WO2012104887A1

WO2012104887A1 - Use of a reticulated dextran polymer as a filter against the inhalation of substances injurious to the health

Info

Publication number: WO2012104887A1
Application number: PCT/IT2012/000037
Authority: WO
Inventors: Paolo Narciso; Enrico IMPERI
Original assignee: Hsd Holding Smart Device S.R.L.
Priority date: 2011-02-04
Filing date: 2012-02-03
Publication date: 2012-08-09
Also published as: ITRM20110051A1; CN103561824A; CN103561824B; IT1404015B1

Abstract

The present invention concerns the use of an electrostatically charged reticulated dextran polymer, as for example QAE Sephadex®, as nasal filter against the inhalation of substances harmful to the health, such as, for example, atmospheric particulate matter, or for the preparation of cigarette filters suitable to lower the percentage of inhaled tar.

Description

Use of a reticulated dextran polymer as a filter against the inhalation of substances injurious to the health The present invention concerns the use of a reticulated dextran polymer as a filter against the inhalation of substances harmful to the health. In particular, the invention concerns the use of an electrostatically charged reticulated dextran polymer, as for example QAE Sephadex^®, as nasal filter against the inhalation of substances harmful to the health, such as, for example, atmospheric particulate matter, or for the preparation of cigarette filters suitable to lower the percentage of inhaled tar.

The exposure to the airborne atmospheric particulate matter in urban atmospheres, represents a risk source both for citizens, for several reasons, and professional workers operating for more or less long periods in the open air. Further cigarette smoke contributes to the problem also and above all for not smoking people in form of passive smoking.

According to base principles for human health, during the last few years various countermeasures as fuel up-grading, high efficiency motors provided with filtering devices suitable to lower exhausted products, ecc. have been implemented.

Nevertheless an increase of respiratory way diseases, resulting from air pollution and, particularly, inhalation of "Atmospheric Particulate Matter", that can be classified according to particle size as PMi₀ , PM_S, PM₂,₅, PMi wherein the numbers represent particle average diameter expressed in micrometers (pm) , occurred. The ultimate action for personal protection following the collective measures, consists of individual protection measures, that is any device that, worn singularly, prevents the penetration into the organism of harmful agents . In the case of Atmospheric Particulate matter where it is necessary respiratory tract, nose and mouth to be protected, mask-like devices are used. Citizen and/or traffic operator worn face masks, although effective, normally are cumbersome and generate stress in the respiratory action, thus the same very rarely by possible users are used.

An ulterior source of substances harmful for organism is represented by cigarette smoke.

Cigarette smoke contains fine particles that can be collected on a buffer filter in laboratory. Thus collected particulate matter, after the extraction of nicotine and water, usually is called "tar" . Lung built-up tar resulting from inhalation of cigarette smoke, is considered the main cause of lung, larynx, oral cavity cancers and respiratory apparatus pathologies like chronic bronchitis, asthma and emphysema .

Disposable filters to be applied to cigarettes or low tar cigarettes in order to lower the tar inhalation, are known. However, new systems that, in addition to lower the percentage of inhaled tar, do not display problems as to cost, cigarette production process and can meet consumer requirements are under investigation.

In the light of above it is therefore apparent the to need to provide for new means suitable to lower the inhalation of body harmful substances both from atmosphere and cigarettes .

Sephadex^® is a reticulated dextran polysaccharide wherein glucose molecules are linearly linked by a l->6 glycosidic bonds, while the reticulation results from a l->4, sometimes also a l->2 and a l->3 glycosidic bonds. In particular, as to QAE Sephadex^®, QAE prefix means that glucose molecules are functionalized with diethyl- (2 -hydroxypropyl) aminoethyl quaternary amine group. The figure below shows an example on how molecules ca be linked in QAE Sephadex^® polymer

wherein R is said diethyl- (2 -hydroxypropyl) aminoethyl group .

Above said polymers generally are employed in laboratory in column chromatography for molecules separation.

The authors of the present invention now have found that a gel based on electrostatically charged reticulated dextran polymers, as QAE Sephadex^®, can be advantageously used as filter against inhalation of substances harmful to the health as for example atmospheric particulate matter or cigarette tar.

The particulate matter adsorption, in addition to physical impact on said gel, results also from electrostatic interaction due to diethyl- (2- hydroxypropyl) aminoethyl functional group making the gel a strong anion exchanger. Whether an ion exchanger is strong or weak depends on R substituent pK: a strong exchanger has very high pK for acids, so that it remains ionized in a wide pH range, in this case from 2 to 12 pH units.

Particularly, in order to be used as nasal filter, QAE Sephadex^® is prepared in form of polyvinyl alcohol hydrogel (PVA, about 2%) , also innocuous and biocompatible, that, possibly can be reticulated using a chemical agent, borax, or more correctly sodium tetraborate decahydrate (Na₂B₄O7*10H₂O) . The latter is a naturally occurring compound covering a large number of uses. Neat or absolute compound as such, like the most chemical compounds, is toxic and therefore as for all the chemical compounds the dangerousness degree thereof results from used amounts . In this case the borax concentration, that however is not in absolute form but chemically bound, is lower than 0.3%.

The amounts of gel forming indicated components are just indicative . and can vary within an unit percentage, balance consisting of > 97% distilled water. Therefore said gel is practically innocuous as it consists almost totally of water.

Said gel is prepared from hot, i.e. approximately 90 °C, prepared 4% PVA solution, to which QAE Sephadex is added, then said product is swollen standing at room temp, for 48 hours or at 90 °C for 2 hours; the solution subsequently is allowed to cool.

A second, again 4%, borax aqueous solution, is prepared at room or higher temp, in order to facilitate the dissolution, which is diluted with distilled water enough for desired dilution. Said two solutions are stirred and mixed at room temperature, resulting in the formation of gel phase.

Additives can be added to gel according to the presents invention, in order to improve the filtering properties or confer fungicide, bactericide or antiviral properties.

Among said additives active carbons, zeolite, beta-glucan, panthenol, lactic acid and propolis can be mentioned.

Active carbons is a large class of carbon based, amorphous materials, with high specific surface area (m²/g) resulting from elevated porosity thereof, thus conferring a spatial geometry determining adsorption properties. It is possible to disperse, at variable concentration, plant origin, as firewood birch carbon, active carbons in gel medium in order adsorbing properties also to be conferred.

Analogously to active carbons another common adsorbing material are zeolites, minerals having a regular and microporous crystalline structure characterized by very large amounts of empty volumes inside of crystals. These minerals display aluminosilicate based structural framework made up of tunnel or cage cavity entrapped cations. Since the cages display crystal symmetry, zeolites represent a class of molecular sieves with greater selectivity than active carbons, the latter displaying irregular cavities. Due to elevated selectivity towards a single chemical substance, unless a well identified target to be intercepted occurs, it is advantageous the use of active carbons, which, although slightly less efficient in terms of adsorption, display a capture activity towards a many types of compounds as above reported.

Beta-glucan is a fibrous, yeast derived, naturally occurring product that does not display side-effects, it is suitable to stimulate autoimmune system and does not cause allergic reactions. It is a plant origin polysaccharide based on a backbone consisting of glucose molecules with few inter- and intra-branches and in the form of B- (1, 3) - (1, 6) -D-Glucan it is an immuno-modulator enhancing the immunity system through the activation of a particular type of white blood cells, i.e. macrophages. In addition, beta-glucan is an anti-oxidant agent suitable to act as free radical scavenger .

Panthenol is pantothenic acid (B5 vitamin) analogous alcohol, it is a transparent water soluble at room temp, viscous liquid. It is an hydrating agent reducing and alleviating possible skin inflammation and irritations particularly suitable for mucosal protection. Viscous nature thereof can help to be a co- adjuvant for capture of PM10 or larger than 0.1 μπι size atmospheric particulate matter along with Sephadex base activity. In the event of contact with nasal walls, it displays, as previously described, both a protective and biologically active action, in fact it naturally occurs as enantiomer, that is two molecules (D and L) having same atoms but with a different spatial disposition with respect a single carbon atom exist, such that said molecules are a mirror image of each other. Specifically it is D-panthenol (dexphantenol) displaying biological activity.

Lactic acid is a yellow viscous colourless/yellowish liquid compound, the chemical not trivial name thereof being 2 -hydroxy propanoic acid, C₃H₆0₃, it plays an important role in many biochemical processes, generally known as being substance conferring characteristic bitter taste to aged milk, but it is also a by-product of muscle anaerobic activity. Not generally known, but of remarkable importance, is antibacterial activity thereof, that, in association to viscosity, can cooperate also with Sephadex for filtration activity of PM10 or larger than 0.1 μιτι size particulate matter. It is water soluble, therein polymerizes spontaneously, conferring therefore further stability to the gel.

Propolis is a resinous substance collected by bees from plant cortex and further treated by addition of wax, pollens and enzymes. It consists essentially of a mixture of aromatic and phenolic compounds with the addition of several different substances (fatty acids, terpenes, amino acids, vitamins, mineral salts, etc), the percentage distribution being very variable depending on seasons, vegetation type. It displays therapeutic, fungicide, bactericide and antiviral properties.

Gel according to the invention is particularly suitable to be used . for device described in O2008/139499 due to ability thereof in filtering harmful substances. The device is suitable to reduce, over a determined number of hours, the exposure to PM10 or larger than 0.1 μτη size particulate matter. The operation principle is based on capture of the airborne particulate matter crossing nasal cavity as a result of respiratory activity. The particulate matter filtration occurs as result of both a mechanical impact and an electrostatic process suitable to absorb and incorporate the solid particles in a stationary phase within the device. According to a possible configuration, the device is made of very soft, biocompatible, medical grade PVC along with additives as reported according to Decreto Ministeriale Italiano on 21 March 1973 and successive updating, corresponding to European Standard EEC 2008/39. Said device consists of a pair of truncated cones that are bridge-linked thus preventing excessive insertion and allowing easy- removal to be carried out . Each truncated cone surrounds a conical helix, made of the same material, in order to increase active internal surface of device, thus maximizing contact thereof with breathed air. On the internal surface of device the biogel according to the presents invention is spread, suitable, due to electrostatic charge and viscosity thereof, to attract and trap chemical agents in the form of airborne particles. Biogel according to the present invention in fact is characterized by high viscosity and has been selected due to strong anion exchanger properties thereof. This principle can be extended to various types of applications involving air flow through a labyrinthine system contacting the atmospheric particulate matter with biogel.

Moreover, the authors of the present invention have found that electrostatically charged reticulated dextran polymers, as QAE Sephadex^®, can be advantageously used as filter for solid airborne tar fraction. Therefore, these compounds can be employed for the preparation of cigarette filters suitable to drastically lower the percentage of inhaled tar. According an embodiment thereof, above described QAE Sephadex^® and PVA gel, possibly in the presence of adsorbing additives like active carbons or zeolite, can be used to imbibe fibres for the preparation of cigarette filters, as for example cellulose acetate fibres. The gel is allowed to dry leaving QAE Sephadex^® adhered on fibres.

It is therefore a specific object of the present invention the use of gel comprising or consisting of reticulated dextran polymer and gelling polymer for the preparation of filter against the inhalation of harmful substances, said polymer of reticulated dextran having glucose molecules each other linked by a l->6 glycosidic bonds, reticulated by a l->4, al->2 or l->3 glycosidic bonds and having one or more ionic functional groups as for example diethyl- (2- hydroxypropyl ) aminoethyl , diethylaminoethyl , carboxy methyl or sulfopropyl, preferably diethyl- (2- hydroxypropyl) aminoethyl .

Among electrostatically charged reticulated dextran polymers, QAE Sephadex^®, DEAE Sephadex^®, CM Sephasex^® and SP Sephadex^® can be mentioned, that, as the different prefix suggests, have different substituent groups, i.e diethyl- (2 -hydroxypropyl) aminoethyl (QAE) , diethylaminoethyl (DEAE) , carboxy methyl (CM) or sulfopropyl (SP) groups, respectively, differing for ion exchanger capacity. DEAE Spehadex^® is weak anion exchanger operating at 2 to 9 pH range; while CM Sephadex^® is weak cation exchanger operating at 6 to 10 pH range; finally SP Spehadex^® is strong cation exchanger operating at 2 to 12 pH range.

Said gelling polymer can be selected from the group consisting of polyvinyl alcohol, agar agar, silicones, polyacrylamide, preferably polyvinyl alcohol. Generally hydrogels consist of water dispersed polymer chains characterized in that aqueous medium content thereof can exceed 99%. Various naturally occurring compounds as agar agar and different saccharide molecules and also artificial compounds as silicones and polyacrylamide can form hydrogels . The choice of said QAE Sephadex and PVA has been suggested by the biocompatibility needs. If it is envisaged the use of gel for a filtration process not involving direct contact with human body, a different formulation taking into consideration other polymers and co-polymers can be considered.

Said gel, in addition to incorporate electrostatically charged reticulated dextran polymer, can further comprise sodium tetraborate decahydrate.

Moreover, the gel to be used according to the invention further can comprise additives selected from the group consisting of adsorbents, as for example active carbons and zeolite, beta-glucan, panthenol, lactic acid, propolis.

Said gel incorporating filter can be a nasal or cigarette filter. Preferably cigarette filter comprises the gel of above mentioned electrostatically charged reticulated dextran polymer, PVA and adsorbents as active carbons and/or zeolite.

Harmful substance means, by an exemplification way, atmospheric particulate matter, tar, for example cigarette released tar.

It is a further object of the present invention a cigarette having a filter comprising above defined gel.

In addition the present invention comprises a fibre for the preparation of cigarette filters impregnated or coated with therein or thereon dried above defined gel.

The present invention concerns moreover a nasal filtering device or disposable cigarette filter comprising above defined gel. The present invention now will be described by an illustrative, but not restrictive way, according to preferred embodiments thereof .

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

Preparation of solutions for approximately 2, 5 kg of gel

Preparation of PVA solution

Dissolve 40g of PVA in 960ml of distilled water, at 90°C over at least 8h avoiding the solution from boiling. Allow to cool at room temp.

Addition of QAE Sephadex

Add to PVA solution 5g of QAE Sephadex powder over 48 hours at room temp or 2 hours at 90 °C.

Preparation of sodium tetraborate solution

Dissolve 9,6g of sodium tetraborate decahydrate in 240ml of hot distilled water (for example 90°C) in order to facilitate the dissolution and stir until the solution does not become clear and allow to cool.

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

Hydrogel formation

Slowly add PVA and QAE Sephadex solution to sodium tetraborate solution under stirring with a glass rod until the gel formation, that is until gel phase and aqueous phase are no longer separated.

The gel must be stored in airtight container, covered with a layer of distilled water in order drying to be avoided.

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

Preparation of solutions for approximately 2,5 kg of gel Preparation of PVA solution

Addition of QAE Sephadex

Preparation of sodium tetraborate solution

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

Additive addition

Add at room temp. 50g of finely powdered additives (active carbons and/or zeolite) to sodium tetraborate solution and stir.

Hydrogel formation

Claims

1) Use of gel comprising or consisting of reticulated dextran polymer and gelling polymer for the preparation of filter against inhalation of harmful substances, said polymer of reticulated dextran having glucose molecules each other linearly linked by a l->6 glycosidic bonds, reticulated by a l->4, al->2 or al->3 glycosidic bonds and having one or more ionic functional groups.

2) Use according to claim 1, wherein said ionic functional groups are selected from the group consisting of diethyl- (2 -hydroxypropyl) aminoethyl, diethylaminoethyl, carboxy methyl or sulfopropyl, preferably diethyl- (2 -hydroxypropyl) aminoethyl .

3) Use according to claim 1, wherein the gelling polymer is selected from the group consisting of polyvinyl alcohol, agar agar, silicones, polyacrilamide, preferably polyvinyl alcohol.

4) Use according to anyone of previous claims, wherein the gel further comprises sodium tetraborate decahydrate .

5) Use according to anyone of claims 1-4, wherein the gel further comprises additives selected from the group consisting of adsorbents, beta-glucan, panthenol, lactic acid, propolis.

6) Use according to claim 5, wherein the adsorbents are selected from active carbons, zeolite.

7) Use according to anyone of previous claims wherein the filter is a nasal filter or a cigarette filter.

8) Use according to anyone of previous claims wherein the harmful substances are selected from atmospheric particulate matter, tar.

9) Cigarette having a filter comprising the gel as defined in anyone of claims 1-6.

10) Fibre for the preparation of cigarette filters coated or impregnated with dried gel as defined in anyone of claims 1-6.

11) Nasal filtering device or disposable cigarette filter comprising the gel as defined in anyone of claims 1-6.