leky-latky/jod/Renessans

An Open Labelled, Active Controlled, Three-Arm, Parallel- Group study of the safety and efficacy of the oral formulation of Oral Iodine Complex (RENESSANS) administered alone and in combination with standard interferon therapy in patients suffering from Chronic HCV Hepatitis.

Ghiasun Nabi, Muhammad Nasir, Ghias ulhasan, Israr Toor, Fawad Zia, Imran Hassan, View ORCID ProfileMuhammad Faisal F Nadeem

• https://doi.org/10.1101/2020.06.27.20141473
• Revrix Abstract
• Iodine has strong antimicrobial properties and has been used in topical applications as antiseptic
• Systemic use in form of iodine complexes derived from dried seaweed extract is beneficial in treating various disorders.
• Hepatitis C Virus (HCV) chronic infection is present in 6-10% of the Pakistani population
• Major healthcare burden that could benefit from innovative therapeutic regimens.
• A pilot study has shown the safety and efficacy of iodine complexes in chronic Hepatitis C virus infection
• Clinical study is aimed to further explore the previous findings
• An open-labeled, active-controlled, three-arm, parallel-group study including 90 patients of chronic HCV infection, each arm having 30 patients.
• 15 mg/day iodine complex only
• Standard of care therapy interferon+ribavirin
• Iodine complex in combination with interferon+ribavirin regimen for 6 months
• Efficacy assessment:
• Rapid Virological Response (RVR) post-treatment at 4 weeks
• Iodine complex+ interferon+ribavirin showed 80% RVR
• Standard of care therapy showed 66.7% RVR
• Early Virological Response (EVR) at 12 weeks
• End of Treatment Viral Response (ETR) at 24/48 weeks
• With iodine complex alone 3.33%
• Interferon+ribavirin showed significant improvement in comparison to interferon+ribavirin alone
• Iodine complex+ interferon+ribavirin showed 90% ETR
• Standard of care therapy showed 76.67% ETR
• No additional adverse events of iodine complex were observed
• Iodine complex showed a significant synergistic effect when combined interferon+ribavirin regimen
• Could be useful in relapsers and non-responders

Renaissance

• Medicinal product, including iodine, potassium iodide starch, ascorbic acid, glucose, sodium chloride and purified water in the following ratio of components (mass%):
• Iodine 0.4 - 2.0
• Potassium iodide 0.8 - 4.0
• Starch 10.0 - 40.0
• Ascobic Acid 0.4- - 2.0
• Glucose 1, 2- - 4.8
• Sodium Chloride 0.3-1.8
• The water purified the rest.

• Makes it possible to obtain a preparation suitable for injection use
• Balanced system of components that is stable in aqueous raster.
• Structure that would preserve the oxidizing ability of iodine in a state in which the possibility of transporting these particles over long distances was realized to distribute it ultimately throughout the body [11]
• The specified composition and certain concentrations of the components in the aqueous solution form the iodine-polymer complex
• Acts as a matrix and forms associates
• From which the active active agent, the active form of iodine, is released
• Starch and glucose participate in the formation of the matrix and associates
• Poly- and monosugar having functional groups of different activity
• Potassium iodide into the drug the formation
• Long time prevents the deactivation of the main active agent
• Carbohydrates are essential components of bacterial cell walls
• Glycoconjugates associated with the function of a number of lectin-type cellular receptors recently discovered on the surface of phagocytic cells.
• Formation of the amylose-iodine complex is associated with the spiral conformation of the amylose chain
• In the center of the spiral of which a channel-shaped cavity is formed with dimensions sufficient to accommodate iodine molecules
• Forms hexagonal crystals
• Does not change the viscosity of amylose solutions.
• Aimed at maintaining its stability and structure
• Responsible for antimicrobial and immunomodulating
• Solutions of crystalline iodide and potassium iodide, sodium chloride and ascorbic acid in distilled water are prepared, as well as a suspension of starch in water. All solutions are mixed and adjusted to 1 liter of water.
• South crystalline iodine is crushed and 16 g of potassium iodide are dissolved in a small amount of purified water. Purified water is added to 150 g of starch to prepare a suspension. Solutions of sodium chloride (9.0 g) and ascorbic acid (10.0 g) are prepared, all are mixed and adjusted to one liter with purified water. The prepared drug has the appearance of a syrupy liquid, color from black to dark blue with a smell characteristic of iodine preparations.

Intraperitoneální aplikace

• Administered intraperitoneally to animals in various doses in undiluted form and diluted in physiological saline
• For rats is 5 ml
• Administered daily once intraperitoneally.
• With dilution in physiological solution of sodium chloride, as well as undiluted.
• Histological structure of the internal organs of experimental animals, which also confirms the non-toxicity of the drug

Antiulcer efficacy of RENESSANS in 10 patients with gastric ulcer and duodenal ulcer

• For 2 weeks showed a high antiulcer effect of the drug
• Monotherapy with the drug RENESSANS ulcer healing was observed in 9 cases
• Regardless of their location (4 — gastric ulcers: media gastric and antral, and 5 ulcers DNA).
• In only one case, taking the drug led to increased pain (ulcer DNA)
• It took the appointment of an injection of an anti-inflammatory drug in all 9 patients with control esophagogastroscopy
• Complete healing of ulcers was established
• Pain relief was observed on the 1-2nd day of taking the drug
• In all cases, no dependence of the healing effect of the drug on the size of ulcers, age and gender of the patients was found
• The data obtained show a high antiulcer efficacy of the RENESSANS preparation [11]

In 13 volunteers who received the drug for 27 days

• Immune status was evaluated twice (before appointment and after 27 days of administration) [11]

Antimicrobial effect

• Not only comparable to the action of aqueous solutions of iodine, but also in some cases exceeds them.
• The results of the assessment of the immune status during the testing of the drug showed the presence of an immunocorrective effect [11]
• Complete bactericidal activity of the RENESSANS drug solution. [11]

Renessans

• Capsule (containing 200mg iodine)
• Syrup (containing 10mg/ml iodine)

An in vitro assessment of anti-SARS-CoV-2 activity of oral preparations of iodine complexes (RENESSANS)

• BioRxiv
• Imran Altaf, Muhammad Faisal Nadeem, Nadir Hussain, Muhammad Nawaz, Sohail Raza, Muhammad Asad Ali, Sohail Hasan, Nazish Matti, Muhammad Ashraf, Ihsan Ulla, Sehar Fazal, Saira Rafique, Muhammad Adnan, Nageen Sardar, Tahir Khan, Muhammad Moavia, Sohaib Ashraf, Zarfishan Tahir, Nadia Mukhtar, Tahir Yaqub
• https://doi.org/10.1101/2020.06.29.171173
• In Vitro anti-SARS-CoV-2 activity of oral formulations (syrup and capsule) of an Iodine-complex (Renessans)
• A monolayer of vero cells were exposed to SARS-CoV-2 in the presence and absence of different concentrations
• Equivalent to 50, 05 and 0.5 mcg/ml of I2 of Renessans
• 0.5 mcg/ml , 5 and 50 mcg/ml concentration of Renessans syrup
• 100% cell survival
• no CPEs and a negligible viral replication
• Renessans, containing iodine, may have potential activity against SARS-CoV-2
• Needs to be further investigated in human clinical trials.
• Use in physical inactivation of SARS-CoV-1, MERS has already been demonstrated
• Use of iodine as a systemic intervention is yet debatable for its toxicity
• Kelp is a dried seaweed rich in vitamins, minerals especially iodine where iodine is complexed with other components.
• An iodine complex formulation has been patented (patent no: 141316, IPO, Pakistan)
• Registered by MTI, Pakistan (DRAP registration # 505620098)
• Clinical trials has successfully been conducted where it was found to be
• Highly effective in the treatment of oligomenorrhea and polycystic fibrosis
• Antiviral efficacy of the studied drug has also been reported for clinical trial against Hepatitis C Virus (HCV)
• In combination with traditional therapy
• Renessans has also been tested for avian influenza virus
• Where it showed an inhibition of cytopathic effects
• Iodine has a history of use in tropical applications
• Exhibited antiviral activity against SARS-CoV, MERS, avian influenza virus and HCV
• We have used non toxic concentrations
• 50 mcg/ml, 5 mcg/ml, 0.5 mcg/ml of Renessans
• Renessans exhibited strong antiviral activity against SARS-CoV-2
• With no/few CPE were observed in drug treated cells as compare to control cells
• Syrup able to complete inhibition of CPE (0%) formation at 50 mcg/ml, 5 mcg/ml
• Tablet able to inhibit 90% CPE formation at same concentrations
• Syrup formulation has better absorption in the cells than capsule form

• Antiviral activity of CupriDyne
• An iodine complex disinfectant solution was evaluated against SARS-CoV-2
• This iodine solution able to inactivate virus in time dependent manner
• Reducing the virus titers by 99%
• Reducing the virus titers below detection limit after 60 min

• Iodine complex had exhibited a virucidal activity against MERS virus
• Virus inactivation of ?99.99% within 15 seconds of application

• Iodine product had reduced the SARS-CoV infectivity to undetectable levels in 2 minutes of exposure in Vero infected Cells

• Iodine complexes have showed strong antiviral activity against SARS-CoV2 and members of this family
• Antiviral potential against other viruses like in
• Human and avian influenza virus
• Influenza A viruses infection up to 97.5 % in MDCK infected cells
• Adenoviral conjunctivitis
• Modified vaccinia virus Ankara

• It is more likely that iodine makes the structural changes on the viral coat
• Through attack on histidine and tyrosine residues
• It is likely that inhibition of SARS-CoV-2 infection at the entry level by blocking the viral attachment to the cell
• Seems to be a general mechanism underlying the inhibitory effect of iodine on other viruses

• RENESSANS (iodine containing oral formulation)
• May have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.

www.biorxiv.org/content/10.1101/2020.06.29.171173v1.full

Renessans patentní složení

• patents.google.com/patent/WO2012158002A1/en

• Components in the following ratio thereof:
• 0.4-2.0% by mass of iodine
• 0.8-4.0% by mass of potassium iodide
• 10.0-40.0% by mass of starch
• 0.4-2.0% by mass of ascorbic acid
• 1.2-4.8% by mass of glucose
• 0.3-1.8% by mass of sodium chloride
• With the remainder being purified water
• A pharmaceutically effective quantity of the preparation is administered
• Intravenously, intramuscularly or perorally

Suspension for internal use

• A syrupy liquid from dark blue to black
• With a characteristic taste and smell characteristic of iodine preparations.
• To 5 ml of the drug was added 5 ml of sodium solution thiosulfate 0.1 M
• The solution instantly bleaches (iodine).
• PH From 3.0 to 5.0 (potentiometric, GF XI, issue 1, p. 1 13).
• Dry residue. Not less than 9.0% (GF XI, issue 2, p. 148).
• Density. 1, 03-1, 08 g / cm 3 (GF XI, issue 1, p. 24) [11]