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Anti-cancer composition loading both platinum compound and synergist

A technology of compounds and synergists, applied in the field of anticancer compositions, can solve the problems of inability to effectively kill tumor cells, burst release, unbalanced release, etc.

Inactive Publication Date: 2007-08-08
JINAN SHUAIHUA PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, the sustained-release excipients used in the existing above-mentioned and other pharmaceutical preparations more or less cause sudden release or uneven release of the drug when the drug is released.
Some drugs are released too slowly, which is not enough to obtain effective drug concentration in the local area, so they cannot effectively kill tumor cells; some release drugs too fast, often causing burst release, which is likely to cause systemic toxic reactions like conventional injections

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] Put 90, 90 and 80mg p(BHET-EOP / TC), BHET-EOP: TC is 80:20) copolymer into three containers of A, B and C respectively, and then add 100 ml of dichloromethane to each , after dissolving and mixing, add 10mg cisplatin, 10mg epirubicin, 10mg cisplatin and 10mg epirubicin respectively, and prepare 10% cisplatin, 10% epirubicin, and microspheres for injection with 10% cisplatin and 10% epirubicin. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection. The release time of the sustained-release injection in physiological saline in vitro is 60-70 days, and the release time in mouse subcutaneous colon cancer is more than 60 days.

Embodiment 2

[0114] 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:

[0115] (1) 5-30% cisplatin, carboplatin or oxaliplatin;

[0116] (2) 5-30% epirubicin, doxorubicin, pirarubicin, valrubicin, or epirubicin; or

[0117] (3) A combination of 5-30% cisplatin, carboplatin or oxaliplatin and 5-30% epirubicin, doxorubicin, pirarubicin, valrubicin or epirubicin.

Embodiment 3

[0119] 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 oxaliplatin, 30mg doxorubicin, 15mg oxaliplatin and 15mg doxorubicin, re-shake and use spray drying method to prepare 30% oxaliplatin, 30% doxorubicin, 15% oxali Microspheres for Injection of Liplatin and 15% Doxorubicin. The dried microspheres are suspended in physiological saline containing 1.5% sodium carboxymethylcellulose to prepare the corresponding suspension-type sustained-release injection. The release time of the sustained-release injection in physiological saline in vitro is 60-65 days, and the release time in mouse subcutaneous lung cancer is about 60 days.

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Abstract

Disclosed is a slow release injection agent of anticancer composition containing platinum-group compounds and synergistic agent, which comprises slow release microspheres and dissolvent, wherein the slow release microspheres comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being conventional dissolvent or specific dissolvent containing suspension adjuvant. The viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose, the platinum-group compounds are selected from cisplatin, Carboplatin, Nedaplatin or Oxaliplatin, the synergistic agent can be selected from tetrazine drugs such as Mitozolomide or Temozolomide, and / or anticancer antibiotics such as Adriamycin, Aclarubicin, Epirubicin, mitomycin or pidorubicin, the slow release auxiliary materials are selected from polyphosphate ester copolymers such as p(LAEG-EOP), p(DAPG-EOP), copolymer or blend of polyphosphate ester with polylactic acid, Polifeprosan, sebacylic acid and PLGA. The anticancer composition can also be prepared into slow release implanting agent for injection or placement in or around tumor with a period of effective concentration maintenance over 60 days, as well as the treatment effect of appreciably lowering general reaction of the drugs, and improving the treatment effect of the non-operative treatment methods such as chemotherapy.

Description

(1) Technical field [0001] The invention relates to an anticancer composition containing a platinum compound and a synergist, belonging to the technical field of medicines. Specifically, the invention relates to a slow-release preparation capable of stably releasing platinum compounds and synergists locally in solid tumors, mainly slow-release implants and slow-release injections, which can prolong the drug release time and increase Drug sensitivity. (2) Background technology [0002] Local application of chemotherapeutic drugs, especially local sustained release, has become the current research direction and focus of solid tumor chemotherapy. 参见(中国专利申请号200510042234.3、03148624.X、200510042236.2、96116041.1、97107078.4、200510042260.6、200510042261.0、200510042262.5、200510042263.X;美国专利US5651986、RE37410)。 [0003] However, the sustained-release excipients used in the above-mentioned and other existing pharmaceutical preparations more or less cause sudden release or uneven release o...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K31/282A61K31/555A61K45/06A61K47/34A61P35/00A61K47/26
Inventor 孙宪君
Owner JINAN SHUAIHUA PHARMA TECH
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