IT202000007348A1 - A gel - Google Patents

Description

Patent Application for Industrial Invention under:

? A GEL?

DESCRIPTION

Field of application

The present invention? applicable to the field of health? and, in particular,? relating to medical devices for health treatment.

Pi? in detail, the present invention refers to a gel that can be used as a device directly on a patient as well as to be used as a device. in combination with other devices such as, for example, breathing devices or room ventilation devices in order to purify the air flows that pass through them.

State of the art

? historically known that the silver has properties? antimicrobial thanks to which it constitutes a valid inhibitor of viruses and bacteria.

Regarding the mechanisms of antimicrobial action of silver, it binds to the thiol? SH groups present in the enzymes causing their deactivation. In particular, silver forms stable S-Ag bonds with compounds containing the? SH groups present in the cell membrane that are involved in energy production and ion transport. Silver also appears to take part in the catalytic oxidation reactions that lead to the formation of R-S-S-R disulfide bonds. The formation of disulfide bridges catalyzed by silver, therefore, leads to the variation of the structure of the enzymes, influencing their function.

Yup ? then discovered the silver Ag + ions have an? activity? increased antimicrobial. In particular, these ions enter the cell and intercalate between the complementary bases purine and pyrimidine with consequent denaturation of the DNA molecule. Moreover,? certain that silver ions associate with DNA once they enter the cell.

In a nutshell, therefore, silver? able to? enter? in bacterial or viral cells by damaging them and it is believed that, to do this, it uses membrane proteins that have, among other things, the function of transporting molecules across the membrane by means of pores, ion channels, ion pumps or specific carriers.

As just said, yes? found that to accentuate his activities? antimicrobial? It is good that silver is found in ionic form such as, for example, in the form of silver nitrate or in a zeolitic matrix or in the form of nanoparticles.

Yup ? observed, however, that the toxicity? some silver? minimal if not zero, also due to the fact that the antibiotic action is carried out on lower order organisms such as bacteria (prokaryotes) and not on complex cells (eukaryotes).

However, yes? found over time the difficulty? to increase the antimicrobial and antibacterial effect of silver to make it more and more? effective.

Yup ? then discovered and experimentally verified that silver has an accentuated activity. antimicrobial in the presence of electric fields. This increase in the effect occurs in the vicinity? of the anode and d? associated with an electrochemical injection effect. Obviously such a feature? result s? interesting, but not easily exploitable except by means of special bulky tools and therefore not very useful to the end user.

Consequently, the use of silver for these purposes is yes ? reduced to almost zero due to the development and massive production of antibiotics. Were the latter equally effective and their effect? been more? easily increased.

However, the frequent use of the same antibiotics has resulted in the development of new bacterial strains that are antibiotic-resistant.

? also notes the existence of numerous forms of filters for the air specialized in the purification of the same from the atmospheric particulate as well as? from other micro and nano agents present in the air.

In this sense, for personal use there are known face masks and filtering devices of small dimensions to be inserted in the cavities. nasal and equipped with both crossing and turbulence filters.

In particular, among the latter? he notes a particular typology of filters which implement a shaped duct so as to create a turbulent effect on the air flow which leads the atmospheric particulate to collide with the walls of the duct itself. These walls are then coated with a gel whose composition? such as to allow micro and nano particles to penetrate it and remain trapped.

Similar types of filters are also applicable in machines for assisted breathing or for the ventilation of environments.

However, a recognized drawback of such filters? their inability? cleaning the air filter from the bacterial and viral load present in it. In some cases, however, the same viruses and bacteria can colonize these filters making them particularly dangerous.

Unfortunately, the use of the aforementioned antibiotics? impractical in these cases.

Presentation of the invention

Purpose of the present invention? at least partially overcome the drawbacks encountered above, providing a medical device that allows to overcome the drawbacks encountered up to now in the use of silver or antibiotics for the inhibition or destruction of bacteria and viruses.

Within that general purpose, a particular purpose? that this medical device is also effective against new antibiotic-resistant bacterial strains.

An additional purpose? that the same medical facility can be easily used by the end user.

Another purpose? that this device is also able to trap harmful particulate so as to be usable inside filters for the purification of air flows.

Consequently, an additional purpose? provide an air flow filter that allows to purify this flow both from harmful particles and from viruses and bacteria.

Those purposes, as well as? others who will appear more? clearly in the following, they are reached by a gel in accordance with the following claims which are to be considered an integral part of the present patent.

In particular, the gel comprises a cross-linked dextran polymer and a gelling polymer. The cross-linked dextran polymer has glucose molecules linked to each other linearly by glycosidic bond? 1-> 6, cross-linked by glycosidic bonds? 1-> 4,? 1-> 2 or? 1-> 3. The same cross-linked dextran polymer also has one or more? ionic functional groups, i.e. the cross-linked dextran polymer? electrostatically charged.

Typically, but not necessarily, the electrostatically charged dextran polymer? consisting of the QAE Sephadex ?.

The Sephadex? ? a cross-linked dextran polysaccharide in which the glucose molecules are linearly connected to each other with a glycosidic bond? 1-> 6, while the cross-linking? due to glycosidic bonds? 1-> 4, sometimes also? 1-> 2 and? 1-> 3. In particular, in the QAE Sephadex ?, the prefix QAE indicates that the glucose molecules are functionalized with the quaternary amine diethyl-2-hydroxypropylaminoethyl.

According to one aspect of the invention, the gel also comprises dispersed silver.

As mentioned, the application of an electrical polarization to a silver element d? result in an antibacterial and antiviral effect on the part of this silver element. Pi? in detail, since? the dispersed silver? of metallic type, part of it assumes ionic form over time and? this form, as mentioned, which has an antibacterial function. The presence of an electric charge amplifies this effect at the anode: in fact it stimulates a greater generation of ions and concentrates the presence of ions produced in surrounding areas.

Advantageously, therefore, in the case of the present invention, the electrostatically charged cross-linked dextran polymer polarizes the silver dispersed in the gel, allowing to decrease, if not zero, the bacterial and viral load of the air flow that hits it. In particular, advantageously, above all the silver present in the peripheral surface of the gel is polarized. In fact, the anion exchanger determines a separation of the charges and the anodic ones are segregated on the external surface, which? moreover, the one that comes into contact with the bodies to be disinfected. L? Dispersed silver therefore becomes more? active or more available in the vicinity? of such anode areas.

The cross-linked dextran polymers mentioned above are generally used in the laboratory in column chromatography to separate molecules. Yup ? nevertheless found that, still advantageously, a gel based on such polymers and electrostatically charged, such as QAE Sephadex ?, can? it can also be used as a filter against the inhalation of substances harmful to health such as atmospheric particulate matter or cigarette tar.

Regarding the dispersed silver, according to another aspect of the invention it? in a quantity comprised between 100 ppm and 1000 ppm by weight referred to the total weight of the same gel.

The dispersion of silver can? take place in different ways. For example, it can? be dispersed in a colloid subsequently used in the synthesis of the gel, for example by replacing the aqueous part used in the synthesis of known analogous gels. According to another example, silver is deposited by stable nanocoating on amorphous particles subsequently dispersed in the gel. In the latter case, the amorphous particles typically include, but not necessarily, hydroxyapatite and / or Teflon.

From all there? it follows that the authors of the present invention have found that a gel such as the one described up to now? advantageously used as a medical aid in all those internal or external treatments, for example also for wounds, skin infections or other, in which an antibacterial and antiviral treatment is also necessary or advisable.

The authors of the present invention have found that a gel such as the one described up to now? advantageously it can also be used as a filter against the inhalation of harmful particulates, such as atmospheric particulate, and of viruses and bacteria. In other words, yes? the use of a gel comprising a cross-linked dextran polymer, a gelling polymer and dispersed silver (where the cross-linked dextran polymer has the glucose molecules linearly linked together by glycosidic bond? 1-> 6, cross-linked by glycosidic bonds has been found advantageous) ? 1-> 4,? 1-> 2 or? 1-> 3 and one or more ionic functional groups) in order to purify an air flow from harmful substances, from a viral load and from a bacterial load.

In addition to the effect due to the dispersion of silver in the gel combined with the presence of cross-linked dextran polymers and ionic functional groups, it is observed that the aforementioned gel allows the adsorption of particles, not only from physical impact on the gel itself, but also due to the electrostatic interaction due to the diethyl-2-hydroxypropylaminoethyl functional group which makes the gel a strong anion exchanger. A strong or weak exchanger depends on the pK of the substituent: a strong exchanger has a very high pK for acids, so that? remains ionized in a wide pH range, in this case between 2 and 12 units? of pH.

Typically Sephadex QAE? it is prepared in the form of polyvinyl alcohol hydrogel (PVA, about 2%), also harmless and biocompatible, which, possibly, can? be cross-linked by means of a chemical agent, borax, or more? properly sodium tetraborate decahydrate (Na2B4O7 * 10H2O). The latter ? a natural compound that covers a wide variety? of uses. The absolute compound itself, like most chemical compounds,? toxic and therefore how all chemical compounds? the quantity? who uses it that determines the degree of danger ?. In this case the concentration of borax, which anyway not? in its absolute form but? chemically bonded,? less than 0.3%.

The quantities of the indicated components that make up the gel are indicative and may vary over the period of the unit? percentage, the remaining? completely made up of distilled water greater than 97%. The gel? therefore almost? harmless as it consists almost entirely of water.

The gel is prepared starting from a 4% solution of PVA prepared by heat, about 90 ° C, in which the Sephadex QAE is subsequently added which needs 48 hours at room temperature or 2 hours at 90 ° C to swell; the solution is then allowed to cool.

A second solution of borax is prepared again at 4%, at room temperature or hot to facilitate its dissolution, which is diluted with distilled water enough for the desired dilution of the gel. The two solutions are then stirred and mixed together at room temperature, obtaining the formation of the gel phase.

Additives can be added to the gel according to the present invention to improve even more. the properties you want. By way of non-limiting example, activated carbons, zeolites, beta-glucan, panthenol, lactic acid and propolis can be mentioned.

The authors of the present invention have discovered that the gel described up to now? particularly suitable for use in a nasal filter device comprising:

? a containment body provided with an intake opening and a delivery opening for the flow of air passing through it;

? one or more? airtight bulkheads, arranged inside the containment body and shaped to force the air flow to collide with the bulkheads and with the internal walls of the containment body, the bulkheads identifying a path free of obstacles for the air flow between the supply opening and the delivery opening,

This device is therefore characterized by the fact that it comprises a gel according to what has been said so far, arranged at least on the bulkheads so that the particulate matter, the viral content and the bacterial content present in the air flow, colliding against the gel, is retained and / or otherwise inhibited or destroyed.

In addition to the antibacterial and antiviral function, the device? able to reduce, for a certain number of hours, the exposure to PM10 or more? small up to 0.1? m. In this case, the operating principle consists in the elimination, or in any case inhibition, of the bacterial and viral load as well as? in the capture of the airborne particulate that crosses the cavity? nasal as a result of the respiratory act.

The filtration of the bacterial and viral load occurs by polarization of the dispersed silver which provides and eliminates these viruses and bacteria.

Particulate filtration takes place both by mechanical impact and by an electrostatic process capable of absorbing and incorporating solid particles in a fixed stationary phase placed inside the device. In one possible configuration, the device? made of medical PVC with additives included in the Italian Ministerial Decree of 21 March 1973 and subsequent updates, corresponding to the European Regulation 2008/39 EEC, biocompatible, very soft. The device consists of a container having a helical wall inside with the purpose of increasing the active internal surface of the device by maximizing the maximum amount of the device. contact with breathed air is possible. The gel according to the present invention is spread on the internal surface of the device, capable, thanks to its electrostatic charge and its viscosity, to attract and trap both the chemical agents in the form of airborne particles and the viruses and bacteria transported. The gel according to the present invention? in fact characterized by a? high viscosity? and ? been selected for its property? of strong anion exchanger. This principle can? be extended to different types of applications which involve a flow of air through a labyrinth system that puts the atmospheric particulate in contact with the gel.

Furthermore, the authors of the present invention have found that electrostatically charged crosslinked dextran polymers, such as QAE Sephadex?, Can be advantageously used as a filter for the solid fraction of airborne tar. Therefore, these compounds can be used in the preparation of cigarette filters capable of drastically reducing the percentage of inhaled tar as well as neutralizing viruses and bacteria present in the air. According to one embodiment, the Sephadex QAE gel? and PVA described above, possibly in the presence of adsorbent additives such as activated carbons or zeolites, can? be used to soak the fibers for the preparation of cigarette filters, such as for example cellulose acetate fibers. Is the gel allowed to dry leaving the Sephadex QAE? adhered to the fibers.

Among the electrostatically charged crosslinked dextran polymers we can mention QAE Sephadex ?, DEAE Sephadex ?, CM Sephasex? and the SP Sephadex? which, as the different prefix suggests, have different substituent groups, which are respectively diethyl-2-hydroxypropylaminoethyl (QAE), a diethylaminoethyl (DEAE), a carboxymethyl group (CM) and a sulfopropyl group (SP) which differ between them for their power in terms of ion exchangers. The Spehadex DEAE? ? a weak anion exchanger that works in a pH range between 2 and 9; while the CM Sephadex? ? a weak cation exchanger that works in the pH range between 6 and 10; finally the SP Spehadex? ? a strong cation exchanger that works in the pH range between 2 and 12.

The gelling polymer can? be diluted using the colloid containing the dispersed silver or distilled water if the silver is deposited on microparticles and then dispersed in the gel. The same polymer can? be selected from the group consisting of polyvinyl alcohol, agar agar, silicones, polyacrylamide, preferably polyvinyl alcohol. In general, hydrogels are formed by polymer chains dispersed in water whose content of aqueous medium can? exceed 99%. Various natural compounds such as agar agar and various saccharide molecules, but also artificial compounds such as silicones and polyacrylamide can form hydrogels. Was the choice of Sephadex QAE and PVA dictated by necessity? of biocompatibility. If you foresee the use of the gel in a filtration process that does not involve direct contact with the human organism, you can? think of a different formulation by considering other polymers and copolymers.

The gel, in addition to comprising the electrostatically charged cross-linked dextran polymer can? further understand sodium tetraborate decahydrate.

The present invention will come now described for illustrative but not limitative purposes, according to its preferred embodiments.

Examples

Example 1: Preparation of the gel of QAE Sephadex, PVA and sodium tetraborate

Preparation of the solutions for about 2.5 kg of gel

Preparation of the PVA solution

Prepare a colloid in which silver particles of approximate size between 50 and 200 nm are dispersed in distilled water.

Dissolve 40g of PVA in a 960ml of this colloid; this operation can? be carried out in two ways: (1) bringing PVA and colloid to 90 ° C for at least 8h avoiding boiling the solution, without mixing; (2) actively mixing PVA and colloid at temperatures below 90 °, for the time necessary to obtain complete dissolution of the PVA, which should not be visible to the naked eye.

Allow to cool to room temperature.

Addition of Sephadex QAE

Add 5g of QAE Sephadex powder to the PVA solution for 48 hours at room temperature for 2 hours at 90 ° C.

Preparation of the sodium tetraborate solution

Dissolve 9.6g of decahydrated sodium tetraborate in 240ml of hot distilled water (eg 90? C) to facilitate the formation of the solution until? does not become transparent and allow to cool.

Dilute the sodium tetraborate solution with 1320ml of distilled water and shake.

Formation of the hydrogel

Slowly add the Sephadex PVA and QAE solution to the sodium tetraborate solution while stirring with a glass rod until gel is formed, i.e. you do not have more? phase separation between gel and aqueous phase.

The gel should be stored in an airtight container, with a layer of distilled water on top to prevent it from drying out.

Example 2: Preparation of the gel of QAE Sephadex, PVA and sodium tetraborate in the presence of additives

Preparation of the solutions for about 2.5 kg of gel

Preparation of the PVA solution

Dissolve 40g of PVA in 960ml of distilled water at 90 ° C for at least 8h avoiding boiling the solution. Alternatively, actively mix PVA and distilled water at temperatures below 90 ° C, for the time necessary to obtain complete dissolution of the PVA, which should not be visible to the naked eye.

Allow to cool to room temperature.

Addition of Sephadex QAE

Add 5g of QAE Sephadex powder to the PVA solution for 48 hours at room temperature for 2 hours at 90 ° C.

Preparation of the sodium tetraborate solution

Dissolve 9.6g of decahydrated sodium tetraborate in 240ml of hot distilled water (eg 90? C) to facilitate the formation of the solution until? does not become transparent and allow to cool. Dilute the sodium tetraborate solution with 1320ml of distilled water and shake.

Adding additives (alternatively)

? Add 50g of fine additive powder (activated carbon and / or zeolite) to the sodium tetraborate solution at room temperature and shake.

? At room temperature, add granules of inert material (for example PFE or Hydroxyapatite), with a particle size indicatively between tens and hundreds of microns, on the surface of which have previously been deposited and made firmly adhered to the nuclei of metallic silver, of indicative size between a few tens and a few hundreds of nanometers.

Formation of the hydrogel

Slowly add the Sephadex PVA and QAE solution to the sodium tetraborate solution while stirring with a glass rod until gel is formed, i.e. you do not have more? phase separation between gel and aqueous phase. The gel should be stored in an airtight container, with a layer of distilled water on top to prevent it from drying out.

Claims (10)

Patent Application for Industrial Invention under: ? A GEL? CLAIMS 1. A gel comprising a cross-linked dextran polymer and a gelling polymer, said cross-linked dextran polymer having the glucose molecules linearly linked together by glycosidic bond? 1-> 6, cross-linked by glycosidic bonds? 1-> 4,? 1 -> 2 or? 1-> 3 and having one or more? ionic functional groups, said gel also including dispersed silver. 2. Gel according to claim 1, wherein said silver dispersed? in a quantity comprised between 100 ppm and 1000 ppm by weight referred to the total weight of said gel. 3. Gel according to claim 1 or 2, wherein said silver dispersed? dispersed in a colloid with which to synthesize said gel. 4. Gel according to claim 1 or 2, wherein said silver dispersed? deposited by means of stable nanocoating on amorphous particles subsequently dispersed in said gel. 5. A gel according to claim 4, wherein said amorphous particles comprise hydroxyapatite. 6. Gel according to claim 4, wherein said amorphous particles comprise Teflon. 7. Use of a gel according to one or more? of the preceding claims in the preparation of a filter for the purification of an air stream from harmful substances, from a viral load and from a bacterial load. 8. Use according to claim 7, wherein the filter? a nasal filter. 9. Use of a gel according to one or more? of claims 1 to 6 as a medical device for the treatment of infections or the like. 10. Nasal filter device comprising: ? a containment body provided with an intake opening and a delivery opening for the flow of air passing through it; ? one or more? bulkheads impermeable to air, arranged inside said containment body and shaped to force the flow of air to collide with said bulkheads and with the internal walls of said containment body, said bulkheads identifying a path free of obstacles for the flow of air between said supply opening and said delivery opening, characterized in that it comprises a gel according to any one of claims 1 to 6 arranged at least on said bulkheads so that the particulate, viral content and bacterial content present in the air flow colliding against said gel, penetrates at least partially and comes into it withheld.