Introduction

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 sapoginins, for example. Bioavailability of Rb1, Rh2 and Rg1 are 1%, 3.4% and 1.9% respectively. Shenyi Capsule, a TCM extract product with ginsenoside 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.

Products Developed on the OBET Platform

Active pharmaceutical ingredients derived from natural herbs are mainly belongs to saponins and their metabolites, for example, ginsenosides, notoginsenosides and dammarane sapogenins. These active ingredients have pleiotropic pharmacological actions and multiple targets functions being widely used as remedies for different kind of disorders. However, pharmacokinetics study has been found that these saponins, which simple conventional formulation as an oral dosage form, are most likely to be hydrolyzed, degraded, or precipitated in gastrointestinal tract due to their special physical and chemical properties. This process leads to a very low blood level and bioavailability and eventually limits the drug potency and efficacy to some extent.

Over several years dedication to research and development, Pegasus Pharmaceuticals has established proprietary OBET formulation approach and made possible to adequately demonstrate multiple chemical constituents of traditional herbal medicine whose chemical constituents are not always well defined and nor is its bioavailability well characterized other than poor absorption at a molecular level. Take ginsenosides, which are mostly saponins and sapoginins, for example. 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. The majority of these liposolubles are precipitated in the gastric-intestinal fluid environment and eventually discharged from the body. Scientists at Pegasus have been well studied the optimization of formulation with unique cosolvents and protectants which improving saponins and sapogenins stability in digestive tract and ensuring  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. To demonstrate OBET efficiency, we compare the bioavailability between OBET designed formulation and other conventional dosage forms. The following Area under the plasma blood concentration versus time curve (AUC) showed that oral capsule (encapsulated powder dammarane sapogenins) has very low bioavailability, oral solution of dammarane sapogenins improved a little bit bioavailability than oral capsule, however, softgel capsule with OBET formulation has greatly enhanced bioavailability. The peak blood level after oral administration is higher than that of intravenous injection. Therefore, bioavailability of Dammarane Sapogenins Softgel Capsule is very satisfactory and 60-70% bioavailability is comparable to conventional dosage forms and meets the clinical needs. Preclinical studies and clinical observations have proven OBET designed Dammarane Sapogenins Softgel Capsule exerts promising clinical effectiveness. Pegasus has successfully developed a line of Dammarane Sapogenins as drug substance formulated CARESENG® Series anticancer botanical products based on proprietary novel technologies, such as CanaQ (Careseng® SG2) and CARESENG® line of natural health products.