphamide; Cyclophosphamide can not suppress the development of ascites, only can prolong the time-to-live of mice, and the complete kill cancer cell of this compound preparation energy reaches the generation of eliminating ascites fully.To liver-cancer solid tumor, take the suppression ratio of this compound recipe under the oral dose of 30mg/kg and be about 70%, and the suppression ratio of cyclophosphamide-a control group is 42.5% (dosage is 40mg/kg).
Embodiment two: to the inhibitory action of B16 melanoma transplanted tumor tumor-bearing mice
Use continuous 6 days oral administrations of this compound preparation 30mg/kg, and 6 days oral administrations of the cyclophosphamide of matched group.Observed through 30 days, oral administered compound group melanoma suppression ratio is 51%, and oral cyclophosphamide 40mg/kg group suppression ratio is 53%, and blank group Total Test mice is dead within 30 days.This illustrates this medicine in the melanomatous in vivo test of treatment, and effect is similar to oral cyclophosphamide.
Claims (4)
1. novel antitumor drug compound recipe preparation method, this compound recipe is Cantharidin class medicine (I) and the compound recipe antitumor drug of artemisinin-based drug (II) with certain attenuation synergistic dosage composition, and the metal ion (for example: ferrum, cobalt, copper, platinum, zinc etc.) that adds respective amount as antitumor promoter, is strengthened the clinical efficacy of this anti-tumor compound.Its therapeutic domain is: malignant tumor such as hepatocarcinoma, pulmonary carcinoma, gastric cancer, breast carcinoma, osteocarcinoma, leukemia, colon cancer, melanoma, fibroma,
2. according to claim 1, the preparation method of a kind of Cantharidin analog derivative and artemisinin derivatives anti-tumor compound, it is characterized in that and to have the Cantharidin class medicine of attenuation synergistic effect dosage (to comprise Cantharidin Cantharidin, norcantharidin Norcantharidinum, Cantharidin sodium SodiumCantharidinate, hydroxycantharidimide N-Hydroxycantharidin, Methyl cantharidinimide Methyleantharidinimide Methylcantharidimide N-Methylcantharidimide) (I) with:
(1) has arteannuin group in the artemisinin derivatives (II) of attenuation synergistic effect dosage
The compound recipe that becomes,
(2) have two hydrogen Herba Artemisiae Annuaes in the artemisinin derivatives (II) of attenuation synergistic effect dosage
The plain compound recipe of forming,
(3) or with the artemisinin derivatives with attenuation synergistic effect dosage (II) in Herba Artemisiae Annuae
The compound recipe that the amber ester is formed,
(4) or with the artemisinin derivatives with attenuation synergistic effect dosage (II) in Herba Artemisiae Annuae
The compound recipe that amber ester sodium is formed,
(5) or with the artemisinin derivatives with attenuation synergistic effect dosage (II) in Hao Jia
The compound recipe that ether is formed,
(6) or with the artemisinin derivatives with attenuation synergistic effect dosage (II) in Artemisia second
The compound recipe that ether is formed,
3. a kind of novel antitumor drug compound recipe preparation method as claimed in claim 1 and the relation of the ingredient in the claim 2, Cantharidin analog derivative (I) is with artemisinin derivatives (II) and promote that the ratio of the metal ion consumption of antitumous effect is I: II: metal ion=1: 1～1000: 0.1～1000
4. a kind of new type antineoplastic medicine as claimed in claim 1, in claim 3 defined scope, according to the efficacy enhancing and toxicity reducing ratio of the best, add a series of pharmaceutic adjuvants that meet the pharmacy regulation and make various dosage forms such as tablet, capsule, electuary, suppository, oral liquid and injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031023843A CN1327842C (en) | 2003-02-12 | 2003-02-12 | Novel compound antineoplastic drug preparing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031023843A CN1327842C (en) | 2003-02-12 | 2003-02-12 | Novel compound antineoplastic drug preparing process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1520823A true CN1520823A (en) | 2004-08-18 |
| CN1327842C CN1327842C (en) | 2007-07-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB031023843A Expired - Fee Related CN1327842C (en) | 2003-02-12 | 2003-02-12 | Novel compound antineoplastic drug preparing process |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014082570A1 (en) * | 2012-11-29 | 2014-06-05 | 昆明制药集团股份有限公司 | Artemether-containing pharmaceutical composition, preparation, and use thereof |
| WO2014082569A1 (en) * | 2012-11-29 | 2014-06-05 | 昆明制药集团股份有限公司 | Use of artemether in preparation of drug for treating leukemia |
| CN106928274A (en) * | 2017-02-28 | 2017-07-07 | 东南大学 | A kind of dihydroartemisinine dliploid derivative, its pharmaceutical composition and application |
| CN110051850A (en) * | 2016-08-26 | 2019-07-26 | 宁国市厚普生物科技有限公司 | A kind of compound is preparing the application in the drug for treating melanoma |
| CN113072588A (en) * | 2021-03-19 | 2021-07-06 | 中国人民解放军空军军医大学 | Tetravalent platinum complex containing artesunate and preparation method and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1068002C (en) * | 1997-04-30 | 2001-07-04 | 中国科学院大连化学物理研究所 | Mesoplatinum anticarcinogen and its synthesis |
| CN1084333C (en) * | 1998-06-17 | 2002-05-08 | 中国科学院上海药物研究所 | Artemisine compounds, their preparing process and medicine composition containing them |
-
2003
- 2003-02-12 CN CNB031023843A patent/CN1327842C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014082570A1 (en) * | 2012-11-29 | 2014-06-05 | 昆明制药集团股份有限公司 | Artemether-containing pharmaceutical composition, preparation, and use thereof |
| WO2014082569A1 (en) * | 2012-11-29 | 2014-06-05 | 昆明制药集团股份有限公司 | Use of artemether in preparation of drug for treating leukemia |
| CN110051850A (en) * | 2016-08-26 | 2019-07-26 | 宁国市厚普生物科技有限公司 | A kind of compound is preparing the application in the drug for treating melanoma |
| CN106928274A (en) * | 2017-02-28 | 2017-07-07 | 东南大学 | A kind of dihydroartemisinine dliploid derivative, its pharmaceutical composition and application |
| CN113072588A (en) * | 2021-03-19 | 2021-07-06 | 中国人民解放军空军军医大学 | Tetravalent platinum complex containing artesunate and preparation method and application thereof |
| CN113072588B (en) * | 2021-03-19 | 2023-10-13 | 中国人民解放军空军军医大学 | Tetravalent platinum complex containing artesunate and preparation method and application thereof |
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| Publication number | Publication date |
|---|---|
| CN1327842C (en) | 2007-07-25 |
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Granted publication date: 20070725 Termination date: 20100212 |