Application of clodronate disodium liposome in adjuvant chemotherapy of tumor adriamycin

A technology of disodium clodronate and doxorubicin, applied in liposome delivery, antineoplastic drugs, medical preparations containing active ingredients, etc., can solve ventricular remodeling and congestive heart failure, myocardial contractility reduce the increase of myocardial fibrosis and other problems, and achieve the effects of reducing pharmaceutical costs, reducing bone metastasis, and reducing myocardial toxicity

Inactive Publication Date: 2020-04-10
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to solve the problems in the prior art that when doxorubicin is used for anti-tumor treatment, it can induce apoptosis and necrosis of myocardial cells, increase myocardial fibrosis, reduce myocardial contractility, and eventually lead to ventricular remodeling and congestive heart failure. Provides the application of clodronate disodium liposome in the preparation of drugs with adjuvant chemotherapy effect on tumor doxorubicin. The property of clodronate disodium liposome is stable. After entering the body, the degradation cycle is long and the drug effect is long-lasting. Good biocompatibility, and it has been reported that disodium clodronate liposomes can inhibit tumor growth

Method used

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  • Application of clodronate disodium liposome in adjuvant chemotherapy of tumor adriamycin
  • Application of clodronate disodium liposome in adjuvant chemotherapy of tumor adriamycin
  • Application of clodronate disodium liposome in adjuvant chemotherapy of tumor adriamycin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] [Example 1] Clodronic acid disodium liposome preparation and characterization detection

[0030] (1) Clodronate disodium liposome preparation

[0031] 1. Preparation method:

[0032] Weigh cholesterol, lecithin and disodium clodronate and put them in a container, add chloroform-methanol mixture, the volume ratio of chloroform to methanol in the chloroform-methanol mixture=2:1, rotate at 50-60°C Thin film evaporation method was used to rotate the film for 20-50min to make a uniform lipid dry film; the thickness of the lipid dry film was 0.1-0.2mm; dry the residual solvent with nitrogen, and then add phosphine dissolved in disodium clodronate Acid buffer solution to fully swell and hydrate the lipid membrane, sonicate for 5 minutes under the condition of ultrasonic power of 400W, then centrifuge at 22000rpm and 10°C for 1 hour, and resuspend the liposomes in the lower layer with phosphate buffered saline solution with pH=7.2. Obtained; the mass ratio of cholesterol to l...

Embodiment 2

[0077] [Example 2] Research on the effect of clodronate disodium liposome on weakening adriamycin cardiotoxicity

[0078] (1) Grouping and handling of animals

[0079] 6-8 weeks old C57BL / 6 male mice, 10 in each group, were divided into normal control group, model control group and clodronate disodium liposome treatment group. (1) The normal control group was injected intraperitoneally with the same amount of normal saline every day for 7 consecutive days; (2) The model control group was injected with the same amount of normal saline intraperitoneally one day in advance, and DOX (doxorubicin) 20 mg / kg was injected intraperitoneally on the second day; (3) Clodronate disodium liposome low-dose experimental group was injected intraperitoneally with 5 μl / g disodium clodronate liposome on the first day, and DOX (doxorubicin) 20mg / kg was injected intraperitoneally on the second day; (4) clodronate The disodium liposome high-dose experimental group was intraperitoneally injected 10 ...

Embodiment 3

[0092] [Example 3] Application of clodronate disodium liposome in the treatment of breast cancer with adriamycin

[0093] (1) Grouping and handling of animals

[0094] 4T1 breast cancer cells (1×10 6 each), until the tumor volume reaches 100mm 3 The time was recorded as the 0th day, and they were divided into random groups, 10 rats in each group, and divided into control group, model control group, and clodronate disodium liposome treatment group. (1) The normal control group was injected intraperitoneally with the same amount of normal saline every day; (2) The model control group was injected with the same amount of normal saline intraperitoneally on the first day, then injected with normal saline once a week, and injected DOX (doxorubicin) 4 mg intraperitoneally on the second day After that, Adriamycin was injected once a week for five consecutive weeks; (3) the clodronate disodium liposome low-dose experimental group was injected intraperitoneally with 5 μl / g clodronate ...

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Abstract

The invention discloses application of liposomal clodronate on the adjuvant treatment aspect of tumor doxorubicin chemotherapy. After an appropriate amount of cholesterol and lecithin are mixed, a chloroform-methyl alcohol mixed solution is added, a rotary thin-film evaporation method is adopted to prepare a uniform dry lipid film, and then a phosphate buffer solution of disodium clodronate is added. The liposomal clodronate has the advantages that it is found that the prepared stable and efficient liposomal clodronate can reduce cardiotoxicity caused by doxorubicin and improve the breast cancer treatment effect of the doxorubicin.

Description

technical field [0001] The invention relates to the application of a medicine, in particular to the new application of clodronate disodium liposome. Background technique [0002] Heart failure has increasingly become the most common and most harmful disease among cardiovascular diseases, and the causes of heart failure are very complex and diverse. Therefore, heart failure has become the focus and difficulty in the field of cardiovascular disease research. Cardiac toxicity and side effects during cancer treatment can also cause heart failure, which seriously affects the quality of life of cancer patients. More importantly, the development of toxicity may lead to the adjustment or even cessation of anti-tumor treatment regimens, affecting the survival of patients ( Binaschi M, et al., 2001). The manifestations of cardiotoxicity caused by antineoplastic drugs are complex and diverse, and common manifestations include arrhythmia, myocardial ischemia, coronary artery disease, h...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K33/42A61K9/127A61K31/704A61P35/00
CPCA61K9/127A61K31/704A61K33/42A61K2300/00
Inventor 周晓阳黄可晴杨静
Owner WUHAN UNIV
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