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Pharmaceutical nanometer composite temperature-sensitive gel for treating biliary tract tumor

A temperature-sensitive gel and nano-composite technology, which is applied in the field of preparation of drugs for treating biliary tumors, can solve the problems of irritation, non-degradation of implants, poor compliance, etc., and achieves good biocompatibility and strong tumor performance. Targeted, high drug loading effect

Active Publication Date: 2017-08-01
上海佶珥技术服务中心 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most of the implants currently in use or in the research and development stage are solid powder or granules, which require special drug delivery devices to implant the drug into the body, and are affected by patient compliance, and it is difficult to deliver drugs in place for deep lesions
Moreover, the biocompatibility of the material is not optimistic. Most implants use rubber-like materials as the controlled-release matrix or membrane, which leads to non-degradation or irritation of the implant, and poor compliance with repeated medication (Gao Renwei. Research on modification of medical silicone rubber materials. Chinese Journal of Medical Devices, 2015,39:122-125)

Method used

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  • Pharmaceutical nanometer composite temperature-sensitive gel for treating biliary tract tumor
  • Pharmaceutical nanometer composite temperature-sensitive gel for treating biliary tract tumor
  • Pharmaceutical nanometer composite temperature-sensitive gel for treating biliary tract tumor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Preparation and Application of Thermosensitive Gel Encapsulated Carboplatin

[0058] Dissolve 200mg carboplatin in 2ml purified water, add 18% (w / w) F-127 and 0.5% (w / v) HPMC-E15, 1% (w / v) MC to dissolve, lyophilize to obtain xerogel agent, rheological properties see figure 2 e.

[0059] To establish an orthotopic model of cholangiocarcinoma in nude mice, the cultured cholangiocarcinoma Hucct1 cells were formulated with serum-free DMEM medium at a concentration of 1×10 7 cells / ml of cell suspension. Nude mice were anesthetized by intraperitoneal injection of 1% (w / v) pentobarbital sodium (350 mg / kg), routinely disinfected, opened the abdomen under the xiphoid process along the linea alba, and sucked the microinjector with tumor cell suspension The needle was inserted into the interstitial space between the hilar bile duct and the portal vein close to the bifurcation of the bile duct, and 100 μl of tumor cell suspension was injected to stop bleeding by compression. ...

Embodiment 2

[0061] Preparation and application of thermosensitive gel loaded with cisplatin (DDP)

[0062] Preparation by solvent-non-solvent method: Dissolve 20 mg of DDP in 5 mL of KOH solution at pH 10, add acid to neutralize under stirring to obtain DDP suspension. The mean particle diameter that above-mentioned makes is 153.7nm ( figure 1 D), the release curve ( image 3 D). Then add 16% (w / w) F-127, 0.5% (w / v) HPMC-K100M to obtain a suspension temperature-sensitive gel, see rheological properties figure 2 d.

[0063] An orthotopic model of gallbladder carcinoma in nude mice was established. Referring to Example 1, the tumor was surgically removed, and the gel was added to the excised site. After it solidified, the gel was closed with bioglue and the wound was sutured. The control group was intravenous systemic administration group (DDP: tail vein administration of 2 mg / kg, twice a week, treatment for 5 weeks) and 0.9% NaCl group. Regular MRI observation. At 6 months, the recu...

Embodiment 3

[0065] Preparation and application of thermosensitive gel containing oxaliplatin (ELO)

[0066] Dissolve 200mg of ELO in 2ml of purified water, add 20% (w / w) F-127 and 0.5% (w / v) HPMC-E15, 0.5% (w / v) HPMC-K100M to dissolve, freeze-dry to obtain dry coagulation Glue.

[0067] To establish a subcutaneous tumor model of gallbladder carcinoma in nude mice, take 30 BALB / C nude mice of 4-6 weeks old, and 15 of them were subcutaneously inoculated with 6X10 6 Human cholangiocarcinoma cell RBE / one, 15 nude mouse tumor models of human cholangiocarcinoma QBC939 cells were established, and 6X10 6Human gallbladder cancer cells GBC-SD / only, the nude mouse tumor model of human gallbladder cancer GBC-SD cells was established. The gel was hydrated and injected into the peritumoral site. After it solidified, the needle was withdrawn. The control group was intravenous systemic administration group (ELO: tail vein administration 6mg / kg, twice a week, treatment for 5 weeks) and 0.9% NaCl group. ...

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Abstract

The invention relates to a pharmaceutical nanometer composite temperature-sensitive gel for treating a biliary tract tumor. The gel is made by coating nanometer particles made from an anti-tumor active substance with a polymer or a targeted-gene-modified polymer which is taken as a carrier material, and adding a temperature-sensitive polymer material to prepare nanometer composite temperature-sensitive gel, or dissolving or suspending the anti-tumor active substance nanometer particles in temperature-sensitive gel. The gel is simple to prepare, is suitable for massive production, and is suitable for preparing a medicine for treating and preventing biliary tract tumors, such as gallbladder carcinoma, intrahepatic cholangiocarcinoma and cholangiocarcinoma, which relapse after operation.

Description

technical field [0001] The invention belongs to a preparation method and application of a drug nanocomposite temperature-sensitive gel for tumor treatment, and is suitable for preparing a drug for treating biliary system tumors. Background technique [0002] In recent years, the incidence of cholangiocarcinoma has increased. Its onset is insidious, its growth is rapid, its clinical symptoms are atypical or lack of specificity, it is difficult to detect in the early stage, and it is often late when it is diagnosed. The malignant degree of biliary tract cancer and gallbladder cancer is very high, the treatment is difficult, and the prognosis is extremely poor. of high attention. At present, surgery is still the only possible way to obtain a radical cure, but only about 10% of early-stage patients can undergo radical resection, and most patients are already at an advanced stage when they are diagnosed, losing the opportunity for surgery; even if patients undergo surgical resec...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K47/34A61K47/10A61K47/38A61K47/36A61K48/00A61K39/395A61K33/24A61K31/282A61K31/337A61K31/704A61K31/136A61K31/4745A61K31/475A61P35/00A61P35/04
CPCA61K9/06A61K31/136A61K31/282A61K31/337A61K31/4745A61K31/475A61K31/704A61K33/24A61K39/39558A61K47/34A61K47/36A61K47/38A61K48/0083A61K2300/00
Inventor 段友容沈鸣黄莉莉丁利黄灿
Owner 上海佶珥技术服务中心
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