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Sustained-release preparation, preparation method and application thereof in preparation of in-situ tumor combined immunotherapeutic medicines

A technology of controlled release preparation and immunogenicity, applied in the field of biomedical nanomaterials, can solve the problems of toxic and side effects, poor drug targeting, increased drug toxic and side effects, etc., and achieves high drug loading, simple preparation, and stable sustained release effect. Effect

Active Publication Date: 2020-11-06
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the safety of combination therapy is still the focus of clinical trials, and some combination therapy programs may further increase the toxic side effects of drugs on the body
The traditional infusion route often produces huge toxic and side effects due to poor drug targeting, which makes it difficult for the drug to play a local role in the tumor

Method used

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  • Sustained-release preparation, preparation method and application thereof in preparation of in-situ tumor combined immunotherapeutic medicines
  • Sustained-release preparation, preparation method and application thereof in preparation of in-situ tumor combined immunotherapeutic medicines
  • Sustained-release preparation, preparation method and application thereof in preparation of in-situ tumor combined immunotherapeutic medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Weigh the prescription according to Table 1, put soybean lecithin (SPC100), sorbitan monooleate (SMO), tocopheryl acetate (TA) and absolute ethanol with different mass ratios in 10mL EP tubes (wherein control TA 10 parts by mass), sealed with sealing glue, then placed on a multi-point magnetic stirrer to stir overnight at 1000 rpm / min, and then placed in an ultrasonic instrument to remove bubbles by ultrasonication to obtain a clear and transparent light yellow liquid crystal precursor solution. Remove the needle part of the 1ml syringe, absorb 0.1ml of the liquid crystal precursor, reinstall the needle of the syringe, inject the liquid crystal precursor into the PBS buffer, check whether it can be injected successfully and observe whether it can form a semi-solid gel and record it. gel time.

[0039] It can be found from Table 1 that with the increase of absolute ethanol, it is easier to form a clear and transparent liquid crystal precursor, and the fluidity is better,...

Embodiment 2

[0043] On the basis of Example 1, we weighed 45 parts by mass of SPC100, 35 parts by mass of SMO, 10 parts by mass of TA and 10 parts by mass of Ethanol to prepare a blank liquid crystal precursor. After the clear and transparent liquid crystal precursor solution was formed, take Part of it was added to a blank ampoule, and the fluidity of the liquid crystal precursor was observed by tilting the ampoule. Then add a certain amount of PBS buffer solution, and tilt the ampoule again after 10 minutes to observe the fluidity of the liquid crystal precursor at the bottom, the results are as follows figure 1 As shown, a semi-solid gel was formed after 10 min. In addition, remove the needle part of the 1ml syringe, absorb 0.1ml of the liquid crystal precursor, reinstall the needle of the syringe, and inject the liquid crystal precursor into the PBS buffer, the results are as follows figure 2 The gel precursors shown form gels immediately upon exposure to aqueous media.

Embodiment 3

[0045] Separately weigh 45 parts by mass of SPC100, 45 parts by mass of GDO, and 10 parts by mass of ethanol in a 10mL EP tube, seal it with sealing glue, and then place it on a multi-point magnetic stirrer to stir overnight at 1000rpm / min, and then place it in an ultrasonic instrument to sonicate Remove the bubbles to clear and transparent light yellow liquid crystal precursor solution. Remove the needle part of the 1ml syringe, absorb 0.1ml of the liquid crystal precursor, reinstall the needle of the syringe and push the liquid crystal precursor into the PBS buffer, the gel precursor will form a gel immediately when it meets water.

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Abstract

The invention discloses a sustained-release preparation, a preparation method and application thereof in preparation of in-situ tumor combined immunotherapeutic medicines and relates to the technicalfield of biological medical nano-materials. The sustained-release preparation adopts liquid crystal gel as a vector, and an immunogenic inducing agent and an immunomodulator are loaded in the liquid crystal gel. The sustained-release preparation is prepared by the steps of preparing a liquid crystal precursor by adopting a simple agitation mixing method and loading the immunogenic inducing agent and immunomodulator. According to the sustained-release preparation, the immunogenic inducing agent and immunomodulator are co-loaded in the in-situ sustained-release liquid crystal gel, and semi-solidgel is in-situ formed after intratumor, peritumoral or postoperative intraluminal administration to release drugs in a sustained way, so that the tumor microenvironment can be effectively adjusted, the effect of inhibiting tumor growth, relapse and metastasis can be achieved, and whole-body toxic or side effect caused by traditional administration means can be reduced. The sustained-release preparation and the preparation method thereof have a potential application prospect in in-situ local treatment of tumors.

Description

technical field [0001] The invention relates to the technical field of biomedical nanomaterials, in particular to a sustained and controlled release preparation and its preparation method and the application of preparation of in situ tumor immunotherapy combination therapy. Background technique [0002] Cancer has long been one of the diseases threatening global public health, and it is also one of the public problems that seriously threaten the health of the Chinese people. Common cancer treatment methods include chemotherapy, radiotherapy, surgical resection, and immunotherapy, among which surgical resection is currently the most important treatment for solid tumors. However, tumor recurrence and metastasis caused by postoperative residual tumor and circulating tumor cells or immunosuppressive microenvironment are still the main causes of patient death. [0003] Cancer immunotherapy has been shown to be a promising therapeutic approach that activates the host's immune sys...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/704A61K31/337A61K31/555A61K31/7068A61K41/00A61K38/17A61K31/708A61K39/395A61K39/00A61K38/20A61K38/19A61K9/06A61K47/24A61K47/14A61K47/22A61P35/00A61P35/04
CPCA61K45/06A61K31/704A61K31/337A61K31/555A61K31/7068A61K41/0057A61K41/0071A61K41/0052A61K41/0042A61K38/177A61K31/708A61K39/39558A61K39/0011A61K38/2066A61K38/193A61K9/06A61K47/24A61K47/14A61K47/22A61K9/0019A61P35/00A61P35/04A61K2300/00
Inventor 张志平胡梅张娇
Owner HUAZHONG UNIV OF SCI & TECH
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