ABSTRACT
Sipponen, Arno. Coniferous resin salve, ancient and effective treatment for chronic wounds - laboratory and clinical studies
Department of Orthopedics and Traumatology, University of Helsinki, Helsinki, Finland and Päijät-Häme Central Hospital, Lahti, Finland.
Natural coniferous resins and other terpenic wood extracts have been raw materials for various products in industry, and have been used as traditional medicines in Finland for hundreds of years, particularly as a home-made salve for skin wounds and infections. Due to the author ́s own positive empirical experiences of natural coniferous resin salve in wound care, the present “resin-project” was set up in order to investigate (1) the antimicrobial properties of the resin and resin salve by microbiological laboratory techniques, and to study (2) the efficacy, feasibility and safety of the resin salve for wound care in objective clinical trials. The thesis comprises four microbiological investigations and two clinical trials.
Microbiological studies with an agar diffusion test and with the European Pharmacopoeia challenge test gave somewhat controversial results indicating that the water solubility of resin and resin salve may affect the assay results. The studies showed that coniferous resin and resin salve were strongly antimicrobial against a wide spectrum of both Gram-positive and Gram-negative bacteria, including the methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant enterococcus (VRE). The resin was, in addition, antifungal against the most common dermatophytes, and against the Candida albicans yeast. The antibacterial action of resin was observed to result from destruction of the bacterial cell wall and cell membrane structures. Microbes, both bacteria and fungi, exposed to resin or resin salve, showed thickening of the cell walls. The cells formed aggregations, showed arrested mitoses, and were finally destroyed according to the observations in scanning and transmission electron microscopy. In electrophysiological experiments with Staphylococcus aureus, the exposure of the micro-organisms to resin and resin acid (abietic acid) caused dissipation of the cell membrane potential and changed the branching of fatty acids in the cell walls. The observed changes were concluded to indicate that the coniferous resin influences the bacterial cell survival via damage to cell membrane functions.
In tests on safety aspects, the coniferous spruce resin or resin salve were not muta- genic in Ames tests. In skin irritation tests in rabbits (ISO 10993-10:2010 standard), the resin salve containing purified coniferous resin 10% (w/w) was “negligibly” irritating.
In in vitro cytotoxicity tests (EN ISO 10993-5:2009 and USP<87>) with mouse fibroblasts in HAM F12 culture medium the salve was markedly cytotoxic but slightly cytotoxic if diluted (1+3) with fresh culture medium. In analyses with gas-liquid chromatography (GLC) and mass spectrometry, the acetone extracts of both pure spruce resin and resin salve contained coumaric acid, a group of diverse resin acids and lignans. All these compounds are potentially biologically active and were calculated to occur in total in purified spruce “callus” resin at a concentration of 300 mg/g of resin (w/w) and 30 mg/g (w/w) of the 10% resin salve, on average.
One of the clinical trials is a randomized, prospective investigation where the efficacy of resin salve treatment for 6 months was compared to the efficacy of hydrofiber dressings (with or without silver) in 37 patients with severe, grade II-IV, pressure ulcers. In this trial the resin salve treatment was, in both per protocol and ITT (intention-to-treat) analysis, significantly more effective (P=0.003) in improving ulcer healing (regarding both the rate of healing per patient (N=23) or per ulcers (N=29)) than the control treatment. All pressure ulcers in all compliant patients (per protocol analysis) in the resin group healed except for one ulcer in one patient (94% (95%CI:84–100%)) whereas less than half (36% (8-65%)) of the ulcers healed in the control group. Resin salve improved the ulcer healing independent of whet- her the ulcer was infected or not. The other clinical trial was an observational and prospective study on efficacy and feasibility of the resin salve treatment in chronic (complicated) surgical wounds in a cohort of 23 patients. In all 23 patients, the wound healed in 43±24 days on average without any draw-backs. In multivariate analysis, the length of the wound was an independent and significant predictor of the healing time. In resin salve therapy, the wounds progressively healed (re- epithelialized) at 2 mm per day on average. In the clinical trials, including a total of 45 compliant patients, one patient (2%; 95%CI:0-5%) had an allergic reaction (allergic contact dermatitis). No other complications or side effects were observed. In calculations of direct costs, the expenses of the pharmaceutical materials were 1.2 € ±0.5 € per day on average among the patients treated with resin salve.
