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Application of BMP2/7 slow release system in glioma treatment

A glioma, slow-release carrier technology, applied in the direction of peptide/protein components, medical preparations containing active ingredients, anti-tumor drugs, etc., to achieve the effect of eliminating possibility, inhibiting proliferation and promoting differentiation

Inactive Publication Date: 2012-11-14
GUANGZHOU LAND UNICOMED BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] 5. With independent intellectual property rights: This new type of BMP is composed of three parts, BMP-2, 7 and a flexible peptide, which together form a complete molecule. We call it a structural analogue, which is a different from BMP2 / 7 new molecules, no reports at home and abroad
[0015] The inventors of this patent coated the buffer solution of BMP directly on the surface of collagen. Although a better release kinetic pattern can be obtained, it is still not enough to maintain enough time to induce osteogenesis. If chemical methods are used to increase BMP and collagen Affinity for cytokines to be released for a longer period of time should be an ideal choice

Method used

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  • Application of BMP2/7 slow release system in glioma treatment
  • Application of BMP2/7 slow release system in glioma treatment
  • Application of BMP2/7 slow release system in glioma treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Rat tumor-bearing survival test

[0044] (1) Materials and methods

[0045] 1. Reagents

[0046] DMEM / F12 (1:1) medium, B27 supplement (Invitrogen), N2 supplement (Invitrogen), trypsin (Sigma), human epidermal growth factor (EGF, Invitrogen), human basic fibroblast growth factor (bFGF, Invitrogen) , Leukemia inhibitory factor (LIF, Chemieon), L-glutamine (Sigma), special grade fetal bovine serum (Hycl.ne), insulin, penicillin and streptomycin (North China Pharmaceutical), L-polylysine (Sigma) , erythrocyte lysate (self-made, containing 0.155mol / LNH4CI, 0.01mol / LKHCO3, 0.1M EDTA), immunomagnetic bead sorting solution 0.5% (v / v) BSA, 2mM EDTA, add 0.01M PBS to 100ml, use 1N NaOH or 1N HCl to adjust the pH value to 7.2, immunomagnetic beads (CD133 + ) Cell Sorting Kit is a product of Miltenyi Biotec, Germany.

[0047] 2. Establishment of Fisher344 rat 9L cell glioma model

[0048] (1) Recovery and culture of 9L cells: Take out the cryopreservation tube from ...

Embodiment 2

[0111] Embodiment 2 The synergistic effect of sustained-release carrier and chemotherapeutic drugs

[0112] (1) Materials and methods

[0113] 1. Recovery and culture of 9L cells: Take out the cryopreservation tube from -80°C, put it into a 37°C water bath quickly, and let it melt for about 1 minute; within 5 minutes at room temperature, dilute to 10% of the original volume with low-sugar DMEM medium times. 800rpm / min low-speed centrifugation for 5min. Remove the supernatant, add fresh medium containing 10% fetal bovine serum, inoculate the cells for culture, and subculture when the cell fusion exceeds 80%.

[0114] 2. Isolation method of rat brain glioma stem cells by immunomagnetic bead method

[0115] The rat glioma cell line 9L was divided into two groups, one group was treated with a small amount of buffer solution (0.5% bovine serum albumin, 2mM ethylenediaminetetraacetic acid, pH7.2 phosphate buffered solution (phosphate buffered solution, PBS) , 0.22μm filter steri...

Embodiment 3

[0149] The drug distribution kinetics characteristic of embodiment 3 sustained-release carrier

[0150] EDC is a kind of carbodiimide compound with good water solubility, which is easy to undergo addition reaction with active hydrogen in alcohol, carboxylic acid, amine and other compounds, and converts into a compound with stable structure, so it is a widely used condensation compound. mixture. It can activate the carboxyl groups on glutamic acid and aspartic acid residues in collagen to form amide bonds with the amino groups on lysine or hydroxylysine in collagen, thereby improving the mechanical properties and thermal stability of collagen.

[0151] Heparin is a linear anionic polysaccharide, and it contains a variety of -OH, -COOH, -SO3H, NH2 and other functional groups, which can be used in the heparinization reaction of polymer materials. Therefore, under the test conditions, the carboxyl group in heparin After being activated by EDC, it reacts with -NH2 and other groups...

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Abstract

The invention discloses an application of BMP2 / 7 slow release system in glioma treatment, wherein the carrier of BMP2 / 7 is collagen covalently bound with heparin. According to the invention, a tumor-burdened rat test, a nude mouse intracranial transplantation tumor test and a nude mouse subcutaneous transplantation tumor test of a BMP2 / 7 slow release carrier are performed to research the synergistic effect of the BMP2 / 7 slow release carrier and chemotherapeutic, the distribution dynamics characteristics of the BMP2 / 7 slow release carrier and the biological compatibility of the BMP2 / 7 slow release carrier, the research clarifies that the composite BMP2 / 7 slow release carrier can form a high-concentration dosing environment and slowly release the BMP2 / 7 at local of the glioma to inhibit the proliferation of the glioma and promote the differentiation of the glioma, and if being matched with such traditional treatment measures as radiotherapy or chemotherapy, the BMP2 / 7 slow release carrier can play a role at different levels and different means to increase the possibility of eliminating the glioma cells.

Description

technical field [0001] The invention relates to the field of glioma treatment, in particular to the application of a BMP2 / 7 slow-release system in the treatment of glioma. Background technique [0002] The incidence of brain tumors is 21 / 100,000 people, accounting for about 2% of all human cancers, and the incidence of brain gliomas accounts for about 60% of brain tumors. According to the data summarized in the third (Sydney) International Tumor Control Conference in 1996, the incidence rate of glioma is 3-10 / 100,000, accounting for 1%-3% of systemic malignant tumors. There are about 40,000 cancer patients. The average survival period of surgery plus radiotherapy and chemotherapy is only 8 to 11 months. So far, there is no long-term follow-up data of large cases of glioma in my country. Due to the high degree of malignancy, rapid metastasis, high recurrence rate, high disability and death rate of brain glioma, there is currently no effective treatment. Therefore, a practi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61K47/42A61P35/00C08H1/06
Inventor 孙奋勇康贤通吴培诚
Owner GUANGZHOU LAND UNICOMED BIOTECH