Slow-released injection containing nolatrexed dihydrochloride and synergist thereof

A technology of sustained-release injection and synergist, applied in the field of medicine, can solve the problems of complicated operation, cost-effective implementation, treatment failure, etc.

Inactive Publication Date: 2009-04-29
SHANDONG LANJIN PHARMA +1
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Not only that, the excessive expansive hyperplasia of solid tumors, the interstitial pressure, tissue elastic pressure, fluid pressure and interstitial viscosity are all higher than those of the surrounding normal tissue. Therefore, it is difficult for conventional chemotherapy to form an effective drug concentration in the tumor. See Kong Qingzhong et al. "Intratumoral placement of cisplatin plus systemic carmustine in the treatment of rat brain tumors" "Journal of Surgical Oncology" 69 pages 76-82 (1998) (Kong Q et al., J SurgOncol.1998 Oct; 69 (2): 76-82), simply increasing the dosage is limited by systemic reactions
Local application of drugs may solve the problem of drug concentration to some extent. However, surgical operations such as drug implantation are more complicated and traumatic. In addition to easily leading to various complications such as bleeding, infection, and decreased immunity, it may also cause or Accelerate tumor spread and metastasis
In addition, the preparation and expensive costs before and after the operation often affect its effective implementation.
[0003] The DNA repair function in tumor cells is significantly increased after chemotherapy, which often leads to the enhancement of tumor cell resistance to anticancer drugs, resulting in treatment failure

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] Put 80mg polyphenylene propane (p-CPP: sebacic acid (SA) 20:80) copolymer into a container, add 100ml methylene chloride, dissolve and mix well, then add 10mg Pemetrexed and 10 mg of camptothecin were re-shaken and spray-dried to prepare microspheres for injection containing 10% of pemetrexed and 10% of camptothecin. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection. The viscosity of the injection is 200cp-650cp (at 20°C-30°C). The drug release time of the slow-release injection in physiological saline in vitro is 20-30 days, and the drug release time in mice subcutaneous is about 30-40 days.

Embodiment 2

[0127] The method step of being processed into sustained-release injection is the same as in Example 1, but the difference is that the contained anticancer active ingredients and their weight percentages are:

[0128] (a) 2-40% camptothecin, hydroxycamptothecin, 9-nitrocamptothecin, podophyllotoxin, trihydroxyisoflavones, letotecan, topotecan, irinotecan Poside, teniposide, 14-hydroxydaunorubicin, amrubicin, erubicin, detorubicin, esorubicin, rhodorubicin, rhrubicin, or zorubicin ;

[0129] (b) 2-40% pemetrexed, pemetrexed disodium, lumitrexed, carmofur, tegafur, temozolomide, zalcitabine, emtricitabine, galocitabine, Ibacitabine, Ancitabine, Decitabine, Flucitabine, Enoxitabine, Mizotabine, Capecitabine, Gemcitabine, Fludarabine, Raltitrexed, Raltitrexed, Dexrazoxane, cladribine, or noratrexed; or

[0130] (c) 2-40% pemetrexed, pemetrexed disodium, lumitrexed, carmofur, tegafur, temozolomide, zalcitabine, emtricitabine, galocitabine, Ibacitabine, Ancitabine, Decitabine, F...

Embodiment 3

[0132] Put 70 mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 25,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 15 mg of emtricitabine and 15 mg of hydroxycamptothecin, and re-shake Dry in vacuo to remove the organic solvent. The dried drug-containing solid composition was frozen and pulverized to make micropowder containing 15% emtricitabine and 15% hydroxycamptothecin, and then suspended in physiological saline containing 1.5% sodium carboxymethylcellulose to obtain the corresponding Suspension-type sustained-release injections. The viscosity of the injection is 300cp-650cp (at 20°C-30°C). The drug release time of the slow-release injection in physiological saline in vitro is 10-15 days, and the drug release time in mice subcutaneous is about 30-35 days.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a slow-release injection containing nolatrexed and a synergistic agent of the nolatrexed, which consists of a slow-release microballoon sphere and a solution medium, wherein, the slow-release microballoon sphere comprises active anti-cancer ingredients and slow-release accessories; and the solution medium is a special solution medium containing a suspending agent. The active anti-cancer ingredients are antimetabolites, such as pemetrexed, rumitrexed, raltitrexed, nolatrexed, carmofur, dexrazoxane, tegafur, zalcitabine, emtricitabine, ibatabine, ancitabine, decitabine, flurocitabine, enocitabine, imidazoletabine, capecitabine, gemcitabine, fludarabine or cladribine, and the like, and synergistic agents of the antimetabolites selected from topoisomerase inhibitors and / or tetrazine compounds; the slow-release accessories are selected from one of polifeprosan, di-fatty acid and decanedioic acid copolymer, polylactic acid copolymer and EVAC or the combination thereof; the viscosity of the suspending agent is 100cp to 3000cp (at the temperature of 20 DEG C to 30 DEG C) and the suspending agent is selected from carboxymethylcellulose sodium and the like. The slow-release microballoon sphere can also be prepared into a slow-release implant used for being injected or put in tumors or the surrounding of the tumors so as to enhance the effects of radiotherapy and chemotherapy.

Description

(1) Technical field [0001] The invention relates to a slow-release injection containing an anti-metabolite drug and / or a synergist thereof and a preparation method thereof, belonging to the technical field of medicines. (2) Background technology [0002] As a commonly used chemotherapeutic drug, antimetabolites have been widely used in the treatment of various malignant tumors. However, its unexpected toxicity and drug resistance greatly limit the application of this class of drugs. The blood vessels, connective tissue, matrix protein, fibrin, and collagen in the tumor stroma not only provide scaffolds and essential nutrients for the growth of tumor cells, but also affect the concentration of chemotherapy drugs around the tumor and in the tumor tissue. Infiltration and diffusion (see Netti et al. "The influence of the status of the extracellular matrix on the drug delivery in solid tumors" "Cancer Research" 60 pp. 2497-503 (2000) (Netti PA, Cancer Res.2000, 60 (9 ): 2497-5...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K9/08A61K9/10A61K31/7068A61K31/4188A61K47/30A61P35/00
Inventor 孔庆忠孙娟贺润萍张志霞
Owner SHANDONG LANJIN PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap