LIPID EMULSION FOR TREATING AIDS

Abstract: A composition for the treatment of patients having Acquired Immune Deficiency Syndrome comprising approximatley 2 to 7 percent by weight soybean oil and approximately 1 to 2 percent by weight egg phosphatide and a method for the parenteral administration of this composition is disclosed.

Description: FIELD OF THE INVENTION The present invention relates to a composition for treating patients with Acquired Immune Deficiency Syndrome. More particularly, this invention relates to a composition for the parenteral administration of a non- or low carbohydrate source of calories for nutritional support and phosphatides to stimulate prostaglandin synthesis. BACKGROUND OF THE INVENTION The number of patients suffering from Acquired Immune Deficiency Syndrome (AIDS) has increased dramatically since the first cases were reported a few years ago. The disease has caused opportunistic infections and secondary cancers in more than 50,000 people in the United States and many more throughout the world. Patients suffering from AIDS are often nutritionally unbalanced and wasted. Weight loss and decrease in serum albumin, total iron binding capacity and retinal binding protein are often seen. Body composition analysis in AIDS patients demonstrates a depletion in total body potassium and body fat content with an increase in extracellular water. These symptoms are often seen in those suffering from chronic malnutrition. A number of factors lead to malnutrition in AIDS patients. These include a decrease in food intake, vomiting, the side effects of therapeutic drugs and a high incidence of malabsorption syndrome with or without diarrhea. When malabsorption syndrome and/or diarrhea do not permit effective oral feeding, parenteral nutrition is indicated. Conventional parenteral nutrition compositions and methods of therapy are unbalanced attempts at nutritional restitution. Known from DE-A-1 249 454 are parenteral emulsion compositions comprising 5-50% soybean oil and 0.05-3% egg phosphatide. Known from FR-A-2 450 608 is a parenteral emulsion composition comprising 10% soybean oil and 1.2% egg phosphatide. Furthermore, parenteral emulsion compositions comprising 10 or 20% triglycerides and 0.9-1.2% egg phosphatide are known from Helwig Arzneimittel, Bd. II, Kap. 31-54, by H. Helwig et al., Wissenschaftliche Verlagsgesellschaft, Stuttgart, 1988, pp. 35-39, 35-48, 35-43. Such compositions contain soybean oil as either the only source of triglycerides or half the source of triglycerides. Such conventional parenteral nutrition compositions contain too high a fat content which, if administered too rapidly, can exacerbate the formation of pro-inflammatory prostanoids and prevent the beneficial effects of low-fatty acid administration. This invention permits administration of the desired level of egg phospholipids and triglycerides over a longer period of time without exacerbating pro-inflammatory prostanoids or inducing fat overload. It is also known that some of the manifestations of AIDS are ameliorated by non-steroidal anti-inflammatory agents. It is believed that these effects are related to a preferential suppression of certain prostaglandins by these agents. Prostaglandins are synthesized in the body from fatty acid precursors which are derived from lipids. The composition, rate of administration and concentration of neutral lipids, fatty acids and lecithins administered parenterally can determine the prostaglandin synthetic pathway and thereby the specific class of eicosanoid being preferentially synthesized. Thus, there is a need for a low fat - high phosphatide parenteral formulation for the treatment of AIDS patients either as a component of total parenteral nutrition of as a parenteral supplement to patients receiving nutrition orally. SUMMARY OF THE INVENTION In accordance with the present invention, there is provided for the treatment of AIDS patients an emulsion composition for parenteral administration comprising a soybean oil emulsion containing egg phosphatide. More particularly, the compositions contain 2 percent by weight soybean oil and 1.2 percent by weight egg phosphatide. The compositions of this invention contain a higher egg phosphatide/triglyceride ratio, in comparison to commercially available fat emulsions, which makes it possible to provide a sufficient level of egg phosphatide to promote mobilization of tissue cholesterol without inducing fat overload. DESCRIPTION OF THE PREFERRED EMBODIMENTS The parenteral compositions of this invention contain 2 percent by weight soybean oil and 1.2 percent by weight egg phosphatide. The most preferred parenteral composition of the present invention contains the following: The soybean oil utilized in the composition of the present invention may be obtained from any commercially available source and should have a fatty acid composition of from 44 to 62 weight percent linoleic acid, from 19 to 30 weight percent oleic acid, from 7 to 14 weight percent palmitic acid, from 1 to 6 weight percent stearic acid, and from 4 to 11 weight percent linolenic acid. The egg phosphatide utilized in the composition of the present invention may also be obtained from commercially available sources and should preferably have a nitrogen to phosphorous molar ratio of from 0.97 to 1.17. The composition of the present invention may be prepared in accordance with known procedures in the art as illustrated by the following example. EXAMPLE 1 Water for injection (approximately 1 liter) is heated and protected by a nitrogen atmosphere. Egg phosphatide (12g) is added to the water and dispersed by agitation at a temperature in the range of 50 to 90°C. Glycerin (25g) is filtered through an 0.8 µm membrane filter and added to the dispersion using a Manton-Gaulin homogenizer to finely divide the egg phosphatide and increase the degree of dispersion. The aqueous phosphatide dispersion is then filtered through a nylon or equivalent membrane of 0.45 µm porosity and the pH is adjusted to a range of 8.5 to 10.5 with sodium hydroxide. Soybean oil, winterized, (20g) is filtered through a 0.45 µm membrane, heated to a temperature in the range of 55 to 95°C and added to the egg phosphatide dispersion with agitation to form a coarse emulsion concentrate which is then homogenized using a Manton-Gaulin homogenizer at a pressure of 14 to 34 MPa (2000 to 5000 psi). The pH is then adjusted to a range of 8.5 to 9.5, if necessary, with sodium hydroxide and the emulsion is filtered through a nylon membrane of at least 0.8 µm porosity with sufficient surface area to provide minimum restriction of flow. The emulsion is then further homogenized in a Manton-Gaulin homogenizer, diluted to a desired concentration with sterile water and the pH adjusted to a range of 8.5 to 9.6 with sodium hydroxide. When used in treating patients with AIDS the emulsions of this invention should be administered parenterally in amounts sufficient to provide 5 to 30 ml/Kg/day.

Claims: Claims for the following Contracting States : BE, CH, DE, FR, GB, IT, LI, NL, SE An emulsion composition for parenteral administration comprising 2 percent by weight soybean oil and 1.2 percent by weight egg phosphatide. An emulsion as in Claim 1 having a pH in the range of 8.5 to 9.5. An emulsion as in Claim 1 which contains glycerine. Use of a composition of any one of Claims 1-3 for manufacturing a medicament for treating a host mammal having Acquired Immune Deficiency Syndrome. Use as in Claim 4 wherein the therapeutically effective amount is in the range of 5 to 30 ml/kg/day. Claims for the following Contracting States : ES, GR An emulsion composition for parenteral administration comprising 2 percent by weight soybean oil and 1.2 percent by weight egg phosphatide. An emulsion as in Claim 1 having a pH in the range of 8.5 to 9.5. An emulsion as in Claim 1 which contains glycerine. Use of a composition of any one of Claims 1-3 for manufacturing a medicament for treating a host mammal having Acquired Immune Deficiency Syndrome. Use as in Claim 4 wherein the therapeutically effective amount is in the range of 5 to 30 ml/kg/day. Process for preparing an emulsion composition for parenteral administration comprising homogenizing 2 percent by weight soybean oil and 1.2 percent by weight egg phosphatide in a pharmaceutically acceptable aqueous solution. Process as in Claim 6 further comprising adjusting the pH to a value in the range of 8.5 to 9.5. Process as in Claim 6 comprising homogenizing said amounts of soybean oil and egg phosphatide with glycerine in a pharmaceutically acceptable aqueous solution.

Inventors: ASKANAZI, JEFFREY DR., LEATHEM, WILLIAM D., SHAW, HOWARD LAURENCE
Applicants: ABBOTT LABORATORIES
Application year: 1989
Main classification: A61K9
IPC codes: A61K31, A61K35, A61K36, A61K9, A61P31, A61K38