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Doxorubicin hydrochloride loaded temperature-sensitive self-healing hydrogel and preparation method thereof

A technology of doxorubicin hydrochloride and hydrogel, which is applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, pharmaceutical formulas, etc. Burst release, quick self-healing, delayed release effect

Inactive Publication Date: 2016-04-27
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to provide a practical, convenient, stable and reliable doxorubicin hydrochloride temperature-sensitive self-healing hydrogel for treating tumors and its preparation method, aiming to overcome the weak mechanical strength and drug breakthrough of traditional temperature-sensitive gels. Insufficient explanation

Method used

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  • Doxorubicin hydrochloride loaded temperature-sensitive self-healing hydrogel and preparation method thereof
  • Doxorubicin hydrochloride loaded temperature-sensitive self-healing hydrogel and preparation method thereof
  • Doxorubicin hydrochloride loaded temperature-sensitive self-healing hydrogel and preparation method thereof

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Experimental program
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specific Embodiment 1

[0024] Weigh a certain amount of PEG 2000 , p-formylbenzoic acid and DMAP were dissolved in 50 mL of dichloromethane, an appropriate amount of EDC.HCL was added, the reaction was stirred at room temperature for 18 hours, and a white solid was obtained by suction filtration. The solid obtained from the reaction was redissolved in dichloromethane, and precipitated with glacial ether, and the operation was repeated three times. The resulting solid was dialyzed in a dialysis bag for two days, and DF-PEG was obtained after freeze-drying. NMR and IR spectra are attached figure 1 .

[0025] Dissolve chitosan (0.04g) in 2mL of glacial acetic acid solution (0.1M), add doxorubicin hydrochloride powder to dissolve, add DF-PEG solution drop by drop under stirring condition, add β -Sodium glycerophosphate solution, continue to stir to make it evenly mixed, and obtain the temperature-sensitive self-healing hydrogel preparation of doxorubicin hydrochloride. The preparation is in a liquid...

specific Embodiment 2

[0026] The temperature-sensitive self-healing hydrogel obtained in Example 1 of the present invention is investigated for self-healing performance, see attached image 3 .

[0027] Preliminary investigation of self-healing ability: the prepared thermosensitive self-healing hydrogel was cut in half from the middle, and one half was stained with methylene blue. Put the cut gels back together to see if the two gels can fully self-heal and return to the original intact gel. Repeat the operation to see if the gel can achieve repeated self-healing.

[0028] Further investigation of self-healing ability: take appropriate amount of chitosan / β-sodium glycerophosphate (CS / β-GP) solution and chitosan / β-sodium glycerophosphate / DF-PEG (CS / β-GP / DF) respectively -PEG) solution in a 2.5mL syringe, placed in a 37±1°C water bath until completely gelled. Take out the syringe, and use a 0.5mm needle to completely inject the gel into the vial until the gel system is completely destroyed. Stand...

specific Embodiment 3

[0029] The temperature-sensitive self-healing hydrogel obtained in Example 1 of the present invention was subjected to an in vitro drug release behavior test, and the release curve is shown in the attached Figure 4 shown.

[0030] Take 1 mL of CS / β-GP solution loaded with doxorubicin hydrochloride and 3 parts of CS / β-GP / DF-PEG solution in a dialysis bag, seal it, and let it gel completely at 37±1°C for a period of time , add 100mL pH6.8 phosphate buffer solution, shake at 100rpm constant temperature. Sampling at the set time point, each sampling is 2ml, at the same time add the same amount of fresh phosphate buffer solution to maintain the effect of the sink, the sampling time is 1h, 2h, 4h, 8h, 12h, 24h, 48h, 72h, Samples were then taken every two days. The sample taken out was filtered through a 0.45 μm microporous membrane, and the subsequent filtrate was taken for injection, and the amount of doxorubicin hydrochloride was measured at a wavelength of 490 nm, and the cumu...

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Abstract

The invention relates to a doxorubicin hydrochloride loaded temperature-sensitive self-healing hydrogel and a preparation method thereof. The doxorubicin hydrochloride loaded temperature-sensitive self-healing hydrogel comprises chitosan, sodium beta-glycerophosphate, and polyethylene glycol with two ends respectively carrying a benzaldehyde group. The preparation method comprises the following steps: forming an imide bond with a self-healing performance through using a reaction of an amino group in the structure of chitosan and the benzaldehyde groups at two ends of the polyethylene glycol, combining the imide bond with chitosan / sodium beta-glycerophosphate temperature-sensitive gel, and loading doxorubicin hydrochloride into the obtained material through physical clathration to prepare the novel temperature-sensitive self-healing hydrogel administration system. The administration system is a liquid at room temperature, and rapidly gelates at a human body temperature after being injected to a tumor position in order to form a medicine reservoir ; and compared with traditional in situ gels, the temperature-sensitive self-healing hydrogel has the advantages of strong mechanical strength, realization of rapid self restoration under the action of outside force or tissue damages to avoid burst release of a medicine, further delay of release of the medicine and prolongation of the detention time of the medicine in the tumor position, medicine effect enhancement and reduction of toxic and side effects.

Description

technical field [0001] The invention relates to a temperature-sensitive self-healing hydrogel loaded with doxorubicin hydrochloride and a preparation method thereof, belonging to the field of pharmaceutical preparations. Background technique [0002] At present, the main methods of tumor treatment are surgical resection, radiotherapy and chemotherapy. In the process of treating malignant tumors, the first consideration of most patients is to remove as much tumor tissue as possible through surgery, but the indications for surgery are limited to early-stage tumors. Adjuvant preoperative radiotherapy or chemotherapy is needed, and some patients also need postoperative radiotherapy and chemotherapy for consolidative treatment. However, during the course of radiotherapy and chemotherapy, the residual tumor cells may cause tumor recurrence or metastasis due to the administration of systemic chemotherapy or local radiotherapy. Therefore, the administration method of intratumoral ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K31/704A61K47/36A61P35/00
CPCA61K9/0019A61K9/06A61K31/704A61K47/36
Inventor 吴正红孟轩羽祁小乐杨蓉姜璎纯
Owner CHINA PHARM UNIV
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