Method of treating dyslipidemic disorders

a dyslipidemic disorder and treatment method technology, applied in the field of dyslipidemic disorders, can solve the problems of reducing serum cholesterol levels by about 20%, side effects and qualifying patient population, and hdls serum levels are regarded as negative risk factors, so as to improve patient comfort, improve the stability of apoa-i complexes, and facilitate administration.

Inactive Publication Date: 2004-04-08
PFIZER INC
View PDF7 Cites 50 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

0043] Use of the ApoA-I-SM complexes according to the invention is also advantageous because lower anticipated doses of the volume of ApoA-I-SM complexes infused or injected leads to faster and easier administration and improved patient comfort.
0044] Use of the ApoA-I-SM c

Problems solved by technology

Indeed, high serum levels of HDLs are regarded as a negative risk factor.
However, each has its own drawbacks and limitations in terms of efficacy, side-effects and qualifying patient population.
The use of such resins at best, however, only lowers serum cholesterol levels by about 20%, and is associated with gastrointestinal side-effects, including constipation and certain vitamin deficiencies.
Moreover, since the resins bind other drugs, other oral medications must be taken at least one hour before or four to six hours subsequent to ingestion of the resin; thus, complicating heart patient's drug regimens.
However, serum HDL cholesterol levels are only moderately increased.
Niacin can increase HDL when used at adequate doses, however, its usefulness is limited by serious side effects when used at such high doses.
Although serum cholesterol may be reduced in certain patient subpopulations, the biochemical response to the drug is variable, and is not always possible to predict which patients will obtain favorable results.
Atromid-S.RTM. has not been shown to b

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method of treating dyslipidemic disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

6.1. EXAMPLE 1

[0123] Preparation of ProApoA-I-Lipid Complexes

[0124] Complexes of proApoA-I and phospholipids are drug candidates that potentially mimic the biological activities of HDL. This example describes the preparation of proApoA-I-phospholipid complexes.

6.1.1. MATERIALS AND METHODS

[0125] Complexes of proApoA-I and lipids were prepared by the cholate dispersion method. Four lipids were used: Phospholipon 90 G (soybean PC), sphingomyelin, dipalmitoyl phosphatidylcholine (DPPC), and 1-palmitoyl-2-oleyl-phosphatidylcholine (POPC).

[0126] A 30 mg / ml cholate solution was made by adding 0.9677 g of cholic acid to 32.25 ml of 2 mM NaHCO.sub.3 buffer.

[0127] To prepare the proApoA-I solution, proApoA-I solution (Eurogentec) at a concentration of 1 mg / ml in 6M urea was employed. 60 ml of the proApoA-I-6M urea solution was dialyzed against 1200 ml of 2 mM NaHCO.sub.3 buffer using a tangential flow filtration unit (Labscale TFF System, Millipore) equipped with a 10 kDa cut off membrane. Fo...

example 2

6.2. EXAMPLE 2

[0138] Further Preparation of ProApoA-I-Lipid Complexes

[0139] Based on the results obtained in Section 6.1 (Example 1), the proportion of SM was increased, in order to produce preferentially a single peak of proApoA-I-SM complexes. This example demonstrates that the proApoA-I to sphingomyelin ratio may be varied to produce a single peak of proApoA-I-sphingomyelin complex at a ratio of 1:2 (wt / wt).

6.2.1. MATERIALS AND METHODS

[0140] ProApoA-I -SM complexes were prepared by the following co-solubilization method.

[0141] ProApoA-I solution in 6M urea (Eurogentec) was concentrated 5 times and dialyzed against 10 volumes of 5 mM NH.sub.4HCO.sub.3. The protein concentration was then measured by performing a Markwell-Lowry protein assay. Protein solution was then lyophilized.

[0142] A 25 mg / ml stock solution of proApoA-I in acetic acid was made by dissolving 128.2 mg of the lyophilized proApo-A-I powder in 5.13 ml of glacial acetic acid (J T Baker).

[0143] A 50 mg / ml stock soluti...

example 3

6.3. EXAMPLE 3

[0149] Pharmacological Efficacy of r-proApoA-I-Sphingomyelin Complexes Compared With r-proApoA-I-POPC Complexes

[0150] ProApoA-I-lipid complexes are drug candidates that potentially mimic the biological activities of HDL. The objective of this study was to compare the pharmacodynamic properties (i.e., mobilization of cholesterol in plasma) of proApoA-I-SM with those of conventional proApoA-I-phosphotidyl choline complexes such as proApoA-I-POPC. Recombinant human proApoA-I (r-proApoA-I) was used in this study. Proapolipoprotein A-I comprises six amino acids (Arg-His-Phe-Trp-Gln-Glu) attached at the amino terminal end of ApoA-I.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Login to view more

Abstract

The invention provides methods of treating or preventing a condition or disorder associated with dyslipidemia with compositions comprising apolipoprotein-sphingomyelin complexes. The methods of the invention permit reduction, by 4- to 20-fold, of the amount of apolipoprotein required for therapeutic administration to bring about an ameliorative effect.

Description

[0001] This application claims priority to U.S. Provisional Application Serial Number 60 / 381,512, filed May 17, 2002, incorporated herein by reference in its entirety.1. TECHNICAL FIELD[0002] The invention provides methods of treating or preventing a disease, condition or disorder associated with dyslipidemia with apolipoprotein-sphingomyelin complexes or pharmaceutical compositions thereof. The invention further provides compositions for treating or preventing a disease, condition or disorder associated with dyslipidemia and methods for the production of the compositions.2. BACKGROUND OF THE INVENTION[0003] Circulating cholesterol is carried by plasma lipoproteins--complex particles of lipid and protein composition that transport lipids in the blood. Four major classes of lipoprotein particles circulate in plasma and are involved in the fat-transport system: chylomicrons, very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Chylomic...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K31/685A61K38/17A61K47/48
CPCA61K31/685A61K38/17A61K38/1709A61K47/48838A61K2300/00A61K47/6917A61P3/06A61P9/10A61P9/12
Inventor DASSEUX, JEAN-LOUIS H.SHENDEROVA, ANNA A.REA, THOMAS J.
Owner PFIZER INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap