In other words, SMCD Platform considers the body as a biological filter and converter-activator, which eliminates 99% of useless components in TCM, and then chemically converts those left into an active form. SMCD Platform traces and collects those metabolic compounds as new drug candidates. New drug developed using this approach is often a multi-compound drug which is much simpler than the original TCM formula. SMCD can be equal to, or even more efficacious and safer than the original TCM formula. SMCD is controllable in quality and compliable to GMP requirements because all the components in an SMCD are identified and characterized. SMCD might also lead to discovery of single-molecular entity drugs.

SMCD Platform is a valid approach to developing new drugs from the wealth of TCM formulae library. Key components of the SMCD technology have been filed for patent in 2004. Using this platform, Pegasus has already produced a series of products and product candidates.
PRODUCTS DEVELOPED ON THE SMCD PLATFORM
More than 60% of all TCM active components are thought to be in the category of saponins. Saponins are also the major medicinal ingredients in ginseng and many other plants. After intake, most of the sugar moieties in saponins are removed in the intestine metabolic system and absorbed into blood as sugarless metabolites, called aglycone sapogenins. Two major metabolites are aglycone protopanaxadiol (aPPD) and aglycone protopanaxatriol (aPPT). Researches have found that aPPD has strong apoptosis induction effect on cancer cells while aPPT can prompt the immune system to attack cancer cells with high specificity. The combination of aPPD and aPPT is our new drug candidate PANDIMEX™. It is obvious that aPPD and aPPT can also be developed into single compound drugs.

Pegasus and its affiliated companies use proprietary chemical process to produce aPPD and aPPT directly from natural materials, bypassing the body’s metabolic system. The composition of the product is clearly identified and characterized, highly consistent and controllable. The two major single compound components have been proven to have multiple pharmacological targets and complementary effects.

OBET PLATFORM

Oral Bioavailability Enhancement Technology is a series of techniques to increase concentration of medicinal ingredients in blood after oral intake.

Oral intake is the most commonly adopted drug delivery route and almost the only route for TCMs. Absorption of medicinal ingredients into blood after oral intake is subject to many factors, such as chemical properties of the ingredients, solubility and dissolving speed, PH level and other conditions in various parts of the gastric-intestinal tract, bowel movement and emptying speed of the stomach, etc. Many natural medicinal ingredients, such as saponin and flavone families, which together account for 90% of TCM ingredients, have very low efficiency in entering blood after oral intake. It has been found that these ingredients, mostly hydrophilic, are quickly hydrolyzed and structurally modified into liposolubles under the influence of gastric acid and enzymes. Except very few metabolites processed and further converted by bacteria in the digestive tract, the majority of these liposolubles are precipitated in the gastric-intestinal fluid environment and eventually discharged from the body. Take ginsenosides, which are mostly spoginins, for example. Bioavailabilities of Rb1, Rh2 and Rg1 are 1%, 3.4% and 1.9% respectively. Shenyi Capsule, a TCM extract product with saponin Rg3 as its main active ingredient, was approved by Chinese SFDA in 2000 even though Rg3 level is too low to be measurable in blood.

An ideal solution to the bioavailability problem of many TCM ingredients is protection of the ingredients in their intact molecular form from effects of gastric-intestinal fluids and increasing stomach absorption as opposed to intestine absorption. Advancing absorption in the upper digestive tract minimizes the ingredients’ contact with digestive fluids and prevents the modification of the ingredients into medicinally inactive substances.

OBET includes a series of organic solvents and conditioning processes to increase the stability of ingredients in the gastric acid environment. Dosage forms designed with OBET ensure ingredients to be absorbed into blood in their intact molecular forms and primarily in the stomach rather than in the intestines. The result is a much higher bioavailability of ingredients in their medicinally active form and greatly enhancement of the pharmacological effects. Key OBET techniques have already been applied for patent.