Anti-cancer composition containing tyrosine kinase inhibitor and alkylating agent
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A tyrosine kinase and inhibitor technology, applied in the field of anticancer compositions, can solve the problems of enhanced tolerance, treatment failure and the like
Inactive Publication Date: 2007-11-21
JINAN KANGQUAN PHARMA TECH
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Problems solved by technology
The latter often leads to increased resistance of tumor ce
Method used
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Effect test
Embodiment 1
[0114] Put 80, 80 and 80 mg of p(BHET-EOP / TC) (BHET-EOP: TC is 80: 20) copolymers into three containers of A, B and C respectively, and then add 100 ml of dichloromethane to each , after dissolving and mixing, add 20mg dasatinib, 20mg carmustine, 10mg dasatinib and 10mg carmustine respectively, and prepare 20% dasatinib, 20 % carmustine, and 10% dasatinib and 10% carmustine microspheres for injection. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection. The drug release time of the sustained release injection in physiological saline in vitro is 60-70 days, and the drug release time in mouse subcutaneous is more than 60 days.
Embodiment 2
[0116]The method step of being processed into slow-release injection is identical with embodiment 1, but difference is that used auxiliary material is the p(BHET-EOP / TC) of 50: 50, containing anticancer active ingredient and weight percent thereof are:
[0117] (1) 5-40% of Dasatinib or Tipifarnib;
[0118] (2) 1-30% carmustine, nimustine or lomustine; or
[0119] (3) Combination of 5-40% dasatinib or tipifarnib and 1-30% carmustine, nimustine or lomustine.
Embodiment 3
[0121] Put 70 mg of p(LAEG-EOP) with a peak molecular weight of 10,000-25,000 into three containers of A, B, and C, respectively, and then add 100 ml of dichloromethane to each, dissolve and mix well, and pour into the three containers respectively Add 30mg tipifarnib, 30mg carmustine, 20mg tipifarnib and 10mg carmustine, re-shake up and use spray drying method to prepare 30% tipifarnib, 30% carmustine, 20 % Tipifarnib and 10% Carmustine for Injection Microspheres. The dried microspheres are suspended in physiological saline containing 1.5% sodium carboxymethylcellulose to prepare the corresponding suspension-type sustained-release injection. The drug release time of the sustained release injection in physiological saline in vitro is 60-65 days, and the drug release time in mice subcutaneous is about 60 days.
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Abstract
The invention is concerned with a kind of sustained and controlled release injection of vanticancer compound of depressor with protein tyrosine kinase and /or alkylating agent, relating to sustained and controlled release microsphere and menstruum. The microsphere has effect component and sustained and controlled release assistant stuff form the depressor with protein tyrosine kinase and/ or alkylating agent, and the menstruum is common menstruum or special menstruum with assistant suspending agent. The viscosity of assistant suspending agent is 100cp to 3000cp (20 to 30 degree) selecting form Carboxymethylcellulose sodium, and so on. The sustained and controlled release assistant stuff are seleted from the polyphosphate ester copolymer or copolymer of polyphosphate ester and polylactic acid, polystyrene propionic double fatty acids and sebacic acid, copolymer of poly (erucic acid dimmer-sebacic acid) or poly (fumaric acid-sebacic acid), such as p(LAEG-EOP), p(DAPG-EOP), p(BHET-EOP/TC), p( BHET-EOP/TC), p(BHDPT-EOP/TC), p(BHDPT-EOP/TC), p(CHDM-HOP) or p(CHDM-EOP). The anticancer compound is made into sustained and controlled release implant and injects or sets in the tumour or on the round of tumour to maintain the effect concentration over 60 days. It reduces the reaction of whole body greatly and increases the cure effect of nonoperative treatments, such as chemoradiotherapy with selectivity.
Description
(1) Technical field [0001] The invention relates to an anticancer composition containing a tyrosine kinase inhibitor and / or an alkylating agent, which is an anticancer slow-release injection and a slow-release implant, and belongs to the technical field of medicines. (2) Background technology [0002] As a class of commonly used chemotherapeutic drugs, tyrosine kinase inhibitors have been widely used in the treatment of various malignant tumors, and the effect is relatively obvious. However, its significant toxicity greatly limits the wide application of this class of drugs. [0003] Due to the excessive expansion and hyperplasia of solid tumors, the interstitial pressure, tissue elastic pressure, fluid pressure and interstitial viscosity are all higher than those of the surrounding normal tissues. Therefore, it is difficult for conventional chemotherapy to form an effective drug concentration in the tumor. In addition, blood vessels, connective tissue, matrix proteins, fib...
Claims
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