Capsaicin is a New Gastrointestinal Mucosal Protecting Drug Candidate in Humans — Pharmaceutical Development and Production Based on Clinical Pharmacology

Abstract

applications of these drugs are contraindicated from the points of gastroenterologist. 4. We earlier proved clearly that the small doses of capsaicin (given orally in doses of nanogram to microgram / kg in animal experiments and 200 to 800 µg in human observations) prevents the aspirin, indomethacin (a mixed COX-1 and COX-2 inhibitor)-induced gastrointestinal mucosal damage. Aims: 1. The development and pharmaceutically production of the planned production of new gastrointestinal mucosal protective drug (capsaicin alone and/or capsaicin in combination with different nonsteroidal anti-inflammatory drugs) for the use in human healthy beings and in patients. 2. For the development and production of a new drug, we had to respect the following aspects: a. the knowledge of the chemical composition of natural origin capsaicin(oids); b. problems of the analytical measurements of capsaicin(oids) in the biological samples (in animals and humans); c. correct and complete preclinical dossier; d. correct dossier of acute and chronic toxicological studies with capsaicin (including the different tests) in two speciments of animal experiments; e. existence of a complete drug master file (DMF); f. the exclusion of pesticides, fusariums, aflatoxin and other toxicological agents (which are used during the plant cultivation in the different countries) from the capsaicin(oids) preparations used for drug production; g. to collect the necessary permissions from the different international and national authrorities before starting of pharmaceutical production of drug alone or in combinations; h. different pharmaceutical controlling measurements and other pharmaceutical aspects of planned drug or drug combinations (such as stability, drug preparation, different pharmaceutical technologies, etc.); i. preparation of different protocols for human human phase examinations (especially for human phase I.); j. to receive the permissions from the the different national authorities to carried out the prepared protocols before starting of the classical pharmacological studies; k. to gather the necessary numbers of experts from the very different scientific fields, who are able to solve all of above mentioned scientific, pharmaceutical, research problems (in animal experiments and in human observations); l. to find accredited institutes to perform human clinical pharmacological (phase) examinations. 2. When we solved all of above scientific problems, the human phase I. examinations with capsaicin alone and with combination+aspirin and capsaicin+diclofenac, the human phase I. examinations were in the

Toxicokinetic Study of a Gastroprotective Dose of Capsaicin by HPLC-FLD Method

“…It was earlier demonstrated that capsaicinoids display analgesic action [5,6,7,8,9], protect the gastric mucosa against the damage caused by the non-steroid anti-inflammatory drugs (NSAIDs) and alcohol [10,11,12,13,14,15], have anti-inflammatory effect [16,17,18], as well as anti-tumor and antioxidant potential [19,20,21]. Much of the published literature on capsaicin relates to capsaicin containing pepper extracts; these extracts are typically a mixture of capsaicin, dihydrocapsaicin, and the minor capsaicinoids nordihydrocapsaicin, homocapsaicin, and homodihydrocapsaicin [22].…”

“…Based on the clinical observations, a drug development program was launched at the University of Pécs to develop a per os applicable capsaicin containing drug to prevent gastrointestinal damage of non-steroid inflammatory drugs [14,15,32,33]. As a part of the program, pharmacokinetic and toxicological studies of capsaicinoids have been performed in the rat and the dog, respectively.…”

“…The present work reports on the development and application of an HPLC method suitable for quantitation of capsaicin and dihydrocapsaicin in experimental dog’s plasma samples collected in the 28-day oral toxicity study of a standardized Capsicum extract Capsaicin Natural (United States Pharmacopeia (USP) 29) [14]. Although previous publications reported on intense hepatic metabolism of the per os administered capsaicinoids [4], as a part of the drug development program, a validated analytical method had to be developed to demonstrate the plasma concentration level of the administered capsaicinoids [14]. The method involves an HPLC-FLD analysis coupled with an automated solid-phase extraction, which gives good precision, accuracy, and recovery of the two capsaicinoids.…”

Introductory Chapter: The General Problems of Human Clinical Nutritional and Pharmacological Observations of Capsaicin in Human Beings and Patients

“…(1) expert's opinion; (2) results of all toxicological studies; (3) chemical stability of the natural capsaicin preparation; (4) results of pharmaceutical industrial formulation from the natural capsaicin; (5) various permissions from our university; (6) the documentation of health insurance of volunteers; (7) preclinical dossiers; (8) documented valid permission on the accreditation of the clinical pharmacological unit for human phase I and II examinations (accreditation controlled by the National Institute of Pharmacy); (9) exact protocols for human clinical pharmacological studies; (10) written information on the planned examinations for the volunteers; (11) request for authorization of a clinical trial on medical products for human use to the competent authorities and ethical committees in the community; and (12) lists of investigators together with their CV and qualifications and data of involved institutes (departments participating in this study) [6].…”

Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases

“…Several researchers have carried out extensive studies with capsaicin in the area of gastroenterology (reviewed in detail elsewhere [177,178]). The gastrointestinal effects of capsaicin portray both beneficial and detrimental outcomes depending on the applied doses.…”