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Sterol enriched mixed lamellarity amphotericin intercalating liposomes in saline and the process for their preparation

A technology of amphotericin and liposomes, applied in the field of mixed lamellar liposomes, can solve problems such as abnormal liver function, low therapeutic activity, and undesired sucrose intake, and achieve the effect of increasing plasma half-life and good biodistribution

Inactive Publication Date: 2007-08-08
LIFECARE INNOVATIONS PVT LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These problems are: low therapeutic activity, abnormal liver function, cholestasis and pulmonary toxicity (Deray, G. 2002, J. Antimicrobial Chemotherapy; 49, Suppl. S1, 37-41)
[0019] Administration of 20-21 mg amphotericin B for a shorter period also leads to undesirable sucrose intake in diabetic patients
Traditional amphotericin B mixtures containing 0.9% sodium chloride are known to cause precipitation of amphotericin B (Martindale, p. 315)

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1. Evaporation of a liposome fraction in methanol to obtain a membrane of the fraction. This membrane is hydrated with an aqueous solution and multilamellar liposomes are obtained by sheering said membranes from each other.

Embodiment 2

[0035] Example 2. Methanol solutions of liposome components were spray dried, then hydrated, and reconstituted in the chosen aqueous medium to obtain mixed lamellar liposome formulations.

Embodiment 3

[0036] Implementation 3. Evaporate the methanol solution of the liposome component to obtain a film of the component, add a selected aqueous medium, and then perform sonication to obtain a liposome preparation that is mainly unilamellar.

[0037] Nature of Biological Therapy

[0038] Ergosterol-PC liposomes with higher liposome concentrations were well tolerated and were found to be safe in terms of both chronic and acute toxicity. These liposomal formulations with up to 15 mg / ml amphotericin B can be administered without any adverse effects associated with injection. LD of these formulations 50 Higher than the reported cholesterol-PC liposomal amphotericin B.

[0039] Toxic nephrotoxicity was detected by measuring the value of creatinine in serum at different time periods after taking the drug. The values ​​of serum creatinine remained significantly unchanged up to the full dose required for complete treatment of leishmaniasis, ie 21 mg / kg body weight.

[0040] Here it is...

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PUM

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Abstract

The present invention relates to sterol enriched mixed lamellarity Amphotericin intercalating liposomes in saline for treatment of infections primarily parasitic infection especially those caused by intracellular protozoan parasites. The invention further relates to increasing circulation time of the drug encapsulated in the liposomes in the blood by subjecting liposomal pharmaceuticals to sonication before administration.

Description

technical field [0001] The present invention relates to amphotericin-added mixed lamellar liposome rich in sterol in saline and a preparation method thereof. Background technique [0002] Leishmaniasis is caused by the intracellular protozoan parasites Leishmania donovani, Leishmania infantum, and Leishmania chagas that live in macrophages. Transmission of the parasite occurs through the bite of an infected female Chrysalis subfamily. Sandflies acquire infected blood when they suck blood from a host that carries the parasite. Humans can suffer from four forms of leishmaniasis with different clinical manifestations. Of these various forms, visceral leishmaniasis (VL), also known as kala-azar, is the most severe, with an almost 100% mortality rate if left untreated. Frequent attacks of fever, weight loss, and hepatosplenomegaly with anemia are typical signs and symptoms of visceral leishmaniasis. [0003] Amphotericin B is a polyene antibiotic produced by soil fungi, Strep...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/7048
CPCA61K31/7048A61K9/127A61P31/00A61P33/02Y02A50/30
Inventor 吉藤德拉·纳提·维玛莉莉·维玛库里山·库马尔·特里帕提
Owner LIFECARE INNOVATIONS PVT LTD
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