MX2008007087A - Chewable compositions with fast release magnolia bark extract - Google Patents

Abstract

A chewable oral composition for oral cleansing, breath freshening, and antimicrobial benefits includes fast release Magnolia Bark Extract in combination with a surface active agent. The effectiveness of Magnolia Bark Extract in inhibiting biofilm formation in the oral cavity is increased by a synergistic combination of the rapidly released Magnolia Bark Extract with a surface active agent in a chewable oral cavity delivery agent, such as chewing gum, chewable candy, and a soft tablet. The fast release of the antimicrobial agents is effectuated by encapsulation or coating of the oral cavity delivery agent.

Description

CHEMICAL COMPOSITIONS WITH QUICK RELEASE OF MAGNOLIA CORTEX EXTRACT CROSS REFERENCE This application claims the priority of the provisional US Patent Application serial number 60 / 742,361, filed on December 2, 2005.

TECHNICAL FIELD The present invention relates, in general, to confectionery compositions and, more particularly, to confectionery compositions containing Magnolia Bark Extract for oral care, and to methods for making and using confectionery compositions.

BACKGROUND OF THE INVENTION There is considerable consumer demand for products that freshen breath and kill bacteria in the mouth. An oral product with breath freshener and bactericidal benefits is a convenient delivery for oral cleansing in the oral cavity and to freshen the breath. Bacteria in the oral cavity, particularly in the tongue, can generate volatile sulfur compounds, which are the main cause of bad breath. Of course, refreshing the breath is a very important part of everyday life. To facilitate proper oral hygiene, oral cleansing and breath freshening practices should be conducted repeatedly throughout the day. However, cleaning and refreshing the breath can sometimes be difficult or inconvenient, depending on the nature of the desired breath freshening and the situation in which the breath freshening should occur. Brushing, flossing, tongue cleaning and gargling, using a variety of devices and compositions, are common oral care practices well suited to the privacy of the home. But such devices and compositions are less convenient for use away from home, where bathing facilities may be scarce, unavailable or unhygienic. Dental plaque is a microbial deposit that forms on the teeth shortly after brushing. Researchers have described it as a soft, concentrated mass, consisting mainly of a large variety of bacteria along with a certain amount of cellular sediments that develop within a short time of brushing away from the teeth. The plate is not removed by rinsing with water. More recently, dental plaque has been described as a diverse community of microorganisms that are found on the surface of teeth as a biofilm. The biofilm is integrated into an extracellular matrix of polymers that originates as much from the surface of the teeth as from the microbial organisms. It is generally recognized that a reduction in dental plaque promotes clean teeth, fresh breath and healthy gums. The biofilm of dental plaque, however, is very resistant to antimicrobial agents. Antimicrobial agents that have been shown to have definite plaque reduction capacities include chlorhexidine, cetylpyridinium chloride (CPC), Triclosan, and Delmopinol. All these are medicines, and not natural agents. It has also been discovered that essential oils such as thymol, eucalyptol, methyl salicylate and menthol, together with other essential oils in an alcohol-based vehicle, reduce plaque. Although thymol is the most effective in reducing plaque, it has an unpleasant taste. Generally, these oils benefit from the presence of an alcohol to facilitate their solubility and their penetration into the biofilm of the plate. Although suitable for oral treatments, such as mouth rinses, high concentrations of alcohols can leave a bitter after taste in oral compositions such as gums, edible films, candies and the like. An active ingredient, or a combination of active ingredients, that can provide the benefits of either removing the plaque, avoiding or slowing plaque formation, or having an anti-inflammatory effect that could help maintain healthy gum condition, would promote the health of the gums and the freshness of the breath. It is known the incorporation of active agents in chewing gums for the purpose of providing oral benefits that include breath freshness and bactericidal properties. These systems have the advantage of providing fast, effective and convenient delivery.

BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to a breath freshening composition that can be used in different edible confectionery products. One aspect of the present invention is directed to the use of confectionery products such as chewing gums, chewy sweets and soft tablets, or confectionery products for animals, such as dog biscuits, confectionery products containing a breath freshening composition. of the present invention. In accordance with the present invention, it has been discovered, unexpectedly, that the magnolia bark extract, in combination with certain active surface agents, is synergistically effective to inhibit the development of the bacteria causing the plaque. The combination of magnolia bark extract and the selected active surface agents shows enhanced development activity against the plaque, in excess of the magnolia bark extract or the active surface agent alone.

The present invention also relates to confectionery compositions containing fast-release magnolia bark extract in combination with a surfactant, designed to have bactericidal and breath-freshening properties. More specifically, the present invention relates to a rapid release oral cavity delivery agent, such as a chewing gum, a chewable candy, a soft tablet or other edible product containing an effective amount of bark extract from the mouth. magnolia in combination with a surfactant, by which the composition of the invention effectively, or kills, the oral bacteria, and freshens the breath during the consumption of the chewable edible product. The surfactant is added to the chewable edible product to synergistically increase the effectiveness of the magnolia bark extract. In one aspect of the invention, a confectionery composition for breath freshening of chewing gum consumers includes a rapid release oral cavity delivery agent and an effective amount of an antimicrobial agent comprising a synergistic of the magnolia bark extract and the surfactant, wherein the synergistic ratio is at least about 1 part magnolia bark extract to 1 part surfactant. Suitable active surface agents include potassium, ammonium or sodium salts. Sodium salts include anionic surfactants, such as alkyl sulfates, including sodium lauryl sulfate, lauryl ether sodium sulfate, and the like. Other sodium salts include sodium lauroyl sarcosinate, sodium latinate, and the like. Suitable ammonium salts include ammonium lauryl sulfate, ammonium lauryl ether sulfate, ammonium lauroyl sarcosinate, ammonium latonate, ammonium cocamidopropyl betaine, and the like. Other suitable active surface agents include emulsifiers, which may be fatty acids (eg, stearic, palmitic, oleic and linoleic acids), their salts, glycerol monostearate, glycerol triacetate, lecithin, mono and triglycerides, and acetylated monoglycerides. . As will be described below, several suitable active surface agents also show some of their own bactericidal properties (killing germs). In another aspect of the invention, there is provided a method for preparing an oral care composition. The method includes the incorporation of an antimicrobial agent in the form of a synergistic ratio of magnolia bark extract and surfactant in a formulation in the amount of from about 0.05% to about 10% by weight, based on the weight of the formulation total, mixing the ingredients until obtaining a uniform mixture, and from there forming the mixture in a suitable coating for an oral composition. In another aspect of the invention, the method for preparing an oral care composition includes the incorporation of an antimicrobial agent in the form of a synergistic ratio of bark extract to magnolia and surfactant in a formulation in an amount of from about 0.05% to about 10% by weight, based on the weight of the total formulation, and the encapsulation of the antimicrobial agent in an oral composition.

DETAILED DESCRIPTION OF THE INVENTION It is known to use chewable confections such as chewing gums as a vehicle for delivering components to the oral cavity, which provide oral benefits such as breath freshening and bactericidal properties. These systems have the advantage of providing a consumer with a convenient and economical method to maintain oral health and fresh breath throughout the day. The present invention is directed to chewable confectionery compositions having antimicrobial properties, comprising rapid libration of the magnolia bark extract and a surfactant. The invention is also directed to a method for reducing or eliminating microorganisms present in the oral cavity, comprising chewing in the oral cavity a confectionery chewable product comprising extract of magnolia bark and a surfactant. Suitable confectionery products include chewing gum, chewable confections, soft tablets and biscuits, containing fast-release magnolia bark extract and a surfactant according to the present invention.

The term "chewing" includes the operations by which an edible product is totally or partially consumed while being kept in the mouth, such as chewed, sucked or dissolved. Keeping the product in the mouth for longer periods of time is expected to be associated with a greater reduction of the microorganisms present in the oral cavity. The periods of time suitable for chewing range from 3-5 minutes, to 20-30 minutes. The phrase "quick release", as used in this specification and the appended claims, refers to the action of edible ingredients that have a release rate greater than that of chewable comestibles, for example, chewing gums treated by the conventional coating procedures. Typically, the fast release action is created by the ingredients that are first released from the comestible, for example, the antimicrobial ingredient of this invention included in the chewing gum. The present invention incorporates the magnolia bark extract released rapidly as the active component for oral bactericidal benefits. It is known that the magnolia bark extract has bactericidal and antifungal properties. For example, magnolol and honokiol are two components of magnolia bark extract with known antimicrobial activity. The magnolia bark extract used in the present invention can be obtained from O'Laughlin Industries, Co., LTD, Guang Zhou Masson Pharmaceutical Co., or at Honsea Sunshine Bioscience and Technology Co. Magnolia bark extract is obtained as a powder. The magnolia bark extract dissolves with the flavor and can be heated before making the oral product. Magnolia bark extract can be formulated using standard formulation techniques in a variety of oral care products. Although it is relatively easy to kill bacteria in solutions, biofilm is a complex environment that provides bacteria protection against environmental threats, as well as synergy between bacterial species (Sharms A et al., 2005, Oral Microbiology and Immunology 20: 39 -42). Therefore, compared to a simple germ killing test, it is much more difficult to show the actual efficacy against the established plaque by an antimicrobial agent. The diffusion in the biofilm is limited, and the bacteria within the mass of the biofilm are protected against exposure to the agent by the extracellular material, such as the glucan and dextran polysaccharides. Thus, it is reasonably easier to avoid plaque formation than to remove an established plaque. In accordance with the present invention, the antimicrobial effects of the magnolia bark extract are improved through the combination of the magnolia bark extract with a surfactant agent. Although the invention is not intended to be limited to any particular theory, it is believed that the combination of a surfactant with a Effective amount of magnolia bark extract can provide a chewable product that promotes the reduction of biofilms in dental plaques and in other areas of the oral cavity, such as the tongue. It is believed that the combination of magnolia bark extract and a suitable surfactant can prevent bacteria from adhering to the acquired film. A chewing gum can thus slow down or prevent the buildup of plaque. In addition, the chewable product of the invention can be effective in removing the existing plaque in combination with enzymes, additional surfactants, abrasives, or combinations thereof. A preferred surfactant is one that increases the solubility of the magnolia bark extract and that can be used as a food additive. Suitable surfactants include, but are not limited to, common surfactants, soaps, wetting agents, and emulsifiers. Some examples of surfactants include, but are not limited to, potassium, ammonium or sodium salts. Sodium salts include anionic surfactants, such as alkyl sulfates, including sodium lauryl sulfate, sodium lauryl ether sulfate, and the like. Other sodium salts include lauroyl sodium sarcosinate, sodium latonate, and the like. Suitable ammonium salts include lauryl ammonium sulfate, ammonium lauryl ether sulfate, lauroyl ammonium sarcosinate, ammonium latonate, ammonium cocamidopropyl betaine, and the like. Other suitable surfactants include emulsifiers, which may be fatty acids (for example, stearic, palmitic, oleic and linoleic acids), their salts, glycerol monostearate, the triacetate of glycerol, lecithin, mono and triglycerides, and acetylated monoglycerides. As will be described below, various suitable surfactants also exhibit their own bactericidal properties (killing germs). The chewable product may also include additional breath freshening or oral health ingredients, which may be antimicrobial in nature. In addition, the additional breath freshening or oral health ingredients may comprise suitable edible salts of zinc or copper, cooling agents, pyrophosphates or polyphosphates, and the like. The invention also includes a method of treatment for reducing the amount or activity of bacteria in the oral cavity of a consumer. The method includes the steps of providing a chewable product that includes magnolia bark extract in an amount sufficient to kill or deactivate the oral bacteria in combination with a surfactant, and cause a person in need of treatment to consume the chewing gum . Bacteria in the person's oral cavity are reduced or inactivated by treatment. In one form, the chewable product is formulated with a rapid release delivery agent in the oral cavity, to deliver at least about 0.001% to about 2.0% concentration of magnolia bark extract to the oral cavity. Otherwise, the chewable product is formulated with a delivery agent to the oral cavity to deliver at least about 0.01% concentration of magnolia bark extract to the oral cavity. To the chewable product are added one or more surfactants so as to improve the effectiveness of the chewable product in delivering an effective amount to the oral cavity. According to one embodiment of the invention, one or more surfactants are present in the chewable product in a concentration ratio of from about 0.001% to about 2.0%. In the chewable product, the magnolia bark extract is combined with a surfactant in a synergistic relationship that provides improved effectiveness in killing the germs. The synergistic relationship ranges from about 1 part of magnolia bark extract to 1 part of surfactant, up to about 4 parts of magnolia bark extract to 1 part of surfactant. A particularly effective surfactant is sodium lauryl sulfate, and a particularly effective synergistic composition is about 2 parts of magnolia bark extract to 1 part of sodium lauryl sulfate. Since the magnolia bark extract is a hydrophobic compound, there are several oral cavity delivery agents that can be used to enhance the release of the magnolia bark extract from the chewable product. For example, in a chewing gum, the basic confectionery composition is hydrophobic, which also inhibits the release of the magnolia bark extract. In the various embodiments of the confectionery composition of the invention, the magnolia bark extract is combined with a surfactant and can be encapsulated, spray dried, or formulated into a coating, or combinations thereof, to facilitate and accelerate the release of magnolia bark extract in the oral cavity. To evaluate the effectiveness of magnolia bark extract, in vitro tests were conducted with three subgingival plaque bacteria associated with bad breath. The protocol for the study of Minimum Inhibitory Concentrations (MIC) is as follows. Chlorhexidine was used as a positive control and water was used as a negative control. Menthol and Tween 80 were used as solvents for the extract of magnolia bark. Tween 80 is the common name for Polysorbate 80. For this study trays were used. microtiter with ninety-six wells. Each well contained 5 x 105 colony-forming units / ml of bacteria, agents diluted serially and medium for bacterial development. All bacterial cultures were incubated at 37 ° C and parked. The bacterial development was estimated spectrophotometrically at 660 nm, after 48 hours. MIC for each test bacterium was defined as the minimum concentration of the limiting turbidity of the test compound at less than 0.05 absorbance measured at 660 nm. Minimum bactericidal concentrations (MBC) were determined using the serial dilutions of the 96-well microtiter plate as described above for the MIC studies. Serial dilutions of the cultures were made in wells that did not show visible growth and 10 microliters of culture were placed in the tray in triplicate on blood agar trays. Visible colonies were recorded after of the incubation of the trays for 48 hours at 37 ° C. For each bacterial test, the number of colony forming units / ml (CFU / ml) was determined in the initial inoculum. MBC was defined as the lowest concentration of a test compound that killed at least 99.9% of the cells present in the initial inoculum. The results of the studies carried out to obtain the MIC and the MBC of the magnolia bark extract (MBE) are as follows. Against Streptococcus mutans, a magnolia bark extract of 90% had a MIC of 5.62 pg / ml. For the Porphyromonas gingivalis, 90% magnolia bark extract had a MIC of 3.91 pg / ml, and the 65% magnolia bark extract had a MIC of 7.82 pg / ml. For Fusobacterium nucleatum 90% magnolia bark extract had a MIC of 3.91 pg / ml and a MBC of 7.82 pg / ml. Against the same organism, the extract of 65% magnolia bark had a MIC and a MBC of 7.82 pg / ml. Chlorhexidine was the positive control and produced a MIC and a MBC of 1.25 pg / ml for the three bacteria. The solvent consisting of water with 10% menthol and 3.8% Tween 80 had no noticeable effects of inhibition of development in any of the three bacteria in the study. It is also known that magnolia bark extract is effective against Actinobacillus actinomyecetemcomitans, Prevotella intermedia, Micrococcus luteus, Bacillus subtilis, Veillonella disper, Capnocytophaga gingivalis, and periodontal microorganisms (Chang B. et al., 1998 , Planta Medica 64: 367-369). Many of these human pathogens they are associated with periodontal diseases (Screiner H.C. et al., 2003, PNAS 100: 7295-7300). It is also known that many of the aforementioned bacterial species congregate to create the biofilm (Rickard A. H. et al., 2003, Trends in Microbiology 1 1: 94-100). In addition to the results described above, the effect of magnolia bark extract on the formation and removal of the biofilm was compared with different herbal and natural ingredients. The comparative tests were performed using green tea extract, Oolong tea extract, licorice and magnolia bark extract. The comparative tests included the determination of the solubility in water, ethanol, mixtures of water: ethanol and other solvents (for example, Tween in water), MIC for the development of S. mutans, MIC for the formation of film of S. mutans in 96-well trays, and the effect of the detachment of the biofilm from S. mutans. Green tea was soluble in water, all other substances were found soluble in a 2: 1 mixture of water: ethanol. The extract of magnolia bark was also soluble in 0.01 μ? of 50% Tween 80 in water. To evaluate the effect on the biofilm formation of Streptococcus mutans, 96-well microtiter trays were used. Each well contained S. mutans (5 to 10 6 CFU / ml), and was serially diluted with the test compounds and the culture medium (brain heart infusion broth (BHI) with 0.5% sucrose). The controls included development medium inoculated without the test compounds. All the trays are incubated at 37 ° C under aerobic condition with development estimated spectrophotometrically (660 nm) after 48 h, using a microtiter tray reader. Then, the float containing the non-adhered cells was removed from each well by aspiration, the bound biofilm mass was dissolved with 200 μ? of 1 N NaOH and the optical density was measured at 660 nm using the microtiter tray reader. Chlorhexidine (40 pg / ml) was used as a positive control. To further assess the effect on the release of the biofilm from S. mutans, sterile 96-well microtiter trays were used, where each well was inoculated with S. mutans (5 x 10 6 CFU / ml), growth medium (BHI supplemented with 0.5% sucrose), and incubated at 37 ° C under aerobic condition for the formation of the biofilm. After 48 hours, the non-adhered float was aspirated and diluted serially. The test compounds were added to the preformed biofilm and incubated at 37 ° C under aerobic condition. The controls included the solvent without the test compounds. After 30 minutes the float from the wells was aspirated and the remaining biofilm after the treatment was dissolved in 200 μ? of 1 N NaOH, and quantified at 660 nm using the tray reader. A positive control of chlorhexidine was used. If detachment of the biofilm occurred by the action of the test compounds, the spectrophotometric absorbance or the optical density (DO = should show a decrease, as compared to the untreated control.

The results of the comparative tests are shown below, in Table 1. The results of the test are presented in units of pg / ml for each of the compounds. In Table 1, and in the Tables Following, the magnolia bark extract is designated as "MBE" and the Chlorhexidine positive control is designated as "CHX".

TABLE 1 Comparative effect in MIC and biofilm (Mg / ml) Test Tea Tea Licorice MBE CHX green Oolong Development of MIC 250 1000 250 7.8 2.5 Formation of 250 250 250 7.8 2.5 MIC biofilm Detachment from > 1000 > 1000 > 10000 > 1000 > 10 MIC biofilm The data shown in Table 1 indicate that none of the compounds tested was more effective than chlorhexidine for Remove the established biofilm. The green tea extract, the extract of Licorice and magnolia bark extract can inhibit the biofilm of S. mutans inhibiting bacterial development, since MIC's are identical for both the development and the biofilm formation. Oolong tea does not inhibited the development of plankton, but was more effective in inhibiting biofilm. Magnolia bark extract was the most effective in inhibiting both the development and biofilm formation, and very within an order of magnitude of the positive chlorhexidine control. Although it is useful to show the comparative effect of magnolia bark extract on biofilm formation and MIC development, the above test procedure may not effectively mimic the in vivo exposure of an oral care product to a plaque biofilm. Developing. In an in vivo situation, the asset could be exposed to the plate for a defined period of time at an established frequency (for example, for 5 minutes, three times a day). Therefore, a series of comparative experiments was conducted to mimic the in vivo use of the potential active ingredients. To perform the tests, the saliva compositions listed in Tables 2 and 3 were prepared.

TABLE 2 Composition of saliva regulator (sterilization of the filter after preparation) Compound mg / L Ammonium chloride 233 Calcium chloride, dihydrate 210 Magnesium chloride, hexahydrate 43 Potassium Chloride 1 162 KH2PO4 (potassium phosphate monobasic) 354 Potassium thiocyanate 222 Sodium citrate 13 Sodium bicarbonate 535 Dibasic sodium phosphate, Na2HP04 375 Urea 173 TABLE 3 Medium supplemented with saliva (filter sterilization after preparation) Ingredient weight% Full saliva 25 Saliva regulator 45 Modified eagle medium (MEM) 20 Soy broth with tripticase 10 A mixed culture system that uses bacteria was used of fresh saliva just collected simulated. Sediments from saliva cells to inoculate hydroxyapatite discs coated with saliva (S-HA). The discs were placed in cell culture trays with 24 wells and incubated up to 3 days. The biofilms were exposed to active on days 2 and 3 (beginning at 18 hours) and quantified on day 4. The number of bacteria was determined by spectrophotometric absorbance or by optical density (OD) at 600 nm. The five phases of the experiment were: film formation; bacterial union; biofilm development; exposure to assets; and bacterial enumeration. To form the films, the HA discs were ultrasonically washed in deionized water and air-dried, then autoclaved. Discs were placed in a 24-well tray with 1 ml of 50% sterile saliva (1 part sterile whole saliva, 1 part saliva regulator, filter sterilization after preparation) for 2 hours with slow stirring at room temperature ambient. The exit was sucked and then the disks were transferred to fresh wells for bacterial binding. To form the biofilms, the bacterial suspension was removed, and the discs were transferred to fresh wells. One ml of medium supplemented with saliva was added and the tray was placed in the incubator for incubation overnight and for the duration of the experiment (up to 72 hours). A raw material solution of 1% magnolia bark extract in 60% ethanol was prepared. The magnolia bark extract samples were prepared at a concentration level of 125, 250, 500 and 1000 pg / ml (ppm) in a phosphate buffered saline solution (PBS), where the negative control was PBS and the positive control was CHX with a 0.12% concentration. The PBS solution had a composition as shown in Table 4.

TABLE 4 Composition of phosphate regulated saline Ingredient g / L NaCl 8.0 KCI 0.2 Na2P04 1 .44 KH2P04 0.24 Amounts of one ml of active ingredients and controls were placed in fresh wells, and the disks were transferred to these wells for 5 minutes. Exposure to chlorhexidine control was one minute, twice a day, to mimic the standard procedure of rinsing the mouth. The exposure to the active ingredients was carried out at 8:00 AM, 12:00 and 4:00 PM. After the timed exposure, the solution was removed and the discs were washed twice with PBS and then transferred to a fresh medium. For some experiments, the medium used during the day was TSB (Tryptic Soy Broth) with a sucrose solution of 50 μ? 40% added to each well (to give a 2% sucrose solution). The medium was not replaced after the midday exposure. After incubation overnight (day 2), the discs were exposed to controls and active. On day 3, the biofilms were exposed again to the tests and controls. On day 4, the discs were removed from the medium, the pH of the medium was measured to obtain an indication of the metabolic activity, and the discs were placed in tubes with 2.5 ml of PBS, vortexed for 20 sec, and then placed in the ultrasonic bath for another 20 sec. The suspension was transferred to vessels and the bacterial cell density was determined by OD measurements at 600 nm. The results of the pH measurements are shown below in Table 5 and the reductions in percentage in DO to PBS control are shown below in Table 6.

TABLE 5 PH measurements Test sample ?? Control PBS 5.4 Control CHX 8.8 MBE 125 5.2 MBE 250 6.0 MBE 500 7.1 MBE 1000 7.6 TABLE 6 Percent reductions in Optical Density at 600 nm Sample of Reduction% DO test PBS Control 0 CHX Control 84 MBE 125 -2 MBE 250 21 MBE 500 53 MBE 1000 59 The results shown in Tables 5 and 6 illustrate clearly the effect and dose response of the bark extract of magnolia in the inhibition of the metabolic activity of the biofilm (determined by the pH of the medium) and biofilm formation (DO). The Chlorhexidine had a strong inhibitory effect on plaque metabolism and on the number of cells. Magnolia bark extract was less effective chlorhexidine, but the concentration of chlorhexidine was slightly higher than ka of the magnolia bark extract. To evaluate the effect of the magnolia bark extract in combination with the surfactant, sodium Iauryl sulfate, five solutions of the active ingredient were prepared using the procedures described above. The chlorhexidine control solution was prepared at a slightly reduced concentration of 0.1% (1000 ppm). MBE solutions were also prepared with concentrations of 500 ppm. Sodium Iauril sulfate was added to two of the magnolia bark extract solutions, to obtain SLS concentrations of 0.05% and 0.1% in the extract solutions of magnolia bark. The tests described above with magnolia bark extract were repeated with the five solutions. The pH results are shown below in Table 7, in which sodium Iauryl sulfate is designated as "SLS".

TABLE 7 PH measurements Test sample pH Control PBS 4.9 Control CHX 8.8 SLS 1000 ppm 5.7 MBE 500 ppm MBE 500 ppm / SLS 500 ppm MBE 500 ppm / SLS 1000 ppm The results of the percentage reduction test in the optical density (OD) are shown in Table 8. Note that the data from the The last row of this Table was taken from a different experiment.

TABLE 8 Optical Density reduction percentage at 600 nm Reduction Test sample% DO Control PBS 0 Control CHX 94 SLS 1000 ppm 61 MBE 500 ppm 65 MBE 500 ppm / SLS? G 500 ppm MBE 500 ppm / SLS 70 1000 ppm MBE 1000 ppm / 88 SLS 500 ppm The results listed above in Tables 7 and 8 show that the control of chlorhexidine had the highest pH and this control also had the lowest OD. Based on the pH data (an indication of metabolic activity), 500 ppm of magnolia bark extract alone were more inhibitors than sodium lauryl sulfate or mixtures of magnolia bark extract / sodium lauryl sulfate. The OD absorbance (bacterial number) data, however, indicate a synergistic effect by reducing the biofilm in the test solutions by combining the extract of magnolia bark and sodium lauryl sulfate. In particular, the results show that 1000 ppm of sodium lauryl sulfate and 500 ppm of magnolia bark extract had similar effects in terms of the amount of plaque, although the extract of magnolia bark inhibited the metabolic activity of the plaque to a greater extent. grade. Magnolia bark extract with sodium lauryl sulfate at 500 ppm reduced plaque development compared to 500 ppm magnolia bark extract alone. In addition, sodium lauryl sulfate at 1000 ppm was less effective than at 500 ppm in combination with 500 ppm magnolia bark extract. The most effective combination was 1000 ppm of magnolia bark extract in combination with 500 ppm of sodium lauryl sulfate. Although we do not wish to be bound by any particular theory concerning the active mechanism of the invention, it is possible that the reason for the paradoxical effect of decreased cell mass with increased metabolic activity of the mixtures of magnolia bark extract / sulphate Sodium lauryl, is related to the action of sodium lauryl sulfate to allow a faster penetration of magnolia bark extract in the biofilm, where it has an immediate effect of killing germs and / or inhibiting their development, but the extract of magnolia bark is also rinsed more easily, so that substantivity and prolonged metabolic effect are minimized. To evaluate the effectiveness in killing germs and the synergistic effect when combining two or more active germ-killing agents, tests were conducted to determine the ratio of MBE to surfactant. The active germ killing and / or surfactant were dissolved in ethanol or in sterile water to give an initial concentration of 0.1% to 1%. The solution was diluted with a nutrient broth to give an initial concentration of 0.05% to 0.5%, which was then serially diluted twice, so that each subsequent dilution contained 50% of the compound concentration of the previous dilution, while that maintained a constant level of nutrients for each dilution. These dilutions were inoculated with representative oral microorganisms, or incubated saliva, and incubated for 24 hours at 37 ° C. For each surfactant, the lowest dilution that was not cloudy was recorded as the MIC. The MBC was determined by transferring 10 microliters of liquid from the non-turbid tubes to fresh development medium and incubated for 48 hours. For each surfactant, the smallest dilution that did not show development was considered the MBC.

Table 9 below shows the MIC of several agents surfactants and emulsifiers in incubated saliva.

TABLE 9 Minimum inhibitory concentration of selected surfactants MIC MIC Sample Sample (ppm) (ppm) Sodium Lauryl Sulfate 50 Sodium Stearoyl Lactylate > 3000 Betaine BF-20 > 1000 Tween 20 > 1000 Tego betaine CKD 25 Sucrose stearate > 500 Tego Betaine ZF 25 Sucrose Distearate > 500 Sodium latonate 500 Chlorhexidine gluconate * 2 Sodium lauroyl sarcosinate * used as a positive control The results show that sodium lauryl sulfate and cocamidopropyl betaine are good surfactant agents, whereas sodium lat- lateum shows a moderate efficacy of germs. Sodium stearoyl lactylate, Polysorbate 20 (commonly known as Tween 20), sucrose stearate, and sucrose distearate, are weak active or do not kill germs.

To evaluate the synergistic effect of an active ingredient in combination with a surfactant, the inhibitory index was computed fractional according to equation (1) below: (1) FIC = [MICA combined with B / MICA SOIO + ICB combined with A / MICB SOIO] where an FIC value of less than 1.0 is synergistic, and an FIC of between 1.0 and 2.0 is additive, and an FIC greater than 2.0 is antagonistic.

Table 10 below shows the MIC values for the combinations of magnolia bark extract / sodium lauryl sulfate and of magnolia bark extract / Tween 20 in S. mutans TABLE 10 Minimum inhibitory concentration of selected surfactants MIC sample (ppm) FIC Sodium lauryl sulfate 100 - Extract of bark of 25 - magnolia MBE / SLS 1/4 50 1 MBE / SLS 3/2 25 0.70 MBE / SLS 4/1 25 0.85 MBE / Tween 20 100/100 25 1 MBE / Tween 20 100/250 > 100 > 2 MBE / Tween 20 100/500 > 100 > 2 Chlorhexidine gluconate * 2 The results indicate that the magnolia bark extract and lauryl sodium sulfate show synergistic effect (FIC <1) when combined in a ratio (MBE / SLS) of between about 1/4 to about 4/1. However, magnolia bark extract and Tween 20 show antagonistic effect (FIC > 2) when combined. In particular, the results show that certain ratios of magnolia bark extract to sodium lauryl sulfate show synergistic effects. Accordingly, the present invention contemplates chewable products such as chewing gums containing a synergistic ratio of magnolia bark extract to a surfactant. From the above experimental results, the magnolia bark extract in combination with a surfactant will produce a synergistic antimicrobial effect in a chewing gum. Chewing gums having a surfactant in a concentration range of about 25 ppm to about 500 ppm, in combination with magnolia bark extract, exhibit synergistic properties to inhibit biofilm formation leading to dental plaque. In addition, chewing gums having a weight ratio of at least about a part of magnolia bark extract to a part of surfactant, will produce a synergistic antimicrobial effect in a chewing gum. In addition, the synergistic relationship of magnolia bark extract to surfactant can vary from about 1 part magnolia bark extract to one part surfactant, up to about 4 parts magnolia bark extract to 1 part surfactant. Accordingly, the present invention contemplates a wide range of chewing gums containing a synergistic combination of magnolia bark extract and a surfactant.

EXAMPLES The Examples listed below are not intended to exclude other variations in the formulations, and the present invention is not limited to these formulations.

Chewing gum formulations In an embodiment of the present invention, an effective amount for the antimicrobial benefit of the rapid release of the magnolia bark extract, in combination with a surfactant, as described above, is present in a formulation of chewing gum. In one aspect of the present invention, the magnolia bark extract is present in an amount of up to about 5% by weight of the chewing gum product. In another aspect of the present invention, the amount of magnolia bark extract is about 1% by weight of the chewing gum product. In still another aspect, the magnolia bark extract is present in an amount of 0.01% by weight of the chewing gum product. Considering the potency of the magnolia bark extract as described in the in vitro studies above, levels as low as approximately 0.005% by weight of the chewing gum product should be effective in the bactericidal properties. The absolute amount of sodium lauryl sulfate in the chewing gum formulation can vary from about 4 mg to about 10 mg. In general, a chewing gum composition typically comprises a water soluble mass portion, a water-insoluble mastic gum base portion and typically water soluble flavoring agents. The portion of the water-soluble mass is dissipated with a portion of the flavoring agent over a period of time during chewing. The base portion of gum is retained in the mouth during chewing. For the formulation of this invention, in addition to the active substance, suitable compounds are used to increase the disintegration of the water-soluble compounds, thereby facilitating the dissolution (rapid release) of the active substance in the vehicle, which comprises MBE and detergent. of food grade. The insoluble gum base generally comprises elastomers, fats and oils, softeners and organic fillers. the basis of Insoluble gum may or may not include wax. The insoluble gum base may constitute about 5% to 95% by weight of the chewing gum, most commonly the gum base comprises about 10% to 50% of the gum, and in some preferred embodiments about 25% by weight. about 35% by weight of the chewing gum. In a preferred embodiment, the chewing gum base of the present invention comprises from about 20% to 60% by weight of synthetic elastomer, up to about 30% by weight of natural elastomer, from about 5% to 55% by weight of plasticizer of elastomer, approximately 4% to 35% by weight of filler, approximately 5% to 35% by weight of softener, and optional minor amounts (approximately 1% or less by weight) of miscellaneous ingredients such as colorants, antioxidants, etc. . Synthetic elastomers include, but are not limited to, polyisobutylene with an average molecular weight of about 10,000 to 95,000, isobutylene-isoprene copolymer (butyl elastomer), styrene copolymers having styrene-butadiene ratios of about 1: 3 to 3: 1, polyvinyl acetate having an average molecular weight of about 2,000 to 90,000, polyisoprene, polyethylene, vinyl acetate vinyl laurate copolymer having a vinyl laurate content of about 5% to 50% by weight of the copolymer, and combinations thereof.

Preferred margins for polyisobutylene are of average molecular weight of 50,000 to 80,000; for styrene they are from 1: 1 to 1: 3 of bound styrene; for polyvinyl acetate they are from 10,000 to 65,000 average molecular weight, the highest molecular weight of polyvinyl acetates being typically used at the base of the bubble gum pump; and for vinyl laurate acetate, a vinyl laurate content of 10%. Natural elastomers include natural rubber, such as smoked or liquid latex and guayule, as well as natural gums such as jelutong, lechi caspi, perillo, sorva, massaranduba balata, chocolate massaranduba, medlar, rosindinha, chewing gum, gutta hang kang, and combinations thereof. The preferred concentrations of synthetic elastomer and natural elastomer vary depending on whether the chewing gum on which the base is used is adhesive or conventional, bubble gum or regular gum, as discussed below. Preferred natural elastomers include jelutong, chewing gum, sorva and massaranduba balata. Elastomer plasticizers may include, but are not limited to, natural pine resin esters such as glycerol esters or partially hydrogenated pine resin, glycerol esters of polymerized pine resin, glycerol esters of partially dimerized pine resin, glycerol esters of pine resin, pentaerythritol esters of partially hydrogenated pine resin, methyl and partially hydrogenated methyl esters of pine resin; Pine resin pentaerythritol esters; synthetics, such as terpene resins derived from alpha, beta, and / or any suitable combinations of the above. Preferred elastomer plasticizers will also vary depending on the specific application, and the type of elastomer that is used. The fillers / texturisants may include magnesium carbonate and calcium, ground limestone, types of silicates such as magnesium and aluminum silicate, clay, alumina, talc, titanium oxide, mono-, di- and triphosphate, cellulose polymers, such as wood, and combinations thereof. The softeners / emulsifiers may include tallow, hydrogenated tallow, hydrogenated and partially hydrogenated vegetable oils, cocoa butter, glycerol monostearate, glycerol triacetate, lecithin, mono and triglycerides, acetylated monoglycerides, fatty acids (eg, stearic, palmitic, oleic and linoleic), and combinations thereof. The colorants and bleaches may include FD &C dyes and lacquers, fruit and vegetable extracts, titanium dioxide, and combinations thereof. The base may or may not include wax. An exemplary wax-free base gum is described in US Patent No. 5,286,500, the disclosure of which is incorporated herein by reference. In addition to a portion of water-insoluble gum base, a typical chewing gum composition includes a portion of water soluble dough and one or more flavoring agents. The water-soluble portion may include dough sweeteners, high intensity sweeteners, agents flavorings, emulsifiers, colors, acidulants, fillers, antioxidants, and other components that provide the desired attributes. The softeners are added to the chewing gum to optimize the chewiness and the mouth feel of the gum. Softeners, also known in the art as plasticizers or plasticizing agents, generally constitute between about 0.5% to 15% by weight of the chewing gum. These include glycerin, propylene glycol, and aqueous solutions of the sweetener such as those containing sorbitol. The hydrolyzate of hydrogenated starch and corn syrups or other starch hydrolysates (sometimes called glucose syrups), and combinations thereof, are particularly preferred because they also function as binders to improve the flexibility and other physical properties of the gum. . Mass sweeteners, or bulking agents, include both sugar and sugar-free components. The dough sweeteners typically constitute from about 5% to about 95% by weight of the chewing gum, more typically from about 20% to about 80% by weight, and more commonly from about 30% to about 60% by weight of the the eraser. Sugar sweeteners generally include saccharide components commonly known in the chewing gum art, including, but not limited to, sucrose, dextrose, matosa, dextrin, dried invert sugar, fructose, levulose, galactose, corn syrup solids, and similar, alone or in combination. Sweeteners without sugar include, but are not limited to, sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, erythritol, trehalose, tagatose, and the like, alone or in combination. High intensity artificial sweeteners can also be used, alone or in combination, with the previous ones. Preferred sweeteners include, but are not limited to, sucralose, aspartame, NAPM derivatives such as neotame, salts of acesulfame, altitamo, saccharin and its salts, cyclamic acid and its salts, glycyrrhizinate, stevia, perilartine, dihydrochalcones, thaumatin, monelin , and the like, alone or in combination. To provide longer lasting sweetness and flavor perception, it may be desirable to encapsulate or otherwise control the release of at least a portion of the artificial sweetener. Techniques such as granulation, wax granulation, spray drying, spray-freezing, fluid bed coating, coacervation, and fiber extension can be used to achieve the desired release characteristics. Sugar combinations and / or sugarless sweeteners can be used such as with the aqueous solutions of sugar or alditol. If a low-calorie gum is desired, a low-calorie bulking agent can be used. Examples of low calorie bulking agents include: polydextrose; raftilose; rapture fructooligosaccharides (NutraFLora); palatinose oligosaccharide; hydrolyzed guar gum (Sun Fiber); or indigestible dextrin (Fibersol). However, other low calorie bulking agents can be used. If desired, a variety of flavoring agents can be used. The flavor can be used in amounts of about 0.1 to 15 percent by weight of the gum, and preferably from about 0.2% to 5% by weight. Flavoring agents may include essential oils, synthetic flavors or mixtures thereof including, but not limited to, oils derived from plants and fruits such as citrus oils, fruit essences, black spearmint oil, spearmint oil, other oils of mint, clove oil, oil of wintergreen, anise, and the like. Artificial flavoring agents and components can also be used. The natural and artificial flavoring agents can be combined in any sensory acceptable manner. The flavors may include a cooling agent to improve the taste and the breath freshening perceived in the product. Coolants include menthol, ethyl p-menthane carboxamide, N, 2,3-trimethyl-2-isopropyl-butanamide, menthyl glutarate (Association of Flavor Extracts Manufacturers (FEMA 4006)), menthyl succinate, carbonate menthol PG, menthol carbonate EG, menthyl lactate, menthyl glyceryl ketal, menthol glyceryl ether, N-tertbutyl-p-menthane-3-carboxamide, p-menthane-3-carboxylic acid glycerol, methyl-2-isopropyl -bicyclo (2.2.1), heptane-2-carboxamide, menthol methyl ether and combinations thereof.

In addition to the magnolia bark extract and the surfactants of the present invention, active ingredients or medicaments may be added for various purposes. If the drug or active is water-soluble in the chewing gum, preferably it will include a base / emulsifier system that leads to the desired concentration of the drug in the saliva (higher hydrophilic balance). If the medicament or active is insoluble in water, the chewing gum preferably includes a base / emulsifier system that leads to the desired concentration of the drug in the saliva (higher lipophilic balance). In manufacturing the chewing gum which includes the active agent or ingredient, the active agent or the drug is preferably added at the start of the mixture. The lower the amount of active ingredient used, the more necessary it becomes to premix those particular ingredients to assume the uniform distribution through the rubber batch. Whether or not a premix is used, the active agent or drug should be added within the first five minutes of mixing. For a faster release, the active agent can be added later in the procedure. Optionally, the chewing gum of the present invention may include additional breath freshener, antimicrobial or oral health ingredients, such as acceptable metal salts of food, selected from zinc and copper salts of gluconic acid, zinc and copper salts of lactic acid, zinc and copper salts of acetic acid, zinc salts and citric acid copper, and combinations thereof. In addition, antimicrobial essential oils and flavoring components such as black spearmint, methyl salicylate, thymol, eucalyptol, cinnamic aldehyde, polyphosphate, pyrophosphate and combinations thereof can be added to the gum composition. Dental health ingredients, such as fluoride salts, phosphate salts, proteolytic enzymes, lipids, antimicrobials, calcium, electrolytes, protein additives, dental abrasives, and combinations thereof, may also be added to the gum composition. In general, chewing gum is manufactured by sequentially adding the various ingredients of the chewing gum to a commercially available mixer known in the art. After the ingredients have been mixed vigorously, the gum mass is discharged from the mixer and formed into the desired shape such as with roll sheets and cut into tablets, extruded in pieces or emptied into pills, which are then coated or sprinkled. Generally, the ingredients are mixed by first melting the gum base and adding it to the running mixer. The base can also be melted in the mixer itself. At this time, color or emulsifiers can also be added. At this time a softener such as glycerin may also be added, together with syrup and a portion of the bulking agent. Other parts of the filler are added to the mixer. Flavoring agents are typically added to the final portion of the bulking agent. The other optional ingredients are added to the batch in a typical manner, known to those of ordinary skill in the art. The base of the chewing gum and the chewing gum product have been manufactured in a conventional manner using separate mixers, different mixing technologies and, frequently, in different factories. One reason for this is that the optimum conditions for the manufacture of the gum base, and for the manufacture of the gum from the gum base and other ingredients such as sweeteners and flavors, are so different that it has been It is impractical to integrate both tasks. The manufacture of the chewing gum base, on the one hand, involves the dispersive mixing (often of high shear) of ingredients difficult to mix, such as elastomer, filler, elastomer plasticizer, softeners / emulsifiers of the base and some Sometimes wax, and typically requires long mixing times. On the other hand, the manufacture of the chewing gum product involves combining the gum base with more delicate ingredients such as product softeners, dough sweeteners, high intensity sweeteners and flavoring agents, using distributive mixing (generally of minor shear). , during shorter periods. During the manufacturing process of the chewing gum, the whole mixing process typically takes five to fifteen minutes, but sometimes longer mixing times may be required. Those skilled in the art will recognize that many variations of the process described above can be followed.

Table 1 1 below lists the examples of the formulations of extract of magnolia bark in a chewing gum. Example 1 is a comparative example of a chewing gum formulation of the art previous.

TABLE 11 Antimicrobial rubber formulas (percentage basis of dry weight) Ingredient Example 1 Example 2 Example 3 Example 4 Example 5 Rubber base 25.21 26.22 25.21 25.21 25.21 Lecithin 0.17 0.17 0.17 2.00 0.17 NaHCO3 0.25 0.25 0.25 0.25 0.25 Sorbitol 50.86 49.86 47.86 45.86 50.36 MBE - 0.10 3.00 2.00 0.50 Manitol 4.25 4.25 4.25 4.25 4.25 Lysine / Glycerin 8.51 8.51 8.51 8.51 8.51 Glycerin 8.50 8.50 8.50 8.50 8.50 Sweetener 0.67 0.67 0.67 0.67 0.67 encapsulated Flavor 1 .58 1 .58 1 .58 1 .58 1 .58 Total 100.00 100.00 100.00 100.00 100.00 In accordance with the invention, each of the formulations in Examples 2-5 is supplemented with a surfactant as described above. In an exemplary formulation, each of Examples 2-5 includes about 0.01% to 2% of a surfactant as described above. In another exemplary formulation, each of Examples 2-5 includes about 2 ppm to 500 ppm of a surfactant as described above. In yet another example formulation, each of Examples 2-5 includes sodium lauryl sulfate and magnolia bark extract in an approximate ratio of 1/4 to 4/1.

Formulation Techniques When formulating the relatively rapid release compositions of this invention, any relevant controlled formulation technique can be applied to prepare an oral composition with controlled release. Therefore, the dosage form can be in the form of a liquid having dispersed particles in a dispersion medium or it can be in the form of a single or multiple unit dosage form to be used as such to disperse in a medium. dispersion before use. For any use that requires quick release, reducing particle size is essential to see the total benefit of the asset. For many assets, there is a critical level required to obtain an answer. Therefore, it is essential that at least one effective amount of the asset be in shape of small particles. The effective amounts depend on the asset and the desired final result. For example, an asset can be added to the rubber coating, which is a water-soluble matrix, so that, during the chewing period, the active can be released quickly resulting in rapid release. This could allow a coating of a chewing gum to be a carrier for an active, specifically for MBE, and for a surfactant. For example, US Patent 6,645,535, which is incorporated herein by reference, discloses a coating made with a syrup having an antacid dispersed therein, resulting in rapid release of the antacid. In the compositions described below, a person skilled in the art will know how to incorporate a part that results in a relatively rapid release of the active substance. As an example, that part can be incorporated in the outermost layer of the coating comprising the active substance, or it can be incorporated in the form of pills formulated without retarding agents neither in the centers nor in a coating. Examples of different controlled-release technologies are: individual units based on a coated matrix, double or triple compression, or multi-layer coating; and multiple units that include units that have a controlled release coating, units that have a controlled release matrix, units that have a controlled release compression coating; and units with a multiple layer coating. In one aspect of the invention, the coated matrix technology is used to cover a slightly soluble and / or swallowable polymer, in which magnolia bark extract (MBE) and / or surfactant is integrated with a barrier Insoluble diffusion. The diffusion of the MBE is controlled by the matrix and the coating. It is possible to use an outer film layer containing MBE, which is applied on the coated matrix. Alternatively, enteric coated units can be integrated into the matrix. In another aspect of the invention, a formulation based on double or triple compression contains a core of a polymer having the magnolia bark extract and the surfactant incorporated therein. This center is covered by compression with a polymer with the MBE incorporated in it or in another concentration than in the center. When triple compression is employed, the coated center is compression coated once more with a polymer with the MBE in the same or in another concentration as in the first coating. Finally, the unit with double or triple compression is covered by sprinkling and the MBE is incorporated in the cover. However, MBE concentrations in different covers can vary markedly. When the MBE of the first layer has been almost depleted, the next layer appears and levels or changes the profile of the release. In a multi-layer coating formulation, an inert center is coated with several layers of diffusion barriers, each barrier containing different concentrations of MBE. The concentration should be the highest on the inner cover and the lowest on the outer cover. The purpose of the concentration gradient is to compensate for the increasing diffusion distance closest to the center. The thickness of the diffusion barriers and the concentration gradients need to be adjusted correctly. Multilayer technologies could be optimized by the use of an enteric polymer, and / or by the use of an amylose-containing film coating, such as a coating containing ethylcellulose and amylose. In addition, the spray coating with the magnolia bark extract and the surfactant gives an immediate triggering of the antimicrobial agent (s). Multiple unit systems can be used, comprising pills, granules, crystals, and mini chewable tablets, or mixtures thereof. In these systems, some units may not be coated, while other units may be formulated as a matrix or a coated matrix. The MBE and the surfactant can also be present in the composition in the form of a multiplicity of individual units such as, for example, pills, mini tablets and chewable crystals, and crystals of the active substances, the two parts can be in a mixture , or can comprise at least two different types of pills, mini tablets or chewable crystals, the first type of pills corresponding to the first part and the second type of pills corresponding to the second part. Alternatively, the quick release in accordance with the invention can also be obtained if the individual units contain relatively large crystals of the active substance of the drug. In those cases, the size of the unit is typically on the micrometer scale. The rapid release of the MBE and surfactant can be achieved with any compound that is a natural fast release compound, or it can be a compound that has been treated in such a way that it possesses rapid release properties during chewing. The contemplated treatment methods include encapsulating, co-drying and dissolving the MBE and surfactant in various solvents including water, alcohols, flavors and the like. In another embodiment of the invention, the antimicrobial effect can be obtained when the active ingredients are encapsulated within a biocompatible biodegradable polymer matrix, in accordance with many of the microencapsulated teachings in the art. The microcapsules may be formed from a polypeptide center or from another biologically active agent encapsulated in a poly (lactide / glycolide) copolymer matrix. Rapid release of MBE and surfactant can be achieved with the use of detergent compatible compositions. The types of compositions useful herein are detergent compatible compositions containing softener particles such as those known in the art, including mixtures of organic dispersion inhibitors (eg, stearyl alcohol and sorbitan fatty esters).

When manufacturing chewing gum, fast-release flavors can result when the flavors are encapsulated in gum arabic. In accordance with one aspect of the invention, the rapid release of the magnolia bark extract and the surfactant can be achieved through its encapsulation in gum arabic. In principle, the controlled release of the sweeteners in the chewing gum is obtained by selecting sweeteners which are naturally fast-release sweeteners, and those which are naturally slow-release sweeteners, and mixing them with the gum base. Accordingly, the antimicrobial compositions of the invention can be mixed with fast-release sweeteners, to obtain that the chewing gum of this invention has rapid release of the antimicrobial compounds during chewing. The fast release sweeteners contemplated by the present invention include low intensity sweeteners, dried reverse sugar, fructose, xylitol, and combinations thereof. Rapid-release sweeteners also include the highest intensity sweeteners that include aspartame, saccharin, cyclamate, dihydrochalcones, alone or in any combination. The specific exceptions of this group are thaumatin and monelin, which are considered slow-release sweeteners. In addition, those skilled in the art will recognize low intensity sweeteners which may also serve as bulking agents in the chewing gum in whole or in part.

In addition, the softener may be combined with the low intensity sweeteners such as in an aqueous solution. It should be noted that sweets and soft, chewable tablets can be manufactured in layers. Accordingly, in another aspect of the invention, the antimicrobial compounds of the invention can be mixed into the ingredients of one or more of the layers, thereby providing rapid release of the active substance. All of the above mentioned combinations of the different types of compositions or formulation techniques apply to the quick release part or the composition of the invention. It should be understood that various changes and modifications to the currently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and competence of the present invention, and without diminishing its intended advantages. Therefore, it is intended that such changes and modifications be covered by the appended claims.

Claims (22)

1. NOVELTY OF THE INVENTION CLAIMS 1 . - An oral composition, comprising: (a) a vehicle for oral delivery; (b) a water soluble portion; and (c) a coating layer that includes an effective amount of an antimicrobial agent comprising a synergistic ratio of magnolia bark extract and a surface active agent, wherein the synergistic ratio is at least about 1 part of bark extract. magnolia to 1 part of surfactant.
2. 2. The oral composition according to claim 1, further characterized in that it comprises a chewing gum, or a chewy candy.
3. 3. - The oral composition according to claim 2, further characterized in that the oral composition comprises a portion of water-soluble mass and a portion with gum base.
4. 4. The oral composition according to any of the preceding claims, further characterized in that the surfactant comprises a bactericidal surfactant.
5. 5. - The oral composition according to any of the preceding claims, further characterized in that the agent The surfactant comprises a salt selected from the group consisting of a sodium salt and an ammonium salt.
6. 6. - The oral composition according to any of the preceding claims, further characterized in that the surfactant comprises an anionic surfactant.
7. 7. The oral composition according to any of the preceding claims, further characterized in that the surfactant comprises sodium lauryl sulfate.
8. 8. - The oral composition according to claim 7, further characterized in that the surfactant comprises from about 0.001% to about 2% sodium lauryl sulfate.
9. 9. - The oral composition according to claim 7 or 8, further characterized in that the synergistic ratio of the magnolia bark extract to sodium lauryl sulfate is about 2 parts of magnolia bark extract to 1 part of lauryl sulfate of sodium.
10. 10. The oral composition according to any of claims 1 to 4, further characterized in that the surfactant comprises a fatty acid or a glyceride. eleven .
11. The oral composition according to any of the preceding claims, further characterized in that the synergistic ratio varies from about 1 part of magnolia bark extract to 1 part of surfactant, up to about 4 parts of magnolia bark extract to 1 part of surfactant agent.
12. 12. The oral composition according to any of the preceding claims, further characterized in that the surfactant comprises from about 0.001% to about 1.0% of the oral composition.
13. 13. The oral composition according to any of the preceding claims, further characterized in that the fast-release antimicrobial agent is encapsulated by double compression or triple compression within the oral composition.
14. 14. The oral composition according to any of the preceding claims, further characterized in that the rapid release antimicrobial agent comprises a spray coating on the surface of the oral composition.
15. 15. The oral composition according to any of claims 1 to 2, further characterized in that the fast-release antimicrobial agent is encapsulated in a coated matrix.
16. 16. - The oral composition according to any of claims 1 to 2, further characterized in that the fast-release antimicrobial agent is encapsulated in a biodegradable polymer matrix.
17. 17. - The oral composition according to any of claims 2 or 3, further characterized in that the fast-release antimicrobial agent is encapsulated in gum arabic.
18. 18. - The oral composition according to claim 3, further characterized by the fast-release antimicrobial agent It comprises a multi-layer coating on the rubber-based portion.
19. 19. The oral composition according to any of the preceding claims, further characterized in that the rapid release antimicrobial agent comprises a system of multiple units.
20. 20. A method for preparing an oral care composition, comprising incorporating an antimicrobial agent, comprising a synergistic ratio of magnolia bark extract and surfactant in a formulation, in the amount of from about 0.05% to about 10% by weight, based on the weight of the total formulation, mixing the ingredients until a uniform mixture is obtained, and then forming the mixture in the coating suitable for an oral composition.
21. 21. The composition according to any of claims 1 to 19, further characterized in that it is to be used in reducing the number or activity of the bacteria in the oral cavity.
22. 22. The use of the composition of any of claims 1 to 19, for the manufacture of a medicament for reducing the number or activity of bacteria in the oral cavity.