Patent Grant
8496915
The present invention relates to a non-cariogenic material and a cariostatic agent, which contain rare sugars. More specifically, the invention relates to a composition comprising the non-cariogenic material in blend and a cariostatic composition comprising the cariostatic agent in blend.
Dental caries (terms “caries tooth, dental caries, and tooth caries, decayed teeth, etc.” mean the same disease; thus, these terms are abbreviated as “caries” hereinafter) is a disease caused by oral bacteria generating acids using sugars, particularly sucrose as a nutritious source to cause decalcification of teeth with the acids (the solubilization of inorganic components phosphoric acid and calcium from dental enamel and dentine with acids) and then decay teeth.
Various theories have been proposed about the detailed etiology of caries. Currently, it is understood that caries is initiated by the deposition of an insoluble, adhesive polysaccharide (insoluble glucan) generated by Streptococcus mutans (sometimes abbreviated as “S. mutans” hereinafter) on the dental surface. Specifically, insoluble glucan is generated from sucrose by bacteria such as Streptococcus mutans; the insoluble glucan deposits on dental surface to form dental plaque by oral bacteria and with food residues. Various microorganisms mainly including Streptococcus mutans can concurrently exist and proliferate in the dental plaque. Through the metabolism of these microorganisms, acids are generated; with the action of the acids, the pH is reduced to cause dental decalcification, leading to tooth decay and additionally to cause the occurrence and progress of caries.
Because caries occur due to the causes described above, one of preferable prophylactic approaches therefor is no intake of sugars causing the generation of insoluble glucan and acids by oral bacteria, such as sucrose. Because sucrose is abundantly contained in the natural kingdom and agricultural products such as fruits and vegetables and is an indispensable item in seasonings and foods for our daily dietary life, it is very hard to achieve no sucrose intake.
In such circumstances, so far, alternative sugars such as Xylitol (patent reference 1, patent reference 2), Palatinit (patent reference 3) and erythritol (non-patent reference 1) have been developed. The effects thereof on the prevention of acid generation and dental plaque formation with caries-inducing bacteria have been elucidated. Additionally, D-arabitol at a sweetness level of about 68% of the sweetness level of sucrose, D-allose at a sweetness level of about 65% of the sweetness level of sucrose and L-mannose at the same sweetness level as that of glucose have been proposed as non-cariogenic materials (patent reference 4). Furthermore, the use of a cyclic tetrose D-psicose as a material inducing a low level of caries has also been suggested (patent reference 5).
Still further, it has been known commonly that dental plaque not only causes decayed teeth but also causes periodontal diseases such as gingivitis and periodontitis (gumboil). Therefore, it is an important issue to suppress or kill etiologic bacteria causing caries or periodontal diseases, such as Streptococcus mutans, so as to prevent such various diseases. Accordingly, oral compositions with such effects have been desired strongly. So as to apply such compositions to the prophylaxis and therapeutic treatment of periodontal diseases, the alternative sugars disadvantageously have problematic safety profiles when used in the oral compositions; the alternative sugars are hardly blended in stable manners in such oral compositions; the alternative sugars disadvantageously affect flavor; the alternative sugars have insufficient effects; and the cost for blending the alternative sugars therein is problematic.
Xylitol is a sugar alcohol belonging to rare sugars and has conventionally been added to favorite foods and foods, for use. It has been known commonly that Xylitol has a high effect on the prophylaxis of caries. It is surely understood that sugar alcohols such as Xylitol, Palatinit and erythritol hardly function as substrates for the glucan synthase generated by Streptococcus mutans and never serve as raw materials for water-soluble and water-insoluble glucan.
Furthermore, it has been indicated that Xylitol has such non-cariogenicity that Xylitol is never utilized by the group Streptococcus mutans and additionally that Xylitol exerts an action to promote the sterilization action against the group Streptococcus mutans and also exerts a recalcification-promoting action. By recent research works, meanwhile, it has been verified that because the group Streptococcus mutans cannot utilize Xylitol as energy, the proliferation and activity of Streptococcus mutans is reduced. In other words, the replacement of a part of sucrose in a sweetener with Xylitol leads to the reduction of the sucrose amount. In such manner, an effect of preventing caries can be obtained. It has been known that conventionally known sugar alcohols with a non-cariogenic action induce for example diarrhea at excess intake thereof and that the use of such sugar alcohols as alternative sugars of glucose and fructose is not appropriate because of the difference in physical properties. Thus, it has been desired the development of a novel non-cariogenic material durable on multiple uses as an alternative sugar.
Specifically, the development of a non-cariogenic material durable on multiple uses as alternative sugars of glucose and sucrose as major caloric sources and as important sweeteners as well as a caries-preventing sweetener containing the same has been desired. It has been expected to find a rare sugar with an effect as an anticarius sweetener among other rare sugars to create a novel “anticarius sweetener” using the same.
In accordance with the invention, it was found a novel non-cariogenic rare sugar with a property that the rare sugar is never metabolized with a bacterium causing caries, namely Streptococcus mutans, i.e. with a property involving no substantial generation of insoluble glucan or acids. Thus, it is an object of the invention to provide a non-cariogenic material in blend with the non-cariogenic rare sugar and a composition containing the same (anticarius sweetener).
In accordance with the invention, a novel cariostatic rare sugar was found, which had a property substantially suppressing acidification via the metabolism with caries-causing bacteria, when existed concurrently with a cariogenic sweetness ingredients to be metabolized with Streptococcus mutans as a caries-causing bacterium. Thus, it is an object of the invention to provide a cariostatic agent comprising the cariostatic rare sugar as well as a cariostatic composition prepared by blending the cariostatic agent.
It is an object of the invention to provide a composition for preventing periodontal diseases (prophylactic agent of periodontal diseases), the composition having excellent cariostatic properties, being safe and stable for a long period of use, and having less effects on flavor.
The inventor made investigations so as to solve the problems. Consequently, the inventor found that a rare sugar in the D form as selected from the group consisting of D-psicose, D-sorbose and D-tagatose as rare sugars, a rare sugar in the L form as selected from the group consisting of L-fructose, L-psicose and L-tagatose or allitol as a rare sugar derivative cannot be assimilated by Streptococcus mutans, so that such rare sugar or rare sugar derivative suppresses the proliferation of Streptococcus mutans, never leading to pH reduction. Thus, the invention relating to a non-cariogenic material has been achieved. Additionally, the inventor found that D-psicose never causes pH reduction (i.e., D-psicose has a cariostatic property) even in the presence of sucrose as an assimilable sugar. The inventor additionally found that the cariostatic property could be enhanced with a combination with catechin. Thus, the invention relating to the cariostatic agent has been achieved.
The gist of the invention resides in the non-cariogenic material described below in (1).
(1) A non-cariogenic material prepared by blending a rare sugar in the D form as selected from the group consisting of D-psicose, D-sorbose and D-tagatose as rare sugars, a rare sugar in the L form as selected from the group consisting of L-fructose, L-psicose and L-tagatose or allitol as a rare sugar derivative, singly or in combination.
The gist of the invention resides in the composition described below in (2) through (7).
(2) A composition containing the non-cariogenic material described in (1).
(3) The composition described in (2), where the composition is a food composition.
(4) The composition described in (3), where the food composition is a food composition with a label telling the use thereof for preventing periodontal diseases.
(5) The composition described in (2), where the composition is an oral composition.
(6) The composition described in (5), where the oral composition is an oral composition with a label telling the use thereof for preventing periodontal diseases.
(7) The composition described in (2), where the composition is a pharmaceutical product or a quasi-pharmaceutical product, or a cosmetic product.
(8) The composition described in (7), where the pharmaceutical product or quasi-pharmaceutical product is a pharmaceutical product or quasi-pharmaceutical product to be used for preventing periodontal diseases.
The gist of the invention resides in a cariostatic agent described below in (9) or (10).
(9) A cariostatic agent comprising a rare sugar in the D form as selected from the group consisting of D-psicose, D-sorbose and D-tagatose as rare sugars, a rare sugar in the L form as selected from the group consisting of L-fructose, L-psicose and L-tagatose or allitol as a rare sugar derivative.
(10) The cariostatic agent described in (9), comprising catechins in combination.
The gist of the invention resides in a cariostatic oral composition described below in (11) or (12).
(11) A cariostatic oral composition prepared by blending the cariostatic agent described in (9) or (10).
(12) The cariostatic oral composition described in (11), where the cariostatic oral composition is a cariostatic oral composition with a label telling the use thereof for preventing periodontal diseases.
The gist of the invention resides in a cariostatic food composition described below in (13) or (14).
(13) A cariostatic food composition prepared by blending the cariostatic agent described in (9) or (10).
(14) The cariostatic pharmaceutical product, quasi-pharmaceutical product or cosmetic composition described in (13), where the cariostatic food composition is a food composition with a label telling the use thereof for preventing periodontal diseases.
The gist of the invention resides in a cariostatic pharmaceutical product or quasi-pharmaceutical product or a cosmetic composition described below in (15) or (16).
(15) A cariostatic pharmaceutical product or quasi-pharmaceutical product or a cosmetic composition prepared by blending the cariostatic agent described in (9) or (10).
(16) A cariostatic pharmaceutical product or quasi-pharmaceutical product or a cosmetic composition described in (15), where the cariostatic pharmaceutical product or quasi-pharmaceutical product is a pharmaceutical product or quasi-pharmaceutical product with a label telling the use thereof for preventing periodontal diseases.
In accordance with the invention, a non-cariogenic material can be provided, which is prepared by blending a rare sugar in the D form as selected from the group consisting of D-psicose, D-sorbose and D-tagatose as rare sugars, a rare sugar in the L form as selected from the group consisting of L-fructose, L-psicose and L-tagatose or allitol as a rare sugar derivative, singly or in combination, which is never metabolized with Streptococcus mutans and which never substantially causes the acidification of dental surface via acid generation. Additionally, various compositions containing the non-cariogenic material, such as food compositions, oral compositions, pharmaceutical products or quasi-pharmaceutical products, and cosmetics products can be provided.
Specifically, the non-cariogenic material of the invention can be blended in various compositions including foods, drinks, feeds, pharmaceutical products, quasi-pharmaceutical products and cosmetic products, as an alternative sweetener of conventional sweetness ingredients comprising sugars such as glucose, fructose, lactose and sucrose and various reduced sugar types, or as a replacement of at least a part of the conventional sweetness ingredients or in addition to the conventional sweetness ingredients. In case that the non-cariogenic material of the invention is contained in for example compositions such as foods or drinks, the risk of affliction with caries is reduced even if the foods or drinks are ingested. In case that all the sweetness ingredients in entirety are substantially composed of the non-cariogenic material of the invention, no possibility of caries affliction exists even through the intake, so that the compositions can be prepared as non-cariogenic food compositions or drinks. In accordance with the invention, further, an oral composition in blend with the rare sugars with a safety profile for humans and great stability can be provided, so that it can be expected that the oral composition of the invention exerts the effect of preventing periodontal diseases, via the blending of the rare sugars.
In case of the concurrent existence with cariogenic sweetness ingredients metabolizable with Streptococcus mutans as a bacterium causing caries in accordance with the invention, a cariostatic agent comprising cariostatic rare sugars with properties of substantially suppressing the acidification of dental surface through the metabolism of the bacterium causing caries, namely D-psicose, D-sorbose, D-tagatose, L-fructose, L-psicose and L-tagatose, and allitol or comprising the cariostatic rare sugars in combination with catechins can be provided. Additionally, cariostatic oral compositions, cariostatic food compositions, or cariostatic pharmaceutical products, quasi-pharmaceutical products or cosmetic compositions comprising the cariostatic agent in blend can be provided. More specifically, the cariostatic agent of the invention is added to products containing assimilable sugars such as glucose, fructose, lactose and sucrose and polyphenols such as catechin, to provide various cariostatic compositions such as oral compositions, food compositions, pharmaceutical products, quasi-pharmaceutical products or cosmetic products. In case that the cariostatic agent of the invention is blended in for example a food composition, it is understood that the risk of affliction with caries is at a level as low as possible even if the food composition is ingested. Even in case of the co-existence of a cariogenic sweetness ingredient with the sweetness ingredients, the possibility of affliction with caries is reduced even after the ingestion, so that the composition can be defined as a cariostatic food composition.
In accordance with the invention, the term “non-cariogenicity” means a phenomenon or state substantially never causing the acidification of dental surface with acid generation since the non-cariogenic material per se is never metabolized with the bacterium causing caries, namely Streptococcus mutans.
Therefore, the term “non-cariogenicity” means the property that the non-cariogenic material per se is never metabolized with the bacterium causing caries so the non-cariogenic material never substantially causes the acidification of dental surface via acid generation. In other words, the property means a profile that as the consequence of culturing in a culture medium supplemented with 1 to 10% by weight of the rare sugars for 20 to 48 hours, the bacterial growth through the metabolism thereof is at a level identical to the bacterial growth level in case of no sugar addition (control) or at the given level or less; or the culture medium pH is at a level identical to the pH level in case of no sugar addition (control) or at the given level or less. The term “non-cariogenicity” means such property.
Additionally, the term “cariostatic” means a phenomenon or state substantially suppressing the acidification of dental surface via the metabolism with the bacterium causing caries, due to the co-existence of the cariostatic material with a cariogenic sweetness ingredient to be metabolized with the bacterium.
Thus, the term “cariostatic property” means a property that via the co-existence with a cariogenic sweetness ingredient to be metabolized with the bacterium, the acidification of dental surface via the metabolism with the bacterium causing caries can be suppressed substantially. Specifically, Streptococcus mutans was cultured in a culture medium supplemented with 1 to 10% by weight of the rare sugars in the co-existence of assimilable sugars. 20 to 48 hours later, the bacterial growth through the metabolism thereof is at the given level or less, compared with the bacterial growth level with no rare sugar addition (control); or the culture medium pH is at the given level or more, compared with no rare sugar addition (control). The term “cariostatic property” means the property described above.
In this specification, herein, the term “caries suppression” or “caries suppressing property” is used to mean both “non-cariogenicity” and “cariostaticity” in combination or “non-cariogenic property” and “cariostatic property” in combination, without any discrimination of these terms.
The “rare sugar” for use in accordance with the invention means a monosaccharide existing at a trace amount in the natural kingdom, while monosaccharides existing abundantly in the natural kingdom are defined as “natural monosaccharides”.
One of the inventors, Ken Izumori, publicly describes the Izumoring linking chart in the patent reference 1. Via the production processes and molecular structures (D- and L-forms) shown in
According to Izumoring of monosaccharides with 6 carbon atoms (hexoses), as shown in the lower column of
It has been known from research works including the research works of the present inventors that these sugars can be converted by reactions with redox enzymes, reactions with aldose isomerase, and reactions with aldose reductases. In the research works so far, the group in the upper part of
When thoroughly examined,
Using Izumoring of monosaccharides with 6 carbon atoms (hexoses), the relation between sugars existing abundantly in the natural kingdom and rare sugars existing at trace amounts is shown. D-Glucose, D-fructose, D-mannose, and D-galactose producible from lactose in milk exist abundantly naturally, but other hexoses except those described above are rare sugars existing at trace amounts. Via the discovery of DTE, D-fructose and D-psicose could be produced from D-glucose; furthermore, D-allose, allitol and D-talitol could be produced. A rare sugar D-psicose has been hardly available so far. A method for producing rare sugars from monosaccharides abundantly existing naturally has been under way of development. D-Psicose can be produced using the technique therefor.
The significance of Izumoring about monosaccharides with 6 carbon atoms (hexoses) is now summarized. Depending on the production process and molecular structure (D form and L form), all monosaccharides can be structurally arranged (formation of structural knowledge), so that the whole image of monosaccharides can be grasped; and efficient and effective approaches for the research works can be selected; the optimal production route can be designed; and deficient parts can be projected.
In accordance with the invention, a rare sugar with the non-cariogenic property, which can be a non-cariogenic material, is a rare sugar in the D form as selected from the group consisting of D-psicose, D-sorbose and D-tagatose as rare sugars, a rare sugar in the L form as selected from the group consisting of L-fructose, L-psicose and L-tagatose or allitol as a rare sugar derivative. In accordance with the invention, further, rare sugars with cariostatic properties, which can be cariostatic agents, are D-psicose, D-sorbose, D-tagatose, L-fructose, L-psicose and/or L-tagatose.
Catechins for use in accordance with the invention are polyphenols contained in tea, and representatively include catechin and epicatechin with two hydroxyl groups in the ring B, epigallocatechin with three hydroxyl groups in the ring B, and epigallocatechin gallate with galloyl group. These catechins are described as active ingredients in compositions against periodontal diseases (U.S. Pat. No. 2,903,210). The effective catechin concentration against caries in the test system is 500 μg/ml, while the concentration of gallocatechin with the highest effectiveness is 125 μg/ml. Additionally, these catechins when polymerized together generate tannin, where the galloyl moiety has almost the same structure as that of gallic acid and pyrogallol. For the suppression of caries with these polyphenols, it is shown that a polyphenol with three hydroxyl groups is particularly effective and even a polyphenol with two hydroxyl groups is also effective (Tsutomu Okubo, Food Style 21, 8, p. 47-51 (2004)). Accordingly, it is understood that polyphenols with two hydroxyl groups, such as caffeic acid contained in coffee, would be effective against caries.
Because these substances are bitter ingredients with strong astringency, however, the resulting taste is significantly deteriorated, disadvantageously from the standpoint of applications thereof to various fields including foods. Examinations should be made about a compound exerting the antibacterial and caries-suppressing properties even when the amount of polyphenols used therein such as catechins is reduced so as to reduce the bitterness.
The non-cariogenic material or the cariostatic agent in accordance with the invention has a non-cariogenic function (action) of a rare sugar contained therein or a cariostatic function (action) of a rare sugar as the cariostatic agent and additionally has various functions (actions) and uses, for example hypoglycemic action and sweetness-giving action (sweetener). For example, D-psicose is at a sweetness level at about 70% of the sweetness level of sucrose and is substantially zero kilocalories (Matsuo et al., J. Nutr. Sci. Vitaminol. 48 pp. 77-80 (2002)), and is therefore useful as a low-calorie sweetener. Additionally, D-psicose may also be used as a thickener, a moistening agent, an excipient, a modifier of physical properties and a filler.
Therefore, the invention relates to various compositions containing the caries-suppressing material (non-cariogenic material or cariostatic agent). As an alternative sweetener of conventional sweetness ingredients comprising sugars such as glucose, fructose, lactose and sucrose and reduced various sugars or in place of at least a part thereof, or in addition to the conventional sweetness ingredients, the non-cariogenic material or cariostatic agent of the invention can be blended in various compositions, preferably at a concentration about 20-fold the concentration of assimilable sugars, so that the resulting compositions can exert the non-cariogenic function (action) or the cariostatic function (action). By allowing the various compositions to contain polyphenols such as catechin (at about 0.002% or more), the cariostatic function (action) can be enhanced. In other words, the inventive material can be blended less (about 10-fold the amount of assimilable sugars). Examples of the use of such compositions include foods (including drinks and feeds for animals), cosmetic products, pharmaceutical compositions and oral compositions. Pharmaceutical products and foods and drinks, for humans and animals, include for example modified milk powder, enteral nutritious agents, health foods and drinks, additives for feeds, and confectionaries. The pharmaceutical products and the foods and drinks should finally be in orally administrable forms, with no specific limitation. Oral compositions for humans and animals include those with conventionally known, appropriate uses, types and forms in the field.
When the caries-suppressing material is used as a food or drink (including food compositions with a label telling the use thereof for preventing periodontal diseases), the caries-suppressing material of the invention (caries-suppressing material containing any of the non-cariogenic material and the cariostatic material) or a processed product thereof may be used as it is or may be blended with other foods or food ingredients according to routine methods for use. The term “processed product” means a processed food containing the food and widely includes apparent foods (foods in the narrow sense) to tablets. For processing, general processing methods for foods may be applicable with no problem, owing to the high thermostability and the high acid stability. The composition of the invention may be in any form of powders, granules, pastes, liquids, and suspensions, with no specific limitation. The composition may be formulated into for example, health drinks and compositions in confectionary tablet forms, where sweeteners, sour agents, vitamins and other various ingredients for routine use in producing drinks are used.
The food composition includes for example appropriate known ones conventionally in the technical field, particularly food compositions with sweetness ingredients, for example drinks, chewing gum, chocolate and candy. Additionally, the food composition can get an enhanced cariostatic function (action) when the food composition contains phenolic compounds such as catechin. The caries-suppressing foods in accordance with the invention are preferably in any one of for example cake, cookies, chocolate, gum, sponge cake (pao de Castella), bread, ice cream, pudding, jelly, bavarois, cream, caramel, jam, bean jam, candies, bar of sweet jellied adzuki-bean paste, bean-jam-filled wafers and confectionaries. Additionally, the caries-suppressing drinks and foods in accordance with the invention are preferably in any of for example carbonate drinks, sour milk beverages, fruit juice drinks, and juice.
For providing the caries-suppressing material in the form of confectionaries such as chewing gum, candies, confectionary tablet, jelly and Gummi, raw material components including the caries-suppressing material of the invention are mixed together under agitation with a kneader, to produce such confectionaries. Additionally, sugar sweeteners such as various maltose and reduced glutinous starch syrup, Siraitia grosenorii extracts and sweeteners at high sweetness levels such as aspartame and stevioside, may also be used concurrently.
The content of the rare sugar is not specifically limited but is generally 0.1 to 99% in the composition so as to achieve the effect. The composition of the invention may additionally contain one or two or more of Xylitol, maltitol, Palatinit, mannitol, sorbitol, palatinose, panose oligosaccharide, lactitol, erythritol, coupling sugar and isomalto-oligo, which are considered to have caries induction-suppressing actions.
In case that the caries-suppressing material of the invention is contained in for example a composition as a food or a drink, it is understood that the risk of caries affliction may be reduced by the intake of the material. In case that the sweetness ingredients in the composition of a food or a drink substantially totally comprise the caries-suppressing material of the invention, the possibility of affliction with caries is substantially zero even when the composition is ingested. Hence, the composition can be said as a caries-suppressing food composition or drink.
In case that the caries-suppressing material of the invention is used as a pharmaceutical composition (including a composition for preventing periodontal diseases), the caries-suppressing material can be added to various pharmaceutical preparations. The pharmaceutical preparations include for example oral administration preparations such as tablets, capsules, granules, powders and syrups. In the caries-suppressing material of the invention, base materials are used as apart thereof. Additionally, these various pharmaceutical preparations can be prepared by using known auxiliary agents in the principal drug according to routine methods, which are for general use in the pharmaceutical preparation field, such as excipients, binders, disintegrators, lubricants, flavor, auxiliary dissolution agents, suspending agents, and coating agents.
In case that the caries-suppressing material is used as an oral composition (including an oral composition as a composition for preventing periodontal diseases), the caries-suppressing material of the invention is used as the essential component. Depending on the shape, various known ingredients may be blended. Known ingredients possibly in blend therein include for example moistening agents, thickeners, agents for reinforcing teeth, sterilizers, pH adjusters, surfactants, enzymes, anti-inflammatory agents, blood circulation-promoting agents, sweeteners, preservatives, colorants, dyes and flavor, which may appropriately be used.
The oral composition may be prepared by blending the caries-suppressing material of the invention according to routine methods and may be prepared into toothpaste, dental cream, tooth powder, dental liquid, oral pasta, mouthwash, tablets for gargling, tablets for washing artificial teeth, massage cream for gingiva, chewing gum, troche, and candies. Most appropriately, the oral composition is in the forms of dental liquids at low viscosity, mouthwash, mouthwash, tablets for gargling and washing agents of artificial teeth for use in dissolution in water. In accordance with the invention, the oral composition means a composition to be masticated or to be used for gargling and includes for example foods such as chewing gum, candies, confectionary tablets, and confectionary films; and quasi-pharmaceutical products such as toothpaste, dental liquid and mouthwash.
The term “cariogenic sugar” means a sugar as a nutritious source for bacteria causing caries to generate non-water-soluble glucan and organic acids, and includes sugars for example sucrose, fructose and glucose. Preferably, the oral composition never contains these cariogenic sugars but may contain non-cariogenic sugars for example sugar alcohols such as Xylitol, maltitol, erythritol, sorbitol, lactitol, reduced palatinose, and mannitol; reduced glutinous starch syrup or sweeteners at high sweetness levels, for example saccharin, sucralose, and Acesulfame K. Nonetheless, the caries-suppressing material of the invention may be used in combination with cariogenic sugars.
In case that the caries-suppressing material is used as an oral composition, ingredients generally blended in oral compositions may appropriately be blended within a range with no deterioration of the invention, depending on the dosage form, other than the ingredients described above. For example, polishing agents, moistening agents, thickeners, surfactants, flavor, sweeteners, colorants, preservatives, pH adjusters and various pharmaceutically active components may be blended within a range without any deterioration of the advantages of the invention.
Polishing agents include for example aluminium oxide, aluminum hydroxide, aluminium silicate, zirconium silicate, silicic anhydride, precipitating silica, silica gel, calcium carbonate, calcium pyrophosphate, calcium hydrogen phosphate, calcium phosphate, tricalcium phosphate, hydroxyapatite, fluoroapatite, halogenated apatite, magnesium carbonate, magnesium phosphate, insoluble sodium metaphosphate, titanium oxide, zeolite and synthetic resin-series polishing agents.
Moistening agents include sugar alcohols such as sorbitol, maltitol, Xylitol and lactitol, and polyhydric alcohols such as glycerin, 1,3-butylene glycol, 1,2-pentanediol, polyethylene glycol, polypropylene glycol and dipropylene glycol.
Thickeners include carboxyvinyl polymer, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, carrageenan, alkali metal salts of aliginic acid such as sodium alginate, gums such as gellan gum, xanthan gum, guar gum, tragacanth gum, karaya gum, veegum, and gum Arabic, and polyvinyl alcohol, polyvinyl pyrrolidone, silica gel and aluminium silica gel.
Surfactants include anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants and specifically include alkyl sulfate salts, alkylbenzene sulfonate salts, sucrose fatty acid ester, lactose fatty acid ester, lauroylsarcosine salts, N-acylglutamate salts, α-olefinsulfonate salts, 2-alkyl-N-carboxy-N-hydroxyethylimidazolium betaine, N-acyl taurine salts, alkylol amide, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hardened castor oil or fatty acid esters thereof, polyglycerin fatty acid ester, sorbitan fatty acid ester, fatty acid ester, polyethylene glycol fatty acid ester, and propylene glycol fatty acid ester.
Flavor includes menthol, peppermint oil, spearmint oil, orange oil, lemon oil, eucalyptus oil, mint oil, acacia oil, anise oil, bitter almond oil, calamus oil, camphor oil, cinnamon oil, cinnamon bark oil, cinnamon leaf oil, rose oil, sandalwood oil, clove oil, herb oil, banana oil, apple oil, methyl salicylate, carbon, anethole, terpenes such as limonene and compound perfume.
Sweeteners include saccharin, sodium saccharin, Xylitol, stevioside, stevia extract, rebaudioside, p-methoxycinnamic aldehyde, neohesperidine dihydroxychalcone, perillartine, thaumatine, glycyrrhizin, glycyrrhizin monoglucoside, hernandulcin, trehalose, aspartame and sorbit.
Colorants include authorized dyes such as Blue No. 1 and Yellow No. 4, titanium dioxide and caramel.
Preservatives include p-oxybenzoate esters, benzoate salts, alkyldiaminoethyl glycine hydrochloride, and phenoxyethanol.
pH adjusters include organic acids such as citric acid, malic acid, and acetic acid and salts thereof; sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, calcium carbonate, calcium hydrogen carbonate, ammonium carbonate, ammonium hydrogen carbonate, sodium potassium carbonate, lithium carbonate, urea, amino acid oligomers, sodium chloride, inorganic calcium such as calcium chloride, calcium nitrate, calcium sulfate, calcium glycerophosphate, and calcium hydroxide, and organic acid calcium salts such as calcium lactate, calcium acetate, calcium malonate, calcium citrate, calcium glycolate, calcium glycerate, calcium tartrate, and calcium phytinate.
Pharmaceutically active Components include allantoin, tocopherol acetate, isopropylmethyl phenol, glycyrrhizinates, glycyrrhezinates, dextrase, chlorophyll, sodium copper chlorophyll, flavonoid, tranexamic acid, mutanase, lysozyme, amylase, protease, lytic enzymes, superoxide dismutase, ε-aminocaproic acid, aluminium allantoin, aluminium chlorohydroxyallantoin, dihydrocholestanol, bisabolol, glycerophosphate, water-soluble inorganic phosphate compounds, fluorides such as sodium fluoride, sodium monofluorophosphate, tin fluoride, potassium fluoride, sodium fluorosilicate, aluminium fluoride, silver fluoride, hexylamine hydrofluorate, decanolamine hydrofluorate, and octadecenylamine hydrofluorate, ethylenediaminetetraacetic acid, zinc citrate, zinc chloride, copper gluconate, chlorhexizine gluconate, copper chloride, polyphosphate salts, pyrophosphate salts, vitamins such as vitamins A, C, E, B6, and pantothenate salts, amino acids such as glycine, lysine and histidine, sodium chloride, sodium bicarbonate, aluminium lactate, potassium nitrate, sarcosinate, polyphenol compounds such as catechins, and crude drugs of plant and animal origins.
Additionally, ethanol, water, silicone substances, sugar alcohols and natural extracts can appropriately be blended. Herein, ethanol is preferably blended at an amount corresponding to 5 to 10% by weight.
The oral composition of the invention is blended together with the ingredients described above by routine methods, to be formulated into various dosage forms.
The type and ratio of the caries-suppressing material of the invention contained in the composition can appropriately be selected by persons skilled in the art, depending on the types and uses of the composition, the caries-suppressing material and other sweetness ingredients. Additionally, the caries-suppressing food composition in accordance with the invention may contain individual appropriate ingredients conventionally known in the technical art, and such caries-suppressing food composition may be prepared and produced by persons skilled in the art according to conventionally known methods.
As described above, the content of the rare sugar is not specifically limited but is generally contained at 0.1 to 99% in the composition to achieve the intended effect. Further, the composition of the invention may additionally contain one or two or more of Xylitol, maltitol, Palatinit, mannitol, sorbitol, palatinose, panose oligosaccharide, lactitol, erythritol, coupling sugar and isomalto-oligo, which are all considered to have non-cariogenicity.
The composition may also contain catechins and tea extracts, in addition to coffee, tea and black tea containing phenolic compounds.
In case that the composition is used as a pharmaceutical composition, the composition is used at an amount variable depending on the symptoms, the age, the body weight, the designing method and the dosage form. Generally, however, the composition is used as a raw material to give sweetness to sugar-coated tablets, gargle and toothpaste.
The invention is now described in detail in the following Examples. But the technical scope of the invention is never limited by these Examples. The bacterial strain for use in experiments was two strains JCM5075 and JCM5175 of Streptococcus mutans (S. mutans).
S. mutans strains characteristically form insoluble glucan on addition of sucrose, to reduce the pH of the culture medium, which is considered to cause decalcification of dental surface to form decayed teeth (the reason why the strains are designated bacteria causing decayed teeth). The S. mutans strain JCM5075 was plated in a Brain Heart Infusion (BHI) broth, for culturing under anaerobic conditions, to visually determine the bacterial growth (potency for forming insoluble glucan: optical density) with naked eyes.
When sucrose was added, JCM5075 formed insoluble glucan, which was deposited on the inner face of a glass tube to form bacterial masses. This is apparently observed with naked eyes (
Based on the results in
S. mutans strains characteristically form insoluble glucan on addition of sucrose, to generate acids and reduce the pH of the culture medium, which is considered to cause decalcification of teeth on dental surface to form decayed teeth (the reason why the strains are designated bacteria causing decayed teeth). JCM 5075 of S. mutans strains and the Brain Heart Infusion (BHI) broth were used to assay the optical density (the increase of the number of the bacterial cells) and the pH change in individual rare sugar solutions with or without sucrose added. As the rare sugars, there were used D-fructose, L-fructose, D-sorbose, L-sorbose, D-psicose, L-psicose, D-tagatose and L-tagatose. The rare sugars used were supplied from the Rare Sugar Research Center, the National University Corporation Kagawa University.
The strain JCM5075 thawed from −80° C. stock was cultured for 48 hours, and was adjusted to OD 0.3. 100 μl of the resulting culture was added to each 2-ml portion of the BHI broths under individual conditions, to assay the optical density and the pH 24 hours later (observation with naked eyes and absorbance: OD600).
After culturing for a given period of time, the culture was observed with naked eyes; and the optical density of apart of the liquid culture was measured with an absorptiometer (OD600). The results are shown in Table 1 and
After collecting a part of the liquid culture and centrifuging the culture, the pH of the resulting supernatant was measured with a pH meter. The results are shown in Table 2 (0, 6, 8, 12 and 24 hours after the addition of the bacteria to the BHI broth) and
No difference in optical density and pH change was observed between 6 and 8 hours later, but a difference therein was observed between 12 and 24 hours later.
With no addition (the BHI broth), no formation of any precipitate (insoluble glucan) was observed under naked eyes, so it was considered that comparison based on OD could be done. Compared with no addition, the suppression of OD increase was observed with D-psicose, D-sorbose, D-tagatose, L-fructose, L-psicose, and L-tagatose as other sugars. It is noted in particular that the suppressive effect of L-tagatose was high. Then, the effect was high in the decreasing order of L-fructose, Xylitol, L-psicose and D-sorbose.
The pH reduction was suppressed with D-sorbose, D-tagatose, L-fructose, L-psicose and L-tagatose. No pH reduction even with 1% sucrose addition in particular strongly suggests the presence of cariostatic action. When 1% sucrose was added to Xylitol, the resulting mixture reduced the pH. This means that these sugars suppress the growth of S. mutans and the potency thereof to generate acids, so a caries-suppressing effect may be expected for these sugars.
As described above, the effect against S. mutans could be verified through the measurement with naked eyes and the change of absorbance (OD) and pH.
D-Psicose and L-psicose were used to assay the actions thereof against S. mutans. D-Psicose and L-psicose were supplied from the Rare Sugar Research Center, the National University Corporation Kagawa University. The S. mutans strain MT 8148 (JCM5175) was plated in a Brain Heart Infusion broth supplemented with agar for culturing at 37° C. for 48 hours. The liquid culture was inoculated in a fresh Brain Heart Infusion broth, for culturing at 37° C. for 24 hours. The liquid culture was inoculated in a phenol red broth (PRB broth) containing a test substance at 1%, for culturing at 37° C.; the bacterial growth (absorbance at 660 nm: OD) and the pH were assayed 48 hours later. As a control, glucose, fructose, sucrose and Xylitol were used. The results are shown in Table 3. After culturing for a given period of time, additionally, the optical density of apart of the liquid culture was measured with an absorptiometer (OD 660 nm).
The results in Table 3 show that as the consequence of the culturing of S. mutans in the culture medium supplemented with D- or L-psicose, glucose, fructose, sucrose and Xylitol, the bacterial growth with addition of D- or L-psicose and Xylitol was represented by OD660, which was 0.05 or less, while the liquid culture was at pH 5.5 or more. Compared with OD=0.26 and pH 3.9 in the liquid culture with glucose addition, a significant difference was observed. Thus, it is assumed that the substances have an excellent caries-suppressing action.
Allitol and D-sorbose were used to assay the actions thereof against S. mutans. Allitol and D-sorbose were supplied from the Rare Sugar Research Center, the National University Corporation Kagawa University. The S. mutans strain (JCM5075) was plated in a Brain Heart Infusion broth containing a 10% test substance, to measure the pH of the liquid culture after 48-hour culturing. As a control, 1% sucrose and 10% Xylitol were used. The results are shown in Table 4.
As in the case of Example 2, the results in Table 4 show that allitol exerted an excellent non-cariogenic property at pH 5.5 or more. Additionally, it is shown that D-sorbose is at a low assimilability with the S. mutans strain.
A cariostatic test with D-psicose was carried out. Additionally, the effect of catechins added was also examined. D-Psicose was supplied from the Rare Sugar Research Center, the National University Corporation Kagawa University. As the catechin, Polyphenon 70A of Mitsui Norin Co., Ltd. was used. The S. mutans strain MT 8148 (JCM5175) was plated in a Brain Heart Infusion broth supplemented with agar, for culturing at 37° C. for 48 hours. Further, the resulting liquid culture was inoculated in a fresh Brain Heart Infusion broth, for culturing at 37° C. for 24 hours. The liquid preculture was inoculated in a phenol red broth (PRB broth) containing sugars and catechins at the following concentrations for culturing at 37° C.; 20 hours later, the pH was measured. As a control, sucrose was used. The results are shown in Table 5.
The results in Table 5 show that D-psicose as a rare sugar at a concentration of 5% exerted an action of suppressing the pH reduction in a culture medium with addition of sucrose, where S. mutans was cultured. Therefore, it was possibly indicated that D-psicose had an excellent cariostatic property. Although it was observed that catechin alone and D-psicose alone could not exert their pH-reducing actions at their individual concentrations, the co-existence of D-psicose at the concentrations with a trace amount of catechin suppressed the pH-reducing action. Hence, it is assumed that D-psicose and catechin exert a cariostatic action via their synergistic actions.
An oral composition using a rare sugar with the cariostatic action in accordance with the invention was prepared on the basis of the composition table in Table 6 (toothpaste).
A mouthwash composition using a rare sugar with the cariostatic action in accordance with the invention was prepared on the basis of the composition table in Table 7 (mouthwash).
A chewing gum using a rare sugar with the cariostatic action in accordance with the invention was prepared on the basis of the composition table in Table 8 (chewing gum).
Using D-psicose in the compositions of the toothpaste, the mouthwash, and the chewing gum in the compositions in Examples 5 through 7, the resulting toothpaste, mouthwash and chewing gum with refreshing sweetness without inducing caries could be prepared.
Herein, existing pharmaceutical ingredients, such as cetylpyridinium chloride, triclosan, cineole, thymol, zinc chloride, methyl salicylate and vitamin E can be added to the toothpaste and the mouthwash composition. Additionally, sugar alcohols with a cariostatic action such as Xylitol can be added to the chewing gum.
The metabolic level of D-psicose itself with a bacterium causing caries, namely S. mutans is low or is hardly observed (non-cariogenicity). Using D-psicose in combination with existing sweeteners, D-psicose exerts an action substantially suppressing bacterial growth and pH reduction with the cariogenic sweetness ingredients therein (cariostatic property) and therefore, D-psicose is widely applicable to for example foods, quasi-pharmaceutical products and pharmaceutical products.
In particular, Xylitol as a sugar alcohol belonging to one group of rare sugars is added to favorite foods and foods for use in daily life, and it is generally known widely that Xylitol exerts a high effect on the prevention of caries. The other rare sugars in accordance with the invention may have an effect as an anticarious sweetener, so these rare sugars would possibly be new “anticarious sweeteners developed in Japan” in place of Xylitol.
It is expected that identical toothpaste, mouthwash and chewing gum would be prepared from D-sorbose, D-tagatose, L-fructose, L-psicose, L-tagatose or allitol, other than D-psicose.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2006-305817 | Nov 2006 | JP | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP2007/056449 | 3/27/2007 | WO | 00 | 1/15/2010 |
| Publishing Document | Publishing Date | Country | Kind |
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| WO2008/056453 | 5/15/2008 | WO | A |
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| 20100166678 A1 | Jul 2010 | US |
