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Hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer as well as synthesis method and application of hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer

A technology of adipic acid dihydrazide and hyaluronic acid, which is applied in the directions of drug combinations, medical preparations with inactive ingredients, and medical preparations containing active ingredients, etc. The problem of poor water solubility of thymoquinone, etc., to achieve the effect of improving tumor targeting

Inactive Publication Date: 2014-06-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, thymoquinone has very poor water solubility, and when it is made into general preparations, the bioavailability in vivo is too low to meet the anti-tumor requirements.

Method used

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  • Hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer as well as synthesis method and application of hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer
  • Hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer as well as synthesis method and application of hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer
  • Hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer as well as synthesis method and application of hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] (1) Synthesis of hyaluronic acid-adipate dihydrazide graft:

[0031] ①Reaction: Take 100mg of hyaluronic acid with a molecular weight of 2000, add it to the aqueous solution of adipic acid dihydrazide with a concentration of 0.05mol / L, adjust the pH to 4.75 with hydrochloric acid, and then add 1-(3-dimethylaminopropyl Base)-3-ethylcarbodiimide hydrochloride, reacted for 1h, during which the pH was adjusted with hydrochloric acid every 5min to maintain it at 4.75;

[0032] ② Termination: When the above reaction time is over, adjust its pH to 7.0 with sodium hydroxide, terminate the reaction, and obtain reaction solution A;

[0033] ③Dialysis and filtration: put the above reaction solution A into a dialysis bag with a molecular weight of 1000, and then dialyze with 0.1mol / L sodium chloride solution, ethanol aqueous solution with a volume ratio of ethanol-water of 25:75, and double distilled water. The time is 1 day. After completion, filter through a microporous membrane...

Embodiment 2

[0038] (1) Synthesis of hyaluronic acid-adipate dihydrazide graft:

[0039] ① Reaction: Take 300 mg of hyaluronic acid, with a molecular weight of 5000, and add it to the aqueous solution of adipic acid dihydrazide with a concentration of 0.15 mol / L, adjust the pH to 4.75 with hydrochloric acid, and then add 1-(3-dimethylaminopropyl Base)-3-ethylcarbodiimide hydrochloride, reacted for 3 hours, during which the pH was adjusted with hydrochloric acid every 10 minutes to maintain it at 4.75;

[0040] ② Termination: When the above reaction time is over, adjust its pH to 7.0 with sodium hydroxide, terminate the reaction, and obtain reaction solution A;

[0041] ③Dialysis and filtration: put the above reaction solution A into a dialysis bag with a molecular weight of 3500, and dialyze with 0.1mol / L sodium chloride solution, ethanol aqueous solution with a volume ratio of ethanol-water of 25:75, and double distilled water successively. The time is 2 days. After completion, filter th...

Embodiment 3

[0046] (1) Synthesis of hyaluronic acid-adipate dihydrazide graft:

[0047] ① Reaction: Take 200 mg of hyaluronic acid with a molecular weight of 3000, add it to adipic acid dihydrazide aqueous solution with a concentration of 0.1 mol / L, adjust the pH to 4.75 with hydrochloric acid, and then add 1-(3-dimethylaminopropyl Base)-3-ethylcarbodiimide hydrochloride, reacted for 2 hours, during which the pH was adjusted with hydrochloric acid every 5 minutes to maintain it at 4.75;

[0048] ② Termination: When the above reaction time is over, adjust its pH to 7.0 with sodium hydroxide, terminate the reaction, and obtain reaction solution A;

[0049] ③Dialysis and filtration: put the above reaction solution A into a dialysis bag with a molecular weight of 3500, and dialyze with 0.1mol / L sodium chloride solution, ethanol aqueous solution with a volume ratio of ethanol-water of 25:75, and double distilled water successively. The time is 2 days. After completion, filter through a microp...

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Abstract

The invention provides a hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer as well as a synthesis method and application of the hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer, belonging to the field of pharmaceutical preparations. The synthesis method comprises the steps of firstly, synthesizing hyaluronic acid-adipodihydrazide; then, grafting thymoquinone; finally, forming the hyaluronic acid-adipodihydrazide-thymoquinone grafted polymer. Compared with the prior art, the synthesis method has the advantages that adipodihydrazide is used as a link span, and thymoquinone is connected to hyaluronic acid, so that the obtained grafted polymer has the characteristic of pH sensitivity release, and the targeting property of thymoquinone to tumors can be remarkably improved.

Description

technical field [0001] The invention relates to a hyaluronic acid-adipic acid dihydrazide-thymoquinone graft and a synthesis method thereof, belonging to the field of pharmaceutical preparations. Background technique [0002] Thymoquinone (TQ) is the main effective monomer isolated from black cumin seed oil in recent years. Studies have found that it has potential anti-cancer and tumor suppressor effects, and can inhibit colon cancer, breast cancer, pancreatic cancer and Lung cancer and other tumor cells grow and induce cell apoptosis; Thymoquinone can also inhibit the metastasis of prostate cancer and other malignant tumors. However, thymoquinone has very poor water solubility, and the bioavailability in vivo is too low to meet the anti-tumor requirements when it is made into general preparations. Therefore, the development of new carriers to improve their bioavailability deserves further study. [0003] There are various cell surface receptors, and selecting the appropri...

Claims

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Application Information

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IPC IPC(8): C08B37/08A61K47/48A61K31/122A61P35/00
Inventor 周建平朱玛郑立发
Owner CHINA PHARM UNIV
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