LYM-X-SORB™ is a chemical (GRAS) formulation that Dr. Yesair invented which enables fat and medicine to be absorbed into the body from the intestines and into the lymphatic system. LYM-X-SORB™ can help the many people who have temporary or permanent, often debilitating, medical conditions which make it impossible for them to digest fat in the normal way. LYM-X-SORB makes it possible for them to survive, even gain weight when ordinarily they would waste away, perhaps die. Such conditions include certain cancers, advanced AIDS, cystic fibrosis, acute alcoholism, dysentery, and many others. Dr. Yesair is concentrating on making LYM-X-SORB based nutritional products available to cystic fibrosis patients as a first step. A business, marketing, and sales plan have been developed for this organized lipid matrix for both the United States and European Cystic Fibrosis (CF) markets. Conservative annual sales of greater than 50 million US dollars and of margins approximating 15 to 30 million US dollars are readily attainable within five years, beginning in 2006.
Why cystic fibrosis?
Dr. Yesair had a close family friend, years ago, who was diagnosed with cystic fibrosis at 18 and died seven years later. As she wasted away, Dr. Yesair began the research which would lead to the LYM-X-SORB technology. Twenty years of development and research have brought us to the point where LYM-X-SORB can be made available for the public. It has been extensively and successfully tested. Most of that testing has been done with cystic fibrosis patients, so they will be the first to benefit from it, fulfilling a personal and professional commitment dating back 25 years. LYM-X-SORB has been endorsed and encouraged by the Cystic Fibrosis Foundation, among other organizations.
Does it work?
Demonstrated benefits to CF patients in a one year, double blind study include: increased energy intake from diet; increased plasma levels of linoleic and a-linoleic acid; increased plasma levels of vitamins A and E and retinal binding protein (Vitamin A); increased growth in terms of weight and height; improved lung functions; fewer hospital stays and improved quality of life due to increased energy and sense of well-being.
When can it be produced?
Once funding is available, it will take approximately six months to bring LYM-X-SORB to the market.
What next?
We propose to begin manufacturing LYM-X-SORB and marketing it to cystic fibrosis patients in North America and Europe, where most of these patients live. At the same time, we foresee expanding its application to other populations: eventually it could mean the difference between life and death to many thousands of sufferers from malnutrition, dysentery, and other ailments. While it is not a cure for dysentery, for instance, it could keep a patient alive until he or she recovered.
How many people will it benefit?
In the initial stages, we expect 30 percent of the 60,000 cystic fibrosis patients in the United States to be using LYM-X-SORB daily within five years.
How was LYM-X-SORB™ conceived as a Drug Delivery Technology?
Initially the literature indicated that phosphatidylcholine, secreted via bile into the upper small intestine inhibited the intestinal absorption of fatty acids (FA) and monoglycerides (MG) which are enzymatically produced from food triglycerides. A pancreatic enzyme, phospholipase A2 removes one fatty acid from phosphatidylcholine (PC) to yield lysophosphatidylcholine (LPC) in the upper small intestine. This phospholipid enhances the absorption of FA and MG. These observations indicated that the combination of LPC, MG, and FA might be forming a lipid complex which enhances their intestinal absorption. Since lipids enhance the absorption of fat-soluable vitamins, the first animal study compared the absorption of vitamin A in triglycerides or in the lipid complex composed of LPC, MG, and FA. Vitamin A was absorbed using both formulations, but its absorption using the lipid complex occurred earlier and greater in the blood of rats.
How was McNeil Pharmaceuticals instrumental in giving this lipid complex an identity?
McNeil had a vitamin A derivative, fenretinamide, which was fat-soluable but had poor oral bioavailability (ca. 15%) using a corn oil/surfactant formulation. This formulation contained 100mg of drug per gm and was a suspension. The object of the lipid complex formulation was an increased bioavailability of at least 30%. The first formulations contained 30-35mg of drug in "solution" in one gm of lipid complex but any further drug additions resulted in suspension. That evening, trying to understand the reason for the maximum solubility (30-35mg/gm), it was noted that the molecular models of LPC were compatible (length, linear, and hydrophilic/lipophilic regions) to that of fenretinamide. The calculation of the molar concentration of 30-35 mg corresponded to the molar concentration of LPC in 1 gm of the lipid complex. The next day the molar concentration of LPC and fenretinamide at 100mg/gm in the lipid complex were equivalent and a crystal clear solution was observed. The oral bioavailability of this formulation (100mg/gm) was 85-90% in fed dogs and 70-75% in the absence of food (See Slide BMP 19). In human bioavailability studies a one-fifth dose (65mg) fenretinamide in the lipid complex showed equivalent plasma concentrations from a 300mg dose in the surfactant/corn oil suspension-formulation (See Slide BMP 19). Based upon these findings, the term LYM-X-SORB was coined and characterized the Lymphatic Absorbability of Xenobiotics (foreign compounds, not made in the body).
How did sponsors of the Investigative Studies come about?
Every investigator that was contractually involved had asked multiple fundamental questions that were pertinent to their study. For example: what was the CMC (critical micelle concentration)? did LXS™ cause damage to the intestine? was it absorbed intact? is LXS™ stable in the presence of bile salts? what drugs are compatible within the inclusion space of LXS™? and what are the structural characteristics of the lipid complex? and what dosage can one expect from oral dosage formulations. The sponsors carried out the necessary experimentation to evaluate the bioavailability of the LXS™/Drug formulation. They have permitted us to use this information in developing an understanding of the LYM-X-SORB™ formulation that is presented in the next section.