Production of Orally Applicable New Drug or Drug Combinations from Natural Origin Capsaicinoids for Human Medical Therapy

Abstract

It is well known that the capsaicin stimulates (in small doses) or impairs (in high doses) the capsaicin-sensitive afferent nerves and the final effects of capsaicin depend on its applied doses. The effects of capsaicin were analyzed on the gastrointestinal mucosal protection and injury in animal experiments and in human beings (from 1980 up to now). From 2005 to 2008 an interdisciplinary group (21 researchers) participated in the production of orally applicable drug or drug combinations from capsaicin for human medical therapy of patients suffering from cardiovascular, degenerative joint and locomotor diseases, who received in their treatments non-steroidal anti-inflammatory compounds (NSAIDs). Our studies were based on the results of the NSAIDs-induced gastrointestinal side effects could be detected by application of small doses of capsaicin. Because natural (plant origin) capsaicin is chemically does not represent a uniform entity and used in the international research, consequently the authors met a lot of unpredictable scientific problems during the time of production of new capsaicin containing (alone or in combinations) drug before receiving official permissions from the different national and international authorities to start the classical human clinical pharmacological studies. This paper summarizes the different steps from the basic physiological and pharmacological notes (in animals), plant cultivation, chemistry of substance(s), animal (general and germinative) acute and chronic toxicology, human actions, basic clinical pharmacology of natural capsaicin (capsaicinoids) to introduce and to develop a new drug (or drug combinations) in the human medical therapy.

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

“…These substances produce the characteristic sensation associated with ingestion of spicy cuisine. Capsaicinoids include seven homologous branched-chain alkyl vanillylamides (capsaicin, dihydrocapsaicin, homocapsaicin I, homocapsaicin II, nordihydrocapsaicin, homodihydrocapsaicin I, homodihydrocapsaicin II) and three straight-chain analogs, octanoyl vanillylamide, nonoyl vanillylamide (nonivamide), and decoyl vanillylamide [1]. Among them, capsaicin and dihydrocapsaicin (Figure 1) are the most abundant compounds responsible for the pungency of the fruits.…”

“…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.…”

It remains a mystery why people living in hot climates consume spicier food

“…If so, one may argue that people in hot climates have to eat more pepper because their oral mucosa is perpetually desensitized due to the constant exposure to capsaicin. 5 …”

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

“…No correct Drug Master File (DMF) for capsaicin (capsaicinoids) has been prepared; No classical animal toxicological (including the germinative function) examinations have been carried out for capsaicin (capsaicinoids); No classical preclinical dossier exists for capsaicin; No classical human clinical pharmacological study (human phase I-II) exists in the international literature.Our research team works in capsaicin research from 1980 using mostly animal experiments, but starting form 1997 we are studiing capsaicin physiology in human investigations (under permission of the the Regional Ethical Committee of Pécs University, Hungary).We actively participated in innovative research of capsaicin (capsaicinoids) to produce a new drug or new drug combinations affecting capsaicin sensitive afferent nerve function offering an absolutely new gate for gastrointestinal pharmacology(Mózsik et al, 2009a,b;2010) …”