Safety Evaluation of Oleoresin-Based Turmeric Formulation: Assessment of Genotoxicity and Acute and Subchronic Oral Toxicity.

Turmeric rhizome (Curcuma longa L.) has been used without concern for safety as a culinary spice and traditional medicine under the ancient Ayurvedic medicinal system of India dating back nearly 4000 years. This preclinical safety evaluation was done to determine the safety of an oleoresin-based turmeric extract (CURCUGEN®). Guidelines from the Organization for Economic Co-operation and Development (OECD) directed the assessment of safety for the in vitro and in vivo application of CURCUGEN®. Safety of the herbal medicine was evaluated through the toxicological assessment of acute, oral, and 90-day repeated dosing, genotoxicity, and mutagenicity study. Genotoxicity tests included the in vitro bacterial reverse mutation test, chromosomal aberration test, and in vivo micronucleus test. The single dose of CURCUGEN® administered orally (gavage) to Sprague-Dawley (SD) rats resulted in a LD50 of >5000 mg/kg body weight. The subchronic assessment of CURCUGEN®, as administered to SD rats over 90 days resulted in a no observed adverse effect level (NOAEL) of 2000 mg/kg body weight/day. CURCUGEN® did not elicit any genotoxic or clastogenic effect in genotoxicity tests. The battery of safety studies carried out demonstrated that CURCUGEN® showed no evidence of general toxicity or genotoxicity.

The enhanced bioavailability of free curcumin and bioactive-metabolite tetrahydrocurcumin from a dispersible, oleoresin-based turmeric formulation.

BACKGROUND: Curcuminoids have been widely studied for human health and disease applications, yet bioavailability remains a hurdle to actualizing all the benefits ascribed to them. The lack of standardization in analysis method, confusion about what constitutes an ideal analyte, and conflicting thoughts around dosing strategies have made it difficult to draw parity between bioavailability and bioactivity and establish a baseline for formulation comparisons. METHODS: This randomized double-blinded, 2-way cross over, single oral dose, comparative bioavailability study differentially evaluates curcumin at the time of its absorption and along various biotransformation pathways, to include free curcumin, the readily usable form of curcumin; individual and composite totals of curcumin and its analogues as exogenously cleaved conjugates, for example, total curcumin, total demethoxycurcumin (DMC), total bisdemethoxycurcumin (BDMC), and total curcuminoids respectively; and the bioactive metabolite of curcumin, total tetrahydrocurcumin (THC). As a primary study objective, the relative bioavailability of CURCUGEN, a novel dispersible, 50% curcuminoids-concentrated turmeric extract was compared to the standard curcumin reference product, curcuminoids 95% standardized extract (C-95), using the maximum concentration (Cmax), and area under the curve (AUC0-t) of free curcumin, total curcumin, total DMC, total BDMC and the curcumin active metabolite, as total THC. RESULTS: The evaluation of free curcumin demonstrated that the Cmax and AUC0-t of the CURCUGEN was 16.1 times and 39 times higher than the Cmax and AUC0-t of C-95. Furthermore, total curcumin, total DMC, total BDMC, and total curcuminoids resulted in AUC0-t of the CURCUGEN at 49.5-, 43.5-, 46.8-, and 52.5-fold higher than C-95, respectively. The relative bioavailability of CURCUGEN for total THC was found to be 31 times higher when compared to C-95. CONCLUSION: As the first human pharmacokinetics study to apply best-practice recommendations and pharmaceutically-aligned guidance in the comprehensive evaluation of a novel curcuminoids formulation, we have established the novelty of said formulation while better standardizing for the common variances and discrepancies between curcuminoids and their derivatives in the literature and commercial marketing, alike.

A Randomized Double-Blind Placebo-Control Study to Assess the Efficacy and Safety of OLNP-05 Versus Placebo for the Treatment of Subjects with Premature Ejaculation.

Premature ejaculation (PE) is one of the foremost sex-related health problems among men. The global occurrence ranges from 20% to 30%, according to various studies. PE has a great impact on the men's quality of life, with deleterious effects such as embarrassment, frustration, and feeling of incompetence. Considering the necessity of treatment of PE, this study was planned to compare the efficacy and safety of OLNP-05 versus placebo for treating subjects suffering from PE. In this randomized clinical study, 60 men with PE were enrolled and randomly assigned to receive either OLNP-05 or placebo one capsule twice daily for a period of 8 weeks. Subjects were evaluated during visits on day 1, day 28, and day 56. Mean change from baseline in intravaginal ejaculatory latency time (IELT), improvement in premature ejaculation profile (PEP), and Clinical Global Impression-Improvement scale (CGI-I) were used to assess the efficacy of treatment. P-value <.05 was considered significant. At the end of the treatment, the improvement in IELT score in the OLNP-05 group was remarkably higher than the placebo. Subjects in the OLNP-05 treatment group also reported significantly greater improvement in PEP subscale score. Majority of OLNP-05-treated subjects were found to be in the "much improved" category as per CGI-I assessment. The result confirms the safety and efficacy of OLNP-05, therefore suggesting that OLNP-05 may be a safe and effective intervention for the management of PE. Trial registration: Clinical Trials Registry India (Registration No: CTRI/2017/08/009226, 02/08/2017).

A Randomized, Double Blind, Placebo Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of Curene® versus Placebo in Reducing Symptoms of Knee OA.

BACKGROUND: Curene® is a bioavailable formulation of turmeric Curcucma longa extract comprising naturally derived curcuminoids formulated with proprietary Aquasome® technology. Curcuminoids were found to have anti-inflammatory properties by inhibiting Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme and hence have potential application in the treatment of Osteoarthritis (OA). To evaluate the safety and efficacy of Curene® a randomized, double blind, placebo controlled, parallel-group study was conducted in subjects with knee OA. Significant improvements in clinical endpoints were observed during the trial along with excellent safety profile. METHODS: Fifty (50) subjects aged between 40 and 75 years who were suffering from unilateral or bilateral OA of the knee for greater than 3 months according to American College of Rheumatology (ACR) criteria were enrolled. They were randomized into two treatment groups; one group received Curene® 500 mg once daily and the other group received placebo. Efficacy was evaluated using change from baseline in Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Biochemical and hematological parameters including urine analysis were performed to evaluate the safety of Curene® in OA patients. RESULT: Forty-six (46) subjects completed the study. The reduction from baseline in total WOMAC score (also subscale scores) and VAS score resulted in statistically significant difference when compared to placebo. It was also found to be safe and well tolerated as there was no incidence of treatment related AEs. CONCLUSION: Curene® results in statistically significant and clinically meaningful reduction in pain, stiffness, and improvement in physical functioning in subjects suffering from knee OA. Curene® also demonstrates excellent safety profile during the study. TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry, India, CTRI/2017/07/009044, registered on 14th July 2017, http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=19264&EncHid=&userName=ocius%20life%20sciences.