HK1140644A - Sugar-coated chewing gum composition and method for producing sugar-coated chewing gum - Google Patents

Description

Sugar-coated chewing gum composition and method for producing sugar-coated chewing gum composition

Technical Field

The present invention relates to a coated chewing gum composition having a high release rate of lactoferrin by chewing, excellent elution in the oral cavity, good long-term storage stability, and excellent periodontal bacterial toxin inactivation, and a method for producing the coated chewing gum composition.

Background

Conventionally, sugar-coated chewing gums in which the surface of the main body of a chewing gum containing a gum base is coated with a sugar coating are known.

The material of the sugar coating is usually a syrup obtained by mixing an aqueous solution of an edible gum with a sweetener such as sugar or syrup, and optionally, a coloring agent, a sour agent, a vitamin, a flavor, and the like. When the surface of the chewing gum body is coated with the sugar syrup, the turntable is rotated to rotate the chewing gum body loaded in the turntable, the sugar syrup is spread thereon, and the entire surface of the chewing gum body is wetted with the sugar syrup. Then, warm air is blown into the rotating turntable to remove moisture of the syrup adhering to the surface of the chewing gum body, and the surface of the chewing gum body is coated with syrup solid components. By further adding syrup and repeating the same steps as described above, a coating film of syrup solids is grown to an appropriate thickness, thereby completing a sugar-coated chewing gum. The purpose of sugar coating is to enhance the appearance of the product by glossing the surface, to solidify the surface to prevent disintegration of the contents, or to facilitate handling by preventing adhesion between products, but there is no report that it contributes to stabilization of active ingredients mixed in the product.

On the other hand, lactoferrin is known to have an action of neutralizing toxins and endotoxins of periodontal bacteria, and therefore, a chewing gum composition containing lactoferrin has been proposed as an effective ingredient to be mixed in an oral composition (patent document 1: Japanese patent laid-open No. 03-220130, patent document 2: Japanese patent laid-open No. 05-255109).

However, the above-mentioned chewing gum composition is a composition in which lactoferrin is mixed into a chewing gum body, and when the surface of the chewing gum body is coated and solidified with a sugar coating, there is a problem that it takes time to release lactoferrin even if the chewing gum is chewed in the mouth, and a sufficient amount of lactoferrin and the like cannot be dissolved even if the chewing gum is chewed, and thus it is difficult to exhibit the effects attributed to lactoferrin.

Further, as for the effect of lactoferrin, pharmacological actions such as infection defense and immune activation (patent document 3: patent No. 3819441) and neutralizing periodontal bacterial toxin and neutralizing endotoxin (patent document 4: japanese patent No. 2005-306890) are known, but the chewing gums of patent documents 1 and 2 are inferior in the effect of lactoferrin, and particularly when lactoferrin is mixed into a slab chewing gum, there are also drawbacks that the high effect derived from lactoferrin cannot be satisfactorily exhibited because lactoferrin enters the gum base.

Further, lactoferrin is a protein, and its structure is broken or unstable at high temperature, so that the storage stability in a preparation is poor, and stable mixing in a preparation for a long time is particularly difficult. There have been proposed a technique of mixing lactoferrin in a tablet (patent document 5: Japanese patent laid-open No. 2004-346020) and a technique of making lactoferrin into a liposome to stabilize it (patent document 6: Japanese patent laid-open No. 2004-359647), but these techniques also make it difficult to stabilize lactoferrin in a preparation for a long period of time. Particularly in chewing gum, there is a problem that lactoferrin is unstable at high temperature when it is taken into the gum base or manufactured, and stable mixing of lactoferrin is difficult.

Therefore, it is desired to develop a coated chewing gum composition and a method for producing a coated chewing gum composition, which can rapidly release lactoferrin by chewing in the mouth, have excellent lactoferrin elution properties and long-term storage stability, and can exhibit excellent effects derived from lactoferrin.

Patent document 1: japanese patent laid-open No. Hei 03-220130

Patent document 2: japanese patent laid-open No. H05-255109

Patent document 3: japanese patent No. 3819441

Patent document 4: japanese patent publication No. 2005-306890

Patent document 5: japanese patent laid-open publication No. 2004-346020

Patent document 6: japanese patent laid-open publication No. 2004-359647

Disclosure of Invention

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a sugar-coated chewing gum composition which has a high release rate of lactoferrin when chewed in the mouth, has excellent dissolution properties, has excellent long-term storage stability, is stable when chewed in the mouth, effectively exerts an excellent effect derived from lactoferrin, and is effective in preventing periodontal disease, and a method for producing the sugar-coated chewing gum composition.

The present inventors have conducted extensive studies to achieve the above object, and as a result, found that: a sugar-coated chewing gum which is capable of preventing periodontal diseases effectively and has a high release rate of lactoferrin into the oral cavity, an excellent elution property, an excellent long-term storage stability, and a high effect of inactivating periodontal bacteria toxins, can be obtained by mixing maltitol and lactoferrin as sugar-coating components for forming a sugar-coating layer of the sugar-coated chewing gum, and coating the surface of a chewing gum body with the sugar-coating components. Moreover, it was also found that: the present inventors have found that a coated chewing gum prepared by coating the surface of a chewing gum body with a composition in which lactoferrin is mixed with a maltitol-containing coating component to form a coating layer is excellent in long-term storage stability, and can stably and effectively exert the effect derived from lactoferrin when chewed in the mouth, without causing the lactoferrin to enter the gum base or to become unstable due to high temperature during production, and that the coated chewing gum is effective for preventing periodontal diseases, and thus the present invention has been completed.

Accordingly, the present invention provides the following sugar-coated chewing gum composition and a method for producing sugar-coated chewing gum.

1. A sugar-coated chewing gum composition comprising a chewing gum body and a sugar-coating layer covering the surface of the chewing gum body, wherein the sugar-coating component for forming the sugar-coating layer contains maltitol and lactoferrin.

2. The sugar-coated chewing gum composition according to claim 1, wherein the chewing gum body or the sugar-coating layer further comprises a dextranase.

3. A process for producing a sugar-coated chewing gum, characterized in that a chewing gum main body is formed, and then the chewing gum main body is coated with a sugar-coating component containing maltitol and lactoferrin to form a sugar-coating layer.

4. The process for producing a sugar-coated chewing gum according to claim 3, wherein the chewing gum main body or the sugar-coating layer further contains glucanase.

The sugar-coated chewing gum composition of the present invention contains maltitol and lactoferrin in the sugar-coating layer, and thus lactoferrin is released quickly by chewing in the mouth, has excellent elution properties, has excellent long-term storage stability, and has an excellent effect of inactivating periodontal bacterial toxins. According to the production method of the present invention, a sugar coated chewing gum having the above-described excellent characteristics can be industrially advantageously obtained.

Detailed Description

The present invention will be described in more detail below. The sugar-coated chewing gum composition of the present invention comprises a chewing gum main body and a sugar-coating layer for coating the chewing gum main body, and contains maltitol and lactoferrin as sugar-coating components for forming the sugar-coating layer, and is prepared into a sugar-coated chewing gum in which the surface of the chewing gum main body is coated with the sugar-coating layer.

Here, the chewing gum body is mixed with a gum base with a sweetener, a flavor, an active ingredient, a coloring agent, and the like, and the main component of the sugar coating layer is maltitol, and contains lactoferrin as an active ingredient, and further is mixed with a binder such as an edible gum, other active ingredients, or a sweetener, a coloring agent, a sour agent, a flavor, and the like.

In the present invention, maltitol used as a sugar coating component is mixed as a stabilizer or sweetener for the effect of lactoferrin in inactivating periodontal bacterial toxins and suppressing the decrease in dissolution rate after long-term storage. Maltitol is obtained by hydrogenating high-purity maltose obtained by saccharifying starch with a maltase, is a sugar alcohol in which glucose and sorbitol are bonded, and exhibits a sweet taste of 80 to 90% by the heat of 1/2 of sucrose. It is slowly hydrolyzed in the digestive tract, and blood sugar after ingestion rises slowly, and thus is used as a low-energy sweetener.

The amount of maltitol to be mixed as the sugar-coat component is preferably 20 to 34% (by mass%, the same applies hereinafter) in the total composition, and particularly preferably 24 to 34%. If the amount of the lactoferrin is less than 20%, the effect of inactivating periodontal bacterial toxins in lactoferrin cannot be sufficiently exhibited, or the sweetness is reduced, which may cause problems in the feeling of use. If the content exceeds 34%, the dissolution rate of lactoferrin after long-term storage may decrease or the sweetness may increase, thereby affecting the flavor.

The maltitol in the sugar-coated layer is preferably blended in a range of 50 to 99.5%, particularly preferably 60 to 95%, of the total components in the sugar-coated layer.

It is also preferable that the sugar coating layer is not mixed with a sweetener such as sugar alcohol other than maltitol.

Lactoferrin is widely distributed in the animal body, and as a biological function of lactoferrin, there have been proposed an antibacterial action, an antiviral action, an ecological defense action, and an endotoxin neutralizing action, a mucin production promoter (Japanese patent laid-open No. H09-12473), a novel pharmaceutical composition (Japanese patent laid-open No. H8-217693), and the like. Lactoferrin is an iron-binding glycoprotein having a molecular weight of 83100, in which 1 polypeptide chain is bound to a sugar chain composed of galactose, mannose, sialic acid, or the like. Commercially available lactoferrin is isolated from colostrum, overmilk, normal milk, terminal milk, etc. of mammals (e.g., human, bovine, ovine, caprine, equine, etc.), skim milk, whey, etc. which are processed products of these milks, by a conventional method (e.g., ion exchange chromatography, etc.), and lactoferrin produced from plants (tomato, rice, tobacco, etc.). In the present invention, commercially available lactoferrin may be used as the lactoferrin, or lactoferrin prepared by a known method may be used, and particularly bovine-derived lactoferrin is preferable. Commercially available lactoferrins derived from cattle include "Senyon lactoferrin (MLF-1) sold by Senyon milk corporation and" lactoferrin "sold by DMV Japan company, and these can be suitably used.

In order to effectively improve periodontal tissue destruction, the amount of lactoferrin to be mixed is preferably 0.01 to 10% (as solid content, hereinafter the same applies) relative to the entire composition, and particularly preferably 0.1 to 5%. If the amount is less than 0.01%, satisfactory effect of inactivating periodontal bacterial toxin may not be obtained, and if it exceeds 10%, the effect of inactivating periodontal bacterial toxin of lactoferrin may be saturated, and the elution property of lactoferrin into the mouth may be lowered.

The ratio of lactoferrin to maltitol in the sugar-coat component is preferably 0.005 to 70%, particularly preferably 0.01 to 60%, and particularly preferably 0.03 to 25% of the amount of maltitol to be mixed.

The sugar-coated chewing gum composition of the present invention is preferably blended with a binder for improving coating properties as a sugar-coating component, and the surface of the chewing gum main body can be coated with the sugar-coating more satisfactorily by blending the binder. As the binder, for example, edible gum such as gum arabic, starch, and the like can be suitably used, and gum arabic is particularly preferable from the viewpoint of easy formation of a coating.

When the binder is mixed, the amount of the binder is preferably 0.1 to 10%, particularly preferably 0.5 to 5%, based on the whole amount of the sugar-coated chewing gum composition, and if less than 0.1%, the sugar coating may not be sufficiently formed, and if more than 10%, the appearance stability, the elution property of lactoferrin, and the like may be affected by discoloration or the like.

The amount of the binder is preferably 0.1 to 40%, particularly preferably 1 to 30%, based on maltitol in the sugar-coating component.

In the present invention, as the gum base to be mixed with the chewing gum main body, a gum base generally used in chewing gum compositions can be used, and examples thereof include polyvinyl acetate resins having an average polymerization degree of 100 to 1000, natural resins (gum arabic, jelutong, fenugreek pectin (ソルバ), etc.), resins for gum bases (base agents) such as polyisobutylene, polybutene, ester gum, etc., fillers such as emulsifiers, calcium carbonate, calcium phosphate, talc, etc., plasticizers or softeners such as hydrous lanolin, stearic acid, sodium stearate, potassium stearate, triacetin, glycerin, etc., and commercially available gum bases mixed with natural wax, petroleum wax, paraffin, etc., specifically, gum base manufactured by ナチユラルベ - ス strain, gum base manufactured by ユ - ス strain, etc., can be used. The gum base may also contain natural pigment such as fructus Gardeniae, Carthami flos, and Monascus purpureus went, or coloring agent such as titanium dioxide.

The amount of the gum base is preferably 10 to 50%, particularly preferably 15 to 30% of the total composition.

In the composition of the present invention, it is preferable that the chewing gum main body or the component for forming the sugar coating layer is mixed with dextranase as an active ingredient, and the dextranase is mixed to impart a tartar formation-inhibiting effect. In particular, it is effective to mix glucanase with the coating component for forming the sugar coating layer, because the effect of inhibiting the formation of tartar is expected to be improved as compared with the case where glucanase is contained in the chewing gum main body.

Conventionally, glucanase has been known to have an effect of inhibiting tartar formation, and many reports have been made on oral compositions containing glucanase (e.g., japanese patent No. 782154). As the glucanase used in the present invention, a known glucanase produced from various glucanase-producing bacteria can be used. For example, glucanase derived from glucanase-producing bacteria such as penicillium, aspergillus, chaetomium, streptomyces, sporotrichum, bacillus and the like can be used, and it is preferable to use glucanase derived from chaetomium filamentous from the viewpoint of glucanase decomposition ability.

As the glucanase, a glucanase obtained by a known method from a known glucanase-producing bacterium belonging to the genus Mucor can be suitably used, and a glucanase produced by MFC ライフテツク (strain) can be used as a commercially available product.

The amount of the glucanase to be mixed is preferably 0.01 to 5%, particularly preferably 0.032 to 3% per 1g of the composition, based on 12,000 units. If the content is less than 0.01%, the effect of removing tartar may not be satisfactorily obtained, and if the content exceeds 5%, the harmful effect such as discoloration may occur. The 1-unit glucanase is an amount of glucanase that produces free reducing sugars corresponding to 1. mu. mol of glucose per minute when the reaction is carried out using glucan as a substrate.

In the sugar-coated chewing gum composition of the present invention, a sweetener such as a sugar alcohol other than maltitol may be mixed into the chewing gum main body in order to impart sweetness to the chewing gum main body. The sweetener preferably contains at least one selected from among commonly used sweeteners such as sugars such as sucrose, glucose, dextrose, invert sugar and fructose, xylitol, erythritol, sorbitol, mannitol, lactitol, palatinose (パラチノ - ス), isomalt (パラチニツト), trehalose, oligosaccharides, reduced syrup, stevia, sucralose, saccharin and aspartame, and particularly preferably contains sucralose, xylitol, isomalt and erythritol from the viewpoint of flavor. When the sweetener is mixed into the chewing gum body, the amount of the sweetener is preferably 0.001 to 70%, particularly preferably 0.01 to 65%.

In the present invention, for the purpose of enhancing sweetness, maltitol may be added to the chewing gum body as required to be a sweetener. In this case, the amount of maltitol to be mixed into the chewing gum body is preferably 1 to 50%, particularly preferably 5 to 40% of the total composition.

In addition, perfumes may be incorporated into the compositions of the present invention. The flavor may be mixed with the sugar coating component for the purpose of imparting flavor to the sugar coating, or may be mixed with the gum base for imparting flavor to the chewing gum base, or may be mixed with both the sugar coating component and the chewing gum base.

As the flavor, 1 or 2 or more kinds of natural flavors, synthetic flavors, and other oily flavors or powdery flavors can be used. Examples of the natural flavor include mastic oil, parsley oil, anise oil, eucalyptus oil, wintergreen oil, cinnamon oil, menthol oil, spearmint oil, peppermint oil, lemon oil, coriander oil, orange oil, lime oil, lavender oil, bay oil, chamomile oil, cardamom oil, caraway oil, cassia oil, lemongrass oil, pine leaf oil, orange oil, rose oil, jasmine oil, iris extract, peppermint, rose, orange flower, citrus oils, mixed fruit oil, strawberry oil, cinnamon oil, clove oil, grape oil, and the like.

Examples of the fragrance material include xanthone, anethole, methyl salicylate, cinnamaldehyde, linalool, linalyl acetate, limonene, menthone, menthyl acetate, pinene, octanal, citral, pulegone, carvacrol acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexanepropionate, methyl anthranilate, ethyl methylanthranilate, vanillin, undecalactone, hexanal, ethanol (ethyl alcohol), propanol, butanol, isoamyl alcohol, hexanol, dimethyl sulfide (dimethylsulfoide), cyclamate, furfural, trimethylpyrazine, ethyl lactate, and ethyl thioacetate (ethyl rioacetate). Examples of the harmonizing flavor containing a simple flavor and/or a natural flavor include strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, tropical fruit flavor, cream flavor, milk flavor, yogurt flavor, fruit mix flavor, and peppermint (herb mint) flavor. The flavor may be in the form of an essential oil, an extract, a solid, or a powder obtained by spray-drying the essential oil, the extract, the solid, or the powder.

The total amount of the perfume is preferably 0.001 to 20%, particularly preferably 0.001 to 5%, of the total amount of the composition, and if the amount is less than 0.001%, the effect may not be sufficiently exhibited, and if it exceeds 20%, the fragrance or texture of the composition may be impaired.

In the composition of the present invention, other additives such as an acidulant, a gloss agent, a thickener, an emulsifier, a pH adjuster, a preservative, and the like may be added as necessary as components to be mixed into the sugar-coating layer or the chewing gum body within a range not to impair the effects of the present invention.

In order to produce a chewing gum from the coated chewing gum composition of the present invention, various components are added to a gum base, kneaded, molded into an appropriate shape, and a chewing gum is prepared by coating a sugar-coated component containing maltitol and lactoferrin on the surface of a chewing gum body to form a sugar-coated layer.

For example, first, a gum base resin is used as a main component, and additives such as dextranase, sweetener, flavor, colorant, and flavoring agent are added to a gum base composed of wax, emulsifier, filler, softener, etc. in predetermined amounts as required, and the mixture is kneaded uniformly at about 50 ℃ using a kneader. Subsequently, the gum is cut into an appropriate shape such as a plate shape or a block shape to obtain a chewing gum body (chewing gum layer). In this case, the mass of the chewing gum body is preferably about 1 to 2 g. The formation of the sugar-coating layer on the surface of the chewing gum body can be carried out by using a sugar-coating pan or a rotary pan.

The sugar coating step may be performed by a usual method using a sugar coating pan or a rotary pan, or may be performed by any of a so-called hard coating method using a syrup prepared by mixing maltitol with an edible gum or the like to prepare an aqueous solution, and a so-called soft coating method in which a finely powdered material composed of powdered sugar or the like and the maltitol syrup are alternately sprinkled. In this case, lactoferrin may be directly added as it is, or may be added after being mixed in advance with a maltitol syrup and/or a maltitol fine powder raw material.

The sugar coating plate or the rotary pan is preferably connected to a drive motor, and is mounted on a rotary drive shaft which is inclined by 10-60 degrees relative to the vertical line, and is an upper open type container with a bottom. For example, FY-TS-220 manufactured by Fuji pharmaceutical machinery may be used. In the case of the soft candy coating method, for example, a chewing gum body molded into an appropriate shape is put in a sugar-coated pan or a rotary pan, a maltitol syrup containing a binder such as a sugar-coated raw material gum arabic is added while the sugar-coated pan or the rotary pan is rotated at 5 to 30 rpm and sprayed on the surface of the chewing gum body, the entire surface of the chewing gum body is coated with the maltitol syrup containing the binder, and then a powder component such as maltitol and lactoferrin or a liquid component such as an oil flavor is mixed and put in advance, and air-dried to form a sugar-coated layer. The drying may be performed, for example, by supplying the powder component to cover the entire coating, or may be performed by blowing air after the powder component is treated. When air supply is performed, the ideal air volume is 3-30 m²For example, the water content is preferably 1 to 3% by drying. It is desirable to repeat this procedure until the proportion of the sugar-coated layer is the whole preparationThe sugar coating layer is formed by 20-45%, especially 30-40% of the sugar-coated chewing gum body (the chewing gum body is coated by the sugar coating layer).

Further, after the sugar-coated layer is formed, a further process such as glossing may be employed, and for example, the glossing process may be performed by applying wax to the surface of the sugar-coated layer of the sugar-coated chewing gum while applying wax to the rotary pan while the rotary pan is rotated by supplying wax. In this case, carnauba wax, candelilla wax, or the like may be used as the wax.

The sugar-coated chewing gum composition of the present invention is prepared into sugar-coated chewing gums having various shapes such as a pellet shape and a quadrangular shape, and is particularly preferably prepared into a quadrangular shape from the viewpoint of being less likely to be damaged and appearance stability.

Examples

The present invention will be described in more detail below with reference to experimental examples, and comparative examples, but the present invention is not limited to the following examples. In each example, unless otherwise specified,% is mass%, and the amount to be mixed is the amount in terms of pure components after drying to remove moisture.

[ Experimental example ]

Sugar-coated chewing gums having compositions shown in tables 1 to 3 were prepared and evaluated by the following methods. The results are shown in tables 1 to 3.

Preparation of sugar-coated chewing gum:

according to the compositions shown in tables 1 to 3, a gum base (ナチユラルベ - ス, manufactured by mitsubishi corporation), xylitol (フ - ドテツク, manufactured by mitsubishi corporation), maltitol (フ - ドテツク, manufactured by mitsubishi corporation), isomalt (manufactured by mitsubishi corporation), erythritol (manufactured by riji corporation), reduced syrup (manufactured by riji corporation), reduced maltose syrup (manufactured by riji corporation), dextranase (12000 unit, manufactured by ライフテツク, manufactured by mitsui corporation), sucralose (manufactured by mitsui 12456 フエフアイ, manufactured by powder flavor and oil flavor) were added and kneaded uniformly using a kneader (manufactured by ト - シン) having a capacity of 1L before and after 50 ℃. The kneaded product was cut into pieces to obtain chewing gum bodies (chewing gum layers). At this time, the mass of the chewing gum body was about 1 g. Thereafter, the molded chewing gum body was put into a sugar-coated pan, the sugar-coated pan was rotated at 15 rpm while sprinkling maltitol or sorbitol syrup containing gum arabic on the surface of the chewing gum, the entire surface of the chewing gum was coated with the maltitol or sorbitol syrup containing gum arabic, the powder component such as crystallized maltitol and lactoferrin was put into the pan, the liquid component such as oil flavor was then put into the pan, and a sugar-coated layer was formed on the surface of the chewing gum body by air-blow drying. The process is repeated until the proportion of the sugar coating layer is 30-40% of the total preparation, and the sugar-coated chewing gum is manufactured. Further, carnauba wax was supplied into the sugar-coated pan, and the surface of the sugar-coated layer of the sugar-coated chewing gum was applied while rotating the sugar-coated pan.

In each example, lactoferrin (food grade) manufactured by DMV japan was used as lactoferrin (the same applies hereinafter).

The method for extracting the lactoferrin from the sugar-coating layer comprises the following steps:

sugar-coated chewing gum 1 pellets having the compositions shown in tables 1 and 3 and the composition shown in comparative example 6 in table 2 were transferred to a 100mL beaker, dissolved in 80mL of a 3% aqueous solution of sodium chloride at 60 ℃ for 30 minutes, then the wall of the beaker was cleaned with a 3% aqueous solution of sodium chloride to make up to 100mL, sonicated for 5 minutes, and filtered through a filter (manufactured by クラボウ Co.) having a pore diameter of 0.45 μm and a membrane diameter of 25 mm. This was used as a rubber extract sample, and the amount of lactoferrin was determined by liquid chromatography under the conditions of experiment 1.

A process for extracting lactoferrin from chewing gum bodies:

sugar-coated chewing gum 1 pellets having the compositions of comparative examples 1 to 5 and 7 shown in Table 2 were put in a mortar, extracted with a milk bar in 80mL of a 3% aqueous solution of sodium chloride, the mortar was rinsed with a 3% aqueous solution of sodium chloride to make up to 100mL, subjected to ultrasonic treatment for 5 minutes, and filtered through a filter (manufactured by クラボウ) having a pore size of 0.45 μm and a membrane diameter of 25 mm. This was used as a rubber extract sample, and the amount of lactoferrin was determined by liquid chromatography under the conditions of experiment 1.

Experiment 1: test for confirming elution amount of lactoferrin in sugar-coated chewing gum

The conditions for setting the liquid chromatography are as follows.

Liquid chromatograph: shimadzu サイエンス high performance liquid chromatograph

Column:

Shodex Asahipak C4P-50 4D

length 150mm x inner diameter 4.6mm

Mobile phase

Acetonitrile solution A, 0.5mol/L sodium chloride aqueous solution which is 10 (vol%): 90 (vol%)

Acetonitrile solution B, 0.5mol/L sodium chloride aqueous solution 50 (vol%): 50 (vol%)

Trifluoroacetic acid was added to the solution A and the solution B in an amount of 0.03% (vol%) respectively. Further, acetonitrile, sodium chloride and trifluoroacetic acid were used as products manufactured by Wako pure chemical industries, Ltd.

Gradient conditions:

liquid a and liquid B started at 50: 50 (vol%), and after 25 minutes the concentration of liquid B was increased linearly to 0: 100 (vol%). After 25 minutes, the mixture was returned to the condition of mobile phase A: B of 50: 50 (vol%), and the solution was kept for 35 minutes under the condition.

Flow rate: 0.8mL/min

Temperature: 30 deg.C

A detector: ultraviolet ray spectral detector (280nm)

Sample amount: 25 μ l

The amount of lactoferrin in the chewing gum extract was determined from the peak area indicated by 0.025% lactoferrin standard solution (mass%), and the lactoferrin elution rate was calculated from the following formula.

The lactoferrin dissolution rate (%) [ (amount of lactoferrin (mg))/(amount of mixed lactoferrin (mg)) in the chewing gum extract) ] × 100

Experiment 2: chewing release test of lactoferrin from sugar coated chewing gum

The test subjects were 10 healthy subjects whose teeth were all normal, and saliva was taken at 1 minute of rest, and the test subjects chewed 2 pieces of sugar-coated chewing gum having the composition shown in tables 1 to 3 for 10 minutes, and saliva was taken every minute. The coated chewing gum was spitted after 10 minutes, and then 1 minute of saliva was taken at rest. The obtained saliva was diluted 5-fold with 3% aqueous sodium chloride solution, filtered through a filter, and then used as an experimental sample, and lactoferrin was quantified by HPLC (high performance liquid chromatography) in the same manner as in experiment 1. The lactoferrin release rates after 5 minutes and 10 minutes were calculated from the following formulas (i) and (ii), and the release rate in saliva was evaluated based on the following criteria. The results of 10 were averaged.

(i) The lactoferrin release rate (%) after 5 minutes was ═ 5 [ (total of lactoferrin amounts (mg) in saliva for 5 minutes)/(mixed lactoferrin amount (mg)) ] × 100

(ii) The lactoferrin release rate (%) after 10 minutes was ═ 5 (total of lactoferrin amounts (mg) in saliva for 10 minutes)/(mixed lactoferrin amount (mg)) ] × 100

Evaluation criteria for the Release Rate of Lactoferrin in saliva (average of 10)

Within 5 min 90% dissolution-

90% or more within 10 minutes

More than 10 parts and less than 90%)

Experiment 3: lactoferrin elution test after long-term high-temperature storage of sugar-coated chewing gum

The sugar-coated chewing gum having the composition shown in tables 1 to 3 was put into a 200mL container with a plug manufactured by letterpress printing, covered with a lid, and placed in a 35 ℃ incubator (incubator IG420 manufactured by ヤマト science), and after 3 months, lactoferrin was extracted from the chewing gum by the same method as described above, and quantified by the same method as in experiment 1. The dissolution rate of lactoferrin after long-term storage at high temperature (35 ℃) in the sugar-coated chewing gum was determined according to the above formula.

Experiment 4: in vitro periodontal germ toxin activity inhibition assay for sugar-coated chewing gum

< preparation of sample >

Sugar-coated chewing gum 1 pellets having the compositions shown in tables 1 and 3 and the composition shown in comparative example 6 in table 2 were transferred to a 100mL beaker, dissolved in 80mL of a 3% aqueous solution of sodium chloride maintained at 60 ℃ for 30 minutes, then the wall of the beaker was cleaned with a 3% aqueous solution of sodium chloride to make up to 100mL, sonicated for 5 minutes, and filtered through a filter (manufactured by クラボウ) having a pore diameter of 0.45 μm and a membrane diameter of 25mm to prepare a sample solution.

Further, 1 pellet of sugar-coated chewing gum having the composition of comparative examples 1 to 5 and 7 shown in Table 2 and 80mL of a 3% sodium chloride aqueous solution were placed in a mortar, extracted with a pestle, the mortar was rinsed with a 3% sodium chloride aqueous solution to make up to 100mL, subjected to ultrasonic treatment for 5 minutes, and filtered through a filter (manufactured by クラボウ Co.) having a pore size of 0.45 μm and a membrane diameter of 25mm to prepare a comparative sample solution.

< evaluation >

An in vitro inhibitory test of periodontal bacterial toxin activity was carried out by the following method, with the exception of the endotoxin detection kit (endospacy) method (manufactured by biochem industries, Ltd.).

100. mu.L of endotoxin (hereinafter abbreviated as Pg. LPS) of Porphyromonas gingivalis 381, which is one of causative bacteria of periodontal disease, 50. mu.g/mL of endotoxin, 100. mu.L of distilled water for injection (hereinafter referred to as "A"), or 100. mu.L of the sample solution obtained by the above-described method or the comparative sample solution (hereinafter referred to as "B") were mixed. After each sample solution was cultured at 37 ℃ for 30 minutes, the solution was diluted 100, 1000, 3000, and 6000 times with distilled water for injection, and for the 3000-time diluted sample, the inhibition rate of the activity of periodontal disease bacteria toxin was determined by the endotoxin test kit method, and the inhibition rate of the activity of toxin was calculated according to the following formula.

Inhibition ratio of toxin Activity (%) [ (A-B)/A ]. times.100

A ═ ABS of (Pg. LPS)^*) - (ABS of distilled Water for injection)^*)

(sample solution or comparative sample solution + Pg-LPS) ABS^*) - (ABS of distilled Water for injection)^*)

^*ABS: absorbance at 545nm

Experiment 5: tartar formation inhibiting effect of sugar-coated chewing gum

2 dragee cores shown in Table 3 were extracted with 30mL of 0.01% albumin phosphate buffer to prepare samples. 1mL of the sample was dissolved in 4mL of a medium containing TSB (Tryptic Soy Broth) prepared by BD corporation, to which 1% of sucrose (manufactured by Wako pure chemical industries, Ltd.) was added, and the sample was placed in a test tube and inoculated with Streptococcus mutans (Streptococcus mutans) which had been anaerobically cultured in advance, followed by anaerobic culture in a slant medium for 18 hours, and the amount of bacteria adhering to the test tube wall was measured. As a control, the same test was carried out using a medium to which no sample was added, and the amount of adhering bacteria (X) at that time was passed₀) And the amount of adherent bacteria (X) using the sample_s) The tartar formation inhibition rate was determined according to the following equation.

Tartar formation inhibition (%) - (X)₀-X_s)/X₀]×100

X₀: amount of adherent bacteria using a culture Medium to which no sample was added

X_s: amount of adherent bacteria using sample

[ Table 1]

[ Table 2]

[ Table 3]

Claims (4)

1. A sugar-coated chewing gum composition comprising a chewing gum body and a sugar-coating layer covering the surface of the chewing gum body, wherein the sugar-coating component for forming the sugar-coating layer contains maltitol and lactoferrin.

2. The sugar coated chewing gum composition of claim 1, wherein the chewing gum body or the sugar coating layer further comprises a dextranase.

3. A process for producing a sugar-coated chewing gum, characterized in that a chewing gum body is formed, and then the surface of the chewing gum body is coated with a sugar-coating component containing maltitol and lactoferrin to form a sugar-coating layer.

4. The process for producing a sugar-coated chewing gum according to claim 3, wherein the chewing gum main body or the sugar-coating layer further contains glucanase.