THERAPEUTIC USE OF RANITIDINE IN THE TREATMENT OF WOUNDS TO THE SKIN AND UNDERLYING TISSUES

Abstract: Ranitidine finds a new therapeutic use for the treatment of wounds to the skin and underlying tissues subject to slow healing, by topical treatment.

Description: - 1 - THERAPEUTIC USE OF RANITIDINE IN THE TREATMENT OF WOUNDS TO THE SKIN AND UNDERLYING TISSUES _ Technical field The present invention refers to a new indication for the 5 therapeutic use of ranitidine. The new therapeutic use of the molecule refers to the treatment of wounds to the skin and to underlying tissues showing a slow tendency to heal with the intervention of repair procedures which evolve by second intention. 10 This is what occurs, for example, in the case of large- scale loss of substance, un-stitched wounds, infected wounds, lacerations, dehiscent surgical wounds, bed sores, and the like. Background art 15 Ranitidine is known to be active in gastritis and in ulcers as a H2-receptor blocking agent. Its chemical denomination is N-[2-(5- dimethylaminomethylfurfurylthio)-ethyl]-N / -methyl-2-nitro- 1,1-ethylenediamine. 20 It is known that ranitidine is a powerful antihistaminic agent, or H2-antagonist, capable of greatly inhibiting gastric secretions, and therefore it is currently used in the treatment of peptic gastroduodenal ulcers and in all those pathologies in which the hydrochloride peptic secretions of 25 the stomach play a fundamentally important part. It is also known, on the other hand, that histamine has a pre-eminent activity in inflammatory processes, which justifies its use, by some researchers, in certain particular flogistic conditions, such as sunburn and acne. 30 Recently, a direct action of histamine itself in tissue repair processes has also been underlined. It has in fact been observed (see Dabrowski and Maskinski, Agents and Actions 1981; 11:122-24) that histamine has a direct influence on the synthesis, the polimerization 35 and the deposit of collagen in the granulation tissue of wounds. In particular, it has been observed that minimum concentrations of histamine show an action which favours the production of collagen, whereas high doses of histamine cause the opposite effect. This double action of histamine has been found to b mediated by H2-type histamine receptors, as said actio appears to be completely inhibited by cimetidine, wherea anti-Hl (mepyramine) drugs do not appear to have th slightest influence. Disclosure of the invention It has therefore been surprisingly discovered, accordin to the present invention, that ranitidine, although it is drug known for its antihistamine activity, is shown to have favourable effect in the healing of external wounds, wher the favourable action of histamine has been experimented. Object of the present invention is therefore the ne therapeutic use of ranitidine in the treament of wounds t the skin and to the underlying tissues showing a slo tendency to heal, in particular due to the effect of repai processes evolving by second intention. Ranitidine is particularly useful in those continua wounds which heal by second intention, in which the greates inflammation effects can be observed. The mechanism of action which can be supposed for sai activity, appears actually to be connected to the larg quantity of endogenous amines produced by the flogisti process, which could determine, as a result of an inhibitin activity on the production of collagen, a delay in th healing of the wound itself. Pharmacological tests. The following clinical tests were carried out. Fourty subjects having a continual lesion of the skin an of the underlying tissues, evolving towards healing by secon intention, were sub-divided into two groups, comparable as to site, size and state of the wound. All those patients were excluded in whom factors of a local or general nature could have interfered with the healing process, such as serious hypodisprotidemia, mellitus diabetes, serious anemia, local circulatory alterations, etc. The size of the wound was evaluated, by measuring bot the extent and depth of the wound and the volume of the residual hollow. The state of the wounds was divided into five classes: 1 - absence of erythema on the surrounding skin; 2 - presence of erythema on the surrounding skin, disappearing on digital pressure (active hyperemia) ; 3 - presence of erythema on the surronding skin, which does not disappear on digital pressure (passive hyperemia) ; 4 - presence of tissue necrosis; 5 - presence of infection. Both groups underwent medication of the wound every other day using the same methods. In both groups, the wound was cleaned, disinfected and if necessary isolated using Dakin's solution. Following this, for patients in the first group only, a topical application of ranitidine at a concentration of 10 mg/ml was made, using the amount of 1 cm 3 of solution for every 3 ml of loss of substance. The wounds treated with ranitidine showed a more rapid tendency to heal. The number of days required to completely fill in the loss of substance was found to be reduced by approximately one quarter in the group treated with ranitidine, compared with the control group. Even the daily percentage of reduction of the wound hollow appeared greater in the subjects treated with ranitidine, sometimes by as much as 40-50%, indicating a stimulating action on the deposit of granulation tissue. It therefore appears that the topical use of ranitidine in continuous lesions with a tendency to heal by second intention has been proved to be of undoubted use. The action favouring the neoformation of granulation tissue showed by the drug can be translated, in fact, into a more rapid obliteration of the wound hollow, greatly shortening the time necessary for cicatrization of ne wound itself. Further tests carried out in similar conditions have shown the benefits of ranitidine when used according to the present invention, in various topical compositions containing a concentration of ranitidine comprised between 3 and 30 g o active substance per 1000 ml of composition. The pharmaceutical composition containing ranitidine fo the use indicated can be in the form of a solution, a emulsion, containing ranitidine alone, or in combination with other auxiliary active agents.

Claims: CLAIMS 1. Use of ranitidine for the manufacture of a medicament for the topical treatment of wounds to the skin and/or to the underlying tissues. 2. Use of ranitidine according to claim 1, in which said wounds are continual wounds which tend to heal by second intention. 3. A pharmaceutical agent for the topical treatment of wounds to the skin and, or to the underlying tissues comprising ranitidine. 4. A method for the treatment of wounds to the skin and, or to the underlyhing tissues comprising applying topically to said wound an amount of uridine effective to aid the healing thereof.

Inventors: MATERAZZI MARIO, MATERAZZI, MARIO
Applicants: POLIFARMA SPA, POLIFARMA S.P.A.
Application year: 1991
Main classification: C07D307
IPC codes: A61K31, A61P17, C07D307