MX2008007108A - Oral compositions comprising propolis - Google Patents

Abstract

Oral compositions are provided that comprise a propolis extract;an oral care active compound chosen from:a cationic antibacterial agent, an anti-attachment agent, a biofilm disruption agent, and an anti-inflammatory agent;and a source of fluoride ions. Further, in certain embodiments, the oral composition comprises an anionic polymeric linear polycarboxylate. The oral composition can be in a form of a mouth rinse, a dentifrice, a confectionary/ a medicament, or a film. Methods of making and using the oral compositions are also provided.

Description

ORAL COMPOSITIONS THAT COMPRISE PROPOLIS CROSS REFERENCE TO RELATED REQUEST This application claims the benefit of the U.S. Provisional Patent Application No. 60 / 752,617 filed December 21, 2005, which is hereby incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION Human periodontal diseases are inflammatory conditions that are the result of complex interactions between periodontopathogens and the immune response system of the host. It is believed that there are two interrelated aspects with the advance of periodontal disease; the first is the activation of the host immune system and the second is the production of oxygen radicals and their related metabolites. The increase in the production of oxygen radicals can contribute to an oxidant tension, which is believed to be involved in periodontal disease.

Gingivitis in inflammation or infection of the gums and alveolar bones that support the teeth. It is generally believed that gingivitis is caused by bacteria in the mouth (particularly bacteria associated with plaque formation) and the inflammatory response triggered by the presence of bacteria and toxins formed as a byproduct of bacteria. Periodontitis is a pathological condition that progressively worsens compared to gingivitis, where inflamed gums begin to withdraw from the teeth, thus forming pockets between them, which ultimately results in the destruction of the bone and the periodontal ligament. Chronic infection and inflammation potentially results in the subsequent loss of teeth.

It is generally believed that the cellular components involved by these diseases and conditions include epithelial tissue, gingival fibroblasts, and circulating leukocytes, all of which contribute to host response to the pathogenic factors generated by bacteria. Even though bacterial infection is often the etiological event in many of these oral diseases, the pathogenesis of the disease is mediated by the host response.

Bacterial infection of oral tissue increases the response of the host immune system and decreases the healing process by inflammatory mediators of regulation ascending that can induce significant tissue damage surrounding the foci of infection.

There is a need for oral care compositions that effectively reduce the development or progression of oral disease, preferably having an active ingredient that decreases the effects of oral disease by preventing or reducing the multiple etiological factors that contribute to the process of oral disease and / or exacerbate it. Furthermore, there is a need to stabilize oral care activities in an oral composition, so that their functionality and bioavailability as administered to a subject in vivo is preserved and stabilized.

BRIEF SUMMARY OF THE INVENTION In certain embodiments, the present invention is directed to an oral composition which comprises: an extract of propolis; an active component for oral care chosen from: a cationic antibacterial agent, an anti-adhesion agent, a biofilm destruction agent or an anti-inflammatory agent; Y a source of fluoride ions.

In certain embodiments, the present invention is directed to a method of preparing an oral composition which comprises: mixing one or more carrier ingredients to form a homogeneous mixture; add a source of fluoride ions to the mixture; adding at least one of: a cationic antibacterial agent, an anti-adhesion agent, a biofilm destruction agent or an anti-inflammatory agent; Y add an extract of propolis to the homogeneous mixture at temperatures less than or equal to about 40 ° C to form the oral composition.

In certain embodiments, the present invention is directed to methods of preventing bacteria from forming a biofilm, suppressing recognition by the immune system of an antigen on an oral surface of a mammal, reducing the response of an immune system, and suppressing the production of one or more mediators of inflammation in an oral surface, comprising administering and applying the compositions of this invention to the oral surface. In certain embodiments, the present invention is directed to methods of maintaining or increasing the systemic health of a mammal comprising applying a composition according to claim 1 to the oral surfaces at least once per day for a period.

DETAILED DESCRIPTION OF THE INVENTION As referred to herein, all references cited herein are incorporated by reference in their totalities. When there is a conflict between a definition in the present revelation and that of a cited reference, the present revelation will prevail. In addition, all the percentages that are expressed are percentages by weight.

In various embodiments, an oral composition comprising an extract of propolis, an active oral care compound drained between: a cationic antibacterial agent, an anti-adhesion agent, a biofilm destruction agent, an anti-inflammatory agent, or mixtures thereof, is provided. same. In some embodiments, the active ingredient may comprise three or more constituents.

For example, in certain embodiments, the active ingredient comprises a third constituent comprising a source of fluoride ions. In other embodiments, the oral composition comprises a polymeric linear polycarboxylate, as described in more detail below.

The compositions of the present invention comprise an extract of propolis. As referred to herein, the terms "propolis", "propolis extract" or a "propolis extract" refer to a composition obtained from a source produced by bees, which are generally classified in the Apidae family, preferably of the genus Apis. For example, appropriate extracts include those that are isolated from a source generated by Api s ellifera (commonly known as the "honey bee"), including its various subspecies (Api s mellifera ssp.), Such as Caucasian Apis mellifera ( the "Caucasian honey bee" or the "western honey bee"). As referred to hereinafter, the terms "propolis", "propolis extract" or a "propolis extract" encompass all appropriate resin products produced by species and subspecies of the Apidae family, as well as synthetic equivalents or semisynthetic of said natural extracts or active components contained therein It has been reported that propolis contains numerous active compounds including many kinds of polyphenolic compounds, flavones, flavonones, phenolic acid, and esters. Although these compounds are not fully understood or characterized, they are generally believed to vary based on geographic location and where the bees are located. In general, on a basis by weight, propolis contains about 45 to about 55% resins and balms (including, for example, flavonoids, phenolic acids, and esters); around 25% to around 35% waxes and fatty acids; around 10% of essential oils; about 5% pollen (including proteins and amino acids derived from proteins); and about 5% of other organic and mineral compounds (including mineral traces, vitamins, ketones, lactones, quinones, spheroids, benzoic acid and esters and sugars); among other compounds.

In certain embodiments, the extract of propolis comprises one or more active compounds that have been isolated from a source of propolis. The propolis extract may include a complement of active compounds that occur naturally in the source of propolis. An extract of propolis of the present invention can include an extract form and at least one active compound, for example two or more active compounds or a series of active compounds derived from a source of propolis. In certain embodiments, various propolis extracts can be provided in hydrophilic or lipophilic carriers, depending on the solvent used during the extraction. The extracts may be in the form of liquid, paste, or dry powder.

It is known that certain microorganisms accumulate and promote the formation of a matrix of dental plaque (for example biofilm) on an oral surface, which in turn facilitates the formation of tartar, gingivitis, periodontitis, caries, candidiasis, and / or stomatitis of the denture, among others. In certain embodiments, the compositions of the present invention inhibit the accumulation of said microorganisms. It has been reported that propolis inhibits the accumulation of microorganisms such as lactobacilli, actinomycetales, leptotrichia, non-β-hemolytic streptococci, enterococcus, miscellaneous gram-positive cocci, neisseria, dipteroid bacilli, fusiform bacilli, bacteroides, spirochetes, fungi (Candida), and combinations thereof. In accordance with the different incorporations, the extract of propolis can provide one or more of the following benefits for oral care: antibacterial, antimicrobial, anti-inflammatory, antioxidant, anticaries, antiplaque and anti-jar.

As used herein, "extraction" or "extraction" of a solid or liquid material refers to contacting the material with an appropriate solvent to remove the desired substance (s) to be extracted from the material. Where the material is solid, it is preferably cleaned of residues and excess waxes, and then disintegrated into small pieces, crushed or ground as a powder before it comes into contact with the solvent. Extractions of this type can be carried out by conventional means known to one skilled in the art; for example, by using an extraction apparatus, such as a Soxhlet apparatus, which retains the solid material in a support and allows the solvent to flow through the material; or by mixing the solvent of the material with each other and then separating the liquid and solid phases or two immiscible liquid phases either by filtration or by sedimentation and decantation. It is preferred that the naturally occurring active ingredients used in oral care compositions be of a reproducible, stable quality and have microbiological safety.

The propolis extract can be prepared by extracting the solid material from propolis using an appropriate solvent. The selection of extraction solvent is typically determined by the final use of the extract and technical feasibility. Preferred non-limiting solvents for Extraction include monohydric solvents, i.e. alcohols such as methane, and ethanol; polyhydric solvents, such as propylene glycol, acetic acid, sodium hydroxide (preferably in combination with water); water, oils, and the like. While other solvents may also be used for the extraction of propolis, such as ether, acetone, benzenes and ammonia, they are generally not considered suitable for use in oral care compositions.

Other extraction methods include steam distillation or supercritical fluid extraction. In one embodiment, the propolis extract is isolated by supercritical fluid extraction (SFE) such as SFE using carbon dioxide (C02), steam distillation or using vehicles such as sunflower or avocado oils. The methods of preparing an extract of propolis may include those known in the art, such as, for example, those described in U.S. Patent Nos. 6,153,222 and 6,153,228 issued to Shibuya et al., And 5,922,324 issued to Aga et al.

Generally, a part of the propolis (on dry basis) is extracted with about 1 to about 50 parts of solvent, preferably from about 10 parts to about 40 parts of the solvent using an apparatus of extraction where the solvent is brought into contact with the matter of propolis to obtain a concentrated extract. The extract may be in the form of a paste, which is then optionally subjected to one or more extraction steps with different solvents to further concentrate the originally obtained paste for a prolonged period, for example about 6 hours to about 2 days, or for about 1 day. Propolis can be extracted with a mixture of polyhydric compounds and water. For example, the extraction solvent may be a mixture of water to propylene glycol in a ratio of about 1: 2 to about 2: 1. In certain embodiments, the first constituent comprising propolis extract comprises one or more active compounds derived from a source of propolis, from about 1 to about 75% by weight of the extract. In certain embodiments, the propolis extract product is in liquid form. Thus, the first constituent comprises about 1 to about 5% by weight of active compounds derived from the source of propolis, about 94 to about 99% solvent and optionally about 0.1 to about 1% of other compounds, such as condoms and impurities.

In several embodiments, the propolis extract is present in the oral composition at about 0.0001 to about 3% by weight, less about 1% by weight, about 0.0002 to about 1% by weight or about 0.0003 to about 0.5% by weight.

As described above, the oral compositions of the present invention further comprise an active compound for oral care chosen from: a cationic antibacterial agent, an anti-adhesion agent, a biofilm killing agent, an anti-inflammatory agent, or mixtures thereof. same. As one skilled in the art can appreciate, an active compound for oral care may fall into one or more of these classifications, since it may have multiple mechanisms and / or effects and may not be limited to a single function or classification. In certain embodiments, the active oral care compound has a functionality or mechanism to prevent and / or treat an oral care disease, wherein the mechanism complements and / or supplements the mechanism provided by the propolis extract described above. Additionally, for the present purposes, the terms "cationic antibacterial agent", "anti-adhesion agent", "biofilm destruction agent" and "anti-inflammatory agent" refer to different compositions of propolis extracts.

In certain embodiments, the active compound for oral care is a cationic antibacterial agent that is highly effective in compositions for oral care for use in certain additions. Cationic antibacterial agents suitable for use in oral compositions include, for example: (i) quaternary ammonium compounds, such as those in which one or two of the substituents in the quaternary nitrogen have from 8 to 20, preferably from 10 to 18 carbon atoms and is preferably an alkyl group, which can be interrupted optionally by an amide, ester, oxygen, sulfur or heterocyclic ring, while the remaining substituents have a lower number of carbon atoms, for example from 1 to 7, and are preferably alkyl, for example methyl or ethyl, or benzyl. Examples of such compounds include benzalkonium chloride, dodecyl trimethyl ammonium chloride, benzyl dimethyl stearyl ammonium chloride, hexadecyltrimethyl ammonium bromide, benzethonium chloride (diisobutyl phenoxyethoxyethyl dimethyl benzyl ammonium chloride) and methyl benzethonium chloride; (ii) pyridinium and isoquinolinium compounds, including hexadecylpyridinium chloride and alkyl isoquinolinium bromides bromides; (iii) pyrimidine derivatives such as hexetidine (5-amino-1,3-bis (2-ethylhexyl) -5-methyl-hexahydropyrimidine); (iv) amidine derivatives such as hexamidine isethionate (4,4'-diamidino-β-diphenoxy-hexane isethionate); (v) bispyridine derivatives such as octenidine dihydrochloride (N, N '[1, 10-decanediildi-l (4H) -pyridinyl-4-ylidene] -bis (1-octanamine) dihydrochloride); (vi) guanides, for example, mono-biguanides such as biguanide p-chlorobenzyl; and N '(4-chlorobenzyl) -N "- (2,4-dichlorobenzyl) biguanide, poly (biguanides) such as polyhexa-methylene biguanide hydrochloride, and bis-biguanides of the general formula (1): wherein A and A1 each represent (i) a phenyl group optionally substituted by (C? -4) alkyl, (C? _4) alkoxy, nitro, or halogen, (ii) a group (C? _? 2) alkyl, or (iii) an acyclic (C4-i2) group; X and X1 represent each one (C? _3) alkylene; R and R1 each represent hydrogen, (C? -? 2) alkyl, or aryl (C? -6) alkyl; Z and Zl are each 0 or 1; n is an integer from 2 to 12; and the polymethylene (CH2) n chain may optionally be interrupted by oxygen or sulfur or an aromatic nucleus (e.g., phenyl or naphthyl); and orally acceptable acid addition salts thereof, examples of said bis-biguanides include chlorhexidine and alexidine. Suitable acid addition salts of these bis-biguanides of the general formula (1) include the diacetate, the dihydrochloride and the digluconate. Suitable acid addition salts of chlorhexidine include the salts of digluconate, diformate, diacetate, dipropionate, dihydrochloride, dihydroxyoride, dilactate, dinitrate, sulfate, and tartrate. Suitable acid addition salts of alexidine include dihydrofluoride and dihydrochloride salts; Y (vii) alkyl esters of Na-acyl amino acids and salts generally represented by formula (2) below: NH R2CONHCH (CH2) nNHCNH2 X COOR (2) where R1 is an alkyl chain of 1 to 8 carbon atoms, preferably 1 to 3 carbon atoms, and more preferably 3 carbon atoms; R2 is an alkyl chain of 6 to 30 carbon atoms, preferably 10 to 12 carbon atoms, and mixtures thereof; and X is an anion. In various embodiments, the R2C0 component comprises a natural fatty acid residue such as a natural fatty acid selected from the fatty acid of coconut oil, fatty acid residue from bait or a residue of mono-fatty acid, such as residues of fatty acids of lauroyl (Ci2), myristyl (C? 4), stearoyl (Ci8), or mixtures thereof. In certain embodiments, the R2C0 component comprises a lauroyl fatty acid residue.

X may be any against anion that provides a reasonable degree of solubility in the water (preferably at least about lg in 1 L of water). Examples of X-anions that form antibacterial ester salts of the above-identified formula include inorganic acid salts, such as those comprising halogen atoms (e.g., chlorine or bromine) or dihydrogen phosphate, or an organic salt such as acetate, tautarate, citrate or pyrrolidone-carboxylate (PCA).

Examples of useful antibacterial esters of the above-identified form where n equal 3 include: N 'methyl ester -cocoyl-L-arginine, N-cocoyl-L-arginine ethyl ester, Na-cocoyl-L-arginine propyl ester, methyl ester of Na-stearoyl-L-arginine, ethyl ester hydrochloride of Is-stearoyl-L-arginine. In one embodiment, the compound derived from arginine is the hydrogen chloride salt of ethyl lauroyl arginine (ELAH). It should be noted that alkyl salts of Na-acyl amino acids are generally classified as cationic antibacterial agents. However, such compounds also tend to have anti-adhesion properties and other properties that prevent plaque formation on the oral surfaces that will be described in more detail.

Thus, in certain embodiments, the cationic antibacterial agent is chosen from: benzethonium chloride, octenidine, hexetidine, hexamidine, cetyl pyridinium chloride (CPC), alexidine, alkyl salts of amino acids of isXacyl (such as ester hydrochloride) of ethyl lauroyl arginine (ELAH)), and mixtures thereof.

In several embodiments, the cationic antibacterial agent is present in the oral compositions in a amount of about 0.001 to about 3%, about 0.005 to about 2% and about 0.01 to about 1%.

In other embodiments, the active compound for oral care is an anti-adhesion agent. Without being limiting with respect to the present invention, the active compounds for oral care are generally believed to operate by one of two predominant anti-adhesion mechanisms (or both). Biofilms (also referred to as films) are a matrix formed on an oral surface, typically a hard tissue surface, comprising bacteria (generally about 60-70% of the biomatrix), bacterial extracellular byproducts, proteins, lipids, and glycolipids. The term "oral surface" encompasses hard and soft tissues within the oral cavity. Hard tissues include teeth, periodontal support, and the like. Soft tissues include the gums, the tongue, the surfaces of the oral cavity and the like. Oral compositions of the various embodiments may be used in a mammalian subject, including, but not limited to, humans and other high-level warm-blooded vertebrate animals, such as felines and canines.

The early stages of biofilm formation include an initial layer of bacteria that adhere to an oral surface, which is generally believed to adhere to ligands or alesinas on the wall of the bacterial cells that interact with receptors on an oral surface. It is believed that bacterial cells adhere to salivary glycoproteins on the oral surface, e.g., enamel. It seems that the bacteria form a stronger adhesion generating extracellular polymers to adhere to the oral surface. The bacteria then grow and divide, forming a dense layer on the oral surface. After a specific density is reached, it is believed that the bacteria rearrange and begin to form pillars and irregular surface structures. In addition, the biofilm matrix is believed to have a complex association of multilayer and diverse substances that form cell clusters attached to the anchoring bacteria of the first layer.

Thus, the anti-adhesion agents can interact with an oral surface to form a protective layer, so that the bacteria and biofilm components can not adhere to the oral surface, thus preventing an initial anchor layer from forming on the surface. oral surface Such an anti-adhesion agent can substantially cover an oral surface, and prevent adhesion of the bacteria and other components of the biofilm matrix. In a second mechanism, of the anti-adhesion agents, the anti-adhesion agent interacts with the bacteria themselves to prevent them from attacking the oral surface, probably interacting with adhesins, ligands, or other components on the surface of bacteria that would ordinarily facilitate a linkage with a receptor or other component on the oral surface. For example, certain active ingredients may interfere with a glycosyl transferase enzyme on the walls of bacterial outer cells, thereby preventing the conversion of various sugars to glucans that would otherwise form the extracellular anchor matrix for the biofilm.

Without limiting the present invention, it is believed that in some embodiments the active compound for oral care is selected to comprise alkyl salts of Na-acyl amino acids, such as ethyl lauroyl arginate hydrochloride (ELAH), the active ingredients function as an anti-stick active ingredient, in addition to a cationic antimicrobial ingredient. ELAH appears to alter the surface energy of hard tissues, such as enamel (reducing surface energy), and in turn, prevents adhesion and adhesion of microorganism that would otherwise form a plaque biofilm on the surface of the tooth . The ELAH appears to have substantivity on the surface of the teeth, so that it remains adhered for a sufficient period of time to effectively prevent the microorganisms adhere to the surface of the teeth, thus preventing or reducing the formation of biofilms.

In several embodiments, a non-stick effect of this type can be obtained at low concentrations, potentially below the Minimum Inhibitory Concentration (MIC, for its acronym in English) for the ELAH. In several embodiments, the application of ELAH as an active ingredient promotes longer and more effective antiplaque benefits at lower concentrations compared to many other antimicrobial ingredients that move by washing in the aqueous oral cavity. Furthermore, without limiting the present invention, we hypothesize that ELAH can interfere with the metabolism of microorganisms in the biofilm, perhaps by regulating arginine, and thus contribute to antimicrobial, antiplaque, antigingivitis, and antiperiodontitis efficacy of the active ingredient in the oral compositions (thereby also acting as a biofilm destruction agent).

In several embodiments, the anti-adhesion agent is present in the oral compositions in an amount of from about 0.001 to about 3%, about 0.005 to about 2% and about 0.01 to about 1%.

In some embodiments, the active compound for oral care is a biofilm destruction agent. A biofilm destruction agent is a compound that prevents the formation of a biofilm and / or attacks an already formed one on an oral surface.

Conventionally enzymes have been selected as biofilm destruction agents, based on the ability of several enzymes to hydrolyse proteins, starch and lipids, which form a part of the biofilm matrix. In certain embodiments, said enzymes include protease enzymes, such as cysteine proteases. In certain embodiments, the biofilm destruction agent is an enzyme selected from: papain, ficin, krilase or mixtures thereof.

Papain is obtained from the latex of the fruit and green leaves of the Carica papaia. Papain hydrolyzes the polypeptides, more specifically, cleaving the carboxy terminus of arginine, lysine, glutamine, tyrosine, glycine, histidine (adjacent to phenylalanine) producing peptides of lower molecular weight. Ficin is obtained by drying and filtering the latex of the Ficus species (fig trees Ficus glabrata). Krilasa is extracted from an Antarctic krill (Euphausia superba). It consists of endo- and exo-peptidases, which include four proteases of serine and four carboxypeptidases.

Other enzymes are also suitable for inclusion in oral compositions as plaque destruction agents. A selected enzyme that can be formulated in combination with a protease enzyme in the aforementioned glucoamylase. Glucoamylase is a saccharifying glucoamylase originating from Aspergillus niger cultivated by fermentation. This enzyme can hydrolyse both the branching points of the α-D-1,6 glucosidic and the α-1,4 glycosidic linkages of the glycosyl oligosaccharides. Additionally useful are a and β-amylase, dextranase and mutanase.

Other enzymes suitable for use as active components for oral care for plaque destruction include lysozyme, derived from egg white. The enzyme can have antibacterial properties facilitating hydrolysis of the walls of bacterial cells by separating the glycosidic bond between carbon number 1 of N-acetylmuramic acid and carbon number 4 of N-acetyl-D-glucosamine. In vivo, these two carbohydrates are polymerized to form the polysaccharide of the cell wall. Additionally, pectinase, an enzyme that is present in most plants, can facilitate the hydrolysis of pectin polysaccharide in sugars and galacturonic acid, thus contributing to the degradation of bacteria and other microorganisms.

Other useful enzymes include lipases such as plant lipase, gastric lipase, pancreatic lipase, lysozyme tannase, serine proteases, bromelain, chymotrypsin, alcalase, amalisees, lactoferin, gingipains, glucose oxidase, elastases and / or cellulases. Other illustrative agents in the destruction of the biofilm for oral care include the synthetic histatin, furanone, and its derivatives and mixtures of any of the foregoing.

In several embodiments, the biofilm destruction agent is present in the oral compositions in an amount from about 0.001 to about 3%, about 0.005 to about 2% and about 0.01 to about 1%.

In certain embodiments, the active compound for oral care is an anti-inflammatory agent. Suitable anti-inflammatory agents include cytosines and prostaglandins. The suppression of one or more of the proinflammatory mediators described above prevents and / or treats tissue damage and / or tissue loss when the tissue becomes inflamed.

Thus, active oral care compounds that serve as anti-inflammatory agents to suppress one or more mediators of inflammation are useful for oral compositions.

Illustrative useful antiinflammatory agents may include those that prevent the accumulation of inflammatory mediators derived from the pathway of arachidonic acid activity that is triggered by the detection by the immune system of an antigen. A class of mediators that modulate inflammatory responses are the metabolites of arachidonic acid, namely prostaglandins, leukotrienes, and thromboxanes, which are produced through the pathway of the enzyme cyclooxygenase or lipoxygenase. These metabolites have been implicated as the main mediators in gingivitis, periodontitis, osteomyelitis and other inflammatory diseases. For example, those anti-inflammatory agents that prevent the accumulation of inflammatory mediators of the pathway of arachidonic acid, include non-steroidal anti-inflammatory drugs (NSAIDs, by its acronym in English). Examples of useful NSAID antiinflammatory agents include indometycin, flurbiprofen, ketoprofen, ibuprofen, naproxen, meclofenamic acid or mixtures thereof.

In certain embodiments, the anti-inflammatory agent is able to suppress recognition by the immune system of one or more antigens produced by pathogens on an oral surface. For example, gram-negative bacteria have endotoxins, generally known as lipopolysaccharide components (LPS), which are embedded within outer walls membranes. The LPS of the bacterial cells serve as antigens that are detected by various cells within the immune system. The recognition of LPS antigens by cells of the immune system, such as CD-14 receptors on monocytes and macrophages, will typically result in an immune system response that includes the production of cytosines, the activation of a cascade complement (e.g. ., histamine release that will result in neutrophilic vasodilation and chemotaxis), and activation of the coagulation cascade. Certain useful anti-inflammatory compounds can prevent an immune system from recognizing one or more antigens present in the oral cavity, such as LPS on the cell walls of gram-negative bacteria. It is believed that said anti-inflammatory drugs are interrelated with the antigen in such a way that the microbe / bacterium is no longer recognized by the receptors of certain cells of the immune system (effectively hiding it against the detection of the immune system) and therefore suppressing a response of the immune system. immune system.

Similarly, in another mechanism for anti-inflammatory agents for oral care, the anti-inflammatory agent serves to reduce or extract one or more oxide substances from reactive oxides within the oral cavity. Reactive oxygen substances (ROS, by their acronym in English) are typically highly reactive products produced during various biochemical processes, and include superoxide anions (02 ~), hydrogen peroxide (H202), and hydroxyl radicals (-0H). The formation of ROS can occur as part of many cellular processes including mitochondrial respiration, immune cell responses, cell damage, heat, radiation of many origins, metabolism of drugs and other chemicals. It is thought that ROS are involved in almost all pathological processes, as well as in the aging process. The increased formation of ROS under pathological conditions is believed to cause cellular damage through the action of these highly reactive molecules by crosslinking the proteins, mutagenizing the DNA, and peroxidating the lipids.

Examples of active oral compounds that are anti-inflammatory agents that serve to reduce one or more ROS in the oral cavity include oral care active compounds comprising at least one flavonoid compound. Flavonoids are generally described as a kind of compounds generally found in plants having the same general structure and include compounds such as flavones, flavanols, flavonols, dihydroplanons, flavonones, and derivatives thereof. In certain embodiments, anti-inflammatory agents for oral care comprise flavonoid compounds with free B-ring and / or flavanols, including flavanols. Compositions comprising flavonoids with free B-ring have been shown to inhibit the activity of the cyclooxygenase enzyme COX-2, for example. Examples of suitable anti-inflammatory agents include those extracts and compounds derived from Scutellaria baicalensis, which contains significant amounts of flavonoids with free B-ring, including baicalein, baicalin, wogonin, and baicalenoside. A description of anti-inflammatory agents useful for oral care comprising flavonoids with free B-ring can be found in U.S. Patent Application 60 / 639,329 issued to Trivedi et al., Filed December 22, 2004.

Certain anti-inflammatory agents that are active ingredients for oral care include a mixture of at least one flavonoid with free B-ring and at least one flavan. Illustrative sources of flavannes can be found in extracts derived from plants of the Fabaceae family, the Mimosoid subfamily, the Acacia genus. For example, flavan appropriate can be isolated from the Acacia catechu plant. The catechin is an example of a flavan widely found in Acacia, which presents, both alone and in combination with flavonoids, antiviral and antioxidant activity, as well as an ability to inhibit the activity of both COX-1 and COX-2 enzymes. A mixture of at least one flavonoid with free B-ring and a flavan is also suitable for use as an anti-inflammatory agent. A description of anti-inflammatory agents for oral care comprising flavonoids with free B-ring and at least one flavan is found in U.S. Patent Application 60 / 639,331 issued to Xu et al., Filed December 22, 2004 .

A commercially available active ingredient for oral care comprising at least one flavonoid with free B-ring and at least one flavan is UNIVESTIN®, which is isolated from plants of the Scutelleria genus, and is manufactured by Unigen Pharmaceuticals, Inc. (Superior, Colorado, USA). A description of the UNIVESTIN® can be found in, for example, the publication of the United States Patent Application 2003/0216481 issued to Jia. UNIVESTIN® inhibits specific enzymes that catalyze oral inflammatory pathways, such as, for example, the enzymes COX-1, COX-2, and 5-LO.

Another appropriate anti-inflammatory agent is oregano extract. As referred to hereafter, "oregano" encompasses all appropriate species and subspecies of the genus Origanum; for example, Origanum vulgare (commonly known as "oregano", "wild oregano" or "wild marjoram"), including its subspecies (Origanum vulgare ssp.), Origanum oni tes (commonly known as "Italian oregano" or "pot marjoram"). "), Origanum majorana (commonly known as" marjoram "or" sweet marjoram ") and Origanum heracleoticum. The subspecies Origanum vulgare includes the O. vulgare ssp. vulgare, O. vulgare ssp. viride, and O. vulgare ssp. hirtum (commonly known as "Greek oregano" or "wild oregano"). Active ingredients useful for oral care comprising oregano extract are explained in U.S. Patent Application 11 / 256,788, Worrell et al., Filed October 24, 2005. Another appropriate anti-inflammatory agent is magnolia extract. , derived from plants in the family Magnoliacea, such as Magnolia officinalis, which typically contains magnolol, honokiol, tetrahydromanololol, and tetrahydrohonokiol, as described in U.S. Patent Application 60 / 640,161 issued to Gaffar et al., filed 29 December 2004 In several embodiments, the anti-inflammatory agent is present in the oral compositions in an amount of from about 0.001 to about 3%, about 0.005 to about 2% and about 0.01 to about 1%.

In certain embodiments, a composition of the present invention further comprises a source of fluoride ions or fluoride-providing components, such as anries and / or anlculus agents in an amount sufficient to supply about 25 ppm to about 5,000 ppm fluoride ions. . Examples of useful fluoride ion sources include inorganic fluoride salts, such as soluble alkali metal salts. For example, in certain embodiments, the source of fluoride in the composition may be sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluorides, including olafluoride dihydrofluoride (N'-octadecyltrimethylenediamine- N, N, N '-tris (2-ethanol)), as well as tin fluoride, such as stannous fluoride.

The syntheanionic linear polycarboxylates are agents that improve efficacy for optional use in oral compositions having certain active ingredients, including antibacterial agents, anlculus or other agents active within the oral composition. Said anionic polycarboxylates are generally used in the form of their free acids, or preferably partially neutralized, or more preferably completely neutralized water-soluble alkali metal salts (e.g., potassium and preferably sodium) or ammonium. The terms "synthe and "linear" exclude known thickeners or gelatins comprising carboxymethylcellulose and other derivatives of cellulose and natural gums, and carbopoles having a reduced solubility due to crosslinks.

Preferred copolymers are 1: 4 to 4: 1 copolymers of anhydride or maleic acid or another ethylenically polymerizable unsaturated monomer, preferably methyl vinyl ether (methoxyethylene) with a molecular weight (MW) of from about 30,000 to about 1,000,000. A preferable copolymer is methyl vinyl ether / maleic anhydride. Examples of these copolymers are available from ISP Corporation under the trade designation GANTREZ®, e. g. , AN 139 (P.M. 1,100,000), AN 119 (P.M. 200,000); S-97 of Pharmaceul Quality (P.M. 1,500,000), AN 169 (P.M. 2,000,000), and AN 179 (P.M. 2,400,000); where the preferred copolymer is S-97 Pharmaceul Quality (P.M. 1,500,000). In several embodiments where a syntheanionic polycarboxylate is included in the oral composition, it is present in amounts of about 0.001 to about 5%, about 0.01 to about 4%, about 0.1 to about 3.5% or about 1 to about 3% of the composition for oral care.

Additional optional oral care compounds that can be included in the oral composition include, for example, antibacterial agents, bleaching agents, additional anti-caries and tartar control agents that were not explained above, periodontal assets, abrasives, breath fresheners, agents for the control of bad odor, desensibiladores of the teeth, salivary stimulants and combinations of the same. Specifically, a non-limiting list of additional compounds for oral care includes non-ionic bacterial agents, including phenolic and bisphenolic compounds, such as, halogenated diphenyl esters, including triclosan (2,4,4'-trichloro-2'-hydroxy diphenylether). , triclocarban (3, 4, 4-trichlorocarbanilide), as well as 2-phenoxyethanol, benzoate esters, and carbanilides Useful anlculum agents include sources of tin ions such as stannous fluoride, stannous chloride, and stannous pyrophosphate, and / or sources of zinc ions, such as zinc chloride, zinc citrate and zinc gluconate.

The oral compositions can be provided in an orally acceptable carrier or vehicle. The carrier can be in a liquid, semi-solid, or solid phase, in the form of a mouthwash, toothpaste (including toothpastes, toothpaste, and prophylaxis pastes), jams (including pills and chewing gum), medicines, films, or any other form known to someone versed in the field. The selection of specific carrier components depends on the desired shape of the product.

Conventional ingredients that can be used to form the carriers listed above are known to those skilled in the art, such as one skilled in the art would recognize, oral compositions optionally include other materials in addition to those components already described, including for example, surfactants, emulsifiers and foam modulators, viscosity modifiers and thickeners, humectants, diluents, additional pH modifiers, emollients, moisturizers, mouth feel agents, sweetening agents, flavoring agents, dyes, preservatives, solvents, such as water and combinations thereof. Any given material can serve multiple purposes between two or more of these material categories. Preferably, said carrier materials are selected for their compatibility and stability with all of the constituents of the active ingredient, including the extract of propolis and the one or more active oral care compounds selected for the oral composition.

Useful typical surfactants are disclosed in the patents referred to and discussed above, including in U.S. Patent No. 4,894,220 and U.S. Patent Application No. 11 / 256,788. Surfactants are generally an important aspect of the oral composition, since they can function as surfactants, foam modulating emulsifiers and / or dispersing agents of the active ingredient. Thus, its selection as to compatibility with the constituents of the active ingredient is important. For example, in embodiments where the oral composition has an active ingredient comprises a cationic antibacterial agent, it is preferable that the carrier comprises surfactants which are not strongly ammonic, since said ammonium components can be bound to the cationic active ingredient potentially reducing its bioavailability.

Suitable surfactants are those that are reasonably stable and foam over a wide pH range. These compounds are known in the art, and include non-soap ammonium (e.g., sodium lauryl sulfate (SLS), N-myristoyl, and N-palmitoyl sarcosine), nonionic (e.g., Polysorbate 20 (polyoxyethylene 20 sorbitan monolaurate, TWEEN 20) and Polysorbate 80 (polyoxyethylene 20 sorbitan mono-oleate, TWEEN 80), Poloxamer 407, available under the trade name Pluronic F127 from BASF Corporation), cationic, suteionic (e.g., cocoa idopropyl) betaine and lauramido propyl betaine), and synthetic amphoteric organic detergents. In embodiments where the active ingredient comprises a cationic compound, the surfactant may be chosen from: nonionic surfactants, cationic surfactants, betaine surfactants, amphoteric surfactants or mixtures thereof. In various embodiments, one or more surfactants are present in the oral composition in an amount of from about 0.001% to about 5%, or about 0.5% to about 2.5%.

In embodiments where the oral composition is in the form of a mouth rinse, an illustrative carrier is substantially liquid. The term "mouthwash" includes mouthwashes, sprays, rinses, and the like. In such a preparation the orally acceptable carrier typically has an aqueous phase comprising either water or a mixture of water and alcohol. In addition, in various embodiments, the oral carrier typically has a humectant, surfactant and / or pH regulating agent.

Depending on the extraction process and the concentration of the propolis extract used in the oral composition, it is possible that the odor and / or taste of the propolis extract is not aesthetically pleasing to some consumers. Thus it is desirable to formulate an oral composition comprising components that reduce any adverse perception of the propolis extract. This can be achieved by including relatively strong flavoring and / or sweetening agents in the oral composition. In addition, in some embodiments the flavoring agent can provide and / or improve the flavors associated with the bee products. Illustrative flavoring substances include those known to one skilled in the art and present in certain embodiments at a concentration of about 0.05% by weight to about 5% by weight.

In embodiments where an oral composition is in the form of a confection, an illustrative carrier is substantially solid or semi-solid. Carriers of jams are known in the industry. For a pellet, the carrier typically comprises a base material for the pellet (for example, comprising a non-cariogenic polyol and / or starch / sugar derivatives), an emulsifier, a lubricant, a flavoring agent, a thickener and optionally a coating material. The carriers of chewing gum generally they have a chewing gum base, one or more plasticizing agents, a sweetening agent, and a flavoring agent.

In embodiments where an oral composition is in the form of a film, an illustrative carrier is substantially solid or semi-solid. Generally, said film carriers comprise a film-forming or water-dispersing agent, such as a hydrophilic polymer. Optionally, the film carrier can also comprise hydrophobic film-forming polymers, either with a removable backing layer or mixed with a hydrophilic film-forming polymer. Film carriers optionally comprise additional ingredients such as plasticizers, surfactants, fillers, bulking agents, and viscosity volumizing agents.

In embodiments where an oral composition is in the form of a dentifrice, an illustrative carrier is substantially solid or semi-solid. Dentifrices typically contain surfactants, humectants, viscosity modifying agents and / or thickeners, abrasives, solvents, such as water, flavoring agents and sweetening agents.

In certain embodiments, an oral composition is in the form of a medicament, such as a non-abrasive gel or a gel that can be applied to the sulcus or gingival margin and used in conjunction with wound dressings, gauze, films, and the like. Such gels can include both aqueous and non-aqueous gels. Aqueous gels generally comprise a polymer base, a thickener, a humectant, a flavoring agent, a sweetening agent and a solvent, typically including water.

In several embodiments, an oral composition is provided within a single component or phase. In other embodiments, the oral composition includes both a first and a second component that are separately maintained. Maintaining the components separately requires only that the components be maintained in such a manner as to substantially prevent the interaction of one component of the oral composition with another component of the oral composition. Typically, a double component oral composition is employed when there is one or more ingredients included in the oral composition. For example, if the active ingredient comprises a second constituent comprising a cationic antibacterial active ingredient, it is advantageous to keep the cationic compound separately from strongly anionic components, such as anionic surfactant ingredients. The separation of components it can be achieved by any means known in the art and includes chemical, physical and mechanical separation means or any combination thereof. For example, the first and second components can be combined but certain components can be maintained separately by wrapping or encapsulating one or both in a film, coating, capsule, micelle, etc.

In several embodiments, a method promotes oral health in an oral cavity and treats plaque on an oral surface of a mammalian subject. In some embodiments, a method of providing one or more oral health benefits of a cavity or a mammalian subject comprises preparing an oral composition in accordance with any of the various embodiments described above, wherein an active ingredient comprises an extract of propolis, a compound active for oral care and a source of fluoride ions. Various embodiments are directed to a method of preventing bacteria from forming a biofilm on an oral surface, a method of suppressing an immune system recognition of an antigen by an oral surface of a mammal, a method of reducing an immune system response. , a method of suppressing the production of one or more mediating methods of inflammation on an oral surface. In these embodiments, the prepared oral composition is brought into contact with an oral surface. The oral composition that Contains the active ingredient comprising an extract of propolis may provide one or more oral health benefits, such as anti-gingivitis, antiperiodontitis, anticaries, antisera, anti-inflammatory, analgesic, anti-aging, and breath freshening.

Thus, any of the various embodiments of the oral care composition described above can be contacted or applied regularly to a surface at least once a day for a period. As used herein, a "period" may refer, for example, to once a day, multiple days a week, or on a long-term daily or weekly basis, or even for the rest of life.

Several embodiments of the present re refer to methods of preparing oral compositions. Propolis extract is a natural product, containing sensitive compounds that can potentially be denatured or damaged by heat treatment. Thus, certain embodiments are directed to methods of making an oral composition comprising mixing one or more carrier ingredients to form a homogeneous mixture and adding an extract of propolis to the homogeneous mixture at temperatures of less than about 40 ° C to form the composition oral. In several incorporations the propolis extract can be added to the oral composition at room temperature, e. g. , less than around 30 ° C or less or equal to around 25 ° C.

Oral compositions can be prepared by mixing the ingredients appropriately. For example, in the preparation of a mouthwash, the propolis extract can be dispersed in a flavoring oil or in an alcohol and then added to a mixture of humectants, surfactants, and water. The resulting rinse product is packaged.

Toothpastes are typically prepared by adding various salts (including fluoride salts, when included in the composition) and sweeteners (e.g., saccharin), and any compound of water-soluble oral care active ingredients, where they are mixed. In another package, all humectants, gums, and polymers can be added together. The aqueous base mixture described above is added to the package with the humectants, gums and polymers. The combined ingredients are optionally heated to a temperature of more than about 40 ° C, for example from about 60 ° C to about 70 ° C, to disperse gums and polymers. The heated mixture is then cooled to less than about 38 ° C (around 100 ° F). The mixture is then combined with abrasive products, where it is mixed at high speed for about 15 to about 20 minutes. The extract of Propolis is mixed with the flavoring oil (and / or alcohol), as are any lipophilic oral care active ingredients. The mixture is mixed with the above water-based mixture, where it is mixed under high speed under vacuum until it is sufficiently dispersed. The surfactant (s) is added and the mixture is mixed once more to disperse it.

In certain embodiments, a method of preparing an oral composition comprises adding an additional oral care active ingredient to the one or more carrier ingredients before mixing. In other embodiments, an additional oral care active ingredient with propolis extracts is added to the homogeneous mixture. Whether the additional active oral care compounds are added to the one or more carrier ingredients before mixing them to form a homogeneous mixture or added to the mixture with the propolis extract after mixing them, will depend on the nature of the additional active ingredient ( for example, if it can withstand heating at a temperature greater than or equal to around 40 ° C and whether it is hydrophobic, hydrophilic, anionic, cationic, or non-ionic). One skilled in the art can easily determine the appropriate point in the method of making the oral composition to add the active ingredients, based on these considerations. For example, in certain additions, when the additional constituent in the active ingredient for oral care comprises a source of fluoride ions the one or more carrier ingredients can be added before mixing them because it is soluble in water.

The oral composition can be incorporated into jams and tropes. Said methods of forming confections (e.g., chewing gum) or something to suck (e.g., pills) are known to one skilled in the art, they can be prepared, for example, by stirring the extracts of propolis and another compound (s). ) active (s) for oral care inside hot gum or coating the outer surface of a gum base (eg, jelly, rubber latex, vinyl resin, among others), desirably with conventional plasticizers or softeners, sugar or other sweeteners or carbohydrates such as glucose, sorbitol and the like. In certain embodiments, the propolis extract is added to the gum base when it is at a temperature less than or equal to about 40 ° C.

When the oral composition is in the form of a film, it can be formed by a series of conventional film forming processes, such as conventional extrusion or solvent-casting processes. For example, to prepare a film by solvent molding, a film forming polymer is dissolved in a Sufficient amount of a solvent that is compatible with the polymer. After a solution has been formed, a plasticizer can be added by stirring, and heat can be applied if necessary to aid dissolution until a clear and homogeneous solution has been formed followed by the addition of the active ingredients, including the Propolis extract, surfactants, bulking agents, and any other ingredients such as flavors and sweeteners at a temperature of, for example, less than about 40 ° C. For ease of use, the dried film can be cut into pieces of an appropriate size and shape and packaged in an appropriate container.

The oral compositions are applied to one or more oral surfaces in the oral cavity, and promote general oral health, including inhibition of plaque formation, gingivitis, periodontitis, halitosis, and the like. In certain embodiments, the oral composition inhibits the growth of various oral bacteria and also provides one of the following: anti-inflammatory activity, destruction of the biofilm and / or anti-adhesion activity. Thus, certain oral compositions simultaneously provide multiple benefits for oral care.

The present invention is further illustrated in the following non-limiting example: EXAMPLE 1 A composition according to the present invention was prepared with the following constituents:

Claims (33)

1. An oral composition comprising: an extract of propolis; an active component for oral care chosen from: a cationic antibacterial agent, an anti-adhesion agent, a biofilm destruction agent or an anti-inflammatory agent; Y a source of fluoride ions.

2. An oral composition as claimed in clause 1, characterized in that the propolis extract is present in an amount of about 0.0001 to about 3%.

3. An oral composition as claimed in clause 1, characterized in that it also comprises a polyhydric compound and water.

4. An oral composition as claimed in clause 1, characterized in that the extract of propolis comprises one or more active compounds derived from a source of propolis in an amount of about 1 to about 5% by weight of the propolis extract.

5. An oral composition as claimed in clause 1, characterized in that it also comprises a linear polymeric anionic polycarboxylate.

6. An oral composition as claimed in clause 5, characterized in that the linear polymeric anionic polycarboxylate is an anionic polymeric copolymer of methyl vinyl ether and maleic anhydride.

7. An oral composition as claimed in clause 1, characterized in that the active compound for oral care is a cationic antibacterial agent selected from benzethonium chloride, octenidine, hexetidine, hexamidine, cetyl pyridinium chloride, alexidine, alkyl salts amino acid esters of Na-acyl or mixtures thereof.

8. An oral composition as claimed in clause 7, characterized in that the active compound for oral care is chosen from: l-lcocoyl-L-arginine methyl ester, Na-cocoyl-L-arginine ethyl ester, Na-cocoyl-L-arginine propyl ester, Na-stearoyl-L-arginine methyl ester, ethyl ester of Na-stearoyl-L-arginine, ethyl ester of Na-lauroyl arginine, salts or mixtures thereof.

9. An oral composition as claimed in clause 1, characterized in that the active compound for oral care comprises ethyl lauroyl arginine ester hydrochloride (ELAH) or cetyl pyrindinium chloride (CPC).

10. An oral composition as claimed in clause 1, characterized in that the active compound for oral care is chosen from: enzymes, histatin, furanone, and derivatives or mixtures thereof.

11. An oral composition as claimed in clause 1, characterized in that the active compound for oral care is chosen from: indometicine, flurbiprofen, ketoprofen, ibuprofen, naproxen, meclofenamic acid, at least one flavonoid with free B-ring , a mixture of at least one flavonoid with free B-ring and at least one flavan, an extract of magnolia, or mixtures thereof.

12. An oral composition as claimed in clause 7, characterized in that the cationic antibacterial agent is present in an amount of from about 0.001 to about 3% by weight.

13. An oral composition as claimed in clause 1, characterized in that the source of fluoride ions is chosen from sodium fluoride, sodium monofluorophosphate or mixtures thereof.

14. An oral composition as claimed in clause 1, characterized in that it is in the form of a mouthwash, toothpaste, jam, medicament or film.

15. An oral composition as claimed in clause 1, characterized in that it also comprises one or more carrier ingredients selected from: surfactants, viscosity modifiers, thickeners, humectants, diluents, pH modifying agents, emollients, moisturizers, agents which provide a mouthfeel, sweetening agents, flavoring agents, solvents, water, dyes or preservatives.

16. An oral composition as claimed in clause 1, characterized in that the active compound for oral care is an anti-adhesion agent present in an amount of about 0.001 to about 3% by weight.

17. An oral composition as claimed in clause 1, characterized in that the active compound for oral care is an anti-inflammatory agent comprising a non-spheroidal anti-inflammatory drug (NSAID).

18. An oral composition as claimed in clause 17, characterized in that the anti-inflammatory agent is chosen from: indometycin, flurbiprofen, ketoprofen, ibuprofen, naproxen, meclofenamic acid, at least one flavonoid with free B-ring, a mixture of at least one flavonoid with free B-ring and at least one flavan, an extract of magnolia or mixtures thereof.

19. An oral composition as claimed in clause 17, characterized in that the anti-inflammatory agent is present in an amount of from about 0.001 to about 3% by weight.

20. An oral composition as claimed in clause 1, characterized in that the active compound for oral care comprises a biofilm destruction agent chosen from: an enzyme, histatin, furanone or derivatives or mixtures thereof.

21. An oral composition as claimed in clause 20, characterized in that the biofilm destruction agent comprises a protease enzyme.

22. An oral composition as claimed in clause 21, characterized in that the enzyme is a papain or ficin.

23. An oral composition as claimed in clause 20, characterized in that the biofilm destruction agent is present in an amount of about 0.001 to about 3% by weight.

24. An oral composition as claimed in clause 1, characterized in that it further comprises a carrier comprising a surfactant selected from: nonionic surfactant, cationic surfactant, betaine surfactant, amphoteric surfactant or mixtures thereof.

25. A method of preventing bacteria from forming a biofilm on an oral surface comprising the step of applying to said oral surface a composition comprising an oral composition in accordance with clause 1.

26. A method of suppressing a recognition by the immune system of an antigen on an oral surface of a mammal, which comprises administering a composition according to clause 1 to said oral surface.

27. A method of reducing an immune system response comprising applying a composition in accordance with clause 17 to an oral surface.

28. The method as claimed in clause 27, characterized in that the response of the immune system is inflammation.

29. A method of suppressing the production of one or more mediators of inflammation on an oral surface, which comprises applying an oral composition in accordance with clause 1 to an oral surface.

30. A method of maintaining or increasing the systemic health of a mammal, which comprises applying a composition according to clause 1 to an oral surface of said mammal at least once a day for at least 2 days.

31. A method of preparing an oral composition, which comprises: mixing one or more carrier ingredients to form a homogeneous mixture; add a source of fluoride ions to the mixture; adding at least one of: a cationic antibacterial agent, an anti-adhesion agent, a biofilm destruction agent or an anti-inflammatory agent; Y add an extract of propolis to the homogeneous mixture at temperatures less than or equal to about 40 ° C to form the oral composition.

32. A method as claimed in clause 31, characterized in that the mixture of one or more carrier ingredients occurs at a temperature greater than or equal to about 40 ° C.

33. A method as claimed in clause 31, characterized in that the one or more carrier ingredients are chosen from among: surfactants, viscosity modifiers, thickeners, humectants, diluents, pH modifying agents, emollients, moisturizers, agents that provide a mouthfeel, sweetening agents, flavoring agents, solvents, water, dyes and preservatives.