WO2022139702A1 - Hydrogels super absorbants pouvant être ingérés, chargés de dioxyde de chlore sous la forme de microparticules, de films et de blocs - Google Patents

Hydrogels super absorbants pouvant être ingérés, chargés de dioxyde de chlore sous la forme de microparticules, de films et de blocs Download PDF

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WO2022139702A1
WO2022139702A1 PCT/TR2020/051377 TR2020051377W WO2022139702A1 WO 2022139702 A1 WO2022139702 A1 WO 2022139702A1 TR 2020051377 W TR2020051377 W TR 2020051377W WO 2022139702 A1 WO2022139702 A1 WO 2022139702A1
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Prior art keywords
chlorine dioxide
hydrogel
composition
microparticles
carboxymethyl cellulose
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PCT/TR2020/051377
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English (en)
Inventor
Ibrahim ISILDAK
Fatih ERCI
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Medisen Medikal Teknolojiler Arastirma Gelistirme San. Tic. Ltd. Sti.
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Priority to PCT/TR2020/051377 priority Critical patent/WO2022139702A1/fr
Publication of WO2022139702A1 publication Critical patent/WO2022139702A1/fr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/20—Gaseous substances, e.g. vapours

Definitions

  • the present invention relates to bactericidal, fungicidal and virucidal complex structures. More particularly, the present invention relates to chlorine dioxide containing ingestible superabsorbent hydrogels and the methods of production and uses thereof.
  • a number of disinfectant compounds having bactericidal, fungicidal and virucidal activity have been developed in order to protect humans, animals and plants from pathogen microorganisms. Most important of these compounds are oxidizing agents. However, many such compounds have undesirable side effects. For example, chlorine gas (CI2) is a very effective disinfecting agent having bactericidal, fungicidal, virucidal and germicidal activity. However, it has high levels of toxicity and is not effective against gram-positive bacteria.
  • ozone gas (O3) Ozone is an oxidizing agent having limited bactericidal, fungicidal and virucidal activity. Ozone has limited solubility in water.
  • H2O2 hydrogen peroxide
  • H2O2 hydrogen peroxide
  • aqueous chlorine dioxide (CIO2)
  • CIO2 aqueous chlorine dioxide
  • the bactericidal, fungicidal and virucidal activity of chlorine dioxide is well-documented in literature.
  • the major downsides of aqueous chlorine dioxide are its limited stability, short shelf-life and low purity.
  • the techniques developed for the preparation of aqueous solutions of chlorine dioxide are well known in the art.
  • patent document WO 2011/086579 discloses a two component system comprising sodium chlorite, (NaCIO2) and sodium persulphate (Na2S20s) or sodium bisulphate (NaHSO4) for producing liquid chlorine dioxide (CIO2) having a concentration between 500 ppm to 50000 ppm as stable and purity above 99%.
  • patent document EP 1 787 953 discloses a method of quickly generating chlorine dioxide at very low concentrations.
  • the persulphate/chlorite ratio in buffer medium was greater than 2.
  • these methods have important disadvantages.
  • the obtained chlorine dioxide solutions have a short shelf-life limited to one to two weeks and are non-transportable.
  • non-stoichiometric reactions can produce impurities and said impurities can cause decomposition of chlorine dioxide leading to more impurities in the final product. Impure chlorine dioxide solutions obtained using these methods cannot be safely used, especially in places containing living organisms.
  • Aqueous chlorine dioxide solutions are not highly stable under normal conditions. Many methods of chlorine dioxide production also generate impurities such as chlorite, chlorate and chlorine gas. The presence of even a small amount of these impurities in the solution can cause autocatalytic reactions leading to generation of harmful side products and reduction in the stability and activity of chlorine dioxide. Chlorine dioxide decomposes into slightly toxic chlorite as an intermediate and further decomposes into non-toxic chloride ion and oxygen.
  • Chlorine dioxide exhibits vapor phase decomposition.
  • Vapor phase decomposition of chlorine dioxide is promoted in the presence of air, specifically oxygen.
  • Chlorine dioxide molecules readily absorb radiation and therefore decomposition is promoted by UV irradiation.
  • Chlorine dioxide decomposition is very strongly promoted by mechanical agitation or shock, which can be compounded by oxygen-triggered decomposition as described above, since mechanical agitation can create air pockets and increase the concentration of dissolved oxygen in the water.
  • Chlorine dioxide decomposition is greater in a container having a large headspace, driven by the vapor pressure of chlorine dioxide, promoting movement from the aqueous phase to the vapor phase.
  • aqueous solutions of chlorine dioxide have limited areas of use. Due to its instability, chlorine dioxide gas may not be transported in many countries or protective agents having oxidizing effect such as carbonates, borates or benzalkonium chloride are added to the solution to limit decomposition. However, these agents can have toxic effects. Chlorine dioxide is rarely transported, because of its explosiveness and instability. Therefore, it is almost always made at the location where it is used.
  • Patent document US 8,202,548 discloses a method of making a composition having the property of being able to store chlorine dioxide includes mixing an aqueous chlorine dioxide solution with a superabsorbent, water- soluble polymer that is substantially unreactive with chlorine dioxide and permitting a mixture formed thereby to form one of a gel and a solid composition.
  • the polymers used in said systems are known to cause toxic effects when ingested.
  • chlorine dioxide stored within said gels is released by degelling the gel and permitting the polymer to precipitate out, where by aqueous chlorine dioxide is recovered from a supernatant above the precipitate, and the recovered aqueous chlorine dioxide is applied to the target.
  • this system requires the additional steps of recovering the loaded chlorine dioxide and removing the gel material rather than being able to be used directly.
  • the present invention aims to improve on the problems in the prior art.
  • the present invention discloses methods for obtaining high purity chlorine dioxide and the synthesis of biocompatible ingestible super absorbent hydrogel structures capable of effectively loading chlorine dioxide.
  • the present invention makes use of a persulphate/chlorite of 0.55, which is slightly above the stoichiometrically required amount, and a catalytic amount of potassium persulphate.
  • Sodium persulphate, sodium chlorite and potassium persulphate are used as solid or in solution.
  • salt solution, serum solution, ethanol, dichloromethane and/or mixtures thereof are used instead of distilled water.
  • the obtained solution is loaded into the ingestible super absorbent hydrogel structures.
  • the present invention discloses chlorine dioxide solution loaded ingestible super absorbent hydrogel structures that overcome the aforementioned problems in the state of the art.
  • the structures have low toxicity and carcinogenicity for living organisms. It is known in the art that chlorine dioxide has a disinfectant effect across a wide pH range. Chlorine dioxide is a bactericidal, fungicidal and virucidal agent that causes no health or environmental problems. It produces no toxic reaction products, such as highly toxic chlorine gas and trihalomethanes and other toxic chlorinated organic compounds as a result of its bactericidal, fungicidal and virucidal effect.
  • the ingestible super absorbent hydrogel structures encapsulating chlorine dioxide of the present invention provide a system for long term storage and transport of chlorine dioxide that is capable of continuously releasing small amounts of chlorine dioxide over a long period of time that is not harmful to human, animal or plant life.
  • the hydrogels can be directly applied to the areas desired to be disinfected without first having to recover the chlorine dioxide loaded therein.
  • the present invention can be safely ingested and also used in a variety of places such as hospitals, offices, public transport and private vehicles, factories and homes.
  • the present invention discloses systems and compositions suitable for the production, use, long term storage, and controlled release of chlorine dioxide. More particularly, the present invention discloses the production of pure aqueous solutions of chlorine dioxide using sodium chlorite, sodium persulphate and potassium monopersulfate, the synthesis of ingestible superabsorbent hydrogel structures and systems wherein chlorine dioxide is effectively loaded into said ingestible superabsorbent hydrogel structures. Said ingestible superabsorbent hydrogel structures are not reactive with chlorine dioxide. Said hydrogel structures are in the form of microparticles, thin films and blocks. Said ingestible superabsorbent hydrogel structures are capable of storing chlorine dioxide loaded therein over a long period of time.
  • the present invention also discloses the use of said ingestible superabsorbent hydrogel structures encapsulating chlorine dioxide for eliminating the viral, bacterial and fungal load of biological and environmental samples.
  • Said ingestible superabsorbent hydrogel structures are pH sensitive and capable of controlled release of chlorine dioxide and the released chlorine dioxide eliminates the viral, bacterial and fungal load of the desired medium.
  • Said ingestible superabsorbent hydrogel structures are not soluble in water and can therefore release chlorine dioxide over a long period of time.
  • Figure 1 illustrates hydrogel structures according to the present invention.
  • Figure 2 illustrates the UV-Vis spectra of pure chlorine dioxide at different concentrations (concentration: 4-500 mg/L).
  • Figure 3 illustrates FTIR spectrum of empty carboxymethyl cellulose hydrogel microparticles.
  • Figure 4 illustrates FTIR spectrum of chlorine dioxide loaded carboxymethyl cellulose hydrogel microparticles according to the present invention.
  • Figure 5 illustrates Raman spectrum of chlorine dioxide loaded carboxymethyl cellulose hydrogel microparticles according to the present invention.
  • Figure 6 illustrates SEM images of empty carboxymethyl cellulose hydrogel microparticles according to the present invention.
  • Figure 7 illustrates SEM images of chlorine dioxide loaded carboxymethyl cellulose hydrogel microparticles according to the present invention.
  • Figure 8 illustrates stability of 500 ppm chlorine dioxide in different salt solutions over time.
  • Figure 9 illustrates stability of chlorine dioxide in carboxymethyl cellulose hydrogel microparticles according to the present invention.
  • the present invention discloses chlorine dioxide loaded ingestible superabsorbent hydrogels capable of long term storage and controlled release of chloride dioxide and the methods of production and uses thereof.
  • Chlorine dioxide containing ingestible superabsorbent hydrogels of the present invention can be used to eliminate the viral, bacterial and fungal load of a desired environment, including but not limited to drinking water, biological fluids and air.
  • the ingestible superabsorbent hydrogel structures of the present invention have limited solubility in water and do not react with the chlorine dioxide encapsulated therein. Pure chlorine dioxide can be stored within said hydrogel structures over a long period of time without decomposing.
  • the ingestible superabsorbent hydrogen structures have a white to yellow to green color in proportion to the amount of chlorine dioxide stored within. The higher the concentration of chlorine dioxide, the greener the hydrogel becomes. Tests have shown that the hydrogels are able to retain 95% of chlorine dioxide after being stored for 2 years in the dark at 6°C. Under standard conditions (25°C and 1 atm) and in the dark, the hydrogel structures are able to retain over 90% of chlorine dioxide without decomposition. The decomposition byproducts found within the hydrogel structures are chloride ion and oxygen. The hydrogel structure protects chlorine dioxide loaded therein from mechanical shock, UV or IR radiation, and air/oxygen penetration.
  • the ingestible superabsorbent hydrogel structures of the present invention are efficient and cost effective as they are produced using the optimum amount of material and contain minimal micro air pockets.
  • said ingestible superabsorbent hydrogel structures are in the form of microspheres.
  • said hydrogel structures can also be in the form of thin hydrogel films, block hydrogels and viscous fluids and any other suitable form known in the art.
  • the ingestible superabsorbent hydrogel structures of the present invention have a large water absorption capacity and can therefore store different amounts of chlorine dioxide therein.
  • Hydrogel microspheres can be prepared in an aqueous dispersion suitable to be sprayed onto the desired environment, such as biological fluids, bodies of water or surfaces. Hydrogels continuously release chlorine dioxide to environment in a controlled manner, therefore the activity of chlorine dioxide in the environment stays constant, minimizing the possible harm caused to the environment and living organisms.
  • Said biocompatible superabsorbent hydrogel matrix does not undergo oxidation or reduction reactions with the chlorine dioxide encapsulated therein and release chlorine dioxide without any harmful byproducts. The speed of release of chlorine dioxide from the hydrogel matrix is dependent on factors such as temperature and pH.
  • sodium and potassium salts of polysaccharides such as carboxymethyl cellulose (CMC) are used to produce said ingestible superabsorbent hydrogel structures.
  • CMC carboxymethyl cellulose
  • MED-CX hydrogel structures in the form of microparticles, films and blocks containing cellulose derivatives, chitosan and collagen produced by MEDISEN Ltd. Sti. Istanbul/Turkey.
  • polymers can be used to produce said hydrogel structures.
  • Other exemplary polymers include polysaccharides such as hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), methyl cellulose (MC), collagen, chitosan, gelatin, alginate and starches.
  • Ingestible superabsorbent hydrogel structures of the present invention are pH responsive, biocompatible and environmentally safe.
  • the pH-responsive hydrogels show swelling/shrinking behavior in response to change in the environmental pH and such hydrogels are of particular interest for controlled release of active ingredients as substantial pH changes are found in various locations in the body and environment. Therefore, said hydrogel structures can be safely and favorably used in environmental, food and pharmaceutical applications.
  • Chlorine dioxide is loaded into the ingestible superabsorbent hydrogel structures by mixing said hydrogel structures in an aqueous chlorine dioxide solution.
  • the amount of chlorine dioxide encapsulated by the hydrogel structure is determined by the swelling ratio.
  • the hydrogel structures of the present invention can swell to at least 10 times their initial weight.
  • the swelling ratio is affected by the temperature and pH. For example, at 25°C and pH 7.4, the preferred embodiment of the hydrogel structure can swell up to 100 times its initial weight. Therefore, the ingestible superabsorbent hydrogel structures of the invention are capable of encapsulating varying amounts aqueous chlorine dioxide.
  • 1 g of ingestible superabsorbent hydrogel structure can contain between 0.01-100 mg chlorine dioxide.
  • 1 g hydrogel encapsulating 100 mg chlorine dioxide 1 g hydrogel sample is mixed with 2 g 50,000 ppm (50,000 mg/lkg) aqueous chlorine dioxide solution.
  • 1 g hydrogel sample is mixed with 0.01 g 1000 ppm (50,000 mg/lkg) aqueous chlorine dioxide solution. Mixing is done under nitrogen for a maximum of 60 minutes. No chemical changes occur in the hydrogel after mixing and the ingestible superabsorbent hydrogel structure retains its physical integrity and stability.
  • UV blocking amber glass or PET containers are used for storing the chlorine dioxide loaded hydrogels in order to prevent unwanted decomposition reactions; however, HDPET, PTFE or PVC containers can also be used. It was determined that chlorine dioxide loaded ingestible superabsorbent hydrogel structures of the present invention can retain chlorine dioxide over a long period of time (2 years) in storage, in contrast to untreated chlorine dioxide solutions which only last up to 1-2 weeks. It was found that chlorine dioxide loaded ingestible superabsorbent hydrogel structures of the present invention do not release a chlorine dioxide smell and retain their white-yellow-green-dark green color depending on the chlorine dioxide concentration indicating that chlorine dioxide is still encapsulated therein.
  • Chlorine dioxide release studies were done by taking air and water samples from the environment over a period of 72 hours after the application of the chlorine dioxide loaded hydrogel structures. The air and water samples were analyzed by spectrophotometer to determine the amount of chlorine dioxide. The bactericidal, fungicidal and virucidal effects of the released chlorine dioxide on environmental and biological samples were tested. It was determined the chlorine dioxide does not decompose and lose its activity in the ingestible superabsorbent hydrogel structures during storage or while in use. During these studies, chlorine dioxide loaded ingestible superabsorbent hydrogel structures were protected from mechanical shock, UV or IR radiation, and heat and air penetration.
  • aqueous solutions of chlorine dioxide loaded the ingestible superabsorbent hydrogels having different viscosities are produced. These viscous solutions can be used as an effective germicide for surgical tools, infected tissues, infected skin and body (mouth, nose, ear, genitals and bowel infections) surfaces.
  • aqueous sodium chlorite solution 100 ml 50% aqueous potassium peroxymonosulfate solution and 100 ml 10% aqueous sodium persulphate solution were mixed and distilled water was added until the solution reached 2 L.
  • the reaction solution was stirred overnight (12 hours) at low speed and 99% pure chlorine dioxide solution was obtained.
  • chlorine dioxide within the solution was transferred to distilled water, ethanol, aqueous sodium chloride solution, phosphate buffer or serum solution containing ingestible superabsorbent hydrogel structures using argon gas.
  • hydrogel structures (microparticles, films or blocks) of 6 wt% NaCMC or 3 wt% NaCMC and 3 wt% HPMC were used for the production of chlorine dioxide loaded ingestible superabsorbent hydrogel structures.
  • the chlorine dioxide solution was diluted to the desired concentrations using distilled water.
  • Hydrogel structures of different weights containing 6 wt% NaCMC or 3 wt% NaCMC and 3 wt% HPMC were obtained. Said hydrogel structures were gently mixed with pure aqueous chlorine dioxide solutions having varying concentrations for 5 minutes in order to load chlorine dioxide into said hydrogel structures. For example, 100 g of 30,000 ppm pure chlorine dioxide solution and 10 g of hydrogel microparticles containing 6 wt% by weight NaCMC were gently mixed for 5 minutes.
  • the obtained chlorine dioxide loaded hydrogel microparticles were transferred to amber glass or colored PET bottles.
  • the bottles were filled up to have a minimal amount of air pocket and the caps were screwed on tightly.
  • the bottles were stored in the dark at 6°C in the fridge.
  • Figure 1 A shows that there was minimal loss of chlorine dioxide over a 6-week period.
  • Empty superabsorbent hydrogel microparticles were also stored in the same way as control. It was found that, the hydrogel microparticles retained their original color, physical structure and shape even after 2 years.
  • Chlorine dioxide loaded hydrogel microparticle samples were also stored at 20°C under fluorescent light for 1 week and tested. It was determined that even under these conditions, loss and decomposition of chlorine dioxide was limited and the hydrogel microparticles retained their color and physical structure.
  • hydrogel structures microparticles, films or blocks
  • 3 wt% NaCMC and 3 wt% HPMC 3 wt% NaCMC and 3 wt% collagen
  • 3 wt% NaCMC and 3 wt% starch 3 wt% NaCMC and 3 wt% alginate
  • 3 wt% NaCMC and 3 wt% chitosan 3 wt% NaCMC and 3 wt% chitosan
  • Results show that chlorine dioxide loaded ingestible superabsorbent hydrogel structures can encapsulate chlorine dioxide without decomposition for a long period of time.
  • UV-Vis spectroscopy was used for the qualitative and quantitative analysis of chlorine dioxide in aqueous solution. UV-Vis spectra of different concentrations of chlorine dioxide solution was taken between 190-600 nm (PGENERAL - T80+). Chlorine dioxide shows maximum absorption at 358 nm.
  • Figure 2 shows the UV-Vis spectrum of different concentrations of chlorine dioxide solutions varying between 4-500 mg/L to serve as a calibration curve. It can be seen absorption increases with concentration and it is possible to determine concentrations down to 2 mg/L by UV-Vis spectroscopy. The amount of chlorine dioxide present was determined by taking UV-Vis measurement at 358 nm and using this calibration curve.
  • FTIR Fourier Transform Infrared Spectrophotometry
  • Figure 5 shows the Raman spectrum of chlorine dioxide loaded CMC-based ingestible superabsorbent hydrogel structures.
  • Raman spectroscopy Perkin Elmer Raman Station 400F was used to analyze chemical bonds and determine functional groups. The peaks at 923 ve 1117 cm’ 1 are thought to belong to chlorine dioxide.
  • the stability of chlorine dioxide over time in different salt solutions was determined using UV-Vis spectroscopy as explained above.
  • the solutions used were water and aqueous H2PO4/HPO4 buffer, NaCI, CaCl2 and FeCl2 solutions (0.05 M).
  • 500 ppm chlorine dioxide solutions were stored in colored glass bottles at 8°C and a 1 ml sample was taken every week. The sample was diluted using 250 ml deionized water and UV-Vis absorbance at 358 nm was measured.
  • Figure 8 shows that over an 8-week period, loss (decomposition) of chlorine dioxide in water and aqueous H2PO4/HPO4 buffer, NaCI and CaCl2 solutions was below 5 wt%, while in aqueous FeCl2 solution, the loss was over 15 wt%.
  • Lyophilized cultures of gram -positive Staphylococcus aureus S. aureus; ATCC 25923) and gram-negative Escherichia coii ⁇ E. coii;K CC 25922) were supplied from Microbiologies Inc. (Saint Cloud, (Saint Cloud, MN, USA).
  • the antibacterial assays were carried out by the agar well diffusion assay. The final concentration of bacteria was adjusted in saline solution (NaCI 0.9%) at 0.5 Macfarland opacity standard (1.5 x 10 8 colony forming units (CFU)/mL. 0.1 ml of bacteria suspension was spread onto cation-adjusted Mueller Hinton agar (MHA, Lab M, UK).
  • MIC minimum inhibitory concentration
  • the MIC was determined to be 1/128 (7.8 pg or 78 ppm CIO2) for S. aureus and 1/32 (31.2 pg or 312 ppm CIO2) for E. coli.
  • Vero permanent cell line Africann green monkey kidney
  • Herpes Simplex Virus type 1 HSV-1
  • DMEM Dulbecco's Modified Eagle's Medium
  • HSV-1 was propagated in Vero cells and HSV-1 titers were obtained in 24-well plates by the Spearman-Karber method and expressed as 50% tissue culture infections dose (TCID50) per 0.1 ml.
  • TCID50 was determined to be 10’ 7 - 5 /0.1 ml as shown in Table 1.
  • the cytotoxicity of chlorine dioxide loaded CMC-based hydrogel microparticles on Vero cells was determined using a modified version of the method described by Andrighetti-Frdhner, et al. ("Cytotoxicity and potential antiviral evaluation of violacein produced by Chromobacterium violaceum.” Memdrias do Institute Oswaldo Cruz 98.6 (2003): 843-848). Vero cell cultures were prepared in 24- well plates using DMEM containing 10% FBS. After a 24-hour period of incubation, the medium was removed from each well and replenished with 100 mg chlorine dioxide loaded CMC-based hydrogel microparticles (10 mg/g or 10,000 ppm chlorine dioxide) by two-fold dilutions up to 1:2048 per well.
  • CPE cytopathic effects
  • Microtitration assay was used to determine the antiviral activity of chlorine dioxide loaded CMC-based hydrogel microparticles (10 mg/g or 10,000 ppm chlorine dioxide) against HSV-1.
  • Vero cell cultures (1 ml per well at 3xl0 5 cells/ml) were prepared in 24-well tissue culture plates (Corning, US). After a 24 hour period of incubation at 37°C in a humidified 5% CO2 atmosphere, the medium was removed from each well and replenished with virus suspension diluted to 100 TCID50 and the 1:512 dilution of 100 mg chlorine dioxide loaded CMC-based hydrogel microparticles (10 mg/g or 10,000 ppm chlorine dioxide) in DMEM.
  • TCID50 was determined to be 10' 2 75 /0.1 ml using Spearman-Karber method as shown in Table 2.
  • MIC Minimum inhibitory concentration
  • potato dextrose agar was inoculated with each mold sample, and incubated at 22.5°C for 7 days to activate the mold.
  • Activated mold colonies were transferred to 10 ml 0.1% Tween 80 (PBS) and a spore stock solution having a concentration of 10 8 spores/ml was prepared.
  • 1 ml spore stock solution was added to 99 ml double strength potato dextrose broth to obtain a 10 6 spores/ml spore suspension.
  • the ingestible superabsorbent hydrogel structures of the present invention are capable of encapsulating high concentrations of chlorine dioxide.
  • the ingestible superabsorbent hydrogel structures of the present invention are also capable of storing pure chlorine dioxide without significant loss or decomposition for a long time (2 years), allowing chlorine dioxide to be stored and transported in a stable manner.
  • the chlorine dioxide loaded CMC-based hydrogel microparticles of the present invention protect chlorine dioxide from mechanical shock, UV or IR radiation, heat and air penetration which can cause decomposition and/or explosion.
  • Said chlorine dioxide loaded CMC-based hydrogel microparticles are biocompatible and can be safely used on humans, animals, plants and other living organisms, surfaces and the environment. The bactericidal, fungicidal and virucidal effect of said chlorine dioxide loaded CMC- based hydrogel microparticles were demonstrated above.

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Abstract

La présente invention concerne des systèmes et des compositions convenant à la fabrication, à l'utilisation, au stockage à long terme, et à la libération contrôlée de dioxyde de chlore. Plus particulièrement, la présente invention concerne des hydrogels super absorbants pouvant être ingérés contenant du dioxyde de chlore et leurs procédés de fabrication et leurs utilisations. Lesdites structures d'hydrogel super absorbant pouvant être ingéré ne sont pas réactives avec le dioxyde de chlore. Lesdites structures d'hydrogel se présentent sous la forme de microparticules, de films fins et de blocs qui peuvent être directement utilisés pour désinfecter l'eau potable, les liquides biologiques, les tissus vivants et les aliments, ainsi que pour désodoriser et stériliser l'air. La présente invention concerne également l'utilisation desdites structures d'hydrogel super absorbant pouvant être ingéré, encapsulant du dioxyde de chlore, pour éliminer la charge virale, bactérienne et fongique des prélèvements biologiques et environnementaux.
PCT/TR2020/051377 2020-12-24 2020-12-24 Hydrogels super absorbants pouvant être ingérés, chargés de dioxyde de chlore sous la forme de microparticules, de films et de blocs WO2022139702A1 (fr)

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Citations (9)

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Publication number Priority date Publication date Assignee Title
US2323593A (en) 1941-10-08 1943-07-06 Mathieson Alkali Works Inc Manufacture of chlorine dioxide
WO1996033947A1 (fr) 1995-04-25 1996-10-31 Kueke Fritz Procede de preparation d'une solution desinfectante renfermant du dioxyde de chlore pour le traitement de l'eau
US5651996A (en) * 1992-03-04 1997-07-29 Arco Research Co., Inc. Method and compositions for the production of chlorine dioxide
US6451253B1 (en) * 1999-04-14 2002-09-17 Vulcan Chemical Technologies, Inc. High concentration chlorine dioxide gel composition
EP1787953A2 (fr) 2005-11-21 2007-05-23 Gojo Industries, Inc. Production de dioxyde de chlore
WO2011086579A1 (fr) 2010-01-18 2011-07-21 Prophylaxis Procédé de production d'une forme liquide stable et pure de dioxyde de chlore
US20120070508A1 (en) * 2010-09-16 2012-03-22 Dharma IP, LLC Methods, Compositions, and Devices for Managing Chlorine Dioxide Release
US8202548B2 (en) 2003-10-09 2012-06-19 Dharma IP, LLC Chlorine dioxide gel and associated methods
US8790630B2 (en) * 2007-03-15 2014-07-29 Taiko Pharmaceutical Co., Ltd. Pure chlorine dioxide solution, and gel-like composition and foaming composition each comprising the same

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2323593A (en) 1941-10-08 1943-07-06 Mathieson Alkali Works Inc Manufacture of chlorine dioxide
US5651996A (en) * 1992-03-04 1997-07-29 Arco Research Co., Inc. Method and compositions for the production of chlorine dioxide
WO1996033947A1 (fr) 1995-04-25 1996-10-31 Kueke Fritz Procede de preparation d'une solution desinfectante renfermant du dioxyde de chlore pour le traitement de l'eau
US6451253B1 (en) * 1999-04-14 2002-09-17 Vulcan Chemical Technologies, Inc. High concentration chlorine dioxide gel composition
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