Composition for tobacco

By employing halogen-free sweeteners like peptide derivatives and flavonoid glycosides in e-liquids and tobacco products, the health risks associated with sucralose are mitigated, providing a safer and sweeter alternative.

JP2025081701APending Publication Date: 2025-05-27JAPAN TOBACCO INC
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Patent Information

Application Number
JP2025030054
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2020-12-21
Filing Date
2025-02-27
Publication Date
2025-05-27

AI Technical Summary

Technical Problem

Existing e-liquids containing sucralose pose health risks due to the generation of harmful chlorine-containing decomposition products when heated in electronic cigarette devices.

Method used

A tobacco composition using a sweetener that does not contain halogen elements, such as peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, sulfamate salts, and proteins, which are safer and provide sufficient sweetness comparable to sugars.

Benefits of technology

The use of halogen-free sweeteners in e-liquids and tobacco products eliminates the risk of generating harmful decomposition products, ensuring a safer and more effective sweetening solution.

✦ Generated by Eureka AI based on patent content.

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Abstract

To provide a composition for tobacco, and an e-liquid and a tobacco product which contain a composition for tobacco.SOLUTION: A composition for tobacco according to the present invention contains a sweetener other than sucralose.SELECTED DRAWING: None
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Description

Technical Field

[0001] The present invention relates to a composition for tobacco. The present invention also relates to an e-liquid or a tobacco product comprising the composition for tobacco.

Background Art

[0002] A general e-liquid for electronic cigarettes (commonly called e-liquid or e-juice) is composed of propylene glycol (PG), glycerin (GL), nicotine, and flavorings.

[0003] One of the attractions of electronic cigarettes is that a wide variety of flavors can be easily enjoyed. Flavorings play a very important role in characterizing the flavor of e-liquids. It is generally believed that when humans perceive flavors, the contribution of the sense of smell and taste among the five senses occupies a large proportion. The role of flavorings in e-liquids is mainly to act on the sense of smell to make humans feel various scents, and it can be said that it is the most important element in constituting the charm of the product. In fact, e-liquids blended with various types of flavorings are commercially available, and it can be said that the quality of the flavorings greatly influences the charm of the product.

[0004] On the other hand, in recent years, e-liquids that attempt to approach the sense of taste, that is, those having some taste, have emerged, and the most common taste quality is sweetness. Many of the flavorings for electronic cigarettes are blended with flavors that are compatible with sweetness such as coffee-like, vanilla-like, and fruit-like, and it is considered that the purpose is to improve the flavor satisfaction of consumers by imparting sweetness.

[0005] The most typical examples of substances having a sweet taste ( "sweeteners") include saccharides. However, the amount of saccharides that can be dissolved in PG or GL, which are the main solvents of e-liquids, is limited, and it is often difficult to formulate an e-liquid with an amount of saccharides sufficient to achieve a sufficient sweet taste in the normal usage form of electronic cigarettes. Also, in the most common heating-type devices as electronic cigarette devices, heating an e-liquid containing a large amount of saccharides may cause problems such as charring of saccharides around the heating site, which may cause device failure. For these reasons, it can be said that the effect of the method of formulating an e-liquid with saccharides for the purpose of expressing a sweet taste is limited.

[0006] In recent years, e-liquids formulated with sweeteners other than saccharides have emerged. Among sweeteners, there are many that express a stronger sweet taste than saccharides, that is, those with a high sweetness level. High-sweetness sweeteners are considered to require less amount than saccharides to express the same degree of sweet taste. Therefore, when used in e-liquids, they have the advantage of being less likely to cause charring around the heating site, which is a problem with saccharides. In recent years, sucralose is one of the most commonly used sweeteners in e-liquids. There are products with sucralose pre-formulated, and dilutions of sucralose are sold for consumers to mix and use with other liquids by themselves.

[0007] Sucralose has a molecular structure in which the hydroxyl groups of sucrose are substituted with chlorine, and it is a high-intensity sweetener said to have a sweetness level 320 - 1000 times that of sucrose (Non-Patent Document 1). To date, it has been approved for use as a food additive in many countries such as the United States, Europe, and Japan. However, research results have been reported in recent years that harmful organochlorine compounds are generated when sucralose is heated at high temperatures (Non-Patent Document 2). The German Federal Institute for Risk Assessment (BfR) has also reached a situation where it publishes an opinion paper on the risks when sucralose is heated (Non-Patent Document 3).

[0008] In recent years, several studies have also been reported on the decomposition products generated when e-liquids containing sucralose are used in heated tobacco devices (Non-Patent Documents 4-5). According to Non-Patent Document 4, it has been shown that sucralose promotes the generation of carbonyls, which are decomposition products of PG and GL, the solvents of e-liquids, and that organochlorine compounds and chlorine are generated as decomposition products of sucralose itself. Carbonyls, organochlorine compounds, and chlorine are all suspected of being harmful to the human body. Furthermore, according to Non-Patent Document 5, chloropropanol compounds such as 3-monochloro-1,2-propanediol and 1,3-dichloropropanol have been detected in the aerosol generated by heating e-liquids containing sucralose. These compounds have been pointed out as components with carcinogenicity and genotoxicity.

[0009] As described above, it has to be said that there are health risks associated with using e-liquids containing sucralose in heated tobacco devices. There is a demand for the development of a sweetener that can be formulated in tobacco products such as e-liquids, has sufficient sweetness comparable to sugars, and is safe.

Prior Art Documents

Non-Patent Documents

[0010]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Non-Patent Document 10

Non-Patent Document 11

Non-Patent Document 12

Non-Patent Document 13

Non-Patent Document 14

Non-Patent Document 15

Non-Patent Document 16

Non-Patent Document 17

Non-Patent Document 18

Non-Patent Document 19

Non-Patent Document 20

Non-Patent Document 21

Non-Patent Document 22

Summary of the Invention

Problems to be Solved by the Invention

[0011] The inventors noted that when using an e-liquid containing sucralose in a heated electronic cigarette device, the generation of chlorine-containing decomposition products is due in part to the fact that highly reactive chlorine is contained within the molecular structure of sucralose. Organic halides, not just chlorine, are known to be highly reactive. The inventors conducted an extensive search for sweeteners applicable to tobacco compositions such as e-liquids among compounds that do not contain halogen elements, replacing sucralose which poses a health risk, and arrived at the present invention.

Means for Solving the Problems

[0012] Although not limited, the present invention includes the following aspects. [Aspect 1] A tobacco composition containing a sweetener other than sucralose. [Aspect 2] The composition according to Aspect 1, containing a sweetener that does not contain a halogen element. [Aspect 3] The composition according to Aspect 1 or 2, wherein the sweetener is selected from the group consisting of peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, sulfamic acid salts, and proteins. [Aspect 4] The composition according to any one of Aspects 1-3, wherein the sweetener is a peptide derivative. [Aspect 5] The composition according to any one of Aspects 1-3, wherein the sweetener is a flavonoid glycoside. [Aspect 6] The composition according to any one of Aspects 1-3 and 5, wherein the sweetener is a neohesperidin derivative. [Aspect 7] The composition according to any one of Aspects 1-3 and 6, wherein the sweetener is a neohesperidin derivative having a sweetness degree of 0.5 or more of the sweetness degree of neohesperidin dihydrochalcone. [Aspect 8] The composition according to any one of aspects 1-3, wherein the sweetener is selected from the group consisting of monellin, thaumatin, glycyrrhizin, stevioside or stevia extract, saccharin, acesulfame potassium, advantame, neotame, aspartame, and neohesperidin dihydrochalcone. [Aspect 9] The composition according to any one of aspects 1-3, wherein the sweetener is selected from the group consisting of glycyrrhizin, stevioside or stevia extract, saccharin, acesulfame potassium, advantame, neotame, and neohesperidin dihydrochalcone. [Aspect 10] The composition according to any one of aspects 1-4 and 8-9, wherein the sweetener is advantame. [Aspect 11] The composition according to any one of aspects 1-4 and 8-9, wherein the sweetener is neotame. [Aspect 12] The composition according to any one of aspects 1-3 and 5-9, wherein the sweetener is neohesperidin dihydrochalcone. [Aspect 13] The composition according to aspect 10, comprising 0.01% by weight or more of advantame. [Aspect 14] The composition according to aspect 10, comprising 0.05% by weight or more of advantame. [Aspect 15] The composition according to aspect 11, comprising 0.05% by weight or more of neotame. [Aspect 16] The composition according to aspect 11, comprising 0.10% by weight or more of neotame. [Aspect 17] The composition according to aspect 12, comprising 0.10% by weight or more of neohesperidin dihydrochalcone. [Aspect 18] The composition according to aspect 12, comprising 0.25% by weight or more of neohesperidin dihydrochalcone. [Aspect 19] The composition according to any one of aspects 1-18, comprising a fragrance. [Aspect 20] The composition according to any one of aspects 1-19 containing nicotine. [Aspect 21] An e-liquid containing the composition according to any one of aspects 1-20. [Aspect 22] A tobacco product containing the composition according to any one of aspects 1-20. [Aspect 23] The tobacco product according to aspect 22, wherein the tobacco product is a combustion-type flavor inhalation article. [Aspect 24] The tobacco product according to aspect 22, wherein the tobacco product is a heat-not-burn flavor inhalation article. [Aspect 25] The tobacco product according to aspect 22, wherein the tobacco product is a snus. [Advantages of the Invention]

[0013] Since the composition of the present invention uses a sweetener different from sucralose containing a halogen atom, it can be safely applied to tobacco. [Brief Description of the Drawings]

[0014]

Figure 1

Figure 2

Figure 3

[0015] Non-limitingly, the present invention includes the following aspects. 1. Composition for tobacco The present invention relates to a composition for tobacco. Non-limitingly, the composition for tobacco contains a sweetener other than sucralose.

[0016] A "sweetener" is a substance used to impart sweetness to foods, beverages, tobacco, etc. In terms of chemical structure, it is roughly classified into sugars, sugar alcohols, amino acids, proteins, terpene glycosides, sulfamides, sulfamate salts, peptide derivatives, flavonoid glycosides, etc.

[0017] A "sugar" is a compound having one aldehyde group or ketone group and a plurality of hydroxyl groups. Sugars having an aldehyde group are classified as aldoses, and sugars having a ketone group are classified as ketoses. Generally, it is often synonymous with carbohydrates (saccharides). In this specification, when referring to "sugar", unless otherwise specified, it also includes compounds in which some hydroxyl groups of the sugar are substituted, such as "sugar halides".

[0018] A "sugar alcohol" is a type of compound formed by reducing the carbonyl group of an aldose or ketose.

[0019] An "amino acid" is a general term for organic compounds having both functional groups of an amino group and a carboxyl group.

[0020] A "peptide" is a general term for molecules in which amino acids are connected in a short chain by peptide bonds. Peptides with 2 amino acid residues incorporated are called dipeptides, those with 3 are called tripeptides, those with 4 are called tetrapeptides, etc. Peptides with 10 or fewer residues are called oligopeptides, and those with many connected are called polypeptides, etc. Generally, long peptides with approximately 50 or more connected may be called "proteins". In this specification, unless otherwise specified, "peptide" may be used to include proteins. A "peptide derivative" refers to a derivative obtained by introducing a substituent into a peptide composed only of amino acids. Examples of peptide derivatization include alkyl esterification of the carboxyl group and alkylation of the amino group.

[0021] "Terpenes" is a general term for secondary metabolites of plants, insects, fungi, etc. that have a hydrocarbon skeleton with isoprene as a structural unit. It was originally a name given to a group of ten-carbon compounds found in large quantities in essential oils, and thus is systematized based on ten carbons. Terpenes with 10, 15, 20, and 30 carbons are called monoterpenes, sesquiterpenes, diterpenes, and triterpenes, respectively. Among terpenes, derivatives with polar functional groups such as hydroxyl groups and carbonyl groups are sometimes classified specifically as terpenoids. "Glycosides" is a general term for compounds in which sugar is bonded to various atomic groups by a glycosidic bond. "Terpene glycosides" are compounds in which sugar is glycosidically bonded to a terpene.

[0022] "Sulfamide" is an inorganic compound with the structural formula H 2 NSO 2 NH 2 Generally, it is obtained from the reaction of sulfuryl chloride and ammonia. In the field of organic chemistry, a group of compounds that are derivatives in which an organic substituent is bonded to the nitrogen atom of sulfamide is also called "sulfamide".

[0023] "Sulfamic acid" is a substance in which the hydroxyl group of sulfuric acid is substituted by an amino group and is called "amidosulfuric acid". It is highly soluble in water and exhibits relatively strong acidity. "Sulfamate" is a salt of sulfamic acid and, for example, sodium, potassium, calcium, or magnesium.

[0024] "Flavonoids" is a general term for plant secondary metabolites formed by the polymerization of coumaric acid CoA and malonyl CoA. Flavonoids are a representative example of a larger group of compounds called so-called polyphenols. "Flavonoid glycosides" are compounds in which sugar is glycosidically bonded to a flavonoid.

[0025] Examples of sweeteners of sugar: sucralose, fructose, sucrose, tagatose, glucose, galactose, trehalose, maltose, isomaltose, lactose Examples of sweeteners of sugar alcohols: xylitol, maltitol, erythritol, sorbitol, mannitol, polyglycitol syrup, arabitol, isomalt, lactitol

[0026] Examples of sweeteners of amino acids: glycine Examples of sweeteners of proteins: monellin, thaumatin Examples of sweeteners of terpene glycosides: glycyrrhizin, stevioside / stevia extract Examples of sweeteners of sulfamides: saccharin Examples of sweeteners of sulfamate salts: acesulfame potassium, sodium cyclamate Examples of sweeteners of peptide derivatives: aspartame, advantame, neotame Examples of sweeteners of flavonoid glycosides: neohesperidin dihydrochalcone

[0027] In one aspect, the sweetener contained in the tobacco composition is other than sucralose. Sucralose, also known as 4,1’,6’-trichlorogalactosucrose, has a structure in which three of the hydroxy groups of sucrose (sucralose) are selectively substituted with chlorine. Sucralose is a kind of sugar containing a halogen element (chlorine) and is a sugar oxide. In this specification, when referring to "sugar", unless otherwise specified, it includes "sugar halides" and "sugar chlorides". In one aspect, the sweetener is not a sugar. In one aspect, the sweetener is neither a sugar nor a sugar alcohol. In one aspect, the sweetener is neither a sugar nor an amino acid. In one aspect, the sweetener is neither a sugar, a sugar alcohol nor an amino acid. In this specification, when referring to "in one aspect", it implies being non-limiting.

[0028] The inventors noted that, in the case of using an e-liquid containing sucralose in a heated tobacco device, one of the factors contributing to the problem of the generation of chlorine-containing decomposition products is that highly reactive chlorine is contained within the molecular structure of sucralose. Even for sweeteners other than sucralose, compounds containing halogen elements other than chlorine, such as fluorine, bromine, and iodine, are assumed to be capable of generating harmful organohalides in the same manner as sucralose. Considering this point, one of the preferable conditions for a sweetener applied to e-liquid is that it is a compound that does not contain a halogen element within its molecular structure.

[0029] In one aspect, the sweetener contained in the composition for tobacco does not contain a halogen element. The "halogen element" includes fluorine, chlorine, bromine, iodine, astatine, and tennessine. In the present invention, the type of halogen element is not particularly limited. In one aspect, the halogen element is chlorine.

[0030] In one aspect, the sweetener is not a sugar and does not contain a halogen element. In one aspect, the sweetener is neither a sugar nor a sugar alcohol and does not contain a halogen element. In one aspect, the sweetener is neither a sugar nor an amino acid and does not contain a halogen element. In one aspect, the sweetener is neither a sugar, nor a sugar alcohol, nor an amino acid and does not contain a halogen element.

[0031] The inventors have found that a sweetener having a chemical structure selected from the group consisting of peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, sulfamate salts, and proteins exhibits a sweetness equivalent to or greater than that of sucralose. In one aspect, the sweetener is selected from the group consisting of peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, sulfamate salts, and proteins. In one aspect, the sweetener is selected from the group consisting of peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, sulfamate salts, and proteins and does not contain a halogen element.

[0032] The inventors have found that a sweetener having a chemical structure selected from the group consisting of peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, and sulfamate salts exhibits a sweetness comparable to or higher than that of sucralose and has sufficient solubility in an organic solvent used in a tobacco composition. In one aspect, the sweetener is used in a state of being completely dissolved in the organic solvent. Being completely dissolved means, in one aspect, a state in which the sweetener does not remain undissolved in the organic solvent under an environment of 25°C ± 2°C. In one aspect, the sweetener is selected from the group consisting of peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, and sulfamate salts. In one aspect, the sweetener is selected from the group consisting of peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, and sulfamate salts and does not contain a halogen element.

[0033] In one aspect, the sweetener is a peptide derivative. In one aspect, the sweetener is a flavonoid glycoside. In one aspect, the sweetener is a peptide derivative and does not contain a halogen element. In one aspect, the sweetener is a flavonoid glycoside and does not contain a halogen element.

[0034] In one aspect, the sweetener is selected from the group consisting of monellin, somatostatin, glycyrrhizin, stevioside or stevia extract, saccharin, acesulfame potassium, advantame, neotame, aspartame, and neohesperidin dihydrochalcone.

[0035] "Monellin" is a protein discovered from plants growing in the tropical rainforest and has two polypeptide chains which are non-covalent bonds, an A chain consisting of 44 amino acid residues and a B chain consisting of 50 amino acid residues. The amino acid sequence of monellin is disclosed, for example, in Non-Patent Document 21.

[0036] "Thaumatin" is also a single-chain protein consisting of 207 amino acid residues, discovered from plants growing in the tropical rainforest, similar to monellin. It is a low-calorie sweetener and is also known as a flavor improver in addition to a sweetener. The amino acid sequence of thaumatin is disclosed, for example, in Non-Patent Document 22.

[0037] "Glycyrrhizin" is an active ingredient contained in the roots of licorice and is a sweetener classified as a triterpenoid glycoside. The name glycyrrhizic acid may also be used. Its IUPAC name is (3-β,20-β)-20-carboxy-11-oxo-30-norolean-12-en-3-yl-2-O-β-D-glucopyranuronosyl-α-D-glucopyranuronic acid.

[0038]

Chemical formula

[0039] Commercially available glycyrrhizin such as that from Tokyo Chemical Industry Co., Ltd. (P / N: G0150), FUJIFILM Wako Pure Chemical Corporation (P / N: 074-03481), etc. can also be used.

[0040] "Stevia extract" is an extract from "Stevia". Stevia (Stevia rebaudiana) is a perennial herb of the genus Stevia in the Asteraceae family native to South Africa and also has the alias amahastevia. Stevia extract contains diterpenoid glycosides such as "stevioside" and Rebaudioside A as sweetening components. Stevioside is also called "stevioside" and has the following chemical formula.

[0041]

Chemical formula

[0042] Stevioside can be commercially available products, for example, those from Tokyo Chemical Industry Co., Ltd. (P / N: S0594), FUJIFILM Wako Pure Chemical Corporation (P / N: 194-16481), etc.

[0043] "Saccharin" has the IUPAC name: 1,1-dioxo-1,2-benzothiazol-3-one, and is also known as o-sulfobenzoic amide, o-benzoic acid sulfimide, 2-sulfobenzoic acid imide. It has a skeleton with a sultam ring fused to the benzene ring.

[0044] [Chemical formula]

[0045] Saccharin is often used in the form of sodium salt for the purpose of improving its solubility in water. It is an artificial sweetener classified as a sulfamide, and is commonly used in foods, especially in the United States, China, etc. Commercially available products such as sodium saccharin dihydrate from Tokyo Chemical Industry Co., Ltd. (P / N: B0131) and sodium saccharin dihydrate from FUJIFILM Wako Pure Chemical Corporation (P / N: 193-08602) can also be used.

[0046] "Acesulfame potassium" is an oxathiazinone dioxide derivative having a sulfamic acid skeleton. Its IUPAC name is potassium 6-methyl-2,2-dioxo-oxathiazine-4-olate, and it is a kind of artificial sweetener classified as a sulfamate.

[0047] [Chemical formula]

[0048] It may also be referred to as acesulfame K. Commercially available products such as those from Tokyo Chemical Industry Co., Ltd. (P / N: A1490) and FUJIFILM Wako Pure Chemical Corporation (P / N: 013-14102) can also be used.

[0049] Advantame is a derivative of aspartame and an artificial sweetener with a peptide backbone. It has a structure in which a 3-(3-hydroxy-4-methoxyphenyl)propyl group is introduced into the amino group of the aspartic acid residue of aspartame. Its IUPAC name is (3S)-3-[3-(3-hydroxy-4-methoxyphenyl)propylamino]-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid.

[0050]

Chem.

[0051] For Advantame, commercially available products such as Advantame monohydrate (P / N: 018-26801) from Fujifilm Wako Pure Chemical Corporation and Advantame monohydrate (P / N: 1011889) from Sigma-Aldrich can also be used. Neotame is a derivative of aspartame and an artificial sweetener with a peptide backbone. It has a structure in which a 3,3-dimethylbutyl group is introduced into the amino group of the aspartic acid residue of aspartame. Its IUPAC name is (3S)-3-(3,3-dimethylbutylamino)-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid.

[0052]

Chem.

[0053] For Neotame, commercially available products such as those from Tokyo Chemical Industry Co., Ltd. (P / N: N1112) and Sigma-Aldrich (P / N: 49777) can also be used.

[0054] Aspartame is an artificial sweetener with a dipeptide backbone consisting of phenylalanine and aspartic acid. It has a structure in which the carboxyl group of the phenylalanine residue is methyl esterified. Its IUPAC name is N-(L-α-aspartyl)-L-phenylalanine-1-methyl ester.

[0055]

Chemical formula

[0056] Commercially available aspartame can also be used, for example, those from Tokyo Chemical Industry Co., Ltd. (P / N: A0997), Fujifilm Wako Pure Chemical Corporation (P / N: 016-11331), etc.

[0057] In one aspect, the sweetener is a neohesperidin derivative. Neohesperidin is a compound known by its IUPAC name: (2S)-7-[[2-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one.

[0058]

Chemical formula

[0059] Neohesperidin is a type of polyphenol contained in citrus fruits and is a flavonoid with bitterness. The term "neohesperidin derivative" refers, without limitation, to derivatives that maintain the disaccharide backbone structure of mannose and glucose of neohesperidin. In one aspect, the neohesperidin derivative is a derivative that maintains the disaccharide backbone structure of mannose and glucose of neohesperidin and the structure of the substituted phenyl group, preferably the structure of 3-hydroxy-4-methoxyphenyl.

[0060] Optionally, the neohesperidin derivatives include neohesperidin dihydrochalcone, glucosyl hesperidin (CAS No.: 161713-86-6), methyl hesperidin (CAS No.: 11013-97-1). In one aspect, the neohesperidin derivative is neohesperidin dihydrochalcone. Neohesperidin dihydrochalcone is a compound with the following chemical formula and CAS No. 20702-77-6.

[0061] [Chemical formula]

[0062] Neohesperidin dihydrochalcone is a sweetener classified as a flavonoid glycoside. Neohesperidin dihydrochalcone is a derivative of neohesperidin that maintains the disaccharide backbone structure of mannose and glucose of neohesperidin and the structure of 3-hydroxy-4-methoxyphenyl. It is reported to have a sweetness intensity about 1000 - 1800 times that of sucrose (Non-Patent Documents 11 and 12).

[0063] Commercially available neohesperidin dihydrochalcone, such as those from Tokyo Chemical Industry Co., Ltd. (P / N: N0675), Sigma-Aldrich (P / N: W381101), etc., can also be used.

[0064] In one aspect, the sweetener is a hesperidin derivative having a sweetness of 0.5 or more times the sweetness of neohesperidin dihydrochalcone. Non-limitingly, the sweetness is determined from the weight ratio of the substance concentration showing the same sweetness intensity as that of sucrose at any concentration set to 1, or the ratio to the threshold value of sucrose determined under the same conditions (Non-Patent Documents 6-11. Depending on the document, the sweetness intensity of sucrose may be set to 100, but in this specification, all are expressed after conversion to 1). Since the sweetness is a relative index to the sweetness intensity of sucrose, it is often expressed as relative sweetness, but these are synonymous, and in the present invention, they are uniformly expressed as "sweetness". However, since sweetness and concentration are not always in a linear relationship, the sweetness may have different values depending on the concentration of sucrose used as a reference. In addition, the sweetness may be affected by conditions such as the dosage, temperature, pH of the test solution, and the number and proficiency of the panelists. "Having a sweetness of 0.5 or more times the sweetness of neohesperidin dihydrochalcone" means satisfying this requirement when the sweetness is measured under substantially the same conditions as neohesperidin dihydrochalcone. Since neohesperidin dihydrochalcone is said to have a sweetness about 1000-1800 times that of sucrose, "having a sweetness of 0.5 or more times the sweetness of neohesperidin dihydrochalcone" means, non-limitingly, that the sweetness is preferably 500 or more, 600 or more, 700 or more, 800 or more, 900 or more, 1000 or more.

[0065] Among the above 10 types of sweeteners, the proteins monellin and thaumatin are considered to show some solubility in the polar solvents propylene glycol (PG) and glycerin (GL). However, in e-liquids that generally coexist with flavors and nicotine, proteins may be insolubilized. Therefore, when monellin or thaumatin is used as a sweetener, the types of flavors that can be used and the blending amount of nicotine may be restricted.

[0066] In one aspect, the sweetener is selected from the group consisting of glycyrrhizin, stevioside or stevia extract, saccharin, acesulfame potassium, advantame, neotame, and neohesperidin dihydrochalcone.

[0067] The tobacco composition may contain one type of sweetener or a combination of two or more types of sweeteners.

[0068] The amount of each sweetener contained in the tobacco composition is not particularly limited. In one aspect, the sweetener is advantame. Without limitation, the tobacco composition contains 0.005 wt% or more, 0.01 wt% or more, 0.02 wt% or more, 0.03 wt% or more, 0.04 wt% or more, 0.05 wt% or more, 0.06 wt% or more, 0.07 wt% or more of advantame. Without limitation, the tobacco composition contains 0.30 wt% or less, 0.20 wt% or less, 0.15 wt% or less, 0.10 wt% or less of advantame.

[0069] In one aspect, the sweetener is neotame. Without limitation, the tobacco composition contains 0.02 wt% or more, 0.03 wt% or more, 0.04 wt% or more, 0.05 wt% or more, 0.06 wt% or more, 0.07 wt% or more, 0.08 wt% or more, 0.09 wt% or more, 0.10 wt% or more, 0.12 wt% or more of neotame. Without limitation, the tobacco composition contains 0.50 wt% or less, 0.40 wt% or less, 0.30 wt% or less, 0.20 wt% or less, 0.15 wt% or less of neotame.

[0070] In one aspect, the sweetener is neohesperidin dihydrochalcone. Non-limitingly, the composition for tobacco contains neohesperidin dihydrochalcone in an amount of 0.05% by weight or more, 0.08% by weight or more, 0.10% by weight or more, 0.12% by weight or more, 0.15% by weight or more, 0.18% by weight or more, 0.20% by weight or more, 0.22% by weight or more, 0.25% by weight or more, 0.28% by weight or more, 0.30% by weight or more. Non-limitingly, the composition for tobacco contains neohesperidin dihydrochalcone in an amount of 0.80% by weight or less, 0.60% by weight or less, 0.50% by weight or less, 0.40% by weight or less, 0.35% by weight or less.

[0071] The composition for tobacco may contain one type of sweetener or a combination of two or more types of sweeteners. The "composition for tobacco" is a composition that contains some or all of the components to impart flavors such as fragrance and sweetness to "tobacco" such as tobacco products and e-liquids. The composition may be liquid or solid, but is preferably a liquid composition. "Tobacco" includes combustion-type flavor inhalation articles, heat-type flavor inhalation articles, tobacco products such as snus, and e-liquids. In one aspect, the composition for tobacco is heated to 150 to 300 °C before use.

[0072] In one aspect, the composition for tobacco may contain other components in addition to the sweetener. Components that the composition may contain include, non-limitingly, fragrances, flavoring agents, taste receptor activity enhancers / inhibitors, sensory receptor activity enhancers / inhibitors, etc. In addition, optionally, coloring agents, wetting agents, and preservatives may be included. The flavoring agents and optional materials may be in any form, such as liquid or solid. They may be single components or combinations of multiple components.

[0073] In one aspect, the composition for tobacco contains a fragrance. Suitable flavors of the fragrance include fragrances selected from tobacco extracts and tobacco components, carbohydrates and sugar-based flavors, licorice, cocoa, chocolate, fruit juices and fruits, spices, liqueurs, herbs, vanilla, and flower-based flavors, either alone or in combination. The fragrance can use a wide variety of fragrance components as described, for example, in "Collection of Well-Known and Conventional Technologies (Fragrances)" (issued by the Patent Office on March 14, 2007), "Dictionary of the Latest Fragrances (Popular Edition)" (compiled by Soichi Arai, Akira Kobayashi, Izumi Yajima, and Michiaki Kawasaki, published by Asakura Shoten on February 25, 2012), and "Tobacco Flavoring for Smoking Products" (June 1972, R. J. REYNOLDS TOBACCO COMPANY). In one aspect, the composition for tobacco contains nicotine.

[0074] 2. E-liquid The present invention also relates to an e-liquid. The e-liquid of the present invention contains the composition for tobacco of the present invention. The "composition for tobacco" of the present invention is as detailed in item "1. Composition for tobacco".

[0075] An e-liquid is a liquid composition for a liquid heating type heating fragrance inhaler (sometimes referred to as an "electronic cigarette"). An e-liquid generally contains propylene glycol (PG), glycerin (GL), nicotine, and a fragrance, etc. The e-liquid containing the composition for tobacco contains a sweetener other than sucralose.

[0076] 3. Tobacco products The present invention further relates to a tobacco product. The tobacco product of the present invention contains the composition for tobacco of the present invention. The "composition for tobacco" of the present invention is as detailed in item "1. Composition for tobacco". "Tobacco products" include, without limitation, combustion type fragrance inhalation articles, heating type fragrance inhalation articles, snus, etc.

[0077] In one aspect, the tobacco product is a combustion-type flavor inhalation article. The "combustion-type flavor inhalation article" is a general combustion smoking article that uses combustion for smoking, including paper tobacco, cigarettes, cigars, etc. Non-limitingly, for example, the tobacco leaves, shredded tobacco, tobacco sheets, etc. used in the combustion-type flavor inhalation article may be used by immersing the composition for tobacco in a liquid state. Alternatively, when manufacturing the combustion-type flavor inhalation article, the composition for tobacco may be used by filling it together with tobacco leaves, shredded tobacco, tobacco sheets, etc.

[0078] In one aspect, the tobacco product is a heat-not-burn flavor inhalation article. The "heat-not-burn flavor inhalation article" uses tobacco leaves, heats the tobacco leaves instead of burning them, and inhales the generated vapor (aerosol). Non-limitingly, the "heat-not-burn flavor inhalation article" generally includes a tobacco-containing segment, a cylindrical cooling segment having perforations on the circumference, and a filter segment. The non-combustion heat-not-burn smoking article may also have other segments in addition to the tobacco-containing segment, the cooling segment, and the filter segment. The tobacco leaves, shredded tobacco, tobacco sheets, etc. used in the non-combustion heat-not-burn smoking article may be used by immersing the composition for tobacco in a liquid state. Alternatively, when manufacturing the non-combustion heat-not-burn smoking article, the composition for tobacco may be used by filling it together with tobacco leaves, shredded tobacco, tobacco sheets, etc.

[0079] In one aspect, the tobacco product may be a snus. Snus, also called "snuff tobacco", is generally used by putting ground tobacco leaves in a sachet and clamping it between the lips and gums. Recently, there has also emerged a form of snus that does not use any tobacco leaves at all, called a nicotine pouch or white snus. These are generally in the form of encapsulating in a sachet, instead of tobacco leaves, a carrier such as cellulose fiber, resin, inorganic salt, etc. that holds nicotine extracted and isolated from tobacco leaves, and are being recognized as a new form of snus. In the present invention, nicotine pouches are also treated as one form of snus. Since snus is neither heated nor burned, no smoke is produced, so it is also called "smokeless tobacco". The tobacco leaves used in ordinary snus or the carrier of the nicotine pouch may be used by immersing the composition for tobacco in a liquid state, etc.

Examples

[0080] Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited to these examples. Those skilled in the art can easily make modifications and changes to the present invention based on the description in this specification, and they are included in the technical scope of the present invention.

[0081] Example 1 Primary screening of sweeteners applicable to e-liquid: Sweetness degree 1-1 Setting of indicators for primary screening The first condition to be considered is solubility in e-liquid. This is because, due to the product characteristics of e-liquid, it is necessary to prepare a uniform solution in which the contents are completely dissolved. Commonly known sweeteners are substances that are originally contained in foods such as sugars and sugar alcohols, or those that have been developed and put into practical use assuming application to foods and beverages like artificial sweeteners. Most of these substances basically show water solubility, and there are also substances that hardly dissolve in organic solvents, so attention is required. The solvents of general e-liquids are PG and GL, and when applying sweeteners to e-liquids, it is necessary to consider their solubility in PG and GL. Theoretically, it can be said that stronger sweetening substances are more advantageous in terms of solubility in PG and GL because it is assumed that a smaller amount of a stronger sweetening substance is required to achieve the same sweetness intensity.

[0082] The sweetness intensity of a sweetener is generally expressed by an index called sweetness degree. The sweetness degree is determined from the weight ratio of the concentration of a substance that exhibits the same sweetness intensity as that of sucrose at an arbitrary concentration, with the sweetness intensity of sucrose being set to 1, or the ratio to the threshold value of sucrose determined under the same conditions (Non-Patent Documents 6-11; in some documents, the sweetness intensity of sucrose may be set to 100, but in this specification, all are expressed after conversion to 1). Since the sweetness degree is a relative index to the sweetness intensity of sucrose, it is often expressed as Relative Sweetness, but these are synonymous, and in this specification, they are uniformly expressed as "sweetness degree". The sweetness degree of sucralose has been reported to be 320-1000 (Non-Patent Documents 1, 7, 9, 13, 14). The inventors calculated the ratio of the sweetness degree of each sweetener reported in the literature and sucralose, and defined that value as the "required magnification assumed to exhibit the same sweetness as sucralose for each sweetener" (e.g., ○○ times that of sucralose; hereinafter referred to as the assumed required magnification), and decided to use it as an index for primary screening. Note that the sweetness degree is generally an index expressing the sweetness intensity in an aqueous solution, and it is fully understood that the sweetness intensity as reported by the sweetness degree does not necessarily appear in the form delivered into the oral cavity after aerosolization like an e-cigarette. However, it is not unreasonable to assume that there is a certain correlation between the value of the sweetness degree expressed in an aqueous solution and the sweetness intensity delivered into the oral cavity after aerosolization, and it was considered to be a reasonable parameter as an index for primary screening.

[0083] Generally known information on sweeteners was widely collected, classified by chemical structure, and the values of the sweetness degree were summarized in Table 1.

[0084]

Table 1

[0085] 1-2 Consideration of Each Sweetener First, we will consider saccharides, which are the most typical sweeteners. Although the sweetness intensity of typical sugars may vary slightly depending on the evaluation method and literature, it generally ranges from about 0.2 to 1.7. Suppose we consider using fructose, which has a relatively strong sweetness intensity among saccharides with a sweetness intensity of 1.15 - 1.80, to achieve a sweetness intensity similar to that of sucralose. Calculated simply from the sweetness intensity of sucralose, which is 320 - 1000, the assumed required magnification of fructose would be approximately 178 - 870 times. When using saccharides with a lower sweetness intensity than fructose, even more sugar would be required in the calculation. It is highly likely that it would be difficult to dissolve such a large amount of sugar in PG or GL, which are the solvents of e-liquid, to the extent that sweetness can be expressed, and it is assumed that it would be difficult to express sufficient sweetness on its own.

[0086] Next, we will consider sugar alcohols, which are often used as substitutes for saccharides in foods and beverages. As shown in Table 1, many sugar alcohols have a lower sweetness intensity than saccharides, generally ranging from 0.3 to 1.2. Even xylitol, which has a relatively strong sweetness intensity among sugar alcohols, has a sweetness intensity of 0.65 - 1.20. To express sufficient sweetness, it is assumed that more sugar alcohol would need to be dissolved in PG or GL, which are the solvents of e-liquid, than the above-mentioned saccharides. From this, it is also assumed that it would be difficult for sugar alcohols to express sufficient sweetness on their own.

[0087] Furthermore, although some amino acids such as glycine are known to have a sweet taste, the sweetness intensity of glycine is 0.9. Similar to the above-mentioned saccharides and sugar alcohols, the sweetness intensity is low, and it is assumed that it would be difficult to express sufficient sweetness on its own.

[0088] Some proteins also exhibit sweetness, such as Monellin and Thaumatin. Monellin and Thaumatin are proteins discovered from plants growing in the tropical rainforest. Monellin has a sweetness intensity of 3000 (Non-Patent Documents 12, 13, 14), and Thaumatin has a sweetness intensity of 1600 - 3000 (Non-Patent Documents 9, 12, 13, 14) and is known as a natural sweetener with a very strong sweetness. When calculating the assumed required magnification using these sweetness intensity values, Monellin is about 0.1 - 0.3 times that of sucralose, and Thaumatin is about 0.1 - 0.6 times that of sucralose. Proteins generally have low solubility in organic solvents, but it is considered that they show a certain degree of solubility in polar solvents such as PG and GL, and there is a possibility of being applicable to e-liquids in trace amounts. From the above considerations, it was determined that Monellin and Thaumatin could be candidates for alternative sweet sources to sucralose in e-liquids and would be used in subsequent studies.

[0089] Next, let's consider glycyrrhizin and stevioside, which are natural sweeteners with the structure of terpene glycosides. Glycyrrhizin (often referred to as glycyrrhizic acid) is a component contained in the roots of licorice and is said to have medicinal effects such as an anti-inflammatory effect (Non-Patent Document 15). Stevioside is a sweetener discovered from the South American asteraceae plant Stevia and is often used in foods, etc. in the state of a Stevia extract, which is a mixture with other related substances derived from Stevia without isolation. The sweetness intensities of glycyrrhizin and stevioside (Stevia extract) are 50 - 300 (Non-Patent Documents 8, 12, 14) and 150 - 300, respectively (Non-Patent Documents 9, 12, 14). When calculating the assumed required magnification using these sweetness intensity values, glycyrrhizin is about 1.1 - 20.0 times that of sucralose, and stevioside (Stevia extract) is about 1.1 - 6.7 times that of sucralose. Since both have highly polar sugar chains in their molecular structures, they are expected to show a certain degree of solubility in polar solvents such as PG and GL. From this, it was determined that glycyrrhizin and stevioside (Stevia extract) could be candidates for alternative sweetening sources to sucralose in e-liquids and were used for subsequent studies.

[0090] Next, we will discuss saccharin, which has a sulfamide skeleton, and acesulfame potassium, which has a sulfamic acid skeleton. Sulfamide and sulfamic acid have structures in which the hydroxy group of sulfuric acid is substituted with an amino group. Sulfamide has two amino groups substituted, and sulfamic acid has one amino group substituted. Saccharin is often used in the form of its sodium salt for the purpose of improving its solubility in water and is a sweetener commonly used in foods, particularly in the United States and China. Acesulfame potassium is a sweetener used in foods in various countries such as Japan, Europe, and the United States. The sweetness intensity of saccharin is reported to be 200 - 550 (Non-Patent Documents 7, 8, 9, 13, 14), and that of acesulfame potassium is 200 (Non-Patent Documents 7, 9, 13, 14). When calculating the assumed required magnification using these sweetness intensity values, saccharin is approximately 0.58 - 5.00 times that of sucralose, and acesulfame potassium is approximately 1.60 - 5.00 times that of sucralose. Since both have a highly polar sulfamide or sulfamic skeleton in their molecular structures, they are expected to show some solubility in polar solvents such as PG and GL. From this, it was determined that saccharin and acesulfame potassium could be candidates for alternative sweetening sources to sucralose in e-liquids and were used in subsequent studies.

[0091] Next, consider sodium cyclamate, which also has a sulfamic acid skeleton. It is known by the common name "Cyclamate" and is approved for use in Europe and China, but is prohibited in Japan, the United States, etc. It is a sweetener with different regulations in different countries. For this reason, foods containing sodium cyclamate are frequently imported from overseas in Japan, and there have been frequent cases of violations of the Food Sanitation Law regarding the use of non-approved additives. Sodium cyclamate has a sweetness intensity of 30 - 80 (Non-Patent Documents 7, 9, 13, 14). Although it is weaker than saccharin and acesulfame potassium, it has a certain level of sweetness. Due to its chemical structure, it is expected to show a certain level of solubility in PG and GL. Therefore, it seems highly likely that it can be applied to e-liquids, but it is expected that many countries will find it difficult to handle in terms of regulations, so it can be said to lack versatility. Therefore, it was decided not to use it in future considerations.

[0092] Next, consider the artificial sweetener aspartame, which is a peptide derivative. Aspartame is used as a food additive in various countries, and its reported sweetness intensity is 100 - 200 (Non-Patent Documents 7, 8, 9, 13, 14). Calculating the assumed required magnification using this sweetness intensity value results in 1.60 - 10.00 times that of sucralose. Since aspartame has multiple polar functional groups in its molecule, it is expected to show a certain level of solubility in polar solvents such as PG and GL. From this, it was determined that aspartame could be a candidate for an alternative sweetening source to sucralose in e-liquids, and it was decided to use it in future considerations.

[0093] Considerations are made regarding Advantame and Neotame, which are also peptide-derived artificial sweeteners with very high sweetness intensities. Both are sweeteners developed by derivatizing aspartame and are approved for use in foods in multiple countries. Advantame has been reported to have a sweetness intensity of 20,000 (Non-Patent Document 13) and is said to have the highest sweetness intensity among synthetic sweeteners known to date. On the other hand, Neotame has been reported to have a sweetness intensity of 7,000 - 13,000 (Non-Patent Documents 13 and 14) and was an artificial sweetener that was said to have the highest sweetness intensity until Advantame was later developed. Since both have very high sweetness intensities that exceed that of sucralose, there is an expectation that the sweetness intensity can be ensured with a very small amount. When calculating the assumed required magnification using the values of the sweetness intensities of both, Advantame is approximately 0.016 - 0.050 times that of sucralose, and Neotame is approximately 0.025 - 0.143 times that of sucralose. Since both have a high possibility of ensuring the sweetness intensity with a very small amount and have multiple polar functional groups in their molecular structures, it is predicted that they will show some solubility in polar solvents such as PG and GL. From this, it was determined that Advantame and Neotame could be candidates for alternative sweetening sources to sucralose in e-liquids and were used in subsequent investigations.

[0094] Finally, we will discuss neohesperidin dihydrochalcone, a flavonoid glycoside. Neohesperidin dihydrochalcone is an artificial sweetener synthesized by derivatizing neohesperidin present in citrus fruits (Non-Patent Document 11), and its sweetness intensity is reported to be 1000 - 1800 (Non-Patent Documents 11 and 12). Neohesperidin dihydrochalcone is a food additive recognized as GRAS (Generally Recognized As Safe) in the United States (Non-Patent Document 16), and it is also registered as food additive E959 as a sweetener in Europe (Non-Patent Document 17), so it can be said that its safety has been confirmed. When calculating the assumed required magnification using the sweetness intensity value of 1000 - 1800 of neohesperidin dihydrochalcone, it becomes about 0.18 - 1.00 times that of sucralose. Since neohesperidin dihydrochalcone has a highly polar sugar chain in its molecular structure, it is expected to show a certain degree of solubility in polar solvents such as PG and GL. From this, it was judged that neohesperidin dihydrochalcone could be a candidate for an alternative sweetening source to sucralose in e-liquids and was used for subsequent studies.

[0095] 1-3 Summary of Primary Screening by Sweetness Intensity When screening candidate substances that could be alternative sweetening sources to sucralose in e-liquids using the assumed required magnification relative to sucralose as an index, 10 types of sweeteners, namely monellin, thaumatin, glycyrrhizin, stevioside (stevia extract), saccharin, acesulfame potassium, advantame, neotame, aspartame, and neohesperidin dihydrochalcone, were selected as useful candidate substances.

[0096] Example 2 Secondary screening of sweeteners applicable to e-liquid: Solubility 2-1 About Monellin and Thaumatin First, let's consider monellin and somatostatin, which are proteins. As mentioned above, although a certain degree of solubility can be expected for polar solvents such as PG and GL, generally, many proteins have low solubility in hydrophobic organic solvents. The protein precipitation method using organic solvents, which is a commonly used experimental technique in the field of biology, utilizes this property of proteins. It might be possible to simply dissolve monellin and somatostatin in PG or GL, but it is necessary to consider that in general e-liquids, in addition to PG and GL, flavors and nicotine also coexist. That is, adding flavors and nicotine may cause proteins such as monellin and somatostatin to become insoluble, and there may be limitations on the types of flavors that can be used and the blending amounts of nicotine.

[0097] 2-2 Confirmation of Solubility of the Remaining 8 Types of Sweeteners Regarding the remaining 8 types of sweeteners, it was decided to confirm the actual solubility in PG / GL. When confirming the solubility, it is necessary to set specific target concentrations for each sweetener.

[0098] 2-2-1. Setting of Target Concentrations The inventor calculated the assumed concentration of each sweetener in the e-liquid by multiplying the assumed required magnification of each sweetener described above by the concentration of sucralose that is generally used. As the concentration of sucralose that is generally used, the information in Non-Patent Document 18 was cited. According to this, it is described that a weak sweetness is expressed by blending 1% (wt / vol) of sucralose in the e-liquid. Assuming that a certain sweetness is expressed if the sucralose concentration reaches 1% (wt / vol), that is, 1 mg / mL, first, a sucralose concentration of 1 mg / mL was set as the reference target, and the target concentration was set by multiplying the assumed required magnification of each sweetener described above by sucralose.

[0099] 2-2-2. Measurement of Weight Concentration of 1 mg / mL Sucralose Liquid In units of weight / volume such as mg / mL, since the liquid density fluctuates due to factors such as the PG / GL ratio of the solvent, the type and amount of sweetener to be dissolved, the influence of coexisting substances such as nicotine and flavor, and temperature, it is not suitable to quantitatively set, compare, and evaluate the sweetener concentration in the liquid. In order to ignore these influences, in the subsequent studies, the PG / GL ratio of the solvent was fixed at a weight ratio of PG:GL = 1:1, and verification was carried out based on weight concentration.

[0100] An experiment was conducted to determine the weight concentration of a 1 mg / mL solution of sucralose. All experiments in this section were carried out at room temperature in a laboratory with air conditioning controlled at 25 °C ± 2 °C. The dilution solvent used was a pre-mixed solution of PG and GL with a weight ratio of 1:1, which was allowed to stand until all the bubbles had completely escaped. The sucralose used was purchased from Tokyo Chemical Industry Co., Ltd. (P / N: S0839).

[0101] 0.500 g of sucralose was weighed into a screw tube. Subsequently, 99.500 g of the dilution solvent was weighed, and then stirred until the sucralose was completely dissolved to obtain a 0.5 wt% sucralose dilution. After standing until all the bubbles had completely escaped, 10.000 g of this dilution was weighed into a 50 mL volumetric flask, and then made up to 50 mL with the dilution solvent to obtain a 1 mg / mL sucralose solution. At this time, the weight of the dilution solvent used for volume adjustment was 46.786 g. From these results, the weight concentration of sucralose in the liquid prepared at a sucralose concentration of 1 mg / mL with a solvent of PG:GL = 1:1 was 0.088 wt%. In the subsequent studies, the liquid with 0.088 wt% sucralose was used as the reference standard.

[0102] 2-2-3. Calculation of the target concentration of each sweetener Based on the 0.088 wt% sucralose calculated in the previous section, the target concentration of each sweetener was determined in weight concentration by multiplying the assumed required magnification of each sweetener relative to sucralose calculated from the sweetness intensity. The results are shown in Table 2.

[0103]

Table 2

[0104] Based on the assumption that a certain degree of sweetness can be expressed if each sweetener is at a concentration above the target, it was used as a guideline when confirming the actual solubility.

[0105] 2-2-4. Dissolution test of each sweetener Regarding the solubility information of each sweetener, there are numerous reference documents available if the solvent is water, ethanol, etc. However, there are almost no reference documents available for the solubility information of PG and GL. Therefore, dissolution tests were carried out using actual substances.

[0106] 2-2-4-1. Reagents used It is known that in addition to stevioside, stevia also coexists with analogs such as rebaudioside A, rebaudioside C, and dulcoside A, and the component composition varies greatly depending on the variety, cultivation conditions, etc. (Non-Patent Document 19). However, their chemical structures are glycosides with a common structure of terpenes (aglycones) bonded to sugar chains, and only the sugar sequences of the glycone are different. From this, it is assumed that there is not much difference in the solubility of these components in PG and GL. Therefore, in this study, a dissolution test was carried out using pure stevioside as a representative. In addition, saccharin is a form commonly used as a food additive, and more stable saccharin sodium dihydrate was used.

[0107] Each sweetener was purchased from the following reagent companies and used. Glycyrrhizin: Tokyo Chemical Industry Co., Ltd. (P / N: G0150) Stevioside: Fujifilm Wako Pure Chemical Corporation (P / N: 194-16481) Saccharin sodium dihydrate: Tokyo Chemical Industry Co., Ltd. (P / N: B0131) Acesulfame potassium: Tokyo Chemical Industry Co., Ltd. (P / N: A1490) Aspartame: Tokyo Chemical Industry Co., Ltd. (P / N: A0997) Advantage: FUJIFILM Wako Pure Chemical Corporation (P / N: 018-26801) Neotame: Tokyo Chemical Industry Co., Ltd. (P / N: N1112) Neohesperidin dihydrochalcone: Tokyo Chemical Industry Co., Ltd. (P / N: N0675)

[0108] 2-2-4-2. Dissolution test procedure This experiment was carried out at room temperature in a laboratory with air conditioning controlled at 25°C ± 2°C. The sweeteners and PG with the weights shown in Table 3 were weighed into screw tubes, and stirring was continued at a speed of 750 rpm for 6 hours with a magnetic stirrer. The presence or absence of undissolved residue was confirmed by visual inspection as appropriate, and stirring was stopped when complete dissolution occurred and the next step was proceeded. If there was undissolved residue even after stirring for 6 hours, it was judged as "insoluble" at that time.

[0109] To each screw tube, GL with the weight shown in Table 3 was further added, and stirring was carried out at a speed of 1000 rpm for 1 hour with a magnetic stirrer. After the stirring was completed, it was confirmed by visual inspection whether re-aggregation had occurred, and those that had become a uniform liquid were judged as "soluble".

[0110] 2-2-4-3. Dissolution test Results and discussion The results of the dissolution test are shown in Table 3.

[0111]

Table 3

[0112] Regarding glycyrrhizin, stevioside, saccharin sodium dihydrate, acesulfame potassium, Advantage, Neotame, and neohesperidin dihydrochalcone, solubilities equal to or higher than the target concentration calculated in section 2-2-3 were confirmed, so it can be said that there is no problem from the perspective of solubility for application to e-liquid. Aspartame had a solubility of 0.15 wt% or more and less than 0.25 wt%, which was lower than that of the other 7 substances and was near the lower limit of the aforementioned target concentration of 0.141 - 0.440 wt%.

[0113] Summary of Primary Screening Based on Solubility (2 - 3) As a result of verifying the solubility in PG / GL, which is the solvent of e - liquid, in seven substances including glycyrrhizin, stevioside (stevia extract), saccharin, acesulfame potassium, advantame, neotame, and neohesperidin dihydrochalcone, solubility above the concentration presumed to be necessary for expressing sweetness was confirmed, and their usefulness for application to e - liquid was confirmed. Aspartame had a slightly low solubility in PG and GL.

[0114] Example 3 Verification of the effect of sweeteners in e-liquid In the verification up to item 2, screening has been carried out on whether it is applicable to e - liquid from the viewpoints of sweetness intensity and solubility. However, as mentioned above, the sweetness intensity is a value representing the sweetness strength evaluated in an aqueous solution. Therefore, it is necessary to confirm whether the candidate sweeteners actually express sweetness in the form of e - liquid. Therefore, in this item, the results of verifying whether the candidate sweeteners actually express sweetness and, if so, in what concentration range are shown.

[0115] 3 - 1 Qualitative Evaluation of Sweeteners For glycyrrhizin, stevioside, saccharin, acesulfame potassium, aspartame, advantame, neotame, and neohesperidin dihydrochalcone, e - liquids with the compositions shown in Table 4 were prepared respectively, and qualitative sensory evaluations were carried out using a Logic Compact device (sales site: https: / / logicvapes.co.uk / about / compact) commercially available in Europe. The evaluation panel consisted of 2 expert panelists who are engaged in the development and sensory evaluation of e - liquids on a daily basis, and the evaluation was carried out in a form where they were allowed to freely describe their comments. The compositions of the evaluated samples and the evaluation results are shown in Table 4.

[0116]

Table 4

[0117] First, as described above, aspartame has limited solubility in PG and GL, and it could not exhibit sufficient sweetness at a concentration that would completely dissolve in a solvent with a PG:GL ratio of 1:1. Since aspartame shows a solubility of about 5% by weight at pH 7 in water (Non-Patent Document 20), it is considered possible to increase the concentration further by adding water as a solubilizing agent.

[0118] In the case of glycyrrhizin, stevioside, saccharin, acesulfame potassium, advantame, neotame, and neohesperidin dihydrochalcone, it was confirmed that a sweetness of a strength perceptible by the expert panel was expressed.

[0119] Among these, it was confirmed that three types, advantame, neotame, and neohesperidin dihydrochalcone, which have high sweetness values, can exhibit sweetness even at low concentrations. This can also be said to be a result that supports the hypothesis described above in Section 1-1, "There is a certain correlation between the value of the sweetness expressed in an aqueous solution and the sweetness intensity delivered into the oral cavity after aerosolization."

[0120] In order to clarify the preferable concentration range for expressing sweetness for the three types of advantame, neotame, and neohesperidin dihydrochalcone for which it was confirmed that sweetness is expressed at low concentrations, further verification was to be carried out.

[0121] 3-2 Verification of the concentration threshold for expressing sweetness Regarding three types of sweeteners, advantame, neotame, and neohesperidin dihydrochalcone, verification of the lower limit of the concentration for expressing sweetness, that is, the threshold value, was carried out in e-liquid. The threshold value was assumed to be "the concentration at which the general consumer can statistically significantly perceive sweetness," and verification was to be carried out by sensory evaluation.

[0122] 3-2-1. Sensory evaluation method The level without any sweetener was set as Reference 1. E-liquids with the compositions shown in Table 5 were prepared with each level having different concentrations of each sweetener as samples, and sensory evaluations were performed on 18 panelists using the aforementioned Logic Compact device. The panelists were asked to compare the intensity of sweetness (defined as the sweetness felt on the tongue or the sweetness remaining in the mouth after inhaling the aerosol) between Reference 1 and the samples of each Lot, and to answer in a forced-choice format which one, Reference 1 or the sample, had a stronger sweetness. Statistical analysis was carried out using a binomial test. The statistically significant level α in the binomial test was set at 0.05, which is commonly used.

[0123] 3-2-2. Sensory Evaluation Results and Analysis The obtained results were statistically analyzed by a binomial test. The null hypothesis H 0 was set as "The probability of choosing Reference 1 and the sample is equal". Under this null hypothesis, when 18 people were surveyed, the number of people who answered "The sample is sweeter" follows a binomial distribution B(18, 0.5). The p-value, which is the probability that the number of people who answered "The sample is sweeter" is greater than or equal to the current result under this null hypothesis, was calculated. The results of the binomial test are shown in Table 6.

[0124]

Table 5

[0125]

Table 6

[0126] 3-2-2-1. Discussion on the Results of the Advantage For Lot A1-1, A1-2, and A1-3 with Advantage added at 0.001, 0.0025, and 0.005% by weight respectively, the p-values were 0.593, 0.593, and 0.593 respectively. Therefore, the null hypothesis was not rejected at the 5% significance level for any of the levels. That is, for Reference 1 without a sweetener, it cannot be said that the sweetness of Advantage is statistically significantly perceived at concentrations of 0.005% by weight or less.

[0127] On the other hand, for Lot A1-4 and A1-5 with Advantage added at 0.01 and 0.02% by weight respectively, the p-values were 0.015 and 0.004 respectively. Therefore, the null hypothesis was rejected for both at the 5% significance level. That is, for Reference 1 without a sweetener, it can be said that the sweetness of Advantage is statistically significantly perceived at concentrations of 0.01% by weight or more.

[0128] From the above results, it is speculated that the threshold at which the sweetness of Advantage can be significantly perceived in the e-liquid is between Lot A1-3 and A1-4, that is, at a concentration greater than 0.005% by weight and less than 0.01% by weight.

[0129] 3-2-2-2. Discussion of the results of NeoTeam For Lot B1-1, B1-2, B1-3, and B1-4 with NeoTeam added at 0.001, 0.005, 0.01, and 0.02% by weight respectively, the p-values were 0.407, 0.996, 0.593, and 0.119 respectively. Therefore, the null hypothesis was not rejected at the 5% significance level for any of the levels. That is, for Reference 1 without a sweetener, it cannot be said that the sweetness of NeoTeam is statistically significantly perceived at concentrations of 0.02% by weight or less.

[0130] On the other hand, for Lot B1-5 with NeoTeam added at 0.05% by weight, the p-value was 0.015. Therefore, the null hypothesis was rejected at the 5% significance level. That is, for Reference 1 without a sweetener, it can be said that the sweetness of NeoTeam is statistically significantly perceived at concentrations of 0.05% by weight or more.

[0131] From the above results, it is speculated that the threshold concentration at which the sweetness of neohesperidin dihydrochalcone can be significantly perceived in e-liquid is between Lot B1-4 and B1-5, that is, greater than 0.02% by weight and less than 0.05% by weight.

[0132] 3-2-2-3. Results and Discussion of Neohesperidin Dihydrochalcone The p-values of Lot C1-1, C1-2, C1-3, and C1-4 containing 0.001, 0.01, 0.02, and 0.05% by weight of neohesperidin dihydrochalcone were 0.952, 0.760, 0.881, and 0.407, respectively. Therefore, the null hypothesis is not rejected at the 5% significance level at any level. That is, it cannot be said that the sweetness of neohesperidin dihydrochalcone is statistically significantly perceived at a concentration of 0.05% by weight or less compared to Reference 1 without a sweetener.

[0133] On the other hand, the p-value of Lot C1-5 containing 0.1% by weight of neohesperidin dihydrochalcone was 0.015. Therefore, the null hypothesis is rejected at the 5% significance level. That is, it can be said that the sweetness of neohesperidin dihydrochalcone is statistically significantly perceived at a concentration of 0.1% by weight or more compared to Reference 1 without a sweetener.

[0134] From the above results, it is speculated that the threshold concentration at which the sweetness of neohesperidin dihydrochalcone can be significantly perceived in e-liquid is between Lot C1-4 and C1-5, that is, greater than 0.05% by weight and less than 0.1% by weight.

[0135] 3-3 Verification of the Concentration Range Exhibiting Sweetness Intensity Equivalent to Sucralose Regarding three types of sweeteners, advantame, neotame, and neohesperidin dihydrochalcone, the concentration range that exhibits a sweetness intensity equivalent to that of sucralose, which is already widely used in e-liquids, was verified. The concentration range that exhibits a sweetness equivalent to that of sucralose was defined as the concentration at which "the general consumer cannot statistically significantly perceive the strength or weakness of sweetness," and it was decided to verify this by sensory evaluation. The concentration of sucralose for comparison was set to 1 mg / mL, which is mentioned in Non-Patent Document 18 as exhibiting sweetness as described in Section 2-2-1. Since the liquid of 1 mg / mL of sucralose is equivalent to 0.088% by weight as measured in Section 2-2-2, this concentration was used as Reference 2.

[0136] 3-3-1. Sensory Evaluation Method Taking the level with 0.088% by weight of sucralose as Reference 2 and each level with varying concentrations of each sweetener as samples, e-liquids were prepared according to the composition shown in Table 7, and sensory evaluation by 18 panelists was carried out using the aforementioned Logic Compact device. The panelists were asked to compare the strength of sweetness (defined as the sweetness felt by the tongue or the sweetness remaining in the mouth after aerosol inhalation) between Reference 2 and each Lot of samples, and they were asked to answer in a forced-choice format of which one, Reference 2 or the sample, had a stronger sweetness, and it was statistically analyzed using a binomial test. The statistically significant level α in the binomial test was set to 0.05, which is commonly used.

[0137] 3-3-2. Sensory Evaluation Results and Analysis The obtained results were statistically analyzed by a binomial test. First, the null hypothesis H 0 was set as "the probability of choosing Reference 2 and the sample is equal." Under this null hypothesis, when surveyed for 18 people, both the number of people who answer "the sample is sweeter" and the number of people who answer "Reference 2 is sweeter" follow the binomial distribution B(18, 0.5). Under this null hypothesis, the probability p 1The value and the probability p that the number of people who answer "Reference 2 is sweeter" is greater than the number of people in this result 2 The values were calculated respectively. The results of the binomial test are shown in Table 8.

[0138]

Table 7

[0139]

Table 8

[0140] 3-3-2-1. Discussion of the Advantage Team Results The p values in Lot A2-1, A2-2, and A2-3 with the advantage team blended at 0.005, 0.01, and 0.02% by weight respectively 1 were 0.593, 0.952, and 0.593 respectively. Therefore, at any level 1 from the p value, the null hypothesis is not rejected at the 5% significance level. That is, when the blending amount of the advantage team is in the range of 0.005% to 0.02% by weight, it cannot be said that the sample exhibits a statistically significantly stronger sweetness than Reference 2. Also, since the p values in Lot A2-1, A2-2, and A2-3 2 were 0.593, 0.119, and 0.593 respectively, at any level 2 from the p value, the null hypothesis is not rejected at the 5% significance level. That is, when the blending amount of the advantage team is in the range of 0.005% to 0.02% by weight, it cannot be said that Reference 2 exhibits a statistically significantly stronger sweetness than the sample either.

[0141] As described above, the p 1 value and the p 2From the values, when the blending amount of advantame is in the range of 0.005 wt% or more and 0.02 wt% or less, it cannot be said that the sample has a stronger sweetness than Reference 2, and at the same time, it cannot be said that Reference 2 has a stronger sweetness than the sample. That is, it is concluded that there is no statistically significant difference in the sweetness intensity between the two in this concentration range.

[0142] On the other hand, since the p 1 value in Lot A2-4 containing 0.05 wt% of advantame was 0.004, the null hypothesis was rejected at a significance level of 5%, and even when judged at a more stringent significance level of 1%, the null hypothesis was rejected. That is, when the blending amount of advantame is 0.05 wt%, it can be said that the sample exhibits a statistically significantly stronger sweetness than Reference 2.

[0143] From the above results, it was confirmed that for Reference 2 containing 0.088 wt% of sucralose, equivalent sweetness is exhibited in the range where the concentration of advantame is 0.005 wt% or more and 0.02 wt% or less, and it was confirmed that a stronger sweetness than Reference 2 is exhibited when the concentration of advantame is 0.05 wt% or more. From this, it is presumed that the boundary concentration of advantame that exhibits a stronger sweetness than Reference 2 exists in the range greater than 0.02 wt% and less than 0.05 wt%.

[0144] 3-3-2-2. Discussion of the results of neotame The p 1 values in Lot B2-1, B2-2, and B2-3 containing 0.01, 0.02, and 0.05 wt% of neotame were 0.407, 0.881, and 0.593, respectively. Therefore, the null hypothesis was not rejected at a significance level of 5% at any level from the p 1 value. That is, in the range where the blending amount of neotame is 0.01 wt% or more and 0.05 wt% or less, it cannot be said that the sample exhibits a statistically significantly stronger sweetness than Reference 2. Also, the p 2Since the values were 0.760, 0.240, and 0.593 respectively, p 2 From these values, the null hypothesis is not rejected at the 5% significance level at any level. That is, it cannot be said that Reference 2 exhibits a statistically significantly stronger sweetness than the sample when the blending amount of neotame is in the range of 0.01% by weight or more and 0.05% by weight or less.

[0145] As described above, p 1 value and p 2 From the values, it cannot be said that the sample has a stronger sweetness than Reference 2 when the blending amount of neotame is in the range of 0.01% by weight or more and 0.05% by weight or less, and at the same time, it cannot be said that Reference 2 has a stronger sweetness than the sample. That is, it can be concluded that there is no statistically significant difference in the sweetness intensity between the two in this concentration range.

[0146] On the other hand, since the p 1 value in Lot B2-4 containing 0.1% by weight of neotame was 0.048, the null hypothesis is rejected at the 5% significance level. That is, it can be said that the sample exhibits a statistically significantly stronger sweetness than Reference 2 when the blending amount of neotame is 0.1% by weight.

[0147] From the above results, it was confirmed that equivalent sweetness is exhibited in the range where the concentration of neotame is 0.01% by weight or more and 0.05% by weight or less with respect to Reference 2 containing 0.088% by weight of sucralose, and it was confirmed that a stronger sweetness than Reference 2 is exhibited when the concentration of neotame is 0.1% by weight or more. Also, it is presumed that the boundary concentration of neotame that exhibits a stronger sweetness than Reference 2 exists in the range greater than 0.05% by weight and less than 0.1% by weight.

[0148] 3-3-2-3. Result Discussion of Neohesperidin Dihydrochalcone The p 2Since the value was 0.015, the null hypothesis was rejected at the 5% significance level. That is, it can be said that at a neohesperidin dihydrochalcone content of 0.05% by weight, Reference 2 exhibits a statistically significantly stronger sweetness than the sample.

[0149] In Lot C2-2 and C2-3 containing 0.1% and 0.15% by weight of neohesperidin dihydrochalcone respectively, the p 1 values were 0.952 and 0.240 respectively. Therefore, at any level, the null hypothesis was not rejected at the 5% significance level based on the p 1 value. That is, in the range where the content of neohesperidin dihydrochalcone is 0.1% to 0.15% by weight, it cannot be said that the sample exhibits a statistically significantly stronger sweetness than Reference 2. Also, in Lot C2-2 and C2-3, the p 2 values were 0.119 and 0.881 respectively. Therefore, at any level, the null hypothesis was not rejected at the 5% significance level based on the p 2 value. That is, in the range where the content of neohesperidin dihydrochalcone is 0.1% to 0.15% by weight, it cannot be said that Reference 2 exhibits a statistically significantly stronger sweetness than the sample either.

[0150] As described above, from the p 1 value and the p 2 value, in the range where the content of neohesperidin dihydrochalcone is 0.1% to 0.15% by weight, it cannot be said that the sample has a stronger sweetness than Reference 2, and at the same time, it cannot be said that Reference 2 has a stronger sweetness than the sample either. That is, it is concluded that there is no statistically significant difference in the sweetness intensity between the two in this concentration range.

[0151] On the other hand, in Lot C2-4 containing 0.25% by weight of neohesperidin dihydrochalcone, the p 1Since the value was 0.015, the null hypothesis was rejected at the 5% significance level. In other words, it can be said that when the amount of neohesperidin dihydrochalcone was 0.25% by weight, the sample expressed a statistically significantly stronger sweetness than Reference 2.

[0152] From the above results, it was confirmed that, compared to Reference 2, which contains 0.088% by weight of sucralose, when the concentration of neohesperidin dihydrochalcone is in the range of 0.05% by weight or less, the sweetness expressed is weaker than that of Reference 2, when the concentration of neohesperidin dihydrochalcone is in the range of 0.1% by weight or more and 0.15% by weight or less, the equivalent sweetness is expressed, and when the concentration of neohesperidin dihydrochalcone is in the range of 0.25% by weight or more, a stronger sweetness is expressed than that of Reference 2. In addition, it is presumed that the boundary concentration of neohesperidin dihydrochalcone at which the sample begins to express a sweetness equivalent to that of Reference 2 is in the range of more than 0.05% by weight and less than 0.1% by weight, and that the boundary concentration of neohesperidin dihydrochalcone at which the sample expresses a stronger sweetness than Reference 2 is in the range of more than 0.15% by weight and less than 0.25% by weight.

[0153] 3-4 Verification of sweetness intensity in the high concentration range The relationship between concentration and sweetness intensity at higher concentration ranges than those tested in the previous section was examined by sensory evaluation for three types of sweeteners, advantame, neotame, and neohesperidin dihydrochalcone.

[0154] 3-4-1. Sensory evaluation method Reference 1 without added sweetener, Reference 2 with 0.088% by weight of sucralose, and samples were prepared for each level with varying concentrations of each sweetener. Sensory evaluations were conducted using the aforementioned Logic Compact device. The sweetness of each sample (defined as the sweetness felt on the tongue or the sweetness remaining in the mouth after aerosol inhalation) was evaluated. When the sweetness intensity of Reference 1 was set at 0 points and that of Reference 2 was set at 5 points, the sweetness intensity of each Lot was evaluated on a scale of 0 - 10 points. A panel of 9 expert panelists who are routinely engaged in the sensory evaluation of e - liquids was selected. The scoring results of the sweetness intensity were tabulated, and to verify whether the sweetness intensity increased in a concentration - dependent manner for the sweeteners, statistical analysis was performed using a t - test. The statistical significance level α in the t - test was set at 0.05, which is commonly used.

[0155] 3 - 4 - 2. Sensory Evaluation Results and Analysis The composition of the evaluated samples and the scoring results are shown in Table 9, and the scoring results presented in a graph are shown in Figures 1 - 3. When the sweetness intensity of a certain Lot was designated as Group 1 and the Lot with a one - step higher sweetener concentration than that Lot was designated as Group 2 (for example, when a certain Lot is A3 - 1, the Lot with a one - step higher sweetener concentration than that Lot refers to A3 - 2), to examine whether the sweetness intensity of Group 2 is significantly stronger than that of Group 1, a one - sided test was conducted at a significance level of 5% using Welch's t - test. At this time, the null hypothesis H 0 is set as "the sweetness intensities of Group 1 and Group 2 are equal". The results of the t - test are shown in Table 10

[0156]

Table 9

[0157]

Table 10

[0158] 3 - 4 - 2 - 1. Discussion of the Advanteam Results In the t-tests between Lot A3-1 and A3-2, and between Lot A3-2 and A3-3, the null hypothesis is rejected at a significance level of 5%. That is, there is a significant difference in sweetness intensity when the blending amount of Advantage is between 0.05 wt% and 0.10 wt%, and between 0.10 wt% and 0.15 wt%. On the other hand, in the t-tests between Lot A3-3 and A3-4, and between Lot A3-4 and A3-5, the null hypothesis is not rejected at a significance level of 5%. That is, there is no significant difference in sweetness intensity when the blending amount of Advantage is between 0.15 wt% and 0.20 wt%, and between 0.20 wt% and 0.30 wt%.

[0159] From the above results, it is considered that in the concentration range where the blending amount of Advantage is 0.15 wt% or less, the sweetness intensity increases significantly with respect to the concentration of Advantage, and in the concentration range higher than 0.15 wt%, the increase in sweetness intensity with respect to the concentration of Advantage becomes gradual.

[0160] 3-4-2-2. Discussion of Results for NeoSweet In the t-tests between Lot B3-1 and B3-2, and between Lot B3-2 and B3-3, the null hypothesis is rejected at a significance level of 5%. That is, there is a significant difference in sweetness intensity when the blending amount of NeoSweet is between 0.10 wt% and 0.15 wt%, and between 0.15 wt% and 0.20 wt%. On the other hand, in the t-tests between Lot B3-3 and B3-4, and between Lot B3-4 and B3-5, the null hypothesis is not rejected at a significance level of 5%. That is, there is no significant difference in sweetness intensity when the blending amount of NeoSweet is between 0.20 wt% and 0.30 wt%, and between 0.30 wt% and 0.40 wt%.

[0161] From the above results, it is considered that in the concentration range where the blending amount of NeoSweet is 0.20 wt% or less, the sweetness intensity increases significantly with respect to the concentration of NeoSweet, and in the concentration range higher than 0.20 wt%, the increase in sweetness intensity with respect to the concentration of NeoSweet becomes gradual.

[0162] 3-4-2-3. Discussion of Results for Neohesperidin Dihydrochalcone In the t-tests between Lot C3-1 and C3-2, between Lot C3-2 and C3-3, and between Lot C3-3 and C3-4, the null hypothesis is rejected at the 5% significance level. That is, there are significant differences in sweetness intensity when the blending amount of neohesperidin dihydrochalcone is between 0.15 wt% and 0.20 wt%, between 0.20 wt% and 0.30 wt%, and between 0.30 wt% and 0.40 wt%. On the other hand, in the t-test between Lot C3-4 and C3-5, the null hypothesis is not rejected at the 5% significance level. That is, there is no significant difference in sweetness intensity when the blending amount of neohesperidin dihydrochalcone is between 0.40 wt% and 0.50 wt%.

[0163] From the above results, in the concentration range where the blending amount of neohesperidin dihydrochalcone is 0.40 wt% or less, it is considered that the sweetness intensity increases significantly with respect to the concentration of neohesperidin dihydrochalcone, and in the concentration range higher than 0.40 wt%, it is considered that the increase in sweetness intensity becomes gentle with respect to the concentration of neohesperidin dihydrochalcone.

[0164] 3-5 Summary of Sweetener Concentration and Sensory Evaluation Results Summarizing the sweetener concentration and sensory evaluation results up to the previous section, it is as shown in Table 11.

[0165]

Table 11

[0166] 3-6 Confirmation of the Influence of Coexisting Substances on Sweetness Expression In the verification up to Section 3-5, the sensory evaluation has been carried out using e-liquids containing only sweeteners. However, ordinary e-liquid products contain coexisting substances such as flavors and nicotine. To confirm the influence of coexisting substances on sweetness expression, neohesperidin dihydrochalcone was used as a representative of sweeteners, and the influence of coexisting substances on sweetness was verified by sensory evaluation.

[0167] Among the Logic Compact products commercially available in Europe, the product with the highest nicotine content has a nicotine content equivalent to 18 mg / mL, which corresponds to approximately 1.6 wt% when converted to weight concentration. Therefore, this content was adopted. Also, the most commonly used tobacco-type flavor in Logic Compact was used as the flavor.

[0168] 3-6-1. Sensory Evaluation Method All samples in this section are formulated with 1.6 wt% nicotine and 5.0 wt% tobacco-type flavor. The level without a sweetener is Reference 3, the level with 0.088 wt% sucralose is Reference 4, and the samples with 0.05, 0.10, 0.15, and 0.25 wt% neohesperidin dihydrochalcone are designated as Lot C4-1, C4-2, C4-3, and C4-4, respectively. E-liquids were prepared according to the compositions shown in Table 12. Note that Lot C4-2 corresponds to "Concentration A at which a significant sweet taste was confirmed" in Table 10, and Lot C4-4 corresponds to "Concentration B at which a sweet taste stronger than 1 mg / mL of sucralose was confirmed" in Table 10. A sensory evaluation was conducted by 6 panelists using the aforementioned Logic Compact device. The evaluation panel consisted of 6 expert panelists who are routinely engaged in the sensory evaluation of e-liquids. The panelists were asked to compare the intensity of the sweet taste (defined as the sweet taste felt on the tongue or the sweet taste remaining in the mouth after aerosol inhalation, excluding the sweet aroma derived from the flavor) of each sample, and to answer in a forced-choice format which sweet taste was stronger between Reference 3 and Lot C4-1 or C4-2, and between Reference 4 and Lot C4-3 or C4-4.

[0169] 3-6-2. Sensory Evaluation Results and Discussion The results obtained are shown in Table 13.

[0170]

Table 12

[0171]

Table 13

[0172] In Lot C4-1 set at 0.05% by weight, which is the lower limit of the threshold concentration A for feeling the sweetness of neohesperidin dihydrochalcone, the number of people who selected the sample and Reference 3 without any sweetener added was the same. On the other hand, in Lot C4-1 set at 0.10% by weight, which is the upper limit of the threshold concentration A, all members of the evaluation panel answered that the sweetness of the sample was stronger, showing a similar tendency to the condition without nicotine or flavoring.

[0173] In Lot C4-3 set at 0.15% by weight, which is the upper limit of concentration B showing the same sweetness as the level with 0.088% by weight of sucralose added, 4 out of 6 panelists answered that the sweetness of the sample was stronger. In Lot C4-4 set at 0.25% by weight, which is the lower limit of concentration C expressing a stronger sweetness than the level with 0.088% by weight of sucralose added, 5 out of 6 panelists answered that the sweetness of the sample was stronger. Even when compared with sucralose, it shows a similar tendency to the condition without nicotine or flavoring.

[0174] From the above results, it was confirmed that the sweetness of neohesperidin dihydrochalcone is similarly expressed even when coexisting with flavoring or nicotine.

[0175] 3-6-3. Summary of Verification of the Influence of Coexisting Substances on Sweetness Expression As a result of verification under the condition of adding nicotine and flavoring, the threshold value (= concentration A) at which the sweetness of neohesperidin dihydrochalcone can be significantly perceived, and the boundary concentration (= concentration B) of neohesperidin dihydrochalcone expressing a stronger sweetness than 1 mg / mL of sucralose liquid, were the same as those without nicotine and flavoring added. The result that the coexistence of nicotine or flavoring has a significant impact on sweetness expression was not obtained. It can also be expected that similar results will be obtained for other sweeteners such as Advantage and Neotame.

Claims

1. A composition for use in tobacco, comprising a sweetener other than sucralose.

2. 10. The composition of claim 1 comprising a halogen-free sweetener.

3. The composition according to claim 1 or 2, wherein the sweetener is selected from the group consisting of peptide derivatives, flavonoid glycosides, terpene glycosides, sulfamides, sulfamates and proteins.

4. The composition according to any one of claims 1 to 3, wherein the sweetener is a peptide derivative.

5. The composition according to any one of claims 1 to 3, wherein the sweetener is a flavonoid glycoside.

6. 6. The composition of any one of claims 1 to 3 and 5, wherein the sweetener is a neohesperidin derivative.

7. 7. The composition of claim 1, wherein the sweetener is a neohesperidin derivative having a sweetness of at least 0.5 of the sweetness of neohesperidin dihydrochalcone.

8. The composition of any one of claims 1 to 3, wherein the sweetener is selected from the group consisting of monellin, thaumatin, glycyrrhizin, stevioside or stevia extract, saccharin, acesulfame potassium, advantame, neotame, aspartame and neohesperidin dihydrochalcone.

9. The composition of any one of claims 1 to 3, wherein the sweetener is selected from the group consisting of glycyrrhizin, stevioside or stevia extract, saccharin, acesulfame potassium, advantame, neotame and neohesperidin dihydrochalcone.

10. The composition of any one of claims 1-4 and 8-9, wherein the sweetener is advantame.

11. The composition of any one of claims 1-4 and 8-9, wherein the sweetener is neotame.

12. The composition of any one of claims 1-3 and 5-9, wherein the sweetener is neohesperidin dihydrochalcone.

13. The composition according to claim 10, comprising 0.01% by weight or more of advantame.

14. The composition of claim 10, comprising 0.05% by weight or more of advantame.

15. 12. The composition of claim 11, comprising at least 0.05% by weight of neotame.

16. 12. The composition of claim 11, comprising at least 0.10% by weight of neotame.

17. 13. The composition of claim 12, comprising at least 0.10% by weight of neohesperidin dihydrochalcone.

18. 13. The composition of claim 12, comprising at least 0.25% by weight of neohesperidin dihydrochalcone.

19. The composition of any one of claims 1 to 18, further comprising a fragrance.

20. A composition according to any one of claims 1 to 19, comprising nicotine.

21. An E-liquid comprising a composition according to any one of claims 1-20.

22. A tobacco product comprising a composition according to any one of claims 1-20.

23. 23. The tobacco product of claim 22, wherein the tobacco product is a combustion flavor inhalation article.

24. 23. The tobacco product of claim 22, wherein the tobacco product is a heated flavor inhalation article.

25. 23. The tobacco product of claim 22, wherein the tobacco product is snus.