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A supramolecular hydrogel system loaded with 10-hydroxycamptothecin and its preparation method

A technology of supramolecular hydrogel and hydroxycamptothecin, which is applied in the field of biomedical materials to achieve the effects of constant drug release rate, high drug loading and high stability

Active Publication Date: 2018-11-20
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In order to solve the problems existing in the existing 10-hydroxycamptothecin supramolecular carrier, the present invention provides a supramolecular water loaded with 10-hydroxycamptothecin Gel system, the drug 10-hydroxycamptothecin is directly entrapped in the system without any chemical modification, the drug loading capacity is high, and the drug can be released at a constant rate

Method used

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  • A supramolecular hydrogel system loaded with 10-hydroxycamptothecin and its preparation method
  • A supramolecular hydrogel system loaded with 10-hydroxycamptothecin and its preparation method
  • A supramolecular hydrogel system loaded with 10-hydroxycamptothecin and its preparation method

Examples

Experimental program
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Effect test

Embodiment 1

[0031] (1) Synthesis of fatty acid esterified grafted polyvinyl alcohol:

[0032] Dissolve polyvinyl alcohol (Mw=10000, 2.2g) in 30ml of N-methylpyrrolidone, heat slowly to 30°C, then add caproyl chloride (0.001mol, 0.13g), lauroyl chloride (0.001mol, 0.22g) 1. Oleoyl chloride (0.001mol, 0.3g). After reacting at room temperature for 24 hours, a sufficient amount of water was added to precipitate out. After standing, filtering, washing twice and vacuum drying, 1.2 grams of fatty acid esterified grafted polyvinyl alcohol was obtained;

[0033] (2) Preparation of supramolecular hydrogel system loaded with 10-hydroxycamptothecin:

[0034] 50mg 10-hydroxycamptothecin and 0.17g step (1) gained fatty acid esterified grafted polyvinyl alcohol were dissolved in 20ml of dichloromethane and N-methylpyrrolidone mixed solvent with a volume ratio of 3:1 to obtain organic Solution A: Dissolve 0.85g of α-cyclodextrin in 20ml of water to obtain an aqueous solution of α-cyclodextrin; slowly ad...

Embodiment 2

[0036] (1) Synthesis of fatty acid esterified grafted polyvinyl alcohol:

[0037] Dissolve polyvinyl alcohol (Mw=50000, 2.2g) in 30ml of N-methylpyrrolidone, heat slowly to 50°C, then add lauroyl chloride (0.001mol, 0.22g), stearyl chloride (0.001mol, 0.3g ), after reacting at room temperature for 12 hours, a sufficient amount of water was added to precipitate out, and 1.1 g of fatty acid esterified grafted polyvinyl alcohol was obtained by standing, filtering, washing twice and vacuum drying;

[0038] (2) Preparation of supramolecular hydrogel system loaded with 10-hydroxycamptothecin:

[0039] 50mg 10-hydroxycamptothecin and 0.25g step (1) gained fatty acid esterified grafted polyvinyl alcohol were dissolved in 20ml of chloroform and N-methylpyrrolidone mixed solvent with a volume ratio of 3:1 to obtain organic Solution A: Dissolve 0.5g of α-cyclodextrin in 60ml of water to obtain an aqueous solution of α-cyclodextrin; slowly add organic solution A to the aqueous solution o...

Embodiment 3

[0041] (1) Synthesis of fatty acid esterified grafted polyvinyl alcohol:

[0042] Dissolve polyvinyl alcohol (Mw=80000, 2.2g) in 30ml N-methylpyrrolidone, heat slowly to 60°C, then add hexanoyl chloride (0.0005mol, 0.065g), stearyl chloride (0.0005mol, 0.15g ), after reacting at room temperature for 36 hours, a sufficient amount of water was added to precipitate out, and 1.0 g of fatty acid esterified grafted polyvinyl alcohol was obtained by standing, filtering, washing twice and vacuum drying;

[0043] (2) Preparation of supramolecular hydrogel system loaded with 10-hydroxycamptothecin:

[0044] 50mg 10-hydroxycamptothecin and 0.5g step (1) gained fatty acid esterified grafted polyvinyl alcohol are dissolved in the dichloromethane and N-methylpyrrolidone mixed solvent that 20ml volume ratio is 3:1, obtain organic Solution A; Dissolve 0.5g of α-cyclodextrin in 100ml of water to obtain an aqueous solution of α-cyclodextrin; slowly add the organic solution A to the aqueous sol...

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Abstract

The invention provides a supermolecule hydrogel system loaded with 10-hydroxycamptochecine and a method for preparing the supermolecule hydrogel system. The supermolecule hydrogel system comprises fatty acid esterified grafted polyvinyl alcohol, alpha-cyclodextrin and the 10-hydroxycamptochecine. At least two types of fatty acid chloride and polyvinyl alcohol are simultaneously esterified to obtain the fatty acid esterified grafted polyvinyl alcohol, the fatty acid chloride selectively includes at least two types of hexanoyl chloride, octanoyl chloride, lauroyl chloride, myristoyl chloride, oleoyl chloride and stearyl chloride, and every two carbon chains of the selected fatty acid chloride are different from each other by six carbon atoms at least. The supermolecule hydrogel system and the method have the advantages that the 10-hydroxycamptochecine can be released from the supermolecule hydrogel system at constant speeds, accordingly, hydrogel is high in safety, the method is simple, and the supermolecule hydrogel system is high in drug-loading capacity and good in stability.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a supramolecular hydrogel system loaded with 10-hydroxycamptothecin and a preparation method thereof. Background technique [0002] Camptothecin is an alkaloid isolated from the unique plant camptothecin in my country. 10-Hydroxycamptothecin is a product in which the hydrogen at the 10th carbon atom of the camptothecin molecule is replaced by a hydroxyl group. It is effective for the treatment of lung cancer and prostate cancer. Cancer, breast cancer and other tumors have significant curative effect, because the toxic and side effects of 10-hydroxycamptothecin are lower than that of camptothecin, especially the urinary system reaction is reduced, so it is more likely to be accepted clinically. However, 10-hydroxycamptothecin is insoluble in water, which limits its practical application. At present, most of the 10-hydroxycamptothecin used clinically in my ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/06A61K31/4745A61K47/40A61K47/32A61P35/00
CPCA61K9/06A61K31/4745A61K47/32A61K47/40
Inventor 黄洁闫晓玉金志敏苗永李清柯海鹏严华勇冯文杰
Owner ZHEJIANG UNIV OF TECH
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