Kourokhitin, a potential drug containing two active substances

Abstract

The currently used drugs usually contain one active substance. Note that it is difficult to use water-insoluble substances, which, even displaying useful pharmacological properties, as a rule, have comparatively low bioaccessibility. Consequently, a high concentration of such substances in the corresponding drugs is required; this is disadvantageous from both the economical standpoint and due to potential toxicity of some substances under these conditions. The aromatic alkaloid tryptanthrin (kouropitin), isolated from several plants, yeast-like fungi, and marine bacteria, displays a wide range of biomedical activities [1‐6]. It is an antiinflammatory agent specifically inhibiting the cyclooxygenase (COX-2) and 5-lipoxygenase (5-LOX) activities, decreases the macrophage production of the proinflammatory agents nitric oxide (NO) and prostaglandin E 2 [1], inhibits some pathogenic fungi, and displays antituberculous and antiprotozoal properties [2, 3]. In addition, tryptanthrin inhibits induction of the growth factors involved in malignant transformation of normal cells and tumor growth, invasion, and metastasizing [4]; causes an in vitro apoptosis of human leukemic cells [5]; and considerably reduces the rate of the azoxymethane-induced intestinal cancer in rats [6]. As this alkaloid is practically insoluble in water and biological fluids, it is necessary to increase its bioaccessibility. A combined use of this alkaloid produced by a single-stage synthesis [7] with another pharmacologically active agent, chitosan, can enhance its bioaccessibility and, moreover, widen the range of its useful pharmacological effects. Chitosan, produced from the natural polysaccharide chitin, displays an absorbing ability towards hydrophobic substances and provides for a prolongation of their effect [8]. It is also important that chitosan is nontoxic, compatible with the human body, and itself displays a wide range of activities, including those compatible with the main pharmacological effects of tryptanthrin [9]. Using these two substances, we have designed a gel form comprising chitosan nanoparticles coated with tryptanthrin; this preparation was named Kourokhitin and is intended for both external and oral administrations. A wider medicinal range of this composition as compared with its individual components as well as possible use of lower tryptanthrin doses was confirmed by the below briefed experiments. The wound-healing activity of Kourokhitin was assessed using the experimental model of thermal and graft wounds [10]. The experimental results are listed in Tables 1 and 2. The main wound healing activity of this preparation is observed in phase II of the wound process in both the burn and stratified graft wounds. After applications of the Kourokhitin gel, the scabs were considerably faster (as early as day 4) formed on animal wounds as compared with the animals treated with methyluracil ointment. Later, we also recorded accelerated epithelization of the wound surface and skin restoration induced by Kourokhitin. The anti-inflammatory properties of Kourokhitin were assessed in the model of nonspecific local inflammation induced with δ -carrageenan injection into the hind paw pad. As is evident from figure, Kourokhitin