Method of treatment of liver disease

A liver disease, calcium channel blocker technology, applied in pharmaceutical formulations, medical preparations containing active ingredients, plant raw materials, etc., can solve problems such as the unconfirmed effect of calcium blockers on hepatic artery blood flow, etc., to reduce silymarin Effects of side effects

Inactive Publication Date: 2012-07-11
HOWARD J SMITH & ASSOC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The effect of low-dose oral calcium blockers on hepatic arterial blood flow has not been established

Method used

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  • Method of treatment of liver disease
  • Method of treatment of liver disease
  • Method of treatment of liver disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0099] Despite the complex composition of silymarin, other researchers have shown that this botanical agent can be formulated in erodible matrices using systems based on glyceryl monostearate and polyethylene glycol 6000 or poloxamer 188 (Cheng et al. 2007). Silymarin and other botanical antioxidants can thus be co-formulated with diltiazem using a number of standard techniques for preparing sustained release formulations. The claims of the present invention relate to the concept of co-formulation of botanical antioxidants with low doses of diltiazem in sustained release formulations, rather than the specific chemical nature of the formulations used.

Embodiment 1

[0109] This example compares the response of hepatocytes to diltiazem, silymarin and the combination of diltiazem and silymarin under oxidative stress.

[0110] Materials and methods

[0111] Including d-cis-diltiazem, silymarin, and dichlorofluoroacetoacetate (DCFH 2 -DA) were purchased from Sigma Chemical, St. Louis, MO. Darwin's modified Elder's medium (DMEM), fetal bovine serum, penicillin and streptomycin were purchased from GIBCO / BRL. MTT (cell proliferation) and ATPase kits were purchased from Sigma (St. Louis, MO). The human hepatoma cell line Chang and PLC / PRF / 5 cells were purchased from the American Type Culture Collection, Rockville, MD (ATCC, Rockville, MD).

[0112] Cell Culture and Drug Therapy

[0113] Chang and PLC / PRF / 5 hepatoma cells in 25 cm supplemented with DMEM 2 in culture flasks at 37°C in 95% air and 5% CO 2 Maintain at least 24 hours in a humidified atmosphere in DMEM containing 10% FBS (DF-10), penicillin and streptomycin (50 units / ml). Cells ...

Embodiment 2

[0148] Example 2: Metabolism studies of diltiazem and silymarin

[0149] The procedure of this example was performed with the rat hepatic cell line H4-IIE cell line. This is a well established hepatocyte model. The cell line exhibits all the main features of normally differentiated rat hepatocytes. This cell line has been used for medical and biochemical research on liver function for 20 years, and its characteristics are not inferior to other normal freshly isolated rat hepatocytes. Oxidative damage was induced by an established method using hydrogen peroxide. Hepatocytes cultured in plastic multiwell plates were incubated with 0.5 mM hydrogen peroxide for 1 hour and then incubated in normal medium for 12 hours under standard incubation conditions. This regimen induces oxidative damage to target cells. Cell damage was assessed by measuring the exclusion of the dye trypan blue and the release of the cytosolic enzyme lactate dehydrogenase.

[0150] To evaluate the rate o...

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PUM

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Abstract

A method of treatment of a subject suffering from liver disease comprising the administration of (i) an oral slow-release formulation of a calcium channel blocker with antioxidant effects and (ii) at least one flavonolignan.

Description

technical field [0001] The present invention relates to methods of treating liver disease and complications including cirrhosis and portal hypertension. Specifically, the present invention relates to a method for treating non-malignant liver diseases such as viral or toxic hepatitis and fatty liver, which cause direct or indirect damage to the liver, and a composition for treating liver diseases. Background of the invention [0002] Nonmalignant liver disease includes toxic hepatitis such as the most common toxic form of alcoholic hepatitis, infection-induced hepatitis such as viral hepatitis, fatty liver, and less commonly autoimmune liver disease characterized by chronic inflammation. [0003] Treatments that attempt to improve liver function are always secondary to treatment of the primary disease process, but there have been many attempts to improve function by targeting components of different pathological processes, including cellular swelling and lack of oxygen. A k...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K36/28A61P1/16
CPCA61K36/28A61K31/554A61K45/06A61P1/16A61K2300/00
Inventor H·J·史密斯
Owner HOWARD J SMITH & ASSOC
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