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Pharmaceutical composition for treating hepatocellular carcinoma and application thereof

A hepatocellular carcinoma and composition technology, applied in the field of medicine, can solve problems such as high concentration of drugs in the body, difficulty in tolerance of patients, lack of targeting of drugs, etc.

Pending Publication Date: 2022-04-01
THE FIRST AFFILIATED HOSPITAL OF GUANGZHOU UNIV OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, existing HDAC inhibitors such as SAHA (Vorinostat) and TSA (Trichostatin A) that have been marketed in the United States have high drug concentration in the body after administration because of the lack of targeting of the drug, making them less effective in the treatment of hepatocellular carcinoma. High toxicity and side effects make it difficult for some patients to tolerate

Method used

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  • Pharmaceutical composition for treating hepatocellular carcinoma and application thereof
  • Pharmaceutical composition for treating hepatocellular carcinoma and application thereof
  • Pharmaceutical composition for treating hepatocellular carcinoma and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Embodiment 1: the preparation of liposomal nanoparticle (LNP-DP1)

[0040] Parameters such as the raw material components and dosage of the liposomal nanoparticles (LNP-DP1) used in this example are shown in Table 1.

[0041] Table 1 Liposome nanoparticle (LNP-DP1) preparation raw material

[0042]

[0043]

[0044] The preparation method of liposomal nanoparticles (LNP-DP1) is as follows:

[0045] Day 1: Preheat alcohol with a concentration of 100% in a water bath to 60°C, weigh all the liquid components in Table 1 according to the molar ratio, add them to the preheated alcohol as required, and fully dissolve them. Dissolve the four liquid components in proportion into an alcohol solution (DODMA / EggPC / Chol / PEG-liqid=45:15:35:5) (dissolve in a water bath at 60°C), slowly drop the mixed solution into it with a syringe and stir quickly In the HEPES solution (20mM, pH7.4), until the solution is a new mixed liquid containing 35% alcohol concentration. MWCO 10,000 Dal...

Embodiment 2

[0054] Example 2: Preparation of liposomal nanoparticles coated with valerenic acid

[0055] Add an equal volume of LNP-DP1 and valerenic acid (mixed at a volume ratio of 1:1) into a centrifuge tube, centrifuge at 2100g for 20 min, centrifuge the nanoparticle valerenic acid complex and concentrate it to 200 μl, centrifuge and let it stand for 20 min before use . Dilute and add medicine according to the required concentration, and prepare freshly before each use. Liposome nanoparticles coated with valerenic acid (LNP-DP1-valerenic acid, referred to as LV) complexes such as figure 1 shown.

Embodiment 3

[0056] Embodiment 3: pharmacological research

[0057] Effects of Valerenic Acid (VA) on HDAC Activity in Liver Cancer Cells

[0058] The HDAC Activity Colorimetric kit (BioVision, USA) was used to detect the effect of valerenic acid (VA) and liposome nanoparticles (LV) coated with valerenic acid on the HDAC activity of M test cells. Dilute the sample to be tested (50-200 μg cell lysate) with double distilled water to 85 μl (final volume) per well. Add 10 μl of 10X HDAC Assay Buffer to each well. 5 [mu]l of HDAC colorimetric substrate was added to each well and the solution was allowed to mix thoroughly. Place the plate to be tested in the incubation phase at 37°C for 1 hour (the incubation time can be extended as appropriate). Add 10 μl Lysine Developer to each well and mix well to stop the reaction. Continue to place the plate to be tested in a 37°C incubator for 30 minutes. Using an Epoch microplate spectrophotometer (Bio-Tek, USA), the OD value of the sample was measu...

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Abstract

The invention relates to the technical field of medicines, in particular to a pharmaceutical composition for treating hepatocellular carcinoma and application of the pharmaceutical composition. The pharmaceutical composition provided by the invention is lipidosome nanoparticles coated with valerian acid and comprises valerian acid and lipidosome, and the valerian acid is coated in the lipidosome. The valeric acid has the capability of remarkably inhibiting HDAC activity, has a remarkable anti-hepatoma effect and also has lower cytotoxicity. The valerian acid is coated in the lipidosome nanoparticles, so that the valerian acid has the targeting property of liver cancer lesions, and the effects of enhancing the effect and reducing toxicity on the treatment of the hepatocellular carcinoma by the valerian acid are achieved.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a pharmaceutical composition for treating hepatocellular carcinoma and its application. Background technique [0002] Primary liver cancer is the sixth most common malignant tumor disease in the world and the second leading cause of cancer-related death, causing nearly 800,000 deaths worldwide every year. In the past 20 years, the incidence of this disease has increased significantly in the Asia-Pacific region, and it has become the fourth most common malignant tumor and the third leading cause of cancer-related death in China. Hepatocellular carcinoma (Hepatocellular Carcinoma, HCC), as the most common clinical histological type of liver cancer, accounts for 85%–90% of primary liver cancers, is the fourth most common cause of cancer-related death worldwide, and is also the fastest growing incidence in the United States. Fastest cancer type (nearly tripled in past 20 years). I...

Claims

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Application Information

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IPC IPC(8): A61K31/19A61K9/127A61K47/28A61K47/24A61P35/00
Inventor 韩睿
Owner THE FIRST AFFILIATED HOSPITAL OF GUANGZHOU UNIV OF CHINESE MEDICINE
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