JP2010516243A - Tobacco products and their manufacture and use - Google Patents

Abstract

A smokeless oral tobacco product comprises a cyclodextrin or cyclodextrin derivative. Such a product can further comprise a flavourant complexed with the cyclodextrin or derivative thereof. Cyclodextrins or their derivative can be used in smokeless oral tobacco products to complex with molecules which arise or solubilize during use of the product and optionally to also release, e.g., flavour or aroma during use of the product.

Description

  The present invention relates generally to smokeless tobacco, tobacco derivatives or tobacco substitutes incorporating cyclodextrins or cyclodextrin derivatives. More particularly, the present invention relates to smokeless tobacco, tobacco derivatives or tobacco substitutes containing cyclodextrins or cyclodextrin derivatives incorporated or bound to cellulosic materials.

  Cyclodextrins are cyclic oligosaccharides composed of 1,4-α-glucoside monomers. They exist naturally as cyclic α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin consisting of 6, 7 and 8 glucose monomers, respectively. Their respective inner diameters are 0.57, 0.78 and 0.95 nm, all having a torus depth of about 0.78 nm. Due to this annular shape, the opening diameter of the internal cavity becomes non-uniform. The narrower opening exposes primary hydroxyl groups to the surrounding solvent, and the wider opening exposes secondary hydroxyl groups. The presence of these hydroxyl groups makes the outer surface of the toric molecule hydrophilic, but the inside of the ring becomes hydrophobic and can be regarded as a hydrophobic cavity.

  Thus, the inside of the ring incorporates a hydrophobic molecule or hydrophobic chemical moiety, outside which the complex can be solubilized in an aqueous environment. In the liquid phase, hydrophobic molecules or moieties can be used to form strong inclusion complexes with cyclodextrins or cyclodextrin derivatives. For example, the solubility of vanillin in water has been found to be higher when β-cyclodextrin is present in a 1: 1 molecular ratio when compared to when β-cyclodextrin is not present in the solution ( Karathanos et al. Food Chemistry 101, pp 652-658). Furthermore, from analytical measurements it can be concluded that vanillin molecules within the cyclodextrin cavity are protected from oxidation.

  This ability to remain water-soluble when forming inclusion complexes makes cyclodextrins a very interesting subject. The complex can be administered to the area of interest, whether it is a body organ or a component of the product, where its molecules within the cyclodextrin have a variety of factors such as heat, enzyme activity and pH changes. Released by factors. Cyclodextrins are also expected to remove specific molecules, often harmful molecules, chemically or by filtration. In environmental cleanup operations, these substances can be removed from contaminated areas by taking advantage of the ability of cyclodextrins to complex with heavy metals such as cadmium.

  Cyclodextrin derivatives are also widely used. For example, 2-hydroxypropyl-β-cyclodextrin is used to formulate drug complexes that improve the solubility of certain pharmaceutically active compounds in water. One use of cyclodextrin derivatives is to provide a smoking cessation enhancer by forming a complex with nicotine and then incorporating the complex into chewing gum as described in International Publication No. WO 91/09599. It is. Alternatively, the chewing gum can provide a flavor complexed with cyclodextrin. Another use of cyclodextrins and derivatives thereof complexed with flavor particles is their use in smoking products. The use of flavors is common in the tobacco field, a wide variety of flavors are known, and flavors are constantly being developed.

  Traditionally, fragrances have been added to whole tobacco, reconstituted tobacco, cigarettes, cigarette filters or packaging materials, often not only affecting the flavor of the product when in use, Improves the scent of the product in use or the scent felt by people near the product during use. One of the challenges in manufacturing and packaging exhibited by many known perfumes is that they are highly volatile and tend to sublime easily. One solution is to complex the perfume with cyclodextrins. For example, US Pat. No. 5,144,964 proposes a water-soluble molecular inclusion complex of a β-cyclodextrin derivative and a lipophilic organic fragrance compound that can be incorporated into a cigarette paper.

  Despite the known use of cyclodextrins, the requirements sought in the art to further provide improved use of these potent compounds remain unmet.

  Accordingly, it is an object of the present invention to provide a novel product incorporating cyclodextrins or cyclodextrin derivatives, ie a smokeless oral tobacco product.

  It is a further object of the present invention to provide novel products incorporating cyclodextrins or cyclodextrin derivatives complexed with perfumes and provided within smokeless oral tobacco products.

  According to one embodiment of the present invention, a smokeless oral tobacco product comprising at least one of tobacco, tobacco derivatives or tobacco substitutes and a cellulosic material is provided. The cellulosic material includes at least one cyclodextrin or cyclodextrin derivative. Tobacco can be encapsulated in cellulosic packaging. The cellulosic material may be, for example, fibrous, woven or non-woven.

  The cyclodextrin or cyclodextrin derivative may be chemically bonded to the cellulosic material. A spacer group may be disposed between the cellulosic material and the cyclodextrin or cyclodextrin derivative. A complexing agent can be placed in the cavity or on the surface, such as by a chemical bond or otherwise such complexing agent can be placed in the cavity of the cyclodextrin or cyclodextrin derivative. It may be complexed with a cyclodextrin or cyclodextrin derivative to be an optional complexing agent. Examples of complexing agents include fragrances, fragrance adjusting agents, and antibacterial agents.

  The fragrance may comprise a monoterpene fragrance, a monocyclic aromatic fragrance or a polycyclic aromatic fragrance, such as (+)-limonene, (-)-limonene, cinnamaldehyde, cinnamonitrile, eugenol, cis-iso. Eugenol, trans-isoeugenol, eugenyl acetate, eugenol methyl / ethyl esters, trans-anethole, cis-anethole, menthol, isomenthol, neomenthol, (+)-menton, (-)-menton, (+)-citronellal , S (+)-carvone, R (-)-carvone, trans-methyl cinnamate, cis-methyl cinnamate, vanillin, capsaicin, phenylpropanoid, aspartame, chocolate, coffee, pyrazines, salt, γ- Glu-Tyr, γ-Glu-Phe, Ol Examples include nithyl-containing peptides, aromatic aldehydes, aromatic aldehydes derivatized as acetals, and lactones.

  Examples of the scent adjusting agent include maltol, ethyl maltol, cis-jasmon, methyl jasmonate, geraniol, nerol, geranyl esters, neryl esters, (+)-citronellol, (-)-citronellol, citral, (+)- Limonene, (−)-limonene and monoterpenes can be included.

  An example of an antibacterial agent is hinokitol.

  According to another embodiment, cyclodextrins or cyclodextrin derivatives are used in the manufacture of smokeless oral tobacco products including tobacco. Alternatively, cyclodextrins or cyclodextrin derivatives complexed with at least one perfume can be used in the manufacture of smokeless oral tobacco products including tobacco. The product can further include a cellulosic material, in which case the cyclodextrin or cyclodextrin derivative is complexed with the cellulosic material, such as by chemical bonding.

  According to another embodiment, a method of complexing at least one cyclodextrin or cyclodextrin derivative with a substance in a smokeless oral tobacco product or a substance produced with a smokeless oral tobacco product, comprising: Preparing a smokeless oral tobacco product comprising cyclodextrin or a cyclodextrin derivative, contacting the product with moisture to wet the product, and complexing the substance with the cyclodextrin or cyclodextrin derivative. A method of including is provided. Here, the cyclodextrin or cyclodextrin derivative comprises at least one perfume, and the method can further comprise releasing the perfume from the cyclodextrin or cyclodextrin derivative after the contact. Examples of substances to be complexed according to this embodiment include benzo (α) pyrene and cadmium.

As used herein, the term “cellulosic material” refers in whole or in part to natural or synthetic cellulose (C ₆ H ₁₀ O ₅ ) n (ie, a long-chain polymeric polysaccharide carbohydrate consisting of β-glucose). For example, lignocellulose, flax fiber, hardwood pulp, conifer pulp, hemp fiber, esparto fiber, kenaf fiber, jute fiber and sisal fiber. The term also refers to a material consisting, in whole or in part, of a cellulose derivative in which the hydroxyl groups of cellulose have been partially or completely reacted with any suitable entity. Examples of the derivatives include cellulose esters such as cellulose acetate or cellulose triacetate. In addition, the term encompasses a mixture of two or more cellulosic materials as well as materials that have been treated to improve performance or improve appearance, such as by bleaching.

  “Cyclodextrin (s)”, “cyclodextrin derivative” or “CD” means any molecule that falls within the category of naturally occurring or synthetic cyclodextrins. The term also encompasses molecules or portions thereof derived from cyclodextrins or wholly or partially synthesized to closely resemble cyclodextrins. Such cyclodextrins or cyclodextrin derivatives are toroidal chiral structures having a hydrophilic, water-soluble outer surface containing hydroxyl groups and a non-hydrophilic (ie hydrophobic) internal cavity. As used herein, the term cyclodextrin refers to α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin, methyl-substituted cyclodextrin, ethyl-substituted cyclodextrin, alkyl-substituted cyclodextrin with linear or branched alkyl groups, hydroxy It may also refer to an alkyl-substituted cyclodextrin (eg, 2-hydroxypropyl cyclodextrin, anionic cyclodextrin, cationic cyclodextrin, quaternary ammonium cyclodextrin, amphoteric cyclodextrin or mixtures thereof).

  “Flavor” or “perfume” refers to any compound or chemical that can stimulate taste when consumed or when placed in a user's mouth. The stimulus may be in the form of an actual taste stimulus or a (pseudo) form received as a taste stimulus as provided by a scented substance. Examples of flavors include citrus ((+)-limonene, (-)-limonene), fruit (benzaldehyde) aromatic plants and spices (cinnamon may be cinnamaldehyde, the scent of green leaves is cis-3-hexenal The clove may be eugenol or other monoterpene fragrances), peppermint (mint flavor such as menthol, isomenthol, neomenthol, etc.), pepper (S (+)-carvone), dill ( R (-)-carvone), ginger (phenylpropanoid), vanilla (vanillin and other aromatic aldehydes), sweetness (sweeteners such as aspartame), chocolate and coffee (pyrazines), licorice, salt (γ- Glu-Tyr, γ-Glu-Phe, ornithyl-containing peptides), but are not limited thereto. The fragrance | flavor which can obtain a desired flavor may be natural or synthetic | combination, Although the said example can be given, it is not limited to them.

  In order to achieve a flavor sensation (or in addition to a fragrance), the scent modifier compound may be complexed to the cyclodextrin according to the present invention. Examples of fragrance modifiers include maltol, ethyl maltol, cis-jasmon, methyl jasmonate, geraniol, nerol, geranyl esters and neryl esters, (+)-citronellol, (-)-citronellol, citral, (+) -Limonene, (-)-limonene and monoterpene aromatic compounds include, but are not limited to.

  By using a fragrance, not only a product with improved flavor can be provided, but also a product having further advantages over existing products. For example, a flavor reduction that mimics the taste of salt can be used to provide a reduced salt product, and an artificial sweetener can be used to provide a low calorie product.

  In addition to (or instead of) the fragrance, other complexing agents can be provided with the cyclodextrins of the present invention. For example, the use of an antibacterial agent such as hinokitol can prolong the shelf life and / or provide a product that can be suitably stored under less severe conditions. Complexing agents such as anti-refrigerants or preservatives can be used to improve product stability and / or minimize undesirable limits on storage and transport conditions. Thus, the complexing agent used in the present invention provides greater freedom of mixing when using fragrances, buffers, additives and moisture during the manufacture of tobacco or tobacco substitutes.

  Smokeless oral tobacco products belong to the category of tobacco products intended for oral use. Such products are placed in the user's mouth and held for some time, often 5-60 minutes. The product may be actively chewed or may remain in the mouth without being chewed. The user may or may not vomit saliva during use. The tobacco part may contain loose tobacco leaves, or chopped, torn or crushed leaves, and the tobacco is compressed into a plug. Good. Chopped, torn or crushed tobacco may be provided in a mouth insert sachet.

  Thus, the term “smokeless oral tobacco product” is not a tobacco product intended to be burned, but instead is placed in the user's oral cavity for a limited time when contact between the user's saliva and the product occurs. Used herein to mean a designed tobacco product. The term also encompasses traditional products such as Swedish snus and American chewing tobacco as well as products sold today and in the future.

The term “spacer group” or “SG” refers to any of the types of molecules that can be used to create a physical or chemical distance between a cyclodextrin and a cellulosic material. Used in the description. Spacer materials are well known in the art, see for example WO 06/53628. Therefore, the spacer group disposed between the cyclodextrin and the cellulosic material can be represented as a CD-SG-cellulosic material. In this material, SG may be an alkylene having up to 10 carbon atoms, the alkylene may be unsubstituted, mono- or polysubstituted with halogen, or one or more. non-adjacent CH ₂ group, as O and / or S atoms are not linked directly to one another, independently of each other in each case, O, S, NH-NR , CO, COO, OCO, OCO-O, S , CO, CO-S, CH = CH or C≡C. Examples of the spacer substance include (CH ₂ ) _p and (CH ₂ CH ₂ O) _q (wherein p is an integer of 2 to 6 and q is an integer of 1 to 3). In some embodiments, the spacer group may be an imidazolidone moiety or (CH ₂ ) _r or (CH ₂ O) _{r where} r is an integer from 1 to 5.

  As used herein, “tobacco, tobacco derivatives or tobacco substitutes” include pure tobacco and recycled tobacco. This term refers to a specific compound, whether extracted from or produced in actual tobacco, such as tobacco derivatives such as nicotine, and structural parts such as the fibrous portion of tobacco leaves. Including various derivatives. Tobacco substitutes can include individual chemicals as well as complex chemical solutions that, when properly adjusted, physically resemble actual tobacco.

  Unless otherwise noted, all materials and equipment are standard products that are commercially available.

  As mentioned above, the present invention relates to smokeless oral tobacco products incorporating at least one cyclodextrin or cyclodextrin derivative. Smokeless oral tobacco products, particularly smokeless oral tobacco products including natural tobacco, contain or release compounds that may pose a risk of injury to the user after large and long-term use of the product. While the technology for identifying and extracting such compounds from natural tobacco has advanced, it is probably especially true for newly identified compounds, but for inclusion in products related to tobacco manufacture. It may be desirable to provide a method for removing such compounds during use of the product so as to minimize the complexing step.

  Thus, the cyclodextrins of the present invention provide a novel means of complexing such potentially harmful compounds before they are carried by the user's saliva and mobilize in the oral cavity. Accordingly, providing cyclodextrins in a manner that removes the complex of cyclodextrin and compound from the user's mouth by combining with one or more substances that would be brewed after use of the product. Is convenient.

  According to one embodiment of the present invention, cyclodextrins are bound to the cellulosic material, for example by chemical bonding. The material is then incorporated into a smokeless oral tobacco product (eg, a filling material) or as a packaging for a sachet product. The conjugation of cyclodextrins is routine and numerous examples of such methods are provided by techniques associated with their chromatographic application.

  Spacers can be provided when chemical bonds are used so that cyclodextrins are not subject to interference from the cellulosic material to which they are attached. This allows the cyclodextrin cavity to freely interact with the surrounding solution in order to release the complexed compound or to remove the target molecule from the free solution.

  Cyclodextrins are known in the art, and methods and materials for selecting specific cyclodextrins based on the molecules contained in the cavities are also known. For example, in use, certain smokeless oral tobacco products release polycyclic aromatic hydrocarbons such as benzo (α) pyrene, ie molecules that are suspected of harming long-term heavy users Can be expected. Benzo (α) pyrene is calculated to have a total length of 0.88 nm for its wide axis. Benzo (α) pyrene cannot form inclusion complexes with α-cyclodextrin but is stable with 1: 1 host-guest complexes with β-cyclodextrin and 1: 2 with γ-cyclodextrin. It is believed to form host-guest complexes (Fielden and Packham, J. Chromatog. 516 (1990) 355-364).

  In order to remove benzo (α) pyrene from the product at the time of use, it may be preferable to take advantage of the nature of benzo (α) pyrene, which is very complexable within the γ-cyclodextrin cavity. Once benzo (α) pyrene is complexed, it is unlikely to return to a free solution, ie, the user's saliva, because benzo (α) pyrene is an extremely highly hydrophobic molecule. By including cyclodextrins in cellulosic materials or cyclodextrins bound to the materials, both cyclodextrins and their complexed benzo (α) pyrene molecules can be extracted after use of the product. it can.

  Instead of (or in addition to) containing a cyclodextrin having cavities, the present invention further provides a step of complexing cyclodextrins with one or more perfumes. These fragrances are released by the cyclodextrins in use, after which the cyclodextrins provide a cavity for complexing with the compound of interest present or produced in the tobacco portion of the product. This provides the additional benefit of flavor release, as well as the benefit of reducing the release of certain compounds into the user's mouth.

  In this aspect of the invention, many perfumes or other additives that are also within the scope of the invention are low molecular weight monocyclic aromatic compounds that form temporary complexes with cyclodextrins, such as saliva Take advantage of the fact that it is easily released upon contact with moisture. γ-Cyclodextrin provides a large cavity where low molecular weight compounds are likely to be easily detached, thereby providing a cavity that can be complexed with another molecule such as benzo (α) pyrene.

  According to one embodiment of the present invention, β-cyclodextrin can be a preferred cyclodextrin for complexing fragrance and fragrance molecules, since β-cyclodextrin has numerous fragrances and fragrances. This is because it provides a cavity of an ideal size for the molecule. In particular, bi-aromatic ring compounds are stably retained in the cyclodextrin complex until they are in a solubilized state. This allows the product to contain a large amount of moisture that does not interfere with the inclusion complex, and is sufficient to release the fragrance only when the user's saliva causes further wetness during use. The solution becomes available. At that time, cyclodextrins freely form complexes with other compounds. Hydrophobic molecules that are likely to be harmful to the user are drawn into cyclodextrins, especially if they move into saliva and are allowed to move in the oral cavity.

  Another feature of the present invention is that molecules complexed with cyclodextrins are presumably more resistant to degradation, degradation and alteration. For example, it is known that the property that fragrance vanillin is easily oxidized is alleviated and that vanillin is complexed with cyclodextrin.

  According to one embodiment of the present invention, when the perfume of interest is a low molecule such as a monocyclic aromatic flavor compound containing one major phenyl moiety (eg, phenylacetaldehyde dimethyl acetal), α-cyclo It is preferred to use dextrins. Release from the inclusion complex takes place slowly and is maintained over a period corresponding to the average use time of the product.

  The approximate range that can be used in practicing the present invention can be readily determined by one skilled in the art. For example, benzo (α) pyrene is known to be present in certain smokeless tobacco products in an amount of about 0.1-10 μg / kg (eg, 1 μg / kg benzo (α) pyrene In a product with 4 mmol / kg benzo (α) pyrene can be released into the user's mouth). Thus, assuming a 1: 1 complex of benzo (α) pyrene and cyclodextrin, and no other molecules complexed with cyclodextrin appear to be present, all benzo (α) from the product To complex pyrene, 0.4-40 mmol / kg cyclodextrin should be provided. In order to compensate for complexation, which is never efficient, and for other molecules that may complex with some of the cyclodextrins, for example, 10 or 20 times the reference amount of cyclodextrin (this You may choose to use (calculated as 4.0 to 800 mmol / kg in the example).

  Because the ratio of cellulosic material to tobacco is highly variable, the amount of cyclodextrin relative to tobacco and tobacco components can be easily adjusted. The cellulosic material may be provided, for example, as a fragment, fiber, leaf or sheet mixed with tobacco, or as a moisture permeable packaging material that encloses tobacco.

  Cyclodextrins may be contained in the gaps in the cellulosic material in a specific pattern such as an irregular pattern or row or by being bonded to the cellulosic material. When the cellulosic material forms a packaging material for a tobacco sachet, cyclodextrins may be included on the side of the sachet that contacts the user or on the side or both sides that contact the tobacco during use. The method of including cyclodextrins in cellulosic materials and the density, arrangement, etc. are the molecules captured by the cyclodextrin design, their relative amounts in the product, the release method and location of the molecules and the timing of the release, etc. Can be optimized according to the factors.

  Perfumes or other additives, if they are included as inclusion complexes with cyclodextrins, are probably about 5% cyclodextrin complexed or 10%, 20%, 30%, 40% %, 50%, 60%, 70%, 80%, 90%, 95% or 100% can be contained in a complexed range. Smokeless oral tobacco products may incorporate all of their fragrances or additives in the cyclodextrin complex, or only a portion of the total fragrances or additives may be present in the complex with the cyclodextrin and the remainder remaining in the conventional You may make it contain according to a means. For example, cyclodextrin immobilized on a cellulosic packaging material may contain 0.85 mol / mol (+)-limonene or 0.95 mol / mol hinokitiol.

  Various conditions can be used to attach β-hydroxypropyl, γ-hydroxypropyl and / or γ-cyclodextrins to the cellulose powder by spacer or linker groups.

Example 1: Cyclodextrin bound to cellulose powder by epichlorohydrin Two samples were prepared by binding epichlorohydrin and cyclodextrin to cellulose using an aqueous potassium carbonate solution.

  A mixture of cellulose (50 g), epichlorohydrin (5 g), potassium carbonate (10 g) and β-cyclodextrin (10 g) was stirred in water (200 mL) at 50 ° C. for 5 hours. The mixture was cooled, filtered, washed thoroughly with water, and then vacuum dried to obtain a first sample PD906 (50.1 g). The second sample was prepared by stirring a mixture of cellulose (50 g), epichlorohydrin (5 g), potassium carbonate (10 g) and γ-cyclodextrin (10 g) in water (200 mL) at 75 ° C. for 14 hours. Prepared. The mixture was cooled, filtered, washed thoroughly with water and dried in vacuo to give sample PD907 (50 g).

  Two samples were prepared by binding epichlorohydrin and cyclodextrin to cellulose using potassium carbonate and butanone.

  A 2-butanone (200 mL) solution of a mixture of cellulose (50 g), epichlorohydrin (5 g), potassium carbonate (10 g) and β-cyclodextrin (10 g) was stirred at reflux (80 ° C.) for 6 hours. The mixture was cooled, filtered, washed thoroughly with water and dried in vacuo to give sample PD911 (46.2 g). To obtain a second sample of this type, a 2-butanone (200 mL) solution of a mixture of cellulose (50 g), epichlorohydrin (5 g), potassium carbonate (10 g) and γ-cyclodextrin (10 g) was refluxed. The mixture was stirred at 80 ° C. for 6 hours. The mixture was cooled, filtered, washed thoroughly with water and dried in vacuo to give sample PD912 (47.1 g).

  Two samples were prepared by binding epichlorohydrin and cyclodextrin to cellulose using aqueous sodium hydroxide.

  A mixture of cellulose (50 g), epichlorohydrin (7 g), sodium hydroxide (6 g) and β-cyclodextrin (10 g) was stirred in water (200 mL) at 50 ° C. for 2 hours and then overnight at room temperature. Stirred in. The mixture was cooled, filtered, washed thoroughly with water (ultra-slow filtration) and dried in vacuo to give sample PD913 (49.4 g). A second sample of this type consists of a mixture of cellulose (50 g), epichlorohydrin (7 g), sodium hydroxide (6 g) and γ-cyclodextrin (10 g) in water (200 mL) at 50 ° C. After stirring for hours, it was prepared by stirring overnight at room temperature. The mixture was cooled, filtered, washed thoroughly with water (ultra slow filtration) and then vacuum dried to obtain sample PD914 (50.8 g).

  When dried, both samples PD913 and PD914 were very difficult to grind with a mortar and pestle. Therefore, these samples were not completely ground.

  When epichlorohydrin is used as the linker group, the method using 2-butanone / potassium carbonate tends to produce a more tanned cellulosic material, but it relies on the reaction of aqueous sodium hydroxide. In general, the whitest material is obtained. Depending on the downstream application, a whiter or lighter cellulose material may be preferred.

Example 2: Cyclodextrins bound to cellulose powder by imidazolidone In these thermal reactions, the following general procedure was used: CD / imidazolidone / magnesium chloride catalyst / aqueous citric acid solution (deionized water) or aqueous methanol solution. After addition to the powder (crystallite size), the slurry was evaporated (about 75 ° C. in vacuo) and the residue was heat treated (about 160 ° C. in air or under a nitrogen atmosphere). The cooled material was washed thoroughly with water and vacuum dried at 65-75 ° C.

  The experimental conditions were almost the same as those disclosed in US Pat. No. 7,109,324. As described herein, magnesium chloride was added to optimize the binding between CD and cellulose, and citric acid was added to maintain the pH at 5.

  A paste was prepared by mixing a solution of β-CD (5 g), imidazolidone (5 g), magnesium chloride hexahydrate (1 g), and citric acid (100 mg) in deionized water (50 mL) with cellulose. This was put in a glass dish in an oven at 155 to 180 ° C. (with a temperature gradient before and after). After 45 minutes, gravimetric determination confirmed that all the water had evaporated and the mixture was left for another 5 minutes. This was cooled, completely washed with water, and then vacuum-dried at 65 to 75 ° C. to obtain a sample PD908 (48 g).

  A paste was prepared by mixing a solution of γ-CD (5 g), imidazolidone (5 g), magnesium chloride hexahydrate (1 g) and citric acid (100 mg) in deionized water (50 mL) with cellulose. The mixture was pre-vacuum dried at 75 ° C. and then heated in an oil bath to 180 ° C. (oil bath temperature) in a glass flask equipped with a magnetic stir bar until the air temperature in the flask reached 160 ° C. This was cooled, completely washed with water, and then vacuum-dried at 65 to 75 ° C. to obtain a sample PD909 (46.6 g).

  A paste was prepared by mixing a solution of γ-CD (5 g), imidazolidone (5 g), magnesium chloride hexahydrate (1 g) and citric acid (100 mg) in deionized water (50 mL) with cellulose. The mixture was pre-vacuum dried at 75 ° C. and then heated in an oil bath to 160-164 ° C. for 5 minutes in a glass flask equipped with a magnetic stir bar (solid temperature: about 150 ° C.). This was cooled, completely washed with water, and then vacuum-dried at 65 to 75 ° C. to obtain a sample PD910 (49.2 g).

  A paste was prepared by mixing a solution of γ-CD (5 g), imidazolidone (5 g), magnesium chloride hexahydrate (1 g) and citric acid (100 mg) in methanol (50 mL) / water (30 mL) with cellulose. The mixture was pre-vacuum dried at 75 ° C. and then heated in an oil bath to 180 ° C. (oil bath temperature) in a glass flask equipped with a magnetic stir bar until the air temperature in the flask reached 160 ° C. This was cooled, thoroughly washed with water, and then vacuum-dried at 65 to 75 ° C. After drying, the material was placed in a glass flask equipped with a magnetic stir bar and then placed in a 175 ° C. oil bath for 15 minutes under a stream of nitrogen. The reaction was placed under nitrogen to see if this affected the tanning of the material. The sample obtained was PD911 (46.2 g).

  A paste was prepared by mixing a solution of γ-HP-CD (5 g), imidazolidone (5 g), magnesium chloride hexahydrate (1 g) and citric acid (100 mg) in deionized water (50 mL) with cellulose. The mixture was pre-vacuum dried at 75 ° C. and then heated in an oil bath under nitrogen to 175 ° C. (oil bath temperature) for 20 minutes in a glass flask equipped with a magnetic stir bar. This was cooled, completely washed with water, and then vacuum-dried at 65 to 75 ° C. to obtain a sample PD917A (48.5 g).

  A paste was prepared by mixing a solution of γ-HP-CD (5 g), imidazolidone (5 g), magnesium chloride hexahydrate (1 g) and citric acid (100 mg) in deionized water (50 mL) with cellulose. The mixture was pre-vacuum dried at 75 ° C. and then heated in an oil bath under nitrogen to 175 ° C. (oil bath temperature) for 20 minutes in a glass flask equipped with a magnetic stir bar. This was cooled, thoroughly washed with water, and then vacuum-dried at 65 to 75 ° C. The dried paste was slurried in methanol (150 mL), vacuum dried at 60 ° C. and then heated in a 175 ° C. oil bath under nitrogen for 20 minutes. The sample obtained was PD917B (49 g).

  The last two thermal reactions were carried out using similar proportions of additives to cellulose as described in US Pat. No. 7,109,324. The mixture was heated to a lower temperature and its effect on the tanning of the material was observed.

  A solution of γ-CD (1.75 g), imidazolidone (4 g), magnesium chloride hexahydrate (1 g) and citric acid (40 mg) was prepared in deionized water (20 mL) and methanol (100 mL). The paste was vacuum dried at 65 ° C. and then heated in an oil bath at 160 to 165 ° C. for 15 minutes. This was cooled, completely washed with water, and then vacuum-dried at 65 to 75 ° C. to obtain a sample PD918 (47.8 g).

  A solution of γ-HP-CD (1.75 g), imidazolidone (4 g), magnesium chloride hexahydrate (1 g) and citric acid (40 mg) was prepared in deionized water (20 mL) and methanol (100 mL). The paste was vacuum dried at 65 ° C. and then heated in an oil bath at 160 to 165 ° C. for 15 minutes. This was cooled, completely washed with water, and then vacuum-dried at 65 to 75 ° C. to obtain a sample PD919 (45.8 g).

  Most of the thermal reaction was tan. The samples with the least yellowing among the above samples were PD916 and PD919.

Example 3: Removal of benzo (α) pyrene with derivatized cellulose The present invention uses derivatized cellulose to remove benzo (α) pyrene (hereinafter sometimes referred to as B (α) P) from an aqueous solution. The characteristics were shown. This also had the effect of confirming that the various cyclodextrin materials described above bound well to cellulose.

  Due to the complex nature of tobacco extracts filled with numerous substances, it can be difficult to quantify molecules such as B (α) P present at low concentrations in the matrix. This problem is particularly acute with fluorescence measurements because the measurement may be affected from time to time by the matrix. This phenomenon is known as fluorescence quenching. For this reason, fluorescence measurements often require extensive sample purification to minimize the detrimental effects of the matrix.

  In order to avoid problematic fluorescence quenching and purification treatments, the following experiment was conducted without using a tobacco matrix. This directly evaluates the complexing ability of the cyclodextrin-cellulose compound with B (α) P molecules outside the aqueous environment, and as a result, the concentration of B (α) P in the sample can be reduced. did it.

That is, a minicolumn containing either a cyclodextrin derivatized cellulose or pure cellulose bed was prepared. A small amount of B (α) P in acetonitrile was injected from the top of the column, followed by a large amount of water. It continued to flow through the column only by gravity, and the resulting eluent was collected and analyzed for B (α) P.
Preparation of mini-column A 150 mm long glass Pasteur pipette (Fisher Scientific, Fisherbrand: FB50251) was plugged with a small amount of untreated glass cotton (Supelco: 2-0384, lot number: 1561-18). Did. After weighing a glass column with a glass cotton plug, either a certain amount of cyclodextrin derivatized cellulose or untreated cellulose (control from the same batch used in the preparation of the CD derivatized cellulose sample) Was added to the column. The material was dry filled without any compression. That is, about 30 mm of solid material was added to each column. The column was kept vertical and gently struck so that all the cavities in the layer disappeared, making sure that the top surface of the floor was approximately horizontal. After packing, the column was weighed to calculate the bed weight. Details are shown in Table 1 below.

Ｂ（α）Ｐ溶液の塗布
Ｂ（α）Ｐのアセトニトリル溶液（標準原液）（濃度５００ｎｇ／ｍＬ）１００μＬ（Ｂ（α）Ｐ：５０ｎｇ）をガラス製カラムの内面にピペットで慎重に移した。この溶液を吸収床の上部３〜５ｍｍに含ませた。
カラムからのＢ（α）Ｐの溶出
１０００μＬの水を、ピペットでカラム内部をゆっくりと流下させた。この添加により床の乾燥材料は徐々に水を含み、同時にＢ（α）Ｐが移動した。最終的に、カラムの底に水滴が現れ、それを２０ｍＬのガラス製バイアルに回収した。床の上面のレベルの水が排出されるのに約８〜１１分を要した。次いで、さらに１０００μＬの水をピペットでカラム内部をゆっくり流下させた。水溶離液を全て回収し、Ｂ（α）Ｐの分析に供した。液体がカラムの外に排出されるのに約２５〜３０分を要した。

Application of B (α) P solution 100 μL of B (α) P acetonitrile solution (standard stock solution) (concentration 500 ng / mL) (B (α) P: 50 ng) was carefully pipetted onto the inner surface of a glass column. This solution was included in the upper 3-5 mm of the absorbent bed.
Elution of B (α) P from the column 1000 μL of water was slowly flowed down the column with a pipette. With this addition, the dry material of the bed gradually contained water, and B (α) P moved at the same time. Eventually, water droplets appeared at the bottom of the column and were collected in a 20 mL glass vial. It took about 8-11 minutes for the water at the top level of the floor to be drained. Next, another 1000 μL of water was slowly flowed down the column with a pipette. All water eluent was collected and subjected to analysis of B (α) P. It took about 25-30 minutes for the liquid to drain out of the column.

Preparation of 100% recovery sample In order to confirm the effect of this system, a 100% recovery sample was also prepared. This sample was not exposed to the column environment at all. That is, it was expected that the added B (α) P was preserved. This sample was prepared by mixing 100 μL of B (α) P acetonitrile solution (standard stock solution) (concentration 500 ng / mL) (B (α) P: 50 ng) with 2000 μL of water in a 20 mL vial.
Analysis of the eluent Reversed phase HPLC with fluorescence detection was used. The column used was 125 × 4.60 mm, 5 microns (Phenomenex Envirosep PP) and was thermostatically controlled at 30 ° C. (thermostat). The mobile phase was water / acetonitrile allocated with the gradient program detailed in Table 2.

励起波長は３７８ｎｍであり、検出波長は４０５ｎｍであった。Ｂ（α）Ｐの溶出は約２０．５分後であった。注入量は５０μＬだった。その結果を表３にまとめて示す。

The excitation wavelength was 378 nm and the detection wavelength was 405 nm. The elution of B (α) P was after about 20.5 minutes. The injection volume was 50 μL. The results are summarized in Table 3.

上記実施例に詳細が記載されているように、
ＰＤ９１７Ａは、γ−ヒドロキシプロピルシクロデキストリンセルロース誘導体であり、
ＰＤ９０８は、β−シクロデキストリンセルロース誘導体であり、
ＰＤ９０９は、γ−シクロデキストリンセルロース誘導体であり、
ＰＤ９１２は、β−シクロデキストリンセルロース誘導体であった。

As detailed in the above example,
PD917A is a γ-hydroxypropylcyclodextrin cellulose derivative,
PD908 is a β-cyclodextrin cellulose derivative,
PD909 is a γ-cyclodextrin cellulose derivative,
PD912 was a β-cyclodextrin cellulose derivative.

  This result shows that B (α) P is only slightly lost when using a pure cellulose column when compared to the recovered sample. However, in the CD-derivatized cellulose column, there is a very dramatic decrease in the amount of B (α) P eluting from the sample PD908, PD909 and especially PD917A columns. In the case of PD912, no decrease in B (α) P was observed.

  The very large B (α) P reduction shown by sample PD917A is particularly suitable for the purposes of the present invention of using γ-cyclodextrin to complex B (α) P. As indicated above, cyclodextrin-cellulose derivatives remove B (α) P in an aqueous environment.

  Examples 1-3 show how to provide the material of the present invention, and Examples 4-8 below show several ways in which the material of the present invention can be incorporated into a product.

Example 4: Smokeless oral tobacco product with cellulosic material Smokeless tobacco for oral use is provided. For example, a mixture of commercially available tobacco can be cut into a size and shape suitable for loose chewing tobacco products. The cut tobacco can then be placed in a case with an aqueous mixture of flavor material and sweetener to obtain a cut cased tobacco containing about 50% moisture. The treated tobacco can be placed on a conveyor belt, stacked on a sheet, moved in a dryer, or placed in it. Tobacco may be heated to about 70 ° C. by a dryer, that is, its moisture may be reduced to about 25%. The next treatment of the tobacco may be a conventional treatment such as applying a top flavoring solution and temporarily storing the finish flavor throughout the tobacco mass.

  Finishing flavoring can serve the dual purpose of adding a top note (the first scent felt) to the tobacco itself and providing a plurality of unbound flavor molecules in the mixture. These molecules appear to migrate towards cyclodextrin in the vicinity of flavored tobacco and its complexes. Moisture conditions cause equilibrium throughout the cellulosic material including the tobacco mass and nearby cyclodextrins.

  Also, in addition to (or instead of) applying the finish flavor solution, cyclodextrins previously complexed with the flavor can be provided. It can be seen that when using cyclodextrins complexed with a perfume, the perfume moves in two directions. That is, a part of the complexed fragrance is detached and moves toward the cigarette, but a part of the fragrance combined with the cigarette is complexed with the cyclodextrins emptied a while ago.

  As noted above, either or both pre-complexed cyclodextrins or “empty” cyclodextrins can be used. For example, a fibrous cellulosic material is immersed in a water bath containing 15 mM β-cyclodextrin and 15 mM imidazolidone. After soaking, heat to 150 ° C. in an oven for 1-5 minutes. When α-cyclodextrin is used, its concentration may be increased to about 130 mM, and when γ-cyclodextrin is used, it may be increased to about 170 mM.

  By this method, an ether (hemiacetal) bond was formed between the imidazolidone and the hydroxyl group of cyclodextrin, whereby the cyclodextrin was bonded to the imidazolidone (spacer group). Imidazolidone binds to cellulose by the formation of an ether bond between itself and the hydroxyl group present in the cellulose. In this way, a cellulosic material that is covalently bonded to a spacer group and then bonded to a cyclodextrin is provided.

  The cyclodextrin-cellulosic material is cut to approximately the same size as the tobacco pieces and mixed with the tobacco. Adjust moisture, pH and other parameters to the extent necessary to provide a product suitable for stable use. For example, a buffer may be used to adjust the pH to greater than about 6.5 or greater than about 7.5. Pack the mixture into a moisture-proof container.

  When using this product, molecules are released by moisture. Benzo (α) pyrene and other polymeric polycyclic aromatic hydrocarbons in tobacco are drawn into the relatively hydrophobic and suitably sized internal cavity of cyclodextrins to form inclusion complexes. The hydrocarbons bonded in this way are removed from the product containing moisture, making it impossible for the hydrocarbons to be absorbed and utilized in the user's mouth.

Example 5 Smokeless Oral Tobacco Product Containing Cellulosic Packaging This embodiment of the present invention includes a sachet product that may be similar to a subdivided Swedish snus product. That is, it is provided as a pouch containing tobacco products intended to fit between the gingival fold of mouth. Nonwoven fabrics can be used as packaging material for such sachets.

  To prepare a cyclodextrin-textile composite, a cyclodextrin derivatized with a spacer group having a reactive element at the end other than the cyclodextrin side of the spacer group (for example, monochlorotriazinyl-made by Wacker GmbH, Germany) Obtain β-cyclodextrin). The reactive material continues to interact with the fabric, thus binding the spacer group to the fabric.

  A unit dose of fine tobacco, for example 0.05-2.0 g (dry weight), suitable for the individual dose, is placed on a fabric bonded to cellulose to form a sachet. In order to increase or change the amount of cyclodextrins in the product, a piece of cellulosic material incorporating cyclodextrins may be mixed with tobacco and then added to the pouch. Conventional snus or tea bag filling equipment may be used. The pouch may be sealed, for example, by heat sealing. For example, when another cellulosic material such as a long fiber cellulose material is substituted, a heat-weldable binder may be added to the material to facilitate heat sealing. Store the product in a moisture-proof container, if necessary, refrigerated before use.

  As an example, small snus products typically contain 0.5 g of tobacco. To complex the benzo (α) pyrene present in the dose of tobacco, 1.9-19 mg of α-cyclodextrin (MW 972) can be bound to the fabric. Alternatively, 2.3-23 mg of β-cyclodextrin (MW 1135) can be bound to the fabric. Alternatively 2.6-26 mg γ-cyclodextrin (MW 1297) can be bound to the fabric. Mixtures of two or more cyclodextrins can be used.

Example 6 Smokeless Oral Tobacco Product Containing Cellulosic Packaging To prepare a perfume-cyclodextrin-cellulose complex, cycloderivatized with a spacer group having a reactive element at the non-cyclodextrin end of the spacer group Obtain dextrin (for example, CAVAMAX W7 CITRAL manufactured by Wacker GmbH, Germany). This reactive material is designed to react with cellulose, whereby the spacer group binds to the cellulosic material and imparts a lemon flavor to the resulting product. A sheet made of a cell-like cellulosic material is used.

  Extraction methods or chemical synthesis provide a select component from tobacco, such as nicotine. These tobacco extracts are applied to a cellulosic material or a synthetic tobacco-like material, and then applied to a sachet-like object formed by wrapping a cellulosic material or a sheet of cellulosic web around the tobacco-like material. Incorporate this.

  The sachets thus provided contain natural or synthetic tobacco extracts rather than raw natural tobacco. The moisture that permeates the sachet during use prompts the lemon flavor to detach from the cyclodextrin and move from the sachet to the surrounding area. At the same time, molecules present in the extract or molecules produced by the extract upon infiltration are moved by moisture through a sheet of cellulosic material bound to the relatively hydrophobic internal cavities of cyclodextrins. To prevent the pouch from slipping out or remaining in the unbonded pouch.

Example 7 Smokeless Oral Tobacco Product Containing Cellulosic Packaging A unit comprising a web-like cellulosic material is provided. 4-40 mg of β-cyclodextrin is bound to the cellulosic web. 1.0 g of standard smokeless tobacco is placed on the cellulosic web to form a sealed sachet.

  Since standard smokeless tobacco is said to contain about 0.1-0.3 mg / kg of cadmium, the amount of β-cyclodextrins is selected corresponding to this amount. Thus, in use, a certain amount of cadmium is released from the tobacco product, and then a portion of it binds to β-cyclodextrins. Contact with cadmium may not be desirable. Thus, complexation with β-cyclodextrins reduces the user's contact with the substance. The most common oxidation state of cadmium is +2, so cadmium may be represented as cadmium (II). Any state and form of cadmium can be encompassed by the present invention.

Example 8 Smokeless Oral Tobacco Product Containing Cellulosic Wrapping Material A sheet of cell-like cellulosic material is provided having a spacer group and then a cyclodextrin derivative bonded to the cellulosic web. The cellulosic web is treated with a mixture of nicotine and fragrance to obtain a nicotine-cyclodextrin inclusion complex and a fragrance-cyclodextrin inclusion complex.

  After the appropriate amount of tobacco in the desired physical form is added to the sheet, it is folded to form a pouch and sealed. Moisture that permeates the sachet during use facilitates the removal of nicotine and perfume from the cyclodextrin and movement out of the sachet. Compounds present in tobacco or compounds produced by tobacco are also moved towards the outside of the sachet by moisture, but due to the relatively sized relatively hydrophobic cavity provided by the bound cyclodextrin , Is drawn into the inclusion complex and does not move outside the pouch.

  Low molecular weight monocyclic aromatic compounds are usually unable to form persistent complexes with cyclodextrins, so when infiltrated, they are quickly released from inclusion complexes, providing nicotine and flavor to the user , Cyclodextrins will be available for binding to larger molecules of interest. A mixture of other cyclodextrins may be used in this form to give the product sustained release characteristics.

  When compared to other typical products, this form requires more precise formation and storage control to maintain low moisture and proper pH to stabilize the initial inclusion complex until use. There is.

  The above description and examples are merely illustrative of the invention and are not intended to limit the invention. Since modifications of the above-described embodiments within the spirit and essence of the present invention by those skilled in the art are possible, the present invention should be construed to broadly include all changes and equivalents within the scope of the appended claims. It should be.

Claims (34)

A smokeless oral tobacco product comprising at least one of tobacco, tobacco derivatives or tobacco substitutes and a cellulosic material,
A product wherein the cellulosic material comprises at least one cyclodextrin or cyclodextrin derivative. The product of claim 1, wherein the product comprises a packaging material encapsulating the tobacco, tobacco derivative or tobacco substitute, and wherein the packaging material comprises the cellulosic material. The product according to claim 1 or 2, wherein the cellulosic material is fibrous. The product according to claim 1 or 2, wherein the cellulosic material is a woven or non-woven fabric. The product according to any one of claims 1 to 4, wherein the cyclodextrin or cyclodextrin derivative is chemically bonded to the cellulosic material. The product of claim 5, wherein a spacer group is disposed between the cellulosic material and the cyclodextrin or cyclodextrin derivative. The product according to any one of claims 1 to 6, wherein most of the cyclodextrin or cyclodextrin derivative is γ-cyclodextrin or a derivative thereof. The product according to claim 7, wherein the cyclodextrin or cyclodextrin derivative is γ-cyclodextrin or a derivative thereof. The product according to any one of claims 1 to 3, wherein at least part of the cyclodextrin or cyclodextrin derivative is complexed with at least one complexing agent. 10. The product of claim 9, wherein the complex of the cyclodextrin or cyclodextrin derivative and the complexing agent is chemically bound to the cellulosic material. The product according to claim 9 or 10, wherein most of the cyclodextrin or cyclodextrin derivative is β-cyclodextrin or a derivative thereof. The product according to claim 11, wherein the cyclodextrin or cyclodextrin derivative is β-cyclodextrin or a derivative thereof. The product according to claim 9 or 10, wherein most of the cyclodextrin or cyclodextrin derivative is α-cyclodextrin or a derivative thereof. 14. A product according to any one of claims 9 to 13, wherein the complexing agent comprises at least one fragrance, scent adjuster or antibacterial agent. 15. A product according to claim 14, wherein the complexing agent comprises a fragrance and the fragrance comprises at least one monoterpene fragrance. 15. The product of claim 14, wherein the complexing agent comprises a fragrance and the fragrance comprises at least one monocyclic aromatic fragrance. 15. The product of claim 14, wherein the complexing agent comprises a fragrance and the fragrance comprises at least one polycyclic aromatic fragrance. The complexing agent contains a fragrance, and the fragrance is (+)-limonene, (-)-limonene, cinnamaldehyde, cinnamonitrile, eugenol, cis-isoeugenol, trans-isoeugenol, eugenyl acetate, eugenol methyl / ethyl Esters, trans-Anethole, cis-Anethole, Menthol, Isomenthol, Neomenthol, (+)-Mentholone, (-)-Mentholone, (+)-Citronellal, S (+)-Carvone, R (-)-Carvone , Trans-methyl cinnamate, cis-methyl cinnamate, vanillin, capsaicin, phenylpropanoids, aspartame, chocolate, coffee, pyrazines, salt, γ-Glu-Tyr, γ-Glu-Phe, ornithyl-containing peptide , Aromatic aldehydes, aceta 15. A product according to claim 14, selected from the group consisting of aromatic aldehydes and lactones derivatized as a diol. The complexing agent contains a scent adjusting agent, and the scent adjusting agent is maltol, ethyl maltol, cis-jasmon, methyl jasmonate, geraniol, nerol, geranyl esters, neryl esters, (+)-citronellol, (-) 15. A product according to claim 14, selected from the group consisting of: citronellol, citral, (+)-limonene, (-)-limonene and monoterpenes. 15. The product of claim 14, wherein the complexing agent comprises an antimicrobial agent and the antimicrobial agent comprises hinokitol. Use of at least one cyclodextrin or cyclodextrin derivative in the manufacture of a smokeless oral tobacco product, characterized in that the product comprises tobacco. Use of at least one cyclodextrin or cyclodextrin derivative complexed with at least one perfume in the manufacture of a smokeless oral tobacco product, characterized in that said product comprises tobacco. 23. Use according to claim 21 or 22, wherein the product further comprises a cellulosic material and the at least one cyclodextrin or cyclodextrin derivative is complexed with the cellulosic material. 24. Use according to claim 23, wherein the at least one cyclodextrin or cyclodextrin derivative is chemically bound to the cellulosic material. Use according to claim 23 or 24, wherein the tobacco is encapsulated in the cellulosic material. The at least one cyclodextrin or cyclodextrin derivative is selected from the group consisting of β-cyclodextrin, β-cyclodextrin derivative, γ-cyclodextrin, γ-cyclodextrin derivative, α-cyclodextrin and α-cyclodextrin derivative. 26. Use according to any one of claims 21 to 25. A method of complexing at least one cyclodextrin or cyclodextrin derivative with a substance in or produced by a smokeless oral tobacco product, comprising:
Providing a smokeless oral tobacco product comprising at least one cyclodextrin or cyclodextrin derivative;
Contacting the product with moisture to wet the product and complexing the substance with the cyclodextrin or cyclodextrin derivative;
Including methods. 30. The method of claim 29, wherein the cyclodextrin or cyclodextrin derivative comprises at least one perfume and further comprising releasing the perfume from the cyclodextrin or cyclodextrin derivative after the contact. 30. The method of claim 28 or 29, wherein the material is a polycyclic aromatic hydrocarbon. 30. The method of claim 29, wherein the polycyclic aromatic hydrocarbon is benzo (α) pyrene. 30. A method according to claim 28 or 29, wherein the material is cadmium. 32. A method according to any one of claims 27 to 31 wherein the product comprises a cellulosic material and the cyclodextrin or cyclodextrin derivative is bound to the cellulosic material. 33. The method of claim 32, wherein the cyclodextrin or cyclodextrin derivative is chemically bound to the cellulosic material. 34. The method of claim 33, wherein a spacer group is disposed between the cellulosic material and the cyclodextrin or cyclodextrin derivative.