WO2003063605A1

WO2003063605A1 - Chewing gum composition containing plant sterol for decrease of flood cholesterol levels and prevention of periodontal disease

Info

Publication number: WO2003063605A1
Application number: PCT/KR2003/000211
Authority: WO
Inventors: Seung-Kwon Noh; Won-Tae Yoon; Doo-Hyeon Lim
Original assignee: Eugene Science Inc.
Priority date: 2002-02-01
Filing date: 2003-01-29
Publication date: 2003-08-07

Abstract

Disclosed is a chewing gum composition containing plant sterols, having 0.01-10.0 wt % of plant sterol which functions to decrease a user's cholesterol level and to prevent periodontal diseases. The gum composition comprises a nanomilled plant sterol-emulsifier dispersion including 30.0-80.0 wt % of plant sterol, and 20.0-70.0 wt % of at least one emulsifier selected from the group consisting of sucrose fatty acid ester, sorbitan fatty acid ester, polysorbate, polyglycerol fatty acid, propylene glycerol fatty acid, and polyglycerin fatty acid ester, mixed, melted and stirred at high rates together. Therefore, the gum composition is effective in decreasing blood cholesterol level in humans and preventing periodontal diseases when being chewed, by increasing bioavailability of the nanomilled dispersion and reducing the amount of the plant sterol.

Description

CHEWING GUM COMPOSITION CONTAINING PLANT STEROL FOR DECREASE OF BLOOD CHOLESTEROL LEVELS AND PREVENTION OF

PERIODONTAL DISEASE

Technical Field

The present invention relates to a chewing gum composition containing plant sterol functioning to hinder absorption of cholesterol and to improve and prevent periodontal diseases.

Background Art

As well known to those skilled in the art, diseases connected with cholesterols have come to the forefront of the social problems in recent years, attributable to continuously increasing ingestion of cholesterols. Since foods having high amounts of cholesterols are frequently consumed, cholesterol contained in the foods increases blood cholesterol levels to cause cardiovascular system diseases, such as hyperlipidemia, arteriosclerosis, dysrhythmia, myocardial infarction, etc. In addition, periodontal diseases are regarded as a representative dental disease along with tooth decay. Although not being a disease of teeth themselves, periodontal disease occurs in periodontal tissues supporting teeth and has an influence on alveolar bone, resulting in that the tissues are destroyed and pyogenesis is progressed. Thereby, bleeding, gingival swelling and teeth loosening may occur, and eventually all teeth may be lost.

Plant sterol or phytosterol is composed of sitosterol, campesterol, ^• and stigmasterol, and plant stanol or phytostanol as a reduced form of the plant sterol or phytosterol includes sitostanol, campestanol and so on. This component is a natural material widely present in plants, for example, beans, corn, wood, tall oils, etc

(hereinafter, referred to as plant sterol' ) . In this regard, the plant sterol is known to have no poisonous character and a structure similar to that of cholesterol, and to hinder absorption of cholesterol, thereby reducing cholesterol levels in blood serum (USA Patent No. 5,578,334) . It is reported that the plant sterol functioning to hinder absorption of cholesterol is effective in treatment of cardiovascular diseases, cardiac coronary artery and hyperlipidemia (Atherosclerosis 28: 325-338) .

In addition to hindrance of absorption of cholesterol by the plant sterol, the plant sterol is reported to have various pharmacological functions, for example, teeth support, . periodontal diseases including tissue diseases, gingivitis, or periodontitis (O.S., O.M. & O.P. March, 1969, 319-332). Further, anti-inflammatory activity (Chem. Pharm. Bull. 35, (12) 4851-4855, 1987)- and anti-bacterial activity (Journal of Ethnopharmacology 40, 181-186, 1993) are reported. However, it is difficult to apply the plant sterol to foods because of insoluble properties to water and oil. Some oil based foods such as margarine have been limitedly developed to contain plant sterol. Thus, there are required plant sterol-containing foods capable of being easily administered, which are advantageous in terms of decreasing blood cholesterol levels, preventing and treating periodontal diseases, and having anti-inflammatory activity and anti-bacterial activity.

Korean Patent Application No. 2000-57652, filed by the present inventors, discloses a method of preparing water- soluble plant sterol dispersion and powders, by solving the insoluble properties of the plant sterol. As such, the plant sterol is dispersed in the state of nanoparticles (particle size : several to several hundreds of nanometers) and thus bioavailability becomes _.very high.

But, there are not developed foods containing the plant steroi and having effects of improving cholesterol levels and periodontal diseases as well as anti- inflammatory and anti-bacterial activities, which are capable of exhibiting the maximal effects even though being simply administered in smaller amounts. The present inventors have attempted to apply such plant sterol to various foods for easier ingestion, and the above effects can be confirmed from the applied foods. In particular, the plant sterol should be orally administered and should come into contact with regions afflicted with periodontal diseases for as much time as possible so that it functions to decrease blood cholesterol levels, to prevent and treat periodontal diseases and to exhibit anti- inflammatory and anti-bacterial activities. Accordingly, a chewing gum is considered as a preferable food form meeting the above conditions. While the gum is chewed, the plant sterol can be easily orally administered. Further, the gum form is suitable for maximization of the effects of the plant sterol on periodontal diseases due to bringing the gum into contact with regions of gingival inflammation.

However, there are many problems for containing the plant sterol in the gum. Since the plant sterol is insoluble to both of water and oil, it is impossible to prepare the gum by a general process. Also, although the plant sterol may be used after it is emulsified to water using a food emulsifier, it is difficult to emulsify the plant sterol . In case where the gum prepared by use of the emulsified plant sterol is chewed, particles of the plant sterol are detectable and thus the feeling upon chewing becomes bad. Further, since the gum has generally a weight of 2.5-3.0 g per piece, an amount of the plant sterol is limitedly contained in the gum. Thus it is difficult to contain the plant sterol in a necessary amount into the gum composition to exhibit the above effects.

Disclosure of the Invention

Leading to the present invention, the intensive and thorough research into chewing gum compositions containing plant sterol, carried out by the present inventors aiming to avoid the problems encountered in the prior art, led to development of a chewing gum composition using a process of preparing a dispersion in which plant sterol is dispersed into particles with a size of nanometers, that has been developed by the present inventors and applied to drinks, in which absorption of the plant sterol is increased in the human body due to very small particle size of the sterol component, whereby various pharmacological functions of the plant sterol, such as anti-inflammatory and anti-bacterial activities, decrease of blood cholesterol levels and prevention and treatment of periodontal diseases, are sufficiently exhibited. As well, when the gum is chewed, the plant sterol component having a size of nanometers is easily dissolved in saliva in the oral cavity and is directly introduced into gingival tissues afflicted with periodontitis and oral inflammation. Thus, the gum composition having excellent therapeutic effects can be prepared.

Therefore, it is an object of the present invention to provide a chewing gum composition containing plant sterol which is advantageous in terms of decrease of blood cholesterol levels due to hindrance of absorption of cholesterol, and prophylaxis of periodontal diseases, without irregular feeling when the gum is chewed.

To _. achieve the above object, the present invention provides a chewing gum composition comprising 0.01-10.0 wt% of plant sterol.

Best Mode for Carrying Out the Invention

The present invention relates to_^ a chewing gum composition containing plant sterol having low blood cholesterol levels due to hindrance of absorption of cholesterol, and improvement and prophylaxis of periodontal diseases .

According to the present invention, the chewing gum composition includes 0.01-10.0 wt% of plant sterol, which hinders absorption of cholesterol to decrease blood cholesterol levels and is effective in .treatment of various periodontal diseases, inflammatory and bacterial diseases. If the amount of the plant sterol is less than 0.01 wt%, the plant sterol fails to function to decrease blood cholesterol levels and prevent and treat periodontal diseases. Meanwhile, if the amount exceeds 10.0 wt%, the chewing gum composition is difficult to prepare and chewing feeling becomes bad. The chewing gum composition of the present invention contains a dispersion in which plant sterol is dispersed into particles with a size of nanometers or its powders.

In order to prepare the dispersion, 30.0-99.5 wt% of plant sterol and 0.5-70.0 wt% of an emulsifier are heated and mixed at 60-200 °C, preferably 120-150 °C. As such, when the amount of the plant sterol is smaller than 30.0 wt%, the emulsifier is used in the relatively large amounts, and thus it is difficult to prepare the gum composition. Further, when the mixing temperature is lower than 60 °C, the formed mi'celles have a particle size of several tens to several hundreds of micrometers and bioavailability is decreased due to relatively large particles of the plant sterol. On the other hand, if the temperature is higher than 200 °C, the sterol component is stable in heat but heat-deterioration of the emulsifier may occur.

The heated mixture of the plant sterol and the emulsifier is added to an aqueous solution and stirred at high speeds. As such, a ratio of the plant sterol to the aqueous solution ranges from 1:10 to 1:10000 (w/w) , preferably from 1:10 to 1:100 (w/w). The stirred solution is treated by use of a τnicrofluidizer to obtain a plant sterol-emulsifier dispersion. Thusly obtained dispersion has the plant sterol with a particle size of 55-1,000 nm, in which 95% or more of particles have a size of 300 nm or smaller. If the particles have a size larger than 1,000 nm, chewing feeling becomes bad due to the relatively large particles. In particular, in view of improvement and prophylaxis of periodontal diseases, the smaller the particle size, the larger the surface area of the particles. Thereby, even though smaller amounts of plant sterol are used, high effect can be obtained.

Water is used as the above aqueous solution, whereby the prepared plant sterol-containing dispersion is evaporated and lyophilized or spray dried, to afford water- soluble plant sterol-containing powders.

Alternatively, 30.0-99.5 wt% of plant sterol and 0.5- 70.0 wt% of the emulsifier are heated and mixed at 60-200 °C, preferably 120-150 °C. Thereafter, the mixed solution is rapidly cooled to 10 °C to give a solidified material, which is then milled to finally obtain plant sterol- containing powders.

The plant sterol of the present invention is selected from among sitosterol, campesterol, stigmasterol, sitostanol, campestanol and mixtures thereof. In addition, other plant sterols may be used. The emulsifier of the present invention should not be "deteriorated at temperatures higher than 60 °C, which is exemplified by sucrose fatty acid ester, sorbitan fatty acid ester, polysorbate, polyglycerol fatty acid, propylene glycol fatty acid, polyglycerin fatty acid ester or mixtures thereof. Preferably, the emulsifier is selected from among sucrose fatty acid ester, sorbitan fatty acid ester, or polyglycerin fatty acid ester.

The prepared plant sterol-emulsifier dispersion or powders are formed to a plant sterol-containing gum composition by general preparation methods.

The chewing gum composition containing the dispersion in which plant sterol is dispersed into particles with a size of nanometers or its powders has high bioavailability due to very small particle sizes. In particular, even though the plant sterol is used in decreased amounts due to nanometer level particles of the plant sterol, the gum composition is effective in decreasing blood cholesterol levels in humans and preventing and treating the periodontal diseases even though only being chewed.

Having generally described this invention, a further understanding can be obtained by reference to certain specific examples which are provided herein for purposes of illustration only and are not intended to be limiting unless otherwise specified. Example 1

Preparation of dispersion in which plant sterol is dispersed into particles with a size of nanometers

5 g of plant sterol (sitosterol 75%, campesterol 10%, stigmasterol sitostanol 15%) and 4.25 g of sucrose fatty acid ester (HLB 11) as an emulsifier were added into a container and melted with stirring at 130-140 °C . After the completely melted solution was further stirred for 1 min, the solution was added to 490.75 g of hot water at 80 °C and then stirred at 6800-7000 rpm for 10 min. Thusly stirred solution was subjected to 1 pass ' treatment at 7000 psi by use of a mi^'crofluidizer (M110EHI, Microfluidics) .

A particle size of the dispersion was analyzed by use of a mastersizer (Malvern Instrument LTD, the British Empire) . The results are given in Table 1, below.

TABLE 1

Example 2

8 g of plant sterol (sitosterol 75%, campesterol 10%, stigmasterol sitostanol 15%) and 0.5 g of sucrose fatty acid ester (HLB 11) as an emulsifier were added into a container and melted with stirring at 130-140 °C . After the completely melted solution was further stirred for 1 min, the solution was added to 491.5 g of hot water at 80 °C and then stirred at 6800-7000 rpm for 10 min. Thusly stirred solution was subjected to 1 pass treatment at 7000 psi by use of a microfluidizer (M110EHI, Microfluidics) .

A particle size of the dispersion was analyzed by use of a mastersizer (Malvern Instrument LTD, the British Empire) . The results are given in Table 2, below.

TABLE 2

Examples 3-4

Preparation of Water-dispersed Plant Sterol Powders The dispersions obtained from the above examples 1 and 2 were spray dried to obtain water-dispersed plant sterol powders .

Example 5 Preparation of Plant Sterol-Emulsifier Powders

5 g of plant sterol (cytosterol 75%, campesterol 10%, stigmasterol cytostanol 15%) and 4.25 g of sucrose fatty acid ester (HLB 11) as an emulsifier were added into a container and melted with stirring at 130-140 °C . After the completely melted solution was further stirred for 1 min, the solution was solidified in a freezing -chamber of -10 °C . The solidified material was milled to afford plant sterol-emulsifier powders.

Example 6 Preparation of Plant Sterol-Emulsifier Powders

8 g of plant sterol (cytosterol 75%, campesterol 10%, stigmasterol cytostanol 15%) and 0.5 g of sucrose fatty acid ester (HLB 11) as an emulsifier were added into a container and melted with stirring at 130-140 °C. After the completely melted solution was further stirred for 1 min, the solution was solidified in a freezing chamber of -10 °C . The solidified material was milled to afford plant sterol-emulsifier powders. Examples 7 -10

Preparation of Plant Sterol-Containing Chewing Gum 250 g of a gum base was preheated to 55 °C, and then mixed with 10 g of glycerin, 120 g of starch syrup, 560 g of a mixture of high-milled sugar and glucose, 10 g of a flavor mixture of peppermint, spearmint and lemon, and 50 g of powders obtained from the above examples 3-6, for 30 min and aged for 36 hours and then cut.

Examples 11-12 Preparation of Plant Sterol-Containing Coating Gum

250 g of a gum base was preheated to 55 °C, and then mixed with 10 g of glycerin, 120 g of starch syrup, 610 g of a mixture of -high-milled sugar and glucose, and 10 g of a flavor mixture of peppermint, spearmint and lemon, for 30 min and aged for 24 hours, and then cut in a suitable form to have a weight of 2.0 g per piece. The cut gum was firstly coated with titanium powders in a coating pan, and then further coated with a coating mixture of each syrup containing 30% of the plant sterol dispersions obtained from the above examples 1 and 2, Arabia gum and bees wax,- to have a whole weight of 2.7 g.

Examples 13-14

Preparation of Plant Sterol-Containing Core Gum

250 g of a gum base was preheated to 55 °C, and then mixed with 10 g of glycerin, -120 g of starch syrup, 610 g of a mixture of high-milled sugar and glucose, and 10 g of a flavor mixture of peppermint, spearmint and lemon, for 30 min and aged for 24 hours, and then cut to have a weight of 2.0 g per piece. The cut gum was introduced in the pan and formed to a dosage form, which was then injected with a mixture of each syrup containing 30% of the plant sterol dispersions obtained from the above examples 1 and 2, a flavor mixture of peppermint, spearmint and lemon, and bees wax, to have a whole weight of 3.0 g.

Example 15

20 persons were allowed to chew two of each of the plant sterol-containing gum obtained from the above example 10 and a gum having the same flavor and taste as the above gum but not containing plant sterol. As such, persons were informed whether the gum contained plant sterol or not. In this test, consistent results were not obtained. It is believed that there is little difference between the gum containing plant sterol and the gum not containing plant sterol.

Example 16

5 persons were allowed to chew the plant sterol- containing gum obtained from the above example 10 for 5, 10, 15 and 20 min. Thereafter, the chewed gums were recovered and the plant sterol remaining in the gum was quantitatively analyzed to evaluate release of the plant sterol from the plant sterol-containing gum. The release test was performed^" by extracting the plant sterol from the chewed gum and analyzing the extracted plant sterol by gas chromatography . The same test was repeatedly performed 5 times. The results are shown in Table 3, below.

TABLE 3 Average Remaining Rate (%)

From the above Table 3, it can be seen that 55% or more of the plant sterol is released from the gum after being chewed for 15 min or longer.

Example 17

50 patients in their twenties suffering from periodontal diseases were selected and were allowed to chew the gum obtained from the above example 10 after each meal for 15 min or longer 3 times/day. The above regimen was continued for 1 week. The patients were not additionally treated for periodontal diseases, and eating habits as well as tooth care habits were not specifically changed. After 1 week and 2 weeks, such disease conditions were observed. The results are shown in Table 4, below.

TABLE 4

From the above Table 4, it can be seen that 92% of persons experienced improvements in their periodontal disease conditions after 2 weeks.

Industrial Applicability

As described above, the present invention provides a chewing gum composition containing plant sterol. The gum composition obtained by using a dispersion in which plant sterol is dispersed into particles with a size of nanometers or its powders has no influence on physical properties of the gum because the plant sterol has very small particle sizes. In addition, since the plant sterol is rapidly released from the gum, it is possible to orally administer the plant sterol contained in the gum within a short time. Further, the plant sterol having a size of nanometers increases bioavailability therof in the human body and can be used in a smaller amount, whereby decrease of blood cholesterol levels and prevention and treatment of periodontal diseases can be achieved even though the gum is only chewed. In particular, in the case of periodontal diseases, the surface area of the plant sterol having a size of nanometers coming into contact with periodontal disease regions is larger than that of conventional materials having a micrometer level particle size. Thus, the gum composition of the present invention is more effective in improvement and prevention of periodontal diseases .

Although the preferred embodiments of the present invention have been disclosed for illustrative purposes, those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without • departing from the scope and spirit of the invention as disclosed in the accompanying claims.

Claims

1. A chewing gum composition containing plant sterol for decrease of blood cholesterol levels and prevention and treatment of periodontal diseases, comprising 0.01-10.0 wt% of plant sterol.

2. The chewing gum composition as defined in claim 1, wherein the plant sterol is dispersed in a particle size of 55-1,000 nm into an aqueous solution and is used in a form of a dispersion or powders.

3. The chewing gum composition as defined in claim 2, wherein the dispersion or powders are obtained by subjecting 30.0-99.5 wt% of plant sterol and 0.5-70.0 wt% of an emulsifier to mixing, melting and high-speed stirring, the emulsifier being selected from among sucrose fatty acid ester, sorbitan fatty acid ester, polysorbate, polyglycerol fatty acid, propylene glycol fatty acid, polyglycerin fatty acid ester, or mixtures thereof.