Anti-angiogenic hydrogel sustained-release preparation and application thereof

An anti-angiogenesis and sustained-release preparation technology, applied in the field of hydrogel sustained-release preparations, can solve the problems of amplifying systemic toxicity, affecting the normal cardiovascular system, etc., so as to reduce the number of administrations, avoid toxicity, and reduce systemic side effects. Effect

Active Publication Date: 2019-10-08
THE AFFILIATED HOSPITAL OF SOUTHWEST MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Existing anti-angiogenic drugs are administered intravenously, which will inevitably affect the normal cardiovascular system while inhibiting tumor angiogenesis, and increasing the local blood drug concentration will inevitably amplify its systemic toxicity

Method used

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  • Anti-angiogenic hydrogel sustained-release preparation and application thereof
  • Anti-angiogenic hydrogel sustained-release preparation and application thereof
  • Anti-angiogenic hydrogel sustained-release preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Preparation of HA-Tyr conjugates

[0023] Weigh 1 g of HA (hyaluronic acid) and 210 mg of Tyr (tyrosine) with a number average molecular weight of about 38,000 to 90,000 and place them in a sterile glass bottle, add 100 mL of deionized water, and place the beaker on a magnetic stirrer to Stir and dissolve at a rate of 800r / min. After complete dissolution, continue to add 1.2g NHS and 1.95g EDAC·HCl, and continue to stir and react at room temperature for 24h. The reaction process is as follows: figure 1 shown. After the reaction, adjust the pH of the reaction solution to be 5 to 7, and pour the reaction solution into a dialysis bag with a molecular weight cut-off of 3500Da. ) for 1 day each, and then freeze-dry the dialyzed solution to obtain a white floc, namely the HA-Tyr conjugate, which was sterilized and stored at low temperature for later use. In addition, different types of HA-Tyr conjugates were prepared by using HA with different number-average mole...

Embodiment 2

[0028] Example 2: Preparation of an anti-angiogenic hydrogel sustained-release preparation

[0029] Weigh the HA-Tyr conjugate prepared by using the ratio No. 1 in Table 1, and prepare multiple solutions with concentration gradients. The concentrations of these solutions are in the range of 10mg / mL~20mg / mL, and then the The angiogenesis drugs were formulated into multiple solutions with concentration gradients, and the concentrations of these solutions were in the range of 0.05 mg / mL to 25 mg / mL, and the HPR solution with a concentration of 25 U / mL and hydrogen peroxide with a concentration of 800 μM were taken for use. Prepare hydrogel slow-release preparation according to the proportioning in table 2, the formation process of slow-release preparation is as follows figure 2 shown.

[0030] Table 2 The proportioning relationship of the hydrogel sustained-release preparation

[0031]

Embodiment 3

[0032] Example Three: In Vitro Drug Release of Hydrogel Sustained Release Preparation

[0033] After mixing the materials according to the proportioning relationship in Table 2, a hydrogel will be formed in about 50s. The in vitro drug release rate of No. 1 proportioning relationship was investigated, and the Endostar water added with hyaluronidase was also investigated. The in vitro drug release rate of the gel, the results are as follows image 3 shown. It can be seen that the anti-angiogenic hydrogel sustained-release preparation of the present invention shows the characteristics of sustained slow release, and it releases about 80% on the 14th day, and the addition of 20~30U / mL hyaluronidase anti- The angiogenic hydrogel drug release was close to 100% on day 3. The hydrogel sustained-release preparations formulated according to the proportioning relationship of No. 2 and No. 3 in Table 2 also showed the characteristics of sustained and slow release.

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Abstract

The invention discloses an anti-angiogenic hydrogel sustained-release preparation and an application thereof. The hydrogel sustained-release preparation includes a HA-Tyr conjugate solution, an anti-angiogenic drug solution, an HPR solution, and hydrogen peroxide; and the HA-Tyr conjugate solution, the anti-angiogenic drug solution, the HPR solution, and the hydrogen peroxide are mixed in a volumeratio of 1:1 to 5: 0.02: 0.02. When the hydrogel sustained-release preparation is applied, the components are placed in a same syringe according to the ratio, the hydrogel sustained-release preparation is injected into the tumor site within 50s, the drug is slowly released at the tumor site, the concentration of local drug is increased, the concentration of blood is reduced, and systemic side effect is reduced; the local application of a drug carrier helps to improve the local inhibitory microenvironment of the tumor, the microenvironmental cellular components can be reorganized and balanced,which provide a synergistic pathway for synergy with other treatments.

Description

technical field [0001] The invention belongs to the technical field of hydrogel sustained-release preparations, and in particular relates to an anti-angiogenesis hydrogel sustained-release preparation and its application. Background technique [0002] In recent years, the incidence and mortality of malignant tumors have increased, posing a serious threat to human health. Existing treatment methods mainly include surgery, radiotherapy and chemotherapy, targeted therapy, immunotherapy and anti-angiogenic therapy. A large number of studies have confirmed that tumor growth and metastasis depend on angiogenesis / lymphangiogenesis, and vascular endothelial growth factor (VEGF) is an important regulator of tumor angiogenesis. Anti-angiogenic drugs can selectively inhibit the proliferation and migration of vascular endothelial cells, so as to inhibit the formation of tumor angiogenesis and cut off the nutrient supply pathway of tumor cells, thereby inhibiting tumor proliferation or ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/36A61K45/00A61K9/06A61K9/00A61P35/00
CPCA61K9/0024A61K9/06A61K45/00A61K47/36A61P35/00
Inventor 林盛傅少志王娜
Owner THE AFFILIATED HOSPITAL OF SOUTHWEST MEDICAL UNIV
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