beta-escin and Pain

Pain is one of the major symptoms of the osteoarthritis (OA). The objective of the study was to evaluate impact of combined therapy with diclofenac, aescin and original glucosamine sulfate on pain severity in patients with OA of different localizations in real life clinical settings in Russia and Ukraine.. Design--prospective, non-controlled, before and after post-marketing study. Study was performed in 38 cities across Russia and Ukraine in 2012. Registered anti-inflammatory and symptomatic slow acting drugs were used according to the registered indications and dosages. In Russian sites combined therapy A using diclofenac ("Dorosan" formulation, Rottapharm S.p.A., aerosole 1%, 3-4 times/day) for two weeks, original glucosamine sulfate ("Dona" formulation, Rottapharm S.p.A.) intramuscular (ampule 200 mg/ml, 2 ml 3 times/week) for 4 weeks and per os (powder 1500 mg, once/day) for 8 weeks was used. In Ukraine sites (scheme B) diclofenac was substituted with topical aescin ("Reparil-Gel" formulation, Madaus AG, tube 400 mg, 2-3 times/day) anti-inflammatory product. Physicians were free to change therapy and study organizers had no impact on prescribing and management practice. Patients with OA of different localizations were included into the study. Pain severity was assessed using numeric rating scale. Total duration of the study was 8 weeks. Questionnaires were distributed to patients via physician out-patient offices. The only endpoint was the difference in median pain severity at the end of the study compared with the baseline level.. In total 4931 patients were included into the study (mean age 57 +/- 12 years, 75% were females). Scheme A was used in 3956 patients and scheme B in 975 patients. The median pain severity decreased from 0.7 at the baseline (interquartile range +/- 0.2) to 0.2 (interquartile range +/- 0.2) after 8 weeks of the study in both treatment regimens (p < 0.001). Limitations of the study include absence of the control group, collection of the questionnaires from physician offices, rather than directly from patients, limited range of clinical data collected and use of single instrument to assess pain severity.. Post-marketing study of combined therapy of OA of different localizations using diclofenac, aescin and original glucosamine sulfate in Russia and Ukraine demonstrated decrease of the pain severity, assessed by numeric rating scale, after 8 weeks of the treatment.

Topics: Aged; Anti-Inflammatory Agents; Cardiovascular Agents; Diclofenac; Drug Therapy, Combination; Escin; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis; Pain; Pain Measurement; Prospective Studies; Russia; Treatment Outcome; Ukraine

To investigate the clinical efficacy and safety of escin-containing gels in the topical treatment of blunt impact injuries.. Competitors in soccer, handball, or karate competitions were enrolled within two hours of sustaining a strain, sprain, or contusion and treated three times with the trial gel within a period of eight hours. Patients were randomised to three parallel groups consisting of two active treatment gels, containing escin (1% or 2%), 5% diethylammonium salicylate, and 5000 IU heparin, or placebo gel. Tenderness produced by pressure was measured at 0 (baseline), 1, 2, 3, 4, 6, and 24 hours after enrollment (within two hours of the injury). Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient.. A total of 158 patients were enrolled; 156 were evaluated in the intention to treat analysis. The primary efficacy variable was the area under the curve for tenderness over a six hour period. The gel preparations containing 1% and 2% escin were significantly more effective (a priori ordered hypotheses testing controlling the multiple alpha = 5% significance level) than placebo (p(1) = 0.0001 and p(2) = 0.0002 respectively). The treatment effects were 5.7 kp h/cm(2) (95% confidence interval (CI) 2.9 to 8.5) and 5.9 kilopond (kp) h/cm(2) (95% CI 2.9 to 8.8) between 1% escin and placebo and between 2% escin and placebo respectively. These results were supported by secondary efficacy variables. The time to reach the baseline contralateral tenderness value (resolution of pain) at the injured site was shorter in the treatment groups than in the placebo group (p<0.0001). Both active gel preparations produced more rapid pain relief than the placebo gel. No relevant differences were detected between the two active gels. The safety and tolerability of the escin-containing gels were excellent.. Escin/diethylammonium salicylate/heparin combination gel preparations are effective and safe for the treatment of blunt impact injuries.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents, Non-Steroidal; Athletic Injuries; Contusions; Double-Blind Method; Drug Combinations; Escin; Female; Gels; Heparin; Humans; Male; Martial Arts; Pain; Salicylic Acid; Soccer; Sprains and Strains; Treatment Outcome; Wounds, Nonpenetrating

The aim of this confirmative, monocentre, double-blind, controlled clinical trial was to investigate whether different escin combinations show differences in comparison to placebo with regard to pain reactions in the topical treatment of sports injuries. A total of 126 patients with blunt injuries of the extremities were randomly allocated to four parallel groups: Reparil-Gel N (n = 32), Reparil-Gel (n = 31), Reparil-Sportgel (n = 32) and a placebo gel (n = 31). All patients were evaluated for efficacy (intention to treat) and tolerability. A per-protocol analysis was also carried out, in which 12 of the 126 patients were excluded due to protocol violations. The intention-to-treat and per-protocol analyses produced similar results. The patients had suffered contusions while participating in soccer, hockey, karate, tae-kwon-do, handball, American football, rugby or tennis. The measured variable was the pressure required at the centre of the lesion to elicit the first pain reaction (tenderness reaction) at measuring time 0 (baseline) and then 1, 2, 3, 4, 6 and 24 h after the injury. The primary variable was the area under the curve (AUC) for tenderness over a six-hour period. The mean AUC differed significantly in the four groups (Kruskal-Wallis test p = 0.0001). Then six pairwise comparisons of two treatment groups each were carried out using the Mann-Whitney test. To control the multiple significance level of 5%, the adjusted p-values according to the Holm-Shaffer method were used in these tests. The three active gels were significantly superior to the placebo gel (Mann-Whitney test, p = 0.0004 in each case) in terms of the AUC. There were no significant differences between the active test substances in terms of the primary variable. The intensity of the pain was also measured on a visual analogue scale (VAS). The pain diminished more rapidly with the Reparil gels than with the placebo. The tolerability of all test substances was good. No adverse events were observed in any of the 126 patients. Escin combination gels are more effective than a placebo and are also well tolerated. Therefore, they can be recommended for the treatment of blunt injuries caused during sports and leisure activities.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Arm Injuries; Athletic Injuries; Double-Blind Method; Drug Combinations; Escin; Female; Gels; Humans; Leg Injuries; Male; Pain; Pain Measurement; Patient Satisfaction; Salicylates; Wounds, Nonpenetrating

The efficacy of Essaven-capsules in venous circulatory disorders of the leg was assessed under the conditions of everyday general practice in a double blind trial including 34 out-patients. During the 4 week-treatment Essaven proved to be significantly superior to a placebo of identical appearance as regards the parameter pain in the legs, skin lesions, circumference of the ankle, and diuretic performance. The dosage was 3 X 2 capsules per day.

Topics: Adult; Chalcone; Clinical Trials as Topic; Diuresis; Double-Blind Method; Drug Combinations; Drug Evaluation; Edema; Escin; Flavonoids; Hesperidin; Humans; Pain; Propiophenones; Saponins; Skin Manifestations; Thromboembolism

Rheumatoid arthritis is among the most common disabling diseases associated with chronic inflammation. The efficacy of the current therapeutic strategies is limited; therefore, new pharmacological agents and formulation approaches are urgently needed. In this work, we developed a thermosensitive gel incorporating escinosomes, innovative nanovesicles made of escin, stabilized with 10% of tween 20 and loaded with a Carbonic Anhydrase Inhibitor (CAI) bearing a Carbon Monoxide Releasing Moiety (CORM) (i.e., CAI-CORM 1), previously synthesized by some of the authors as a new potent pain-relieving agent. The light scattering analysis of the developed formulation showed optimal physical parameters, while the chromatographic analysis allowed the quantification of the encapsulation efficiency (90.1 ± 5.91 and 91.6 ± 8.46 for CAI-CORM 1 and escin, respectively). The thermosensitive gel, formulated using 23% w/v of poloxamer 407, had a sol-gel transition time of 40 s and good syringeability. Its stability in simulated synovial fluid (SSF) was morphologically evaluated by electron microscopy. Nanovesicles were physically stable in contact with the medium for two weeks, maintaining their original dimensions and spherical shape. The viscosity increased by about 30- to 100-fold with the temperature change from 25 °C to 37 °C. The gel erosion in SSF occurred within 9 h (88.2 ± 0.743%), and the drug's passive diffusion from escinosomes lasted 72 h, allowing a potential sustained therapeutic effect. The efficacy of a single intra-articular injection of the gel containing escinosomes loaded with CAI-CORM 1 (3 mg/mL; 30 μL, CAI-CORM 1 formulation) and the gel containing unloaded escinosomes (30 μL, blank formulation) was evaluated in a rat model of Complete Freund's Adjuvant (CFA)-induced rheumatoid arthritis. CAI-CORM 1 formulation was assessed to counteract mechanical hyperalgesia, spontaneous pain, and motor impairments on days 7 and 14 after treatment. The histological evaluation of the joints stressed the improvement of several morphological parameters in CFA + CAI-CORM 1 formulation-treated rats. In conclusion, the hybrid molecule CAI-CORM 1 formulated in escinosome-based thermosensitive gel could represent a new valid approach for managing rheumatoid arthritis.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Carbonic Anhydrase Inhibitors; Escin; Inflammation; Pain; Rats

To investigate the effects of intrathecal escin and clonidine, used alone or in combination, in the treatment of neuropathic pain in rats and the possible mechanism.. Ninety-six male SD rats weighing 250-300 g were chronically implanted with lumbar intrathecal catheters. One week later, the left L5 and L6 spinal nerve roots were ligated to establish the model of spinal nerve ligation neuropathic pain (SNL). The rats were then randomly divided into 16 groups (n=6), including the control (saline), escin, clonidine, escin+clonidine, and the antagonist groups. Mechanical withdrawal threshold was assessed before and at 5, 10, 20, 30, 40, 50 and 60 min after intrathecal administration was evaluated. The maximal possible effect (MPE) was calculated and the effect of the treatments on the neuropathic pain. Isobolographic analysis was performed to characterize any potential interactions between the drugs.. MPE was significantly higher in escin group (20, 40 microg), clonidine group (2, 5, 10 microg) and escin+clonidine group [1/4, 1/2 (escin ED(50)+clonidine ED(50))] than in the saline group (P<0.05). Intrathecal escin (5-40 microg) or clonidine (1-10 microg) alone dose-dependently alleviated neuropathic pain. Isobolographic analysis suggested a synergistic effect between escin and clonidine. Intrathecal pretreatment with yohimbine (20 microg) antagonized the effects of clonidine (P<0.01) and attenuated the action of the combination treatment with escin and clonidine (P<0.05).. Intrathecal escin and clonidine alone can dose-dependently relieve neuropathic pain. Escin and clonidine produce a synergistic effect for pain relief, which may involve the actions of alpha(2) receptor and Ca(2+) channel.

Topics: Analgesics; Animals; Clonidine; Drug Synergism; Escin; Injections, Spinal; Male; Pain; Random Allocation; Rats; Rats, Sprague-Dawley; Spinal Nerve Roots