Patent Description:
The usefulness of drug delivery systems and the distribution and emission of essential oils through cellulosic substrates, in the most diverse applications of, for example, antimicrobial and antioxidant action, should not be neglected [<NUM>], as evidenced by some previous studies. Among these systems, we have protective food packaging produced by coating paper with paraffin and cinnamon essential oil [<NUM>], a sheet of paper coated with a grapefruit seed extract rich in polyphenols [<NUM>] and the grafting of eugenol onto paper, while a polycarboxylic acid promotes crosslinking between cellulose chains [<NUM>], to name a few examples. A more recent work proposes antimicrobial wrapping paper with an essential oil of dill [<NUM>].

Active compounds in essential oils range from small molecules, such as monoterpenes and low molecular weight (MW) aldehydes [<NUM>], to non-volatile entities, including triterpenes, sterols, and polyphenols [<NUM>]. For example, eucalyptus essential oils are characterized by having terpenes and terpenoids in abundance. Of these, high MW compounds prevail in wood [<NUM>], while leaves mainly host low MW (<<NUM>/mol) compounds [<NUM>]. A major disadvantage of adding monoterpene compounds to paper by simple addition, either during sheet formation or as a coating component, is their tendency to evaporate along with water.

There is, for example, in the context of incorporating essential oils into cellulose and into water itself, as in <CIT> [<NUM>], the solution of adding the essential oil or bacterial agent directly to the pulp mixture; and the immersion of the paper in the essential oil itself, as in <CIT> [<NUM>]. However, the stability of papers with extracts and essential oils over time is, generally, not indicated.

The patent application <CIT> [<NUM>] describes a process for coating paper, in which the aqueous coating consists of a starch modified through its reaction with an enzyme from the group of cyclodextrin glycosyl transferases, and which aims to make the surface of a paper sufficiently smooth and resistant.

Patent application <CIT> [<NUM>] also describes this type of enzymes for the modification of starch and their application in paper production to increase the retention of starch and thus, consequently, the strength of the paper incorporating it.

Patent application <CIT> describes methods of immobilizing uncomplexed cyclodextrins and complexed cyclodextrins to polysaccharide containing substrates, such as cellulose fibers. The cyclodextrins in <CIT> are said to be immobilized by covalently bonding the cyclodextrin to the substrate, without having to first derivatize or otherwise modify the cyclodextrin.

Patent application <CIT> depicts a weaving modified starch size technology, specially a kind of immobilized starch of alpha-cyclodextrin and preparation method thereof, where the material quality of the starch forms specific numbers of cornstarch, alpha-cyclodextrin, malic acid, sodium hypophosphite and deionized water.

There is thus a need for a method for coating cellulosic materials with essential oils to ensure the retardation of evaporation of these essential oils and other components of interest depending on their application, thereby ensuring their use for a longer time during the distribution and emission of essential oils in the most diverse applications such as, for example, antimicrobial and antioxidant action.

These applications find value at least in the following fields: public or private healthcare systems, including antiseptic printing papers, antiseptic posters for hospitals and antiseptic fibres for gowns; the food industry, in the context of containers with prolonged emission of natural active compounds; the pharmaceutical industry, e.g. to provide additional protection for pill boxes; and the paper and textile industries, to produce and supply the materials required in the mentioned applications.

The present invention relates to a method for coating cellulosic material comprising the following steps:.

According to a preferred embodiment, step a) comprises the following steps:.

According to a preferred embodiment, the polycarboxylic acid is a <NUM>,<NUM>,<NUM>,<NUM>-Butanetetracarboxylic acid.

According to a preferred embodiment, the cyclodextrin is selected from the group consisting of alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-alpha-cyclodextrin, hydroxypropyl-beta-cyclodextrin, hydroxypropyl-gamma-cyclodextrin, methyl-alpha-cyclodextrin, methyl-beta-cyclodextrin, methyl-gamma-cyclodextrin, acetyl-alpha-cyclodextrin, acetyl-beta-cyclodextrin, acetyl-gamma-cyclodextrin, succinyl-alpha-cyclodextrin, succinyl-beta-cyclodextrin, succinyl-gamma-cyclodextrin and <NUM>-beta-cyclodextrin sulfobutyl ether.

According to a preferred embodiment, the polycarboxylic acid is <NUM>,<NUM>,<NUM>,<NUM>- acid tetracarboxylic butane.

According to a preferred embodiment, the cellulosic material is a paper product.

According to a preferred embodiment, the cellulosic material is a textile material.

According to a preferred embodiment, the essential oil is selected from the group consisting of essential oils of wood, leaves, and fruits of plants.

According to a preferred embodiment, the coating medium consists of a roller coating.

According to a preferred embodiment, the mean for coating a surface of a cellulosic material consists of dipping the cellulosic material in an aqueous dispersion of the coating formulation.

The approach of the present invention involves the use of cyclodextrins to prolong the ability of cellulosic material to emit volatile active compounds in time.

A cyclodextrin is any cyclic oligosaccharide, composed of anhydroglucose units joined by α-<NUM>,<NUM>-type bonds, and with their functional groups oriented such that it has a hydrophobic cavity and a hydrophilic exterior. The most common compounds in this family are, but not limited to, alpha-cyclodextrin, with <NUM> anhydroglucose units; beta-cyclodextrin, with <NUM> units; the gamma-cyclodextrin, with <NUM> units, and the respective cyclodextrins functionalized with the hydroxypropyl group, that is, hydroxypropyl-alpha-cyclodextrin, hydroxypropyl-beta-cyclodextrin, hydroxypropyl-gamma-cyclodextrin, functionalized with the methyl group, that is, methyl-beta-cyclodextrin, methyl-gamma-cyclodextrin, functionalized with the acetyl group, i.e. acetyl-alpha-cyclodextrin, acetyl-beta-cyclodextrin, acetyl-gamma-cyclodextrin, and functionalized with the succinyl group, i.e. succinyl-alpha-cyclodextrin, succinyl-beta-cyclodextrin, succinyl-gamma-cyclodextrin.

In the context of the present invention, native cyclodextrin refers to a cyclodextrin that has not been subjected to chemical modification.

In the context of the present invention, chemical modification refers to the process by which the molecular structure of a starch is modified through a reaction, incorporating cyclodextrins by covalent bonds.

Covalent bond is a region of high electron density between two atomic nuclei, wherein the electron clouds of the interacting atoms overlap. In the context of the present invention, the covalent bonds generated involve, at least, one oxygen atom of a polycarboxylic acid and one carbon atom of a carbohydrate, namely cyclodextrin and/or starch. In the context of the present invention, polycarboxylic acid is an organic compound with more than one carboxyl group, -COOH, such as citric acid, <NUM>,<NUM>,<NUM>,<NUM>-butanetetracarboxylic acid, maleic acid or fumaric acid. In the context of the present invention, starch consists of a polysaccharide of glucose units having alpha-<NUM>,<NUM> and alpha-<NUM>,<NUM> linkages. Modified starch in this invention refers to any starch derivative which contains, by means of covalent linkages, alpha-, beta- or gamma-cyclodextrin structures, such that at least one anhydroglucose unit of the starch is linked to a cross-linking agent which, in turn, is linked to an anhydroglucose unit of the cyclodextrin. Native starch, in turn, refers to starch that has not undergone any chemical modification.

In the context of the present invention, volatile active compound means any organic compound having, at <NUM>, a vapor pressure equal to or greater than <NUM> kPa, and which is commercially appreciated for having antioxidant, antimicrobial, anti-inflammatory, cytotoxic, or other types of activity of health interest, for the preservation of food, or for the preservation of the material itself. In the context of the present invention, macroscopic homogeneity refers to the observation of a single phase with the naked eye, without using any diffractometers, microscopes, spectrophotometers, or other instruments to differentiate between a continuous phase and a dispersed phase, either because dissolution is complete or because the dispersed particles are not appreciable to the naked eye.

In the context of the present invention, cellulosic material includes paper material and textile material.

In the context of the present invention, paper material relates to, for example and not limited to, tissue paper, packaging paper, printing and writing paper or any paper that may have a starch coating.

In the context of the present invention, textile material includes textile-based materials that may include a starch treatment, such as, for example and not limited to, cotton or rayon.

In the context of the present invention, essential oils are liquids, consisting of natural active or aromatic compounds, which are extracted from plant material such as, but not limited to, woods, leaves, and fruits. The essential oils considered in the present invention have at least one volatile active compound.

Means for coating a surface of a cellulosic material, in the context of the present invention, relates to means for applying and evenly distributing coatings to a substrate, whether by bonding press, curtain coating, roller and/or scraper coating, printing, or dipping. Roller coating considers the application of a coating to a substrate by means of one or more rollers of, for example, but not limited to, rubber or steel.

In the context of the present invention, retarding the evaporation of essential oils on the surface of cellulosic materials means preserving, for <NUM> days or more, volatile active compounds which, without modifications to conventional coating processes, would completely evaporate together with water during drying or during the first <NUM> days.

In the context of the present invention, moisture content refers to the amount of water in a solid material, which can be determined gravimetrically, either by means of a thermobalance or by drying in an oven until constant weighting.

The present invention thus relates to a method for coating a cellulosic material comprising the steps of chemically modifying a starch with cyclodextrins, obtaining a modified starch, followed by the step of redispersing this modified starch in water and using the aqueous dispersion in any of the steps of coating a cellulosic material. The method allows protection of volatile active compounds that would otherwise evaporate together with water during drying and by exposure to air of the final product. The described method allows the retardation of the evaporation of essential oils on the surface of cellulosic materials.

The modified starch was synthesized by cross-linking, via ester linkages, in one or two steps. In one form of realization of the invention, a starch was mixed with beta-cyclodextrin, <NUM>,<NUM>,<NUM>,<NUM>-butanetetracarboxylic acid and in contact with the sodium hyposulfite catalyst in an aqueous medium at <NUM>-<NUM>. After observation of macroscopic homogeneity, most of the water was evaporated until the mixture showed a moisture content <<NUM>%, either by being dried at room temperature for more than <NUM> or by being heated. The solid was then placed in an oven at <NUM> - <NUM> for <NUM>-<NUM>. Washes were carried out with a mixture of water and alcohol until it was possible to isolate the modified starch. This form of surface modification of the starch is called one-step cross-linking.

In an experimental option, a cyclodextrin ester was previously obtained. In the two-step cross-linking, cyclodextrin was mixed with <NUM>,<NUM>,<NUM>,<NUM>-butanetetracarboxylic acid (BTCA) and in contact with the catalyst sodium hypophosphite in an aqueous medium at <NUM>-<NUM>. After observation of complete dissolution, most of the water was evaporated until the mixture had a moisture content of less than <NUM>%, either by being dried at room temperature for more than <NUM> or by being heated. The solid was then placed in an oven at temperatures between <NUM> and <NUM> for <NUM> to <NUM>. The product, named cyclodextrin ester, was isolated by dissolving it in water, by rejecting the insoluble part, and by subsequent precipitation with an alcohol. In a second step, a starch was mixed with the cyclodextrin ester and in contact with the sodium hyposulphite catalyst in aqueous medium at temperatures from <NUM> to <NUM>. After observation of macroscopic homogeneity, most of the water was evaporated. The solid was then placed in an oven at <NUM>-<NUM> for <NUM>-<NUM>. Washes with a water-alcohol mixture succeeded in isolating the modified starch obtained by two-step cross-linking.

The substitution of the main starch derivatives with cyclodextrin is shown quantified in Table <NUM>. The gravimetric method is based on the difference in weight of the native starch and the modified starch. The spectrophotometric method is based on the absorption of phenolphthalein, which forms a <NUM>:<NUM> complex with beta-cyclodextrin.

Proton nuclear magnetic resonance spectra are shown in <FIG> for beta-cyclodextrin, polycarboxylic acid and for the cyclodextrin ester. They allow to calculate the average degree of substitution of the cyclodextrin ester, which, in the case of having carried out the first esterification at <NUM> for <NUM> and the second esterification at <NUM> for <NUM>, is <NUM>,<NUM>±<NUM>,<NUM>.

Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) are shown in <FIG> for native and modified starch. The most relevant absorption bands, due to the elongation of a carbon-oxygen double bond that is not in the native starch, are marked. This figure also shows the condensed structures of the substituted starch monomer. An example of an ester bond, with an absorption band at <NUM>-<NUM>, is marked with a star. An example of a free carboxyl group, with an absorption band at <NUM>-<NUM>, is marked with a ring.

As the modified starch has a higher molecular weight than the starting starch, in one embodiment of the invention, this was compensated for by prior hydrolysis. Prior to the cross-linking reaction, the molecular weight of the polymer to be modified should be lower than the molecular weight of the polymer commonly used for paper coating. The modified starch was redispersed in water under strong stirring and was heated to <NUM>-<NUM>. After <NUM>-<NUM>, and upon observation of macroscopic homogeneity, it was allowed to cool to <NUM>-<NUM> without stopping the stirring. <NUM>,<NUM>-<NUM>,<NUM> of an essential oil was added, and the suspension continued under stirring until macroscopic homogeneity was again observed.

In one experimental option, the modified starch together with the essential oil, thus constituting the coating formulation, was placed on the paper by coating with one or two rolls. In an experimental option, the modified starch and essential oil were placed on the paper by dipping it in an aqueous dispersion of modified starch and essential oil.

Table <NUM> shows the surface and optical properties of the paper coated by this method, with and without essential oil, compared with uncoated paper and the paper coated with unmodified starch. The modified starch did not produce any reduction in whiteness and even good printing properties were maintained. However, the reduction in air permeability or Gurley porosity as well as the reduction in roughness from the base paper were slightly less than using native starch. Anyway, in formulations containing essential oil, the differences between starch and modified starch are minor in the case of permeability or not significant in the case of roughness.

The substitution of native starch by modified starch had no significant effects on the printing quality using inkjet printers, as can be observed in <FIG>. The gamut area values were similar and correspond, in both cases, to a good color fixation.

The volatile active compounds of the essential oils which were incorporated into the paper by coating were eventually released into the air, under the usual conditions of ambient temperature and humidity, either in the case of a conventional starch coating or in the case of the coating with the modified starch which is described in this invention. The difference is the speed with which these compounds were evaporated, which was lower in the case of the modified starch. Therefore, cellulosic materials coated with formulations consonant with this invention can be used as long-lasting emitters of active compounds, e.g., to ensure food preservation without using sulfites, iron bags or synthetic preservatives.

The permanence of volatile active compounds in the coated paper could be directly evaluated using a gas chromatograph coupled to a mass spectrometry detector (GCMS). The equipment used consisted of: Agilent Technologies 7820A chromatograph; Agilent Technologies <NUM> detector; G43 stationary phase; helium as carrier gas.

An essential oil from eucalyptus wood was used because it contained not only volatile active compounds, but also compounds with a vapor pressure lower than <NUM> kPa at <NUM>. More specifically, this essential oil contained, as determined using the mentioned equipment: α-pinene: <NUM>/g; monoterpenes other than α-pinene: <NUM>/g; monoterpenoids (<NUM>,<NUM>-cineol, α-terpineol and α-terpinyl acetate): <NUM>/g; sesquiterpenes (aromadendrene and others): <NUM>/g; epiglobulol <NUM>/g; globulol: <NUM>/g; β-eudesmol: <NUM>/g; other sesquiterpenoids: <NUM>/g; esters: <NUM>/g; alkanes: <NUM>/g; aromatic hydrocarbons: <NUM>/g.

Papers coated with this essential oil and with different starches, namely the modified starch in the present invention and the native starting starch, were exposed to air for <NUM> to <NUM> days at a temperature of <NUM> and a relative humidity of approximately <NUM>%. The same operation was carried out for papers coated with hydroxytyrosol extracted from olives, evaluating the effects of modified and unmodified starch.

To study the ability of paper with essential oils, and with native and modified starches, to release the bioactive compounds from these oils, the configuration of <FIG> was constructed. Headspace Solid Phase Microextraction (HS-SPME) consists of exposing a SPME fiber consisting of polydimethylsiloane, divinylbenzene and Carboxen® to the vapors released from a sample of paper coated according to Example <NUM> and with native starch. The exposure time to air, at a temperature of <NUM> and a relative humidity of approximately <NUM>%, was <NUM>. The exposure time to the fibre, also at <NUM>, but in a system closed to the transport of matter, was <NUM>. Then, the fibre was inserted in the gas chromatograph, using the same column and configuration used for the determination of the oil composition, as mentioned above.

During the first day of drying, the greatest release of compounds with a tendency to evaporate together with water occurred, namely monoterpenes and monoterpenoids, including <NUM>,<NUM>-cineole. Therefore, as presented in <FIG>, after one day of exposure, the equilibrium of the vapor in contact with the sample was still very rich in volatile active compounds, i.e., of low molecular weight; however, a large part of these compounds was lost in contact with air in the case of native starch.

The hypothesis of protection of volatile active compounds by functionalization of starch with cyclodextrins was confirmed with a liquid-solid extraction using ethanol as solvent. Table <NUM> shows the composition obtained after an extraction with ethanol, containing fluorobenzene at a concentration of <NUM>/mL. In both cases, with native starch and modified starch, high amounts of lower vapor pressure compounds, namely epiglobulol, globulol and aromadendrene, were still present after the week of exposure. However, as shown in Table <NUM>, no low molar mass compounds were detected by GCMS, except α-terpinyl acetate, which was found in very similar proportion in both cases. The chemical modification with cyclodextrins, therefore, allowed to keep significant amounts of <NUM>,<NUM>-cineole, α-pinene and α-terpineol, which are otherwise lost in contact with the atmosphere.

<FIG> refers to the evaluation of the antioxidant capacity, understood in terms of inhibition of the <NUM>,<NUM>-diphenyl-<NUM>-picrylhydrazyl radical (DPPH). In a first step, papers coated according to Example <NUM>, together with papers where native starch was used instead of modified starch, were exposed to air, and out of reach of sunlight or other sources of ultraviolet radiation, at a temperature of <NUM> and a relative humidity of approximately <NUM>%. After <NUM> days of exposure, hydroxytyrosol was extracted from the papers with a mixture of methanol and dichloromethane (MeOH/DCM, <NUM>%, v/v), incubating the samples at <NUM> for <NUM>.

A <NUM>,<NUM> solution of DPPH was prepared in the above-mentioned mixture, MeOH/DCM. <NUM>,<NUM> of this solution was mixed with <NUM>,<NUM>-<NUM>,<NUM> of the extracts in MeOH/DCM. More MeOH/DCM was added until the volume was adjusted to <NUM> and the flask was kept out of light. After <NUM>, the absorbance at <NUM> was calculated using a Shimadzu spectrophotometer, UV-<NUM>. The negative control assay was performed by an identical extraction with MeOH/DCM of the papers coated with native starch and modified starch, but without active compounds. Similarly, hydroxytyrosol itself was evaluated, directly using this compound extracted from the olive (fruit and leaves) instead of the paper extracts.

<FIG> revealed a low IC50 value for the extract used, confirming its strong antioxidant capacity. <FIG> showed that after <NUM> days of exposure to air, papers containing modified starch retained higher antioxidant power than those coated with native starch.

Prior to modification, and to compensate for subsequent cross-linking, the molecular weight of the starch normally used in surface treatments was reduced by hydrolysis with alpha-amylase: <NUM>,<NUM>µL of standard enzyme solution per gram of starch, <NUM>, <NUM>, denaturation with zinc sulphate.

<NUM> beta-cyclodextrin, <NUM> BTCA and <NUM> sodium hypophosphite were mixed in <NUM> of water. Under stirring, it was heated to <NUM>. The solution was poured over a metal container, where it was allowed to dry for <NUM>. Then, the container was inserted into an oven at <NUM> for <NUM>. The resulting solid was redissolved with <NUM> of water; the particles not dissolved at <NUM> were discarded. <NUM> of depolymerized corn starch and <NUM> of sodium hypophosphite were added to the solution. The new suspension was poured over the metal container, where it was allowed to dry for <NUM>. Then, the rack was inserted into an oven at <NUM> for <NUM>. This modified starch was obtained in two-steps and was washed with a mixture of water and ethanol, <NUM>% v/v. This modified starch contained <NUM>,<NUM> mmol of cyclodextrin per gram of polymer.

<NUM>,<NUM> of modified starch was suspended in <NUM>,<NUM> of water at <NUM>. It was heated to <NUM> under vigorous stirring and left at <NUM> for <NUM> or until macroscopic homogeneity was observed, while replenishing water to compensate for evaporation losses. Without stopping stirring, it was allowed to cool down to <NUM> and <NUM>,<NUM> of an essential oil of eucalyptus wood was added. Quickly, the drops of oil became imperceptible to the naked eye and the mixture was apparently homogeneous. The mixture was then used to coat a sheet of paper using a Mathis roller coater at <NUM>/min and under infrared radiation. The coated sheet was dried on a metal plate by means of a thermoventilator at <NUM>-<NUM> for <NUM>. This sheet had a mass gain of <NUM>,<NUM>-<NUM>,<NUM>/m<NUM> compared to the uncoated sheet.

<NUM> of beta-cyclodextrin, <NUM> of BTCA and <NUM> of sodium hypophosphite were mixed in <NUM> of water. Under stirring, it was heated to <NUM>. The solution was poured over a metal container, where it was allowed to dry for <NUM>. Then, the rack was inserted into an oven at <NUM> for <NUM>. The resulting modified starch obtained in one-step was washed with a mixture of water and ethanol, <NUM>% v/v. This modified starch contained <NUM>,<NUM>-<NUM>,<NUM> mmol of cyclodextrin per gram of polymer.

A modified starch suspension was prepared as in the previous example. Instead of essential eucalyptus oil, <NUM>,<NUM> of hydroxytyrosol, a compound with higher antioxidant activity, was added. An uncoated sheet of paper was impregnated in the modified starch and hydroxytyrosol suspension by means of the "KSV Nima Dip Coater" equipment for <NUM>. This sheet had a mass gain of <NUM>-<NUM>/m<NUM> compared to the uncoated sheet.

<NUM> starch, <NUM> beta-cyclodextrin and <NUM> <NUM>,<NUM>,<NUM>,<NUM>-butanetetracarboxylic acid were mixed in <NUM> water and stirred under heating at <NUM>.

The long reaction at high temperature and low pH produced significant hydrolysis of cyclodextrin and starch, resulting in the presence of non-cyclic oligosaccharides, unreacted acid, and a lower viscosity than expected for its consistency. To separate the unwanted compounds, the modified starch was isolated by precipitation, adding <NUM> of ethanol at room temperature (<NUM> to <NUM>), and keeping the suspension, without stirring, at room temperature (<NUM> to <NUM>) for at least <NUM>. The ethanol/water soluble phase was discarded.

Claim 1:
A method for coating cellulosic material comprising the following steps:
a) obtaining a solid modified starch by means of a covalent bond of a starch with a cyclodextrin and a polycarboxylic acid;
b) redispersing the solid modified starch obtained in step a) in water, under agitation and heating at temperatures from <NUM> to <NUM> until the observation of a macroscopic homogeneity of the resulting mixture;
c) cooling the mixture resulting from step b) up to temperatures from <NUM> to <NUM> under continuous agitation;
d) adding <NUM>-<NUM> of an essential oil to the resulting mixture of step c), under agitation until macroscopic homogeneity is observed in the resulting coating formulation and wherein the latter has <NUM> to <NUM> mmol of a cyclodextrin per gram of starch;
e) coating with the coating formulation resulting from step d) through means for coating a surface of a cellulosic material.