Alginic acid-adriamycin amycin bonding medicine and preparation method thereof

A technology of doxorubicin hydrochloride and alginic acid, which is applied in the direction of pharmaceutical formulations, antineoplastic drugs, drug combinations, etc., can solve the problems of lack of release of doxorubicin, poor biocompatibility, cumbersome preparation process, etc., and achieve good biological activity and Effects of biocompatibility, slow release, and stable performance

Active Publication Date: 2014-03-19
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Abstract
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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, which c

Method used

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  • Alginic acid-adriamycin amycin bonding medicine and preparation method thereof
  • Alginic acid-adriamycin amycin bonding medicine and preparation method thereof
  • Alginic acid-adriamycin amycin bonding medicine and preparation method thereof

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preparation example Construction

[0030] The invention also provides a preparation method of the alginic acid-doxorubicin bond medicine, which comprises:

[0031] Mixing and reacting the buffer solution in which doxorubicin hydrochloride is dissolved with alginic acid to obtain the alginic acid-doxorubicin bond drug having the structure of formula (I);

[0032] Alternatively, the buffer solution in which doxorubicin hydrochloride is dissolved is mixed and reacted with alginic acid and sodium cyanoborohydride to obtain an alginic acid-doxorubicin bond drug having a structure of formula (II).

[0033] The alginic acid-doxorubicin bond drug with the structure of formula (I) is prepared according to the following method:

[0034] First, doxorubicin hydrochloride is dissolved in a buffer solution to obtain a mixed solution; the doxorubicin hydrochloride has the structure shown in formula (III):

[0035]

[0036] The buffer solution is preferably an acetate buffer solution, specifically a sodium acetate-acetic acid buffer sol...

Embodiment 1～8

[0056] Prepare the acetate buffer solution with pH=5. Measure 5 mL of each buffer solution and place them in 8 round-bottom flasks. Add 0.05 g of doxorubicin hydrochloride to each flask. After stirring and dissolving in the dark, According to the dosage ratio in Table 1, add alginic acid and sodium cyanoborohydride to each flask. The number average molecular weight of the alginic acid is 3141 g.mol -1 , And then seal each reaction bottle, follow the reaction conditions in Table 1, and react for 52 hours in the dark. After the reaction, adjust the pH of each reaction solution to 7.4 with sodium bicarbonate solution, and then dialyze with a dialysis bag with a molecular weight cut-off of 7000 Dalton for 48 hours. After filtration After freeze-drying, the alginic acid-doxorubicin-conjugated drugs were obtained. The experimental results are shown in Table 1. Table 1 shows the reaction conditions and yields of the alginic acid-doxorubicin-conjugated drugs prepared in Examples 1-8 of t...

Embodiment 9～16

[0062] Prepare the acetate buffer solution with pH=5, and place 5 mL of each buffer solution in 8 round-bottom flasks. According to the ratio in Table 2, add doxorubicin hydrochloride to each flask, avoid light After stirring and dissolving, add alginic acid and sodium cyanoborohydride to each flask according to the dosage ratio in Table 2. The number average molecular weight of the alginic acid is 3141g.mol -1 , And then seal each reaction flask, and react for 52 hours at 40°C in the dark. After the reaction, adjust the pH of each reaction solution to 7.4 with sodium bicarbonate solution, and then dialyze with a dialysis bag with a molecular weight cut-off of 7000 Dalton for 48 hours, filter and freeze-dry to obtain respectively Alginic acid-doxorubicin bond drugs, the experimental results are shown in Table 2. Table 2 shows the reaction conditions and yields of the alginic acid-doxorubicin bond drugs prepared in Examples 9-16 of the present invention, where i represents alginic...

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Abstract

The invention provides an alginic acid-adriamycin amycin bonding medicine which has a structure shown in a formula (I) or (II), wherein n is degree of polymerization of alginic acid, and n is greater than or equal to 7 but less than or equal to 1507. The alginic acid-adriamycin amycin bonding medicine is prepared by taking alginic acid, sodium cyanoborohydride and adriamycin amycin as raw materials. As the raw material alginic acid ahs good bioactivity and biocompatibility, the alginic acid-adriamycin amycin prepared has good bioactivity and biocompatibility. Meanwhile, alginic acid and adriamycin amycin are connected through oxime bonds, and can be quickly released in a tumor tissue or cell under a lower pH value condition, so that the pesticide effect is enhanced. The reductive alginic acid-adriamycin amycin bonding medicine with the structure shown in the formula (II) further has a more stable performance, is more slowly to release adriamycin amycin, and reaches an ideal long-acting treatment.

Description

Technical field [0001] The present invention relates to the technical field of chemical bond drugs, in particular to an alginic acid-doxorubicin bond drug and a preparation method thereof. Background technique [0002] Doxorubicin, also known as 1,4-hydroxydaunorubicin, 1,4-hydroxyn-diamycin, doxorubicin, and hydroxyerythrubicin, is an anthracycline antibiotic with a high-efficiency and broad-spectrum anti-tumor The drug is a kind of cell cycle non-specific drug and has the strongest effect on S phase. It mainly acts by inserting cell DNA, thereby triggering topoisomerase II to destroy the tertiary structure of DNA. So far, doxorubicin is considered to be a powerful clinical chemotherapeutic drug, which mainly treats solid tumors such as liver cancer, lung cancer, gastric cancer, breast cancer, ovarian cancer, bladder cancer, and thyroid cancer. [0003] At present, clinically, doxorubicin chemotherapy is mainly administered through intravenous administration. However, the drug is...

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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