Glucan-adriamycin conjugate drug and preparation method thereof

A technology of dextran and doxorubicin, which is applied in the field of dextran-doxorubicin bonded drugs and its preparation, can solve the problems of lack of release of doxorubicin, poor biocompatibility, and low drug loading, and achieve Good bioactivity and biocompatibility, slow release, enhanced efficacy

Active Publication Date: 2014-03-26
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The Chinese patent whose publication number is CN102406946A discloses a kind of macromolecular bonded drug, first, polyethylene glycol monomethyl ether, carboxylated doxorubicin derivatives, 1-(3-dimethylaminopropyl)-3-ethyl Carbodiimide hydrochloride and N-hydroxysuccinimide react in an organic solvent to obtain a reaction mixture, and then add poly (L-lysine) or chitosan to the reaction mixture to obtain Polymer doxorubicin-bonded drug; Chinese patent publication No. 101234205A discloses a polymer doxorubicin-bonded drug with targeting function, which is assembled by mixing two polyethylene glycol-polylactic acid block copolymers The polylactic acid chain end of the first polyethylene glycol-polylactic acid block copolymer is connected with doxorubicin, and the polyethylene glycol chain end of the second polyethylene glycol-polylactic acid block copolymer is connected with There is lactose, which has a sustained release function; lactose has a targeting function, whic...

Method used

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  • Glucan-adriamycin conjugate drug and preparation method thereof
  • Glucan-adriamycin conjugate drug and preparation method thereof
  • Glucan-adriamycin conjugate drug and preparation method thereof

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preparation example Construction

[0031] The present invention also provides a preparation method of a dextran-doxorubicin bonded drug, comprising:

[0032] mixing and reacting a buffer solution in which doxorubicin hydrochloride is dissolved with dextran to obtain a dextran-doxorubicin bonded drug having a structure of formula (I);

[0033] Or mix and react the buffer solution in which doxorubicin hydrochloride is dissolved with dextran and sodium cyanoborohydride to obtain the dextran-doxorubicin bonded drug with the structure of formula (II).

[0034] The dextran-doxorubicin bonded drug with the structure of formula (I) is prepared according to the following method:

[0035] First, doxorubicin hydrochloride is dissolved in a buffer solution to obtain a mixed solution; the doxorubicin hydrochloride has the structure shown in formula (III):

[0036]

[0037] The buffer solution is preferably an acetate buffer solution, specifically a sodium acetate-acetic acid buffer solution; the pH value of the buffer s...

Embodiment 1～8

[0056] Prepare an acetate buffer solution with pH=5, take 5 mL of the prepared buffer solution and place them in 8 round-bottomed flasks respectively, add 0.05 g of doxorubicin hydrochloride to each flask, stir and dissolve in the dark, and then According to the dosage ratio in Table 1, add dextran and sodium cyanoborohydride to each flask, the number average molecular weight of the dextran is 5000g.mol -1 , then seal each reaction bottle, according to the reaction conditions in Table 1, react in the dark for 52h, after the reaction, adjust the pH of each reaction solution to 7.4 with sodium bicarbonate solution, then use a dialysis bag with a molecular weight cut-off of 7000Dalton for dialysis for 48h, filter Freeze-dried to obtain dextran-doxorubicin bonded drugs respectively. The experimental results are shown in Table 1. Table 1 shows the reaction conditions and yields of the dextran-doxorubicin bonded drugs prepared in Examples 1 to 8 of the present invention. , wherein, ...

Embodiment 9～16

[0062] Prepare an acetate buffer solution with pH=5, take 5 mL of the prepared buffer solution and place them in 8 round-bottomed flasks respectively, add doxorubicin hydrochloride to each flask according to the ratio in Table 2, and keep away from light. After stirring and dissolving, add dextran and sodium cyanoborohydride to each flask according to the dosage ratio in Table 2, the number average molecular weight of the dextran is 5000g.mol -1 , then seal each reaction bottle, and react in the dark at 40°C for 52h. After the reaction, adjust the pH of each reaction solution to 7.4 with sodium bicarbonate solution, then dialyze with a dialysis bag with a molecular weight cut-off of 7000Dalton for 48h, filter and freeze-dry to obtain Dextran-doxorubicin bonded drug, the experimental results are shown in Table 2, Table 2 is the reaction conditions and yields of the dextran-doxorubicin bonded drug prepared in Examples 9-16 of the present invention, wherein, i represents Molar ra...

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Abstract

The invention provides a glucan-adriamycin conjugate drug, which adopts the structure shown in the formula (I) or the formula (II) of the Specification, and n is the degree of polymerization of the glucan and is equal to or greater than 10 and equal to or smaller than 3125. According to the invention, the glucan, sodium cyanoborohydride and adriamycin are used as raw materials to prepare the glucan-adriamycin conjugate drug; as the glucan as a raw material has good biological activity and biocompatibility, the prepared glucan-adriamycin has good biological activity and biocompatibility; besides, the glucan is connected with the adriamycin through an oxime bond, so that the glucan-adriamycin conjugate drug can be released quickly in tumor tissue or a cell under the condition of relatively low pH value, so that the drug effect is improved; reduced glucan-adriamycin conjugate drug adopting the structure of the formula (II) of the Specification has relatively stable performance, and the adriamycin can be released relatively slowly, so that ideal long-acting therapy can be realized.

Description

technical field [0001] The invention relates to the technical field of chemically bonded drugs, in particular to a dextran-doxorubicin bonded drug and a preparation method thereof. Background technique [0002] Doxorubicin, also known as 1,4-hydroxydaunorubicin, 1,4-hydroxydaunomycin, doxorubicin, hydroxyerythrobimycin, is an anthracycline antibiotic with high efficiency and broad-spectrum anti-tumor The drug is a cell cycle non-specific drug and has the strongest effect on the S phase. It mainly inserts into the DNA of the cell, thereby triggering topoisomerase II to destroy the tertiary structure of the DNA to exert its drug effect. So far, doxorubicin has been considered as a powerful clinical chemotherapy drug, mainly for the treatment of solid tumors such as liver cancer, lung cancer, gastric cancer, breast cancer, ovarian cancer, bladder cancer, and thyroid cancer. [0003] At present, clinical chemotherapy of doxorubicin mainly exerts its drug effect through intraven...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K31/704A61P35/00
Inventor 丁建勋许维国庄秀丽陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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