Entecavir compound nano-preparation and preparation method thereof

A kind of entecavir and nano-composite technology, which is applied in antiviral agents, pharmaceutical formulas, active ingredients of heterocyclic compounds, etc., can solve the problems of adverse reactions such as gastrointestinal irritation, low utilization rate of entecavir, and difficulty in controlling drug efficacy, and achieve reduction Adverse reactions and gastrointestinal irritation, solving poor bioavailability, and improving bioavailability

Active Publication Date: 2014-07-09
山东世博金都药业有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] First of all, the applicant found in the research to solve the problem of poor bioavailability of oral entecavir drugs
After entecavir is taken orally into the digestive system, it is easily destroyed by the digestive juice in the human body, making the plasma concentration of entecavir low, and it is impossible to obtain a good therapeutic effect
Although there is a design involving the use of carriers to carry entecavir to intestinal absorption in the prior art, the carrier selected in the prior art has a poor encapsulation effect on entecavir, resulting in a low utilization rate of entecavir, and adverse reactions and gastrointestinal tract increased irritation
[0008] Secondly, although there is a design in the prior art that uses a carrier to carry entecavir, the particle size of the composite particles formed by the carrier and entecavir in the prior art is relatively large, and cannot be better absorbed by somatic cells through the membrane
The applicant found in the research that the size of the existing entecavir nanocomposite micelles is uneven and the particle size distribution is wide, while the particle size distribution of the entecavir nanocomposite micelles is wide, which may easily cause the absorption rate of entecavir to be unstable and the drug effect is difficult to control

Method used

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  • Entecavir compound nano-preparation and preparation method thereof
  • Entecavir compound nano-preparation and preparation method thereof
  • Entecavir compound nano-preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] 1) Mix 1000 mg of hydrogenated soybean lecithin, 200 mg of cholesterol, 100 mg of a compound of chenodeoxycholic acid and sodium taurodeoxycholate at a ratio of 1:1 by weight, and 100 mg of vitamin E to obtain a total mixture, and add the total mixture to 80m1 , with a volume fraction of 99.5% ethanol solution, and ultrasonically dissolve it in a water bath to form an organic solution ①; the organic solution ① uses CO 2 Dissolve in supercritical extraction equipment, the temperature of the extraction kettle is 60°C, the pressure of the extraction kettle is 30MPa, the temperature of the separation kettle is 65°C, the pressure of the separation kettle is 10MPa, and an organic solution is formed②;

[0042] 2) Add 300mg of entecavir into 0.01mol / L, pH7.4 phosphate buffer according to the mass volume ratio of 8g / L, and dissolve it by ultrasonication in a water bath to form entecavir into a solution;

[0043] 3) Inject the organic solution ② into the entecavir solution obtain...

Embodiment 2

[0047] 1) Mix 950 mg of soybean lecithin, 250 mg of cholesterol, 120 mg of a compound of chenodeoxycholic acid and sodium taurodeoxycholate at a ratio of 1:1 by weight and 180 mg of vitamin E to obtain a total mixture, and add the total mixture to 70m1, volume In the ethanol solution with a fraction of 98.0%, the water bath ultrasonically dissolves it to form an organic solution ①; the organic solution ① uses CO 2 Dissolved in supercritical extraction equipment, the temperature of the extraction kettle is 55°C, the pressure of the extraction kettle is 25MPa, the temperature of the separation kettle is 60°C, and the pressure of the separation kettle is 12MPa to form an organic solution②;

[0048] 2) Add 390mg of entecavir into 0.01mol / L, pH7.4~7.6 phosphate buffer according to the mass-volume ratio of 7.5g / L, and dissolve it by ultrasonication in a water bath to form entecavir into a solution;

[0049] 3) Inject the organic solution ② into the entecavir solution obtained in ste...

Embodiment 3

[0053] The present embodiment adopts following preparation method:

[0054] 1) Mix 400mg of soybean lecithin, 100mg of cholesterol, 50mg of the complex of chenodeoxycholic acid and sodium taurodeoxycholate at a weight ratio of 1:1, and 20mg of vitamin E to obtain a total mixture, and add the total mixture to 50m1, In an ethanol solution with a volume fraction of 99.0%, dissolve it in a water bath with ultrasonic waves to form an organic solution ①; use CO 2 Dissolve in supercritical extraction equipment, the temperature of the extraction kettle is 60°C, the pressure of the extraction kettle is 30MPa, the temperature of the separation kettle is 65°C, the pressure of the separation kettle is 10MPa, and an organic solution is formed②;

[0055] 2) Add 100mg of entecavir into 0.01mol / L, pH 7.4~7.6 phosphate buffer according to the mass volume ratio of 6g / L, and dissolve it by ultrasonication in a water bath to form entecavir into a solution;

[0056] 3) Inject the organic solution...

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Abstract

The invention provides an entecavir compound nano-preparation and a preparation method thereof, and belongs to the technical field of entecavir medicinal preparations. The preparation comprises the following components in parts by weight: 3-6 parts of entecavir, 3-11 parts of phospholipid, 1-3 parts of cholesterol, 0.2-2 parts of cholic acid, 0.2-2 parts of bile salt, 0.5-4 parts of vitamin E and 1-6 parts of mycose, wherein the cholic acid and the bile salt are added in equal weight part. The preparation method comprises the following steps: preparing an organic solution from phospholipid, cholesterol, cholic acid, bile salt and vitamin E; and preparing an entecavir solution from entecavir with phosphate buffer; mixing the two solutions, stirring, volatizing, granulating and lyophilizing the mixture to prepare dry powder of the entecavir compound nano-preparation. The entecavir nano-compound micell in the entecavir compound nano-preparation is small in size and narrow in grain diameter distribution, and has high bioavailability; the preparation method of the compound nano-preparation is easy to operate, and high in production efficiency.

Description

technical field [0001] An entecavir nanocomposite preparation and a preparation method thereof belong to the technical field of entecavir pharmaceutical preparations. Background technique [0002] Entecavir is 2-amino-9-[(1S,3R,4S)-4-hydroxy-3-hydroxymethyl-2-methylenecyclopentyl]-1,9-dihydro-6H-purine-6- Ketone monohydrate is an oral antiviral drug for the treatment of hepatitis B infection. It can selectively inhibit hepatitis B virus. It is mainly used for the treatment of adults with active virus replication and continuous increase in serum transaminases, or active liver histology Lesions of chronic hepatitis B. Entecavir was listed in the United States in 2005 by Pepsi-Myers Squibb. [0003] Entecavir chemical structure [0004] [0005] Molecular formula: C 12 h 15 N 5 o 3 ·H 2 O. [0006] Molecular weight: 295.30. [0007] First of all, the applicant found in the research to solve the problem of poor bioavailability of oral entecavir drugs. After entecav...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K9/19A61K9/127A61K31/522A61K47/28A61K47/46A61P31/20
Inventor 阎敬武邸春盛杜成德
Owner 山东世博金都药业有限公司
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