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A targeted complement antibody microcapsule preparation for the treatment of alcoholic liver disease and its preparation method and application

A targeted technology for alcoholic liver disease, applied in biochemical equipment and methods, antibodies, microcapsules, etc., can solve the problems of immune regulation imbalance, low biological activity, and inability to localize, and achieve long-term action time and targeted strong effect

Active Publication Date: 2019-11-08
GUANGXI MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Liquid-phase regulatory factors are a variety of liquid-phase serum proteins, which cannot be localized, and their regulation will inevitably affect the conditioning, inflammation, and bactericidal effects that are beneficial to the body at the same time, which will easily lead to imbalanced immune regulation and low biological activity. limitations, thus greatly limiting its practical clinical application value

Method used

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  • A targeted complement antibody microcapsule preparation for the treatment of alcoholic liver disease and its preparation method and application
  • A targeted complement antibody microcapsule preparation for the treatment of alcoholic liver disease and its preparation method and application
  • A targeted complement antibody microcapsule preparation for the treatment of alcoholic liver disease and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Effect of complement antibody CR2-Crry on acute alcoholic liver injury (see image 3 ).

[0031] Eighteen C57BL / 6 wild-type mice were used and randomly divided into three groups with 6 mice in each group. In the alcohol treatment + complement antibody protein treatment group, each mouse was given intraperitoneal injection of 0.25mg CR2-Crry 30 minutes before the alcohol gavage; ) by intraperitoneal injection, while the control group was given intragastric administration of isocaloric dextrin solution, and the mice were sacrificed 6 hours later to obtain serum and liver samples. Serum samples were used to detect liver function, and liver tissue samples were tested for C3 deposition by immunofluorescence.

[0032] Test results such as image 3 As shown, the detection results confirmed that the complement antibody can significantly reduce liver damage while inhibiting complement activation.

Embodiment 2

[0033] Example 2: Effect of complement antibody CR2-Crry on chronic alcoholic liver injury.

[0034] Twenty-four C57BL / 6 wild-type mice were used and randomly divided into three groups with 8 mice in each group. The alcoholic fatty liver degeneration model (Alcoholic Fatty Liver, AFL) was fed with liquid alcohol feed (Nantong Trophy Feed Technology Co., Ltd., TP4030D) according to the NIAAA method (National Institute on Alcohol Abuse and Alcoholism), and the control group was fed with isocaloric control feed (Nantong Trofe Feed Technology Co., Ltd., TP4030C), the AFL+CR2-Crry group was given intraperitoneal injection of 0.25 mg CR2-Crry every day after the 10th day of alcohol feed feeding, and the AFL group was given the same amount of NS treatment, and the pups were killed after 6 consecutive days. Serum and liver samples were collected from mice. Serum samples were used to detect liver function and complement levels, and liver tissue samples were used to detect liver fat de...

Embodiment 3

[0037] Effect of complement antibody CR2-Crry on liver injury and liver regeneration after liver resection in the context of alcoholic liver disease.

[0038] The specific modeling process is shown in Example 2. On the basis of chronic alcoholic liver disease, we further adopted a 70% liver resection model, and collected serum and liver tissue samples for related testing 48 hours after the operation.

[0039] Test results such as Figure 5 As shown, the test results confirm that: in the background of chronic alcoholic liver disease, liver resection is performed, and complement antibodies can significantly reduce liver injury and improve liver regeneration after hepatectomy while inhibiting complement activation.

[0040] The application of a targeted complement antibody microcapsule oral liquid preparation is mainly used in the treatment of alcoholic liver disease. The method of use is: take orally, twice a day, 1ml (1.0g antibody) each time, and one month is a course of trea...

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Abstract

The invention discloses a targeting addiment antibody micro-capsule preparation for treating alcoholic liver disease, a preparation method thereof and an application thereof. The preparation method includes steps of cloning addiment antibody contained protein gene to an expression carrier pEE14.1 with high expression target protein in Chinese hamster ovary cell (CHO); and then transfecting CHO cell; through subculture, screening the high-output addiment antibody protein expression cell system; through a cell rotary culture technology, enlarging the production and purification; acquiring the addiment antibody protein CR2-Crry; then preparing the addiment antibody protein to be an addiment antibody lipidosome micro-capsule; at last, performing membrane filtering, sterilization and split charging, acquiring the targeting addiment antibody micro-capsule preparation for treating alcoholic liver disease. The preparation is supplied to patients suffering from alcoholic liver disease; the dosage of addiment antibody micro-capsule is 2.0g addiment antibody / day, and applied twice per day. The preparation has the advantages of strong targeting property, high efficiency, safe, and no influence on general immunity function of the host.

Description

technical field [0001] The invention relates to the development of new drugs for treating alcoholic liver disease, in particular to a targeted complement antibody microcapsule preparation for treating alcoholic liver disease, its preparation method and application. Background technique [0002] Alcohol-induced liver disease (ALD) is a liver disease caused by long-term heavy drinking, including fatty liver, alcoholic hepatitis, liver fibrosis, and cirrhosis. Alcoholism is the second leading cause of liver damage after hepatitis viruses. In recent years, the incidence of ALD in China has been on the rise, and it has become a frequently-occurring and common disease that seriously threatens human health. 80% to 90% of ethanol is metabolized in the liver. After being catalyzed by alcohol dehydrogenase, it is oxidized to acetaldehyde, which is then catalyzed by acetaldehyde dehydrogenase into acetic acid, and finally forms carbon dioxide. In the process of ethanol oxidation, a l...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K9/50A61K39/395C12N15/85C07K19/00A61P1/16
CPCA61K9/1277A61K9/5015A61K39/3955C07K14/70596C07K2319/00C12N15/62C12N15/85C12N2800/107
Inventor 何松青袁观斗徐庆唐博钟伏弟
Owner GUANGXI MEDICAL UNIVERSITY