JP6372025B2 - Chewing composition containing triterpenes - Google Patents

Description

  The present invention relates to a chewing composition containing triterpenes. More specifically, it is a chewing composition containing a triterpene clathrate containing no sodium and comprising a triterpene clathrated in a cyclodextrin, and the dissolution property and taste of the triterpene in the oral cavity are improved. It relates to a chewing composition.

Triterpenes are a group of compounds that are composed of six isoprenes and are a group of terpenes having a molecular formula of C ₃₀ H ₄₈ , all of which are highly fat-soluble, insoluble in water and soluble in organic solvents and the like.
In the plant kingdom, triterpenes are widely distributed in the form of esters in combination with free radicals, saponins as glycosides, and acids.
Among the triterpenes, those having five rings are classified as pentacyclic triterpenes, and representative examples thereof include oleanolic acid, ursolic acid, maslinic acid, corosolic acid, hederagenin and the like.
Among them, oleanolic acid is contained in many plants such as grape, olive, perilla, apple, jujube, and clove, and it is a functional ingredient with physiological activities such as growth inhibition of caries fungus, anti-hepatitis, antitumor, and antioxidant action. Has been attracting attention in recent years.
With regard to oleanolic acid, an oral composition utilizing its pharmacological action has been proposed (Patent Document 1, Patent Document 2), paying attention to the growth inhibitory effect of the caries fungus.
However, in reality, even if a chewing composition such as chewing gum containing oleanolic acid is produced in anticipation of a sustained effect in the oral cavity, oleanolic acid is adsorbed on the gum base and the active ingredient does not elute into the oral cavity at all. Exists.
In addition, the reported pharmacological action of oleanolic acid has been confirmed by using oleanolic acid dissolved in an organic solvent such as dimethyl sulfoxide as a sample. It has been pointed out that there is a problem that it is insoluble and the same effect cannot be obtained (Patent Document 3).
As a method for improving water solubility while maintaining the pharmacological action of oleanolic acid, inclusion with cyclodextrin has been proposed (Patent Document 3). However, in this method, in order to dissolve oleanolic acid in the inclusion, it is necessary to add sodium hydrogen carbonate or the like to make it alkaline, but this addition increases bitterness and chews as a food, particularly in the oral cavity for a long time. There existed the problem of the taste which cannot be used with chewing gum, and the manufacturing problem that it foams when making an inclusion compound into powder, and workability | operativity worsens.
Accordingly, a chewing composition having improved triterpene dissolution properties and taste in the oral cavity is desired.

JP-B 63-26083 JP 01-290619 A JP-A-4-187658

  Therefore, the present inventors have found a method for producing a triterpene inclusion product that does not contain sodium without adding sodium bicarbonate or the like to make it alkaline when clathrating triterpenes with cyclodextrin. Thus, a chewing composition having improved dissolution property and taste in the oral cavity was completed.

That is, the present invention is as follows.
[1] A chewing composition comprising a triterpene clathrate containing no sodium and comprising a triterpene clathrated in a cyclodextrin.
[2] The chewing composition according to [1], wherein the mass ratio of triterpenes to cyclodextrins is 1: 6 to 1:16.
[3] A triterpene clathrate containing no sodium and comprising a triterpene clathrated in cyclodextrin.
[4] A method for producing an inclusion product containing triterpenes that does not contain sodium, wherein a triterpene is included in a cyclodextrin, (1) a step of preparing an alcohol solution of the triterpene, (2) a cyclodextrin A step of preparing an aqueous solution of (3), a step of bringing the solution obtained in (1) and the solution obtained in (2) into contact and inclusion, and (4) the reaction product obtained in (3). The said manufacturing method which consists of a process made into dry powder.

  A chewing composition comprising a triterpene clathrate containing cyclotridextrin and a triterpene clathrate containing no sodium, thereby improving the dissolution property and taste of triterpenes in the oral cavity. Can be obtained.

(Chewing composition)
The chewing composition of the present invention is chewed in the oral cavity, or chewed in the oral cavity, and specifically includes gums such as chewing gum (including plate gum, granule gum, and sugar-coated gum) ), Foods such as gummy and nougat; pharmaceuticals such as chewing agents, chewable tablets, troches and buccal tablets. Chewing gum is preferable

  The chewing composition of the present invention includes a triterpene in a form in which a triterpene is included in a cyclodextrin (a triterpene inclusion product). The proportion of triterpenes contained in the inclusion can be appropriately selected from the range of 0.1 to 50% by weight, but the preferable upper limit is 30% by weight, more preferably 20% by weight or 15% by weight. Can be mentioned. Moreover, as a preferable minimum, 0.5 weight%, More preferably, 1 weight% or 5 weight% can be mentioned. More specifically, a range of preferably 0.5 to 30% by weight, more preferably 1 to 20% by weight or 5 to 10% by weight can be exemplified.

  The cyclodextrin used in the present invention is a host molecule (inclusion compound) having a structure in which 6, 7, 8 or more glucoses are cyclically bonded by α-1,4 bonds, and usually α, β, The γ and δ types are known. In the present invention, α-, β-, γ-, and δ-type cyclodextrins and derivatives thereof can be used, but β- or γ-cyclodextrins are preferable. More preferred is γ-cyclodextrin.

The triterpenes used in the present invention are compounds having a basic skeleton having 30 carbon atoms, and typical examples thereof include pentacyclic triterpenes. Here, the pentacyclic triterpene is a kind of triterpenes, and is a pentacyclic compound composed of 6 isoprene units, which basically has 30 carbon atoms, but is rearranged, oxidized, Also included are those that are desorbed or alkylated and have about the number of carbon atoms.
These can be obtained from natural plants or artificially. Moreover, a commercial item can also be utilized suitably. Pentacyclic triterpenes are generally classified according to their skeleton. For example, oleanane triterpenes, ursan triterpenes, lupine triterpenes, hopane triterpenes, seratane triterpenes, freederan triterpenes, taraxelan triterpenes, taraxastane triterpenes, multiflorane triterpenes, germanic Examples include triterpenes.
Among the pentacyclic triterpenes, for example, representative examples of oleanane triterpenes include oleanolic acid, maslinic acid, and representative examples of ursan triterpenes include ursolic acid and corosolic acid.
Among them, oleanolic acid is contained in many plants such as grape, olive, perilla, apple, jujube and clove.
In the present invention, the origin and production method of the triterpenes are not limited as long as they can be taken or edible as pharmaceuticals or foods. For example, it can be obtained by extracting a raw grape squeezed lees under hot conditions and purifying it under alkaline conditions.

  “Triterpene inclusions that do not contain sodium” means that the triterpene inclusions by cyclodextrin do not contain sodium, specifically, the triterpenes contained in the inclusions are in the form of free radicals that are not sodium salts. It means to exist. A triterpene clathrate containing no sodium can be obtained by inclusion of triterpenes without addition of sodium hydrogen carbonate, sodium carbonate, sodium hydroxide or the like when clathrated with cyclodextrins.

In the present invention, inclusion of triterpenes with cyclodextrin is performed by preparing and mixing an alcohol solution of triterpenes and an aqueous cyclodextrin solution.
In the present invention, C _1-6 alcohol or water-containing C _1-6 alcohol is used as a solvent for the alcohol solution of triterpenes. Preferably, 50% to 100% ethanol is used, and more preferably, 80% to 100% ethanol is used.
In the present invention, when preparing an alcohol solution of triterpenes, it is not appropriate to add an alkali such as sodium hydrogen carbonate, sodium carbonate, sodium hydroxide, or potassium hydroxide because it causes a deterioration in taste such as bitterness.
In the present invention, the concentration of triterpenes in the alcohol solution of triterpenes is preferably 20 mg / ml or less, more preferably 10 mg / ml or less.
In the present invention, the concentration of the cyclodextrin aqueous solution is preferably 10 to 500 mg / ml, more preferably 100 to 300 mg / ml.
In the present invention, the triterpene alcohol solution and the cyclodextrin aqueous solution preferably have a mass ratio of triterpenes to cyclodextrin contained in the solution of 1: 6 to 1:16, more preferably 1: 9 to 1:11. Inclusion is performed by mixing so that
After inclusion, unnecessary components are removed by filtration or centrifugation, and then concentrated and dried by a known method, and powdered to obtain an inclusion.

  The upper limit of the triterpene content in the triterpene clathrate of the present invention is preferably 50% by weight, more preferably 30% by weight or 20% by weight. A preferred lower limit is 0.1% by weight, more preferably 1% by weight or 5% by weight. More specifically, the range is preferably 0.1 to 50% by weight, more preferably 1 to 30% by weight or 5 to 20% by weight.

  The chewing composition of the present invention may contain triterpenes in the form of the above-mentioned triterpene inclusions. The chewing composition of the present invention can contain conventionally known components according to the type and shape of the chewing composition, and can be prepared according to a conventionally known production method. In addition, the ratio of the triterpene clathrate compounded in the chewing composition of the present invention is not particularly limited, but it can be appropriately selected from the range of usually 0.01 to 50% by weight in 100% by weight of the chewing composition. . Preferably it is 0.1 to 40 weight%, More preferably, it is 1 to 30 weight%.

  Ingredients other than the triterpene inclusions to be blended in the chewing composition of the present invention include gum base, thickener, brightener, emulsifier, spice extract, sugar, fats and oils, flavor, sweetener, acidulant, colorant, Examples include softeners, antioxidants, seasonings, and reinforcing agents.

  In the present invention, as the gum base, methyl acetylricinoleate, urushi wax, ester gum, Elemi resin, cucumber cucumber wax, ozokerite, opopax resin, kauri gum, carnauba wax, candelilla wax, guaiac resin, guayule, gutta kachu, guttahancan, gutta percha, glycerin fatty acid ester , Gallow, copaiba balsam, copal resin, rubber, rubber decomposition product, rice bran wax, vinyl acetate resin, sugar cane wax, sandalac resin, shellac, gelton, sucrose fatty acid ester, solver, sorbitan fatty acid ester, sorbin ha, talc, calcium carbonate, Dammar resin, Chicle, Chilte, Tunu, Low molecular weight rubber, Niger gutta, Nyuko, Paraffin wax, Far balsam, Propylene glyco Fatty acid ester, powdered pulp, powdered buffalo, Venezuela reticle, benzoin gum, jojoba wax, polyisobutylene, polybutene, microcrystalline wax, mastic, massalandoba chocolate, beeswax, myrrh, moclaw, montan wax, lanolin, tricalcium phosphate, phosphorus Examples may include various ingredients approved as gum bases for food additives such as calcium monohydrogenate, lecte debaca, rosidinha, and rosin, and mixtures thereof. When the gum base is included, the ratio of the gum base to be blended in the chewing composition of the present invention can be usually 10 to 35% by weight, preferably 20 to 30% by weight.

  Examples of sweeteners include monosaccharides, disaccharides, oligosaccharides, sugar alcohols, and high-intensity sweeteners. Preferably, sugars such as sucrose, fructose, liquid sugar, glucose, and oligosaccharide; aspartame, licorice, xylose, sucralose, stevia, acesulfame K 2, thaumatin, stevia, alytem, neotame, xylitol, saccharin salt, glycyrrhizin, lacanca, etc. Can be mentioned.

  As coloring agents, β-carotene, turmeric pigment, carotenoid pigment, red pepper pigment, anato pigment, red pigment, orange pigment, cacao pigment, caramel pigment, gardenia pigment, chlorophyll, sicon pigment, perilla pigment, spirulina pigment, erythrosin, tartrazine, Examples include onion pigment, tomato pigment, blueberry pigment, purple potato pigment, purple potato pigment, marigold pigment, chlorophyll, lutein, copper chlorophyll, grape skin pigment, riboflavin, and riboflavin 5 ′ sodium phosphate ester.

  Thickeners include gum arabic, alginic acid and its salts, carrageenan, carboxymethylcellulose and its salts, xanthan gum, chitin, chitosan, guar gum, glucosamine, gellan gum, tara gum, hydroxypropyl cellulose, corn starch, agar, dextran, tragacanth gum, seed gum, Pullulan, pectin, and rhamsan gum, microfibrous cellulose, microcrystalline cellulose, seaweed cellulose, mannan and other polysaccharides; proteins such as sodium caseinate and gelatin; polyvinyl alcohol, sodium polyacrylate, sodium polyphosphate and the like Examples of the polymer compound include natural polymers such as a yellow aloe extract, yeast cell wall, konjac potato extract, and nata de coco.

Examples of acidulants include adipic acid, itaconic acid, citric acid, monopotassium citrate, tripotassium citrate, trisodium citrate, gluconodeltalactone, gluconic acid, potassium gluconate, sodium gluconate, succinic acid, succinic acid Monosodium, disodium succinate, sodium acetate, DL-tartaric acid, L-tartaric acid, DL-sodium tartrate, sodium L-tartrate, carbon dioxide, lactic acid, sodium lactate, glacial acetic acid, phytic acid, fumaric acid, monosodium fumarate , DL-malic acid, DL-sodium malate, phosphoric acid, and the like.

  Examples of the softener include glycerin, sorbitol, and propylene glycol.

  As fragrances, menthol, dl-menthol, menthone, vanillin, ethyl vanillin, cinnamic acid, piperonal, d-borneol, maltol, ethyl maltol, camphor, methyl anthranilate, methyl cinnamate, cinnamic alcohol, methyl N-methylanthranilate , Methyl β-naphthyl ketone, limonene, linalool, and allyl isothiocyanate.

  The chewing composition of the present invention is preferably a chewing gum. For example, chewing gum can be prepared according to known methods and procedures. At this time, the triterpene inclusions can be blended in an arbitrary step.

  EXAMPLES Examples will be shown below for specifically explaining the present invention, but the present invention is not limited to the following examples.

[Preparation of purified oleanolic acid product]
(1) 0.1M KOH was added to 100 g of raw grape skin and extracted at 40 ° C. for 2 hours.
(2) The pH was adjusted to neutral and filtered.
(3) The filtrate was purified with an ion exchange resin and then concentrated to obtain a purified oleanolic acid product.

[Preparation of oleanolic acid inclusions]
A. Preparation method of oleanolic acid inclusion product (1) A purified product of oleanolic acid was dissolved in 90% ethanol to which NaHCO ₃ was added if necessary at a concentration of 5 mg / ml.
(2) Various cyclodextrins were dissolved in water at a concentration of 50 mg / ml.
(3) The oleanolic acid purified product solution and the cyclodextrin solution were mixed at a ratio such that the mass ratio of the oleanolic acid purified product and the cyclodextrin was as shown in the table.
(4) The mixture obtained in (3) was concentrated and replaced with water and then freeze-dried to obtain an inclusion product.
B. Evaluation of solubility of oleanolic acid inclusions 50 mg of oleanolic acid inclusions is dissolved in 5 ml of water, x indicates that a large amount of precipitation occurs, Δ indicates that a slight amount of precipitation occurs, and no precipitation occurs. A solution that became a turbid solution was evaluated as ○, and a solution that had a high transparency was evaluated as ◎.
C. Method for evaluating the workability of oleanolic acid inclusions In the above step A- (4), when the concentration / water replacement is performed, the foaming property is high and the concentration / water replacement cannot be performed normally. Is high, but if it takes a long time, it can be concentrated and replaced with water, and “◯” indicates that there is no particular problem in performing concentration and water replacement.
D. Evaluation method of the taste of oleanolic acid inclusions The oleanolic acid inclusions of β-cyclodextrin and γ-cyclodextrin were each subjected to a sensory evaluation of the flavor of 50 mg and kept in the oral cavity with intense bitterness. "XX" for those that are difficult to taste, "X" for those that have a strong bitter taste and are clearly unsuitable as foods, and "△" for those that have a slight bitter taste that may impair the taste when added to foods The foods that did not feel bitter and had no problems even when added to food were evaluated as “◯”.

(Mass ratio of triterpenes and cyclodextrins in inclusion)
The results showed the effect on the solubility of inclusions when the mass ratio of purified oleanol and β-cyclodextrin was changed under the condition that 5% by mass of sodium bicarbonate was added to the inclusions. Table 1 shows.

この結果よりオレアノール精製品とβ-サイクロデキストリンの質量比が１：６〜１：１６の場合に良好な溶解性が示され、１：９〜１：１１で最も良好な溶解性が観察された。

From this result, good solubility was shown when the mass ratio of oleanol purified product to β-cyclodextrin was 1: 6 to 1:16, and the best solubility was observed from 1: 9 to 1:11. .

(Effect of addition of sodium hydrogen carbonate on solubility of clathrate)
Table 2 shows the results of the effect of inclusion of sodium hydrogen carbonate on the inclusion inclusion solubility when inclusion is carried out at a mass ratio of oleanol purified product to β-cyclodextrin of 1:32 and 1: 9. Table 3 shows. In addition, the sodium hydrogencarbonate density | concentration in a table | surface is the mass% with respect to the obtained clathrate.

これらの結果より、炭酸水素ナトリウムを一定量添加すると包接物の溶解性が改良される傾向にあるが、オレアノール精製品に対するβ-サイクロデキストリンが多いと改良の程度に限度があること、またオレアノール精製品に対するβ-サイクロデキストリンを少なくすることで、炭酸ナトリウムを添加しなくても包接物が溶解性を示すことが明らかとなった。

From these results, the solubility of the clathrate tends to be improved by adding a certain amount of sodium hydrogen carbonate, but there is a limit to the degree of improvement when there is a large amount of β-cyclodextrin in the purified oleanol product, and oleanol It was clarified that the inclusions showed solubility without adding sodium carbonate by reducing the amount of β-cyclodextrin in the purified product.

(Influence of the type of cyclodextrin when sodium bicarbonate is not added)
The results showing the effect on the solubility of inclusions in the case of inclusion by changing the type of cyclodextrin with the mass ratio of purified oleanol and cyclodextrin being 1:10 without adding sodium bicarbonate. Table 4 shows.

これらの結果より、アルカリを添加しない場合のトリテルペン包接物の溶解性は、γ-サイクロデキストリンによるものが最も高いことが示された。

From these results, it was shown that the solubility of the triterpene clathrate when no alkali was added was highest with γ-cyclodextrin.

(Influence on taste and workability by adding sodium bicarbonate)
When β-cyclodextrin and γ-cyclodextrin were clathrated at a mass ratio of oleanol purified product to cyclodextrin of 1: 9, the solubility, taste and workability of the clathrate by the addition of sodium bicarbonate Tables 5 and 6 show the results showing the effects of the above. In addition, the sodium hydrogencarbonate density | concentration in a table | surface is the mass% with respect to the obtained clathrate.

この結果から炭酸水素ナトリウムを添加することで溶解性は改善されるが、包接物に対しわずか０．３質量％の炭酸水素ナトリウムが含まれるだけで味を損なうことが明らかとなり、食品への適用、特に長時間口腔内で咀嚼するチューインガムのような食品への適用には適さないことが示された。また炭酸水素ナトリウムの添加により、包接物の乾燥粉末化工程において発泡するなど作業性を損なうことが明らかとなった。

From this result, the solubility is improved by adding sodium hydrogen carbonate, but it is clear that the inclusion of only 0.3% by mass of sodium hydrogen carbonate in the clathrate impairs the taste. It has been shown to be unsuitable for application, particularly for foods such as chewing gum that is chewed in the oral cavity for extended periods of time. Moreover, it became clear that the addition of sodium hydrogen carbonate impairs workability such as foaming in the dry powdering process of the clathrate.

[Gum containing oleanolic acid inclusions]
(Manufacture of gum)
A gum was prepared according to the composition of Table 7 below so that 0.15 parts by mass of oleanolic acid clathrate and non-inclusion oleanolic acid was included as oleanolic acid per 100 parts by mass of the gum. The clathrate was clathrated without adding sodium hydrogen carbonate at a mass ratio of oleanolic acid to γ-cyclodextrin of 1:10.
Specifically, the material was blended at 70 ° C. with a gum base (main component, vinyl acetate resin) with the composition shown in Table 7 and kneaded. After mixing, the mixture was cooled to room temperature and formed into granules.

(Dissolution test from gum)
The gums prepared above were weighed 1.5 g each, and three subjects chewed for 6 minutes, and the saliva during chewing and the gum residue after chewing the gum for 6 minutes were collected.
Regarding the gum residue, the gum was dissolved in a mixed solution of chloroform / methanol / water, and the chloroform layer was recovered and used as a sample for analysis of oleanolic acid content by HPLC.
Measurement of oleanolic acid content in saliva and after mastication at column (GL Science, ODS-3, 150 × 2.1 mm id) temperature 40 ° C., flow rate 1.0 mL / min, wavelength 210 nm Measured according to conditions.
About the oleanolic acid inclusion-containing gum and the non-inclusion oleanolic acid-containing gum, the average value of oleanolic acid content in saliva and after chewing residue (mass%, n) = 8) is shown in Table 8.

この結果から、未包接オレアノール酸をガムに配合した場合、咀嚼した時に未包接オレアノール酸がほとんどガムから溶出されず、ガム中に残ることが確認できた。これに対し、オレアノール酸包接物を配合したガムは、配合したオレアノール酸包接物の半分以上が唾液に溶出している事が確認できた。

From this result, it was confirmed that when unencapsulated oleanolic acid was blended with the gum, unencapsulated oleanolic acid was hardly eluted from the gum when chewed and remained in the gum. On the other hand, it was confirmed that the gum blended with the oleanolic acid clathrate eluted more than half of the blended oleanolic acid clathrate into the saliva.

Claims (2)

A method of producing a triterpene clathrate containing no sodium, wherein a triterpene is clathrated in a cyclodextrin,
(1) Step of preparing an alcohol solution of triterpenes (2) Step of preparing an aqueous solution of cyclodextrin (3) Contacting the solution obtained in (1) with the solution obtained in (2) The said manufacturing method which consists of a process which is a process to make a reaction product obtained by the mass ratio of triterpenes and cyclodextrins 1: 9-1: 11 and (4) (3) dry powder. Triterpenes is formed by inclusion in cyclodextrin, a process for the preparation of a chewing composition containing triterpenes clathrate containing no sodium,
(1) Step of preparing an alcohol solution of triterpenes
(2) Step of preparing an aqueous solution of cyclodextrin
(3) A step of contacting and inclusion of the solution obtained in (1) and the solution obtained in (2), wherein the mass ratio of triterpenes to cyclodextrins is 1: 9 to 1:11 A process and
(4) a step of converting the reaction product obtained in (3) into a dry powder;
(5) The said manufacturing method including the process of mix | blending the dry powder obtained by (4) with a chewing composition .