CN101132806A - Method of reducing oral tissue inflammation using magnolia extract - Google Patents
Method of reducing oral tissue inflammation using magnolia extract Download PDFInfo
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- CN101132806A CN101132806A CNA2005800487933A CN200580048793A CN101132806A CN 101132806 A CN101132806 A CN 101132806A CN A2005800487933 A CNA2005800487933 A CN A2005800487933A CN 200580048793 A CN200580048793 A CN 200580048793A CN 101132806 A CN101132806 A CN 101132806A
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Abstract
A method for treating a mammal having oral tissue inflammation is provided, where the inflamed oral tissue is contacted with a safe, efficacious, non-irritating oral composition having an anti-inflammatory agent comprising a magnolia extract. The magnolia anti-inflammatory active ingredient reduces one or more mediators of inflammation and reduces inflammation in oral tissue. The oral composition can be in the form of a mouth rinse; dentifrice, including toothpaste, gels, powders, lozenges; medicament gel; animal products; and the like.
Description
Related application is introduced
The application has required the priority of the U.S. Provisional Patent Application sequence number 60/640,161 of December in 2004 submission on the 29th, and its content here is introduced into as a reference.
Background of invention
Gingivitis is to support the gingiva of tooth and the inflammation or the infection of alveolar bone.Gingivitis is considered to usually by the antibacterial in the mouth (antibacterial that causes during particularly plaque forms) and caused as the toxin that by-product forms by antibacterial.Think that this toxin has caused the inflammation of oral cavity tissue in the mouth.Comparing periodontitis with gingivitis is running down the stage of disease, and in this stage various focusing depths represented and begin from the tooth atrophy and form periodontal pocket, it finally may cause skeleton and pericemental destruction.Support the bacterial infection of the structure of dentition can comprise gingivitis and periodontitis, but also may comprise for example infection of mandibular bone of skeleton that surgical operation causes.Further, oral tissue inflammation can be by surgical operation, local damage, wound, necrosis, oral hygiene or a plurality of systematic root are caused improperly.
It has been generally acknowledged that the cellular component that these diseases and state are involved comprises epithelial tissue, gingival fiber archeocyte and circulation leukocyte, these all cellular components all help main body to being responded by the virulence factor that antibacterial produced.The modal bacterial pathogen relevant with these oral cavity infections is streptococcus (for example, Streptococcus mutans), the unicellular bacterium of porphyrin, Actinobacillus, lopsided bacterium and staphylococcus, Fusobacterium nucleatum, the flourish Salmonella of Xiao Wei, actinomyces naeslundii and the unicellular bacterium of porphyromonas.Though bacterial infection often is the etiology incident in many above-mentioned oral diseases, the pathogeny of these diseases mediates by the main body response.The circulation of polymorphonuclear neutrophisls (PMNs) is to cause infection site ergogenic main cause to occur.Became functionalization and discharge toxic chemical substance of PMNs and other inflammatory cellular mediators thing usually, this is to cause the destructive partly cause of infection focus surrounding tissue.
Therefore, the bacterial infection of oral cavity tissue has stimulated the immunoreation of main body and has caused that by rise the inflammatory mediators of tangible tissue injury has weakened healing process.The arachidonic acid metabolite of called after prostaglandin and leukotriene is the mediators that a kind of its effect to inflammatory response has been studied widely, and they produce by cyclo-oxygenase or lipoxygenase pathway.These metabolite are considered to the main mediators in gingivitis, periodontitis, osteomyelitis and other inflammation disease.
The various compositionss that are used to prevent and treat the oral inflammation that is caused by bacterial infection have been described in the prior art.Particularly, for the accumulation of the inflammatory mediators that prevents to be derived from arachidonic acid pathway, nonsteroidal anti-inflammatory drug (NSAIDs) has been successfully used to treat the patient who suffers from by caused periodontal of arachidonic acid metabolite and inflammation disease.Test and clinical data have shown that indometacin, Flurbiprofen axetil, ketoprofen, ibuprofen, naproxen and meclofenamic acid have the significant effect of improving to the minimizing of prostaglandin and leukotriene in injury of alveolar bone and the odontopathy model.Yet a major defect that often uses NSAIDs is possible cause pained, gastric ulcer, gastrointestinal hemorrhage and toxicity.
Other Therapeutic Method comprises that use antimicrobial therapeutics and antibiotic are to eliminate potential infection.These treatments are worked to reducing stimulus (antibacterial), but can not influence the immunne response of main body to the secreted toxin of antibacterial easily.In addition, some antibiotic and other antimicrobial therapeutics may cause the ulcer of oral mucosa, cause spalling gingivitis, decolouring, the long-time use potential antibiotic resistance in back and owing to stimulate caused tissue inflammation to worsen.Need a kind of nonirritating antiinflammatory composition for oral cavity that can in the ill mammalian object that day by day increases, reduce oral tissue inflammation effectively.
Summary of the invention
In one embodiment, provide a kind of treatment to suffer from the method for the mammalian object of oral tissue inflammation.This method comprises that the oral cavity tissue that makes inflammation contacts with composition for oral cavity, and described composition for oral cavity comprises anti-inflammatory activity composition and the oral cavity acceptable carrier of being made up of extract of magnolia basically.This composition for oral cavity is by reducing the inflammation that one or more inflammatory mediators reduce oral cavity tissue.
In another embodiment, provide a kind of method that reduces oral tissue inflammation in the mammalian object.The oral cavity tissue of inflammation is contacted with composition for oral cavity, and described compositions comprises basically the anti-inflammatory activity composition and the oral cavity acceptable carrier of the non-quantity of stimulus of being made up of extract of magnolia.This composition for oral cavity does not stimulate the oral cavity tissue of inflammation, and by reducing the inflammation that one or more inflammatory mediators further reduce oral cavity tissue.
In an embodiment of the invention, provide a kind of treatment to suffer from the method for the mammalian object of oral tissue inflammation.This method comprises that the oral cavity tissue that makes inflammation contacts with composition for oral cavity, and described composition for oral cavity comprises anti-inflammatory activity composition and the oral cavity acceptable carrier of being made up of extract of magnolia basically.This composition for oral cavity reduces inflammation by reducing one or more inflammatory mediators.The oral cavity acceptable carrier comprises that one or more are selected from the orally active composition of antitartar agents, antibacterial, caries preventive agent, brightening agent, desensitizer, vitamin, suitable enzyme, flavorants, deodorant and combination thereof.
Have been found that the compositions and methods of the invention by provide safety, stable, non-irritating and efficiently oral care composition be better than oral cavity of the prior art anti-inflammatory composition as antiinflammatory and pain management.Further, described composition for oral cavity comprises natural and from the antiinflammatory component of plant source.The description of carrying out has here shown the further purposes of the present invention, benefit and embodiment.
Detailed Description Of The Invention
The invention provides a kind of method for the treatment of the mammalian object of suffering from oral tissue inflammation in the oral cavity.This method comprises and comprises safe, effective and nonirritating composition for oral cavity and contact.
" inflammation " of oral cavity tissue typically refers to the localised protection that the causes reaction by the damage of tissue or destruction, it is used for destroying, dilution or isolate the infringement agent and wounded tissue the two.In acute form, it is characterized in that pain, heating, rubescent, swelling and afunction.Chronic inflammatory disease is that process and principal character are to form new connective tissue slowly.The low level form of the prolongation of normally acutely inflamed continuation of chronic inflammatory disease or inflammation (for example relevant form) and cause nonvolatil histologic lesion usually with periodontitis or gingivitis.On the histology, inflammation relates to complicated series of events, comprises arteriole, blood capillary and thin vein expansion with permeability and blood flow increase; Fluidic oozing out, described fluid comprises plasma protein, and leukocyte is to the migration of inflammation part.Inflammation is corresponding to the short inflammatory cell mediators that has improved or the level of cell h substance, for example, and as antigen and antibody results of interaction or the effect by antigen and primed lymphocyte.
In some embodiments, when composition for oral cavity was contacted with oral cavity tissue, it provided the analgesic effect to inflamed oral tissue, had therefore reduced pain and sensitivity in the mammalian subject cavity tissue.In some embodiments, repeat contacting of oral care composition and inflamed oral tissue termly.
Therefore, in numerous embodiments of the present invention, the composition for oral cavity that will comprise Drymotaenium miyoshianum (Mak.) Mak. with the concentration that reduces one or more inflammatory cellular mediators deposits yields is applied to the oral cavity tissue position of inflammation.In numerous embodiments of the present invention, the anti-inflammatory magnolia active component of composition for oral cavity has suppressed the formation of multiple short scorching mediators simultaneously, and described short scorching mediators for example is PGE
2With TNF-α the two.Each independent mediators has different mechanism usually aspect the pathogeny of disease.
Therefore, In some embodiments of the present invention, contain the composition for oral cavity that comprises Drymotaenium miyoshianum (Mak.) Mak. anti-inflammatory activity composition and can further play following effects, promptly offset molten effect of inherent atrophic debility of bones and counteracting because cellular mediators molecule, for example PGE
2Caused with excessive generation and the activity of TNF-α to osteoplastic inhibition.By this way, some embodiment of the present invention provides and has been used to reduce alveolar bone loss, tooth loss and by wound and/or stand the destructive method to jawbone that patient infection caused of inflammation, and the composition for oral cavity of its numerous embodiments of the present invention by will comprising extract of magnolia is applied directly to affected inflamed oral tissue surface and realizes.
In numerous embodiments, composition for oral cavity comprises the antiinflammatory of following concentration, can reduce one or more short scorching mediators, for example PGE under this concentration significantly
2Generation with TNF-α.Yet just as recognized by those skilled in the art, the formation that suppresses this cellular mediators fully also may be harmful to mammalian object, thereby according to some embodiment of the present invention, production of cytokines is not suppressed fully.Therefore, in numerous embodiments, the extract of magnolia active component is present in the composition for oral cavity with finite concentration, this concentration can prevent one or more inflammatory mediators (it has stoped the intrinsic mechanism of chronic disease) overexpression, but still allows the mediators molecule (it is polyphenic) of certain expectation fully to produce to keep homeostasis and normal cell function on datum-plane.
The source of oral tissue inflammation comprises bacterial infection, surgical operation, local wound, wound or necrosis, a plurality of system cause of disease that cause or non-disease association for example oral sanitary habit or the tooth hygiene custom improperly of excessive erosion.Increase relevant oral disease with inflammatory cellular mediators thing activity, the indefiniteness example of state and obstacle comprises gingivitis, periodontitis, stomatitis, because neutrophils reduces the loss of tooth that is caused, dental pulp disease and sequela thereof, acute and chronic stomatocace, fusospirillary gingivitis, the molten damage that disappears (resoprtive legions) of osteoclast/ondontoclast mediation, dental caries, the wounds delay healing, acute and the chronic osteomyelitis of periodontal bone injury and jawbone.
In some embodiments, the present invention is used to prophylactic generation.Here employed term " prevention " is relevant with the prophylactic treatment to the oral cavity of mammalian object, the composition for oral cavity of this treatment by will comprising the anti-inflammatory activity composition with have inflammation, oral cavity tissue ill or the damage tendency contacts and realizes.
In some embodiments, providing a kind of is used for the treatment of in oral disease and obstacle and the oral cavity and the raise method of relevant state of inflammation, infection and one or more short inflammatory cell mediators levels." treatment " is included in the inflammatory reaction generation that caused by disease or the patient's condition or health and applies the composition for oral cavity that comprises extract of magnolia after manifesting.By treatment, Inflamed tissue, inflammation, disease or state improve or are prevented to the state development that worsens.For example, after the inflammation cascade event takes place, apply extract of magnolia and comprised " treatment " to disease or inflammatory/infectious symptoms.
In some embodiments, Therapeutic Method comprises the extract of magnolia that will treat effective dose over a period to come with the administration of multiple interval, the described regular period be from a week to throughout one's life.For example, the conventional method of oral disease, state and obstacle that treatment is relevant with inflammation, infection and the rising of one or more inflammatory mediators levels comprises the composition for oral cavity that comprises extract of magnolia of the useful amount of drug treatment, and this administration is based on every day.
In numerous embodiments, use with contact can be with washing, apply, brush or use suitable cladding material cambium layer.Further, the accidental contact during contact can be included in and eat or chew.In a plurality of embodiments, using of compositions comprises the use bringing device, described bringing device makes the anti-inflammatory activity composition that comprises extract of magnolia and is maintained to abundant length the time of contact between the destination organization, so that allow one or more inflammatory mediators, for example PGE
2With TNF-α, propagation carry out the pharmacology and suppress.
The invention provides a kind of efficient composition for oral cavity that is used for reducing the mammalian object oral tissue inflammation.This composition for oral cavity comprises anti-inflammatory component and oral cavity acceptable carrier, and described anti-inflammatory component is made up of extract of magnolia basically.
Here " oral care composition " of indication is to be suitable for administration or to be administered to the mammalian subject chamber reaching the arbitrary composition of oral cavity tissue on every side.In numerous embodiments, oral care composition is in order to swallowing, but keeps the sufficiently long time to produce the effectiveness of expection in the oral cavity.In some embodiments, particularly in animal product, provide in the embodiment of composition for oral cavity at those, for example pet food, feed for pet additive be (for example for described animal product, therapeutic agent) or chew toys, described composition for oral cavity can be to be ingested the harmless low concentration of animal.Preferably, being used for concrete material of the present invention and compositions is that pharmacy or cosmetics are acceptable.As used herein, " oral cavity is acceptable " like this or " cosmetics are acceptable " component are suitable for the people and/or animal is used, thereby desired therapeutic, prevention, sense organ, modification or dressing effect are provided and the component of adverse side effect (for example toxicity, stimulation and anaphylaxis) improperly can not occur, described effect and rational benefit/risk are than matching.The invention provides the oral care composition that utilization will have active component and be used to have the people of inflamed oral tissue or the method that other mammalian object is used to provide therapeutic effect, described active component comprises extract of magnolia.
Compositions of the present invention comprises extract of magnolia.Go out as referred to here, this Drymotaenium miyoshianum (Mak.) Mak. " extract " is from Magnoliaceae, synthetic or the semi-synthetic equivalent of for example Cortex Magnoliae Officinalis (Magnolia officinalis) (hereinafter referred to as " the Drymotaenium miyoshianum (Mak.) Mak. ") dried cortex of plant or the extract of bark, or this extract or its active component or chemical compound.Preferably, the active substance that Drymotaenium miyoshianum (Mak.) Mak. cortex (Cortex Magnoliae Officinalis bark) extract contains comprises magnolol, honokiol, tetrahydrochysene magnolol and tetrahydrochysene honokiol, and it demonstrates sterilization idiocratic to Streptococcus mutans in external minimal inhibitory concentration (MIC) test.Should be understood that any plant from Magnoliaceae family all is suitable for the present invention and can uses in alternate embodiment, therefore described extract preferably comprises the chemical compound that is selected from magnolol, honokiol, tetrahydrochysene magnolol, tetrahydrochysene honokiol and composition thereof of antimicrobial valid density.
Extract of magnolia has reduced the expression of the short scorching mediators in one or more oral cavity tissues, cytokine particularly, the nitrogen oxide that comprises prostaglandin, leukotriene, tumor necrosis factor-alpha (TNF-α), interleukin and use in vitro tests cell culture is induced the expression of form.Extract of magnolia has also reduced the infiltration of PMN to the position that is difficult to use animal model.
Here use, " extracting (extracting) " of solid or fluent material or " extracting (extraction) " meaning are that material is contacted with appropriate solvent to send the material that hope is extracted from material.When material is solid, preferably its with it is carried out drying, pulverizing or grinding before solvent contacts.Such extraction can be undertaken by conventional process well known by persons skilled in the art, and for example, by using extraction element, such as apparatus,Soxhlet's, it is retained in solid material in the memorizer and allows solvent streams to cross described material; Perhaps by solvent and material mixing are in the same place, then with liquid phase and solid phase or two kinds of immiscible liquid phase separation, for example by filtering or separating with decant by sedimentation.
In one embodiment, extract of magnolia is made by exsiccant magnolia plant bark, and can prepare by using appropriate solvent to extract bark.Preferred solvent comprises methanol, ethanol, dichloromethane, hexane, cyclohexane extraction, pentane, petroleum ether, chloroform, hydrochloric acid, ethylene dichloride and hydrofluoroalkane, such as 1,1,1, and 2-tetrafluoroethane or HFA-13A.Usually, a plant tissue (dry basis) is with about 5 to about 50 parts, preferred about 15 parts are extracted to about 30 parts solvent use extraction element, solvent contacts with bark to obtain spissated slurry in described extraction element, make described slurry accept the processing of the other extraction step of one or more use different solvents then, further concentrate the initial slurry that obtains with the time by an elongated segment, the time of described prolongation is preferably about 6 hours to about 1-2 days, more preferably about 1 day.In the extracting method of a simplification, with the Drymotaenium miyoshianum (Mak.) Mak. bark of the drying of powder type, pulverizing and hydrofluoroalkane (for example 1,1,1,2-tetrafluoroethane (HFA-13A)) contact to be forming spissated final extraction, and described extraction has produced the extract of the magnolol that contains have an appointment 5 to about 50% honokiol and about 5 to about 50%.
In preferred embodiment, the natural extract active component that is used for oral care composition is reproducible, stable and has microbiological safety.In an embodiment of the invention, extract of magnolia is by using carbon dioxide (CO
2) supercritical fluid extraction (SFE) isolating.Supercritical fluid is to have between the gas of " routine " state and the gas of the characteristic between the liquid.The characteristic of supercritical fluid has been controlled in the variation of pressure, its can from more as the qualitative change of gas to more as the character of liquid, this depends on its application.Supercritical fluid uses easily and obtains, cheap and environmentally safe solvent (CO
2And H
2O).Carbon dioxide is nontoxic, unexplosive, easy acquisition and removes from extract product easily.Arriving that the operative temperature of SFE is normally low is medium.Therefore, SFE has produced solvent-laden hardly product, and has further avoided any possible aging reaction.
The natural impurity that may be present in other extracting method can not be present in the product of SFE extraction usually.For example, chemical compound makes cholic acid and alkaloid such as pocket, and for example magnocurarine and tubocurarine are maintained at low concentration (for example, usually less than percent 0.0002).Therefore, extracting with SFE in the embodiment of Drymotaenium miyoshianum (Mak.) Mak., extract is substantially free of because the chemical modification that heating and water are caused does not exist solvent residues and other artifact.
Further, some magnolia SFE extract is that cosmetics are acceptable in the extreme.Some Drymotaenium miyoshianum (Mak.) Mak. extracting method has produced dun product, so even described product also is difficult to be formulated in the oral care composition under low concentration owing to color deeply.In some embodiments, SFE extracts and has made the extract of magnolia (bright cream-coloured product) of brighter color, and it is specially adapted to aesthetic charming oral cavity composition preparation.
In numerous embodiments, preferred active antibacterial composition comprise magnolol, honokiol one of them, perhaps the two all comprises.Magnolol and honokiol are the xenol chemical compounds of nonionic, and its structure is thought as follows:
Magnolol
Honokiol
In addition, tetrahydrochysene magnolol and tetrahydrochysene honokiol are the hydrogenated analogs of magnolol and honokiol, find that they often are present in the extract of magnolia with less relatively concentration, therefore can be included in the anti-inflammatory component.
Therefore, as will be described in greater detail below, in numerous embodiments of the present invention, the extract of magnolia of effective dose comprises one or more reactive compounds: magnolol, honokiol, tetrahydrochysene magnolol and tetrahydrochysene honokiol and composition thereof, described reactive compound is used in the oral cavity by the caused inflammation part of infection, environmental toxin or wound, to suppress the excessive generation of inflammatory cellular mediators thing in the oral cavity tissue.The extract of magnolia of effective dose has reduced the level or the activity of short scorching mediators fully, in by the oral cavity tissue of treatment target, the concentration in the mammalian object being reduced to datum-plane, and unnecessarily do not suppress the activity of mediators between all cells.
In numerous embodiments, extract of magnolia of the present invention comprises magnolol, honokiol with about 2% to about 95% amount, or its both.In other embodiments, extract of magnolia includes magnolol, honokiol with about 5 to about 50% amount, or its both.In an embodiment of the invention, magnolol exists with about amount of 30 to 50%.In another embodiment, honokiol is with about amount of 10 to 50%, more preferably exists with 30 to 50% amount.Wherein those useful here extract of magnolia are commercially available acquisitions.A kind of such extract extract to obtain by HFA-13A, and it comprises about 37% magnolol and about 15% honokiol.
In addition, the concentration of extract of magnolia depends on the relative concentration of reactive compound in the extract in oral care composition, therefore, can expect that the amount that extract of magnolia exists can change with the amount that those skilled in the art approved.The concentration of active component generally depends on the form of composition for oral cavity.For example, based on easy dispersion, the active component that mouthwass (mouthrinse) generally has relatively low concentration, and dentifrice, gel or dentifrice have higher concentration to obtain identical dosage delivered.Similarly, confectionery composition generally has the concentration range of active component of relative broad so that they are in dissolving or can disperse fully when being chewed.
Though the restriction of the theory of the present invention that do not carry the baby it has been generally acknowledged that near extract of magnolia bactericidal level the target location (minimum inhibitory concentration) (conjugate by magnolol, honokiol or two reactive compounds is measured) in the oral cavity arrives between about 20 μ g/mL (ppm) at about 10 μ g/mL (mg/kg or 1,000,000/(ppm)).For example, can infer in some cases that for the residual activity chemical compound in the oral cavity, minimum inhibitory concentration (MIC) or bactericidal level approximately are between about 16 μ g/mL (ppm) at about 8 μ g/mL (ppm).
In extremely sensitive tissue, the Drymotaenium miyoshianum (Mak.) Mak. of high concentration may cause potentially to be stimulated and exacerbate inflammation, rather than reduces it.Though the state that the probability of additional inflammation depends on single object with to the reaction of stimulus object and other variable relevant with treatment, preferably extract of magnolia is offered described object with nonirritating concentration." nonirritating " meaning is meant with contacting of the composition for oral cavity with active component and does not increase ulcer, pain, rubescent or coarse that also do not increase the weight of or worsen the inflammation of oral cavity tissue, wherein said active component comprises extract of magnolia.
Therefore, though extract of magnolia has both sterilization and antiphlogistic effects is useful, in some cases, the concentration of the nonirritating antiinflammatory of Drymotaenium miyoshianum (Mak.) Mak. may be lower than bacteriocidal concentration.Further, Drymotaenium miyoshianum (Mak.) Mak. may make the tooth decolouring under high concentration.Therefore, in some embodiments of the present invention, extract of magnolia has relatively low target dosage delivered to Inflamed tissue, and can estimate by the residual concentration of the magnolia active compounds in the plaque samples of compiling after using a hour.For example, in some embodiments, the concentration of magnolol and/or honokiol is less than about 20 μ g/mL.In other embodiment, the extract of magnolia that is present in the plaque samples of compiling is lower than about 10 μ g/mL.In some embodiments, extract of magnolia is present in the bacterial plaque of compiling with the concentration that is lower than about 5 μ g/mL.Under each concentration, extract of magnolia all has antiphlogistic effectiveness.In some embodiments, anti-inflammatory magnolia active is sent having concurrently under the relatively low concentration of antiphlogistic effects and fungistatic effect.In other embodiment, anti-inflammatory magnolia active is lower than bactericidal level and only provides anti-inflammatory efficacy to Inflamed tissue owing to dosage.
In other embodiment of the present invention, extract of magnolia is present in the oral care composition with about 0.001 to about 10% amount.Just as recognized by those skilled in the art, above-mentioned concentration depends on the concentration of active component.In one embodiment, extract of magnolia is present in the oral care composition with about 0.001 to about 3% amount.In other embodiment, extract of magnolia exists with the amount less than 1%, and for example extract exists with the concentration of about 0.01 to about 1% amount.In a preferred implementation, extract of magnolia is present in the oral care composition with about 0.3% concentration.
In numerous embodiments of the present invention, composition for oral cavity comprises anti-inflammatory component and oral cavity acceptable carrier, and described anti-inflammatory component is made up of Drymotaenium miyoshianum (Mak.) Mak. basically.Here employed " oral cavity acceptable carrier " is meant the combination of the material or the material that can be used for the present composition safely, and it has rational benefit/risk ratio, and extract of magnolia can associate with described carrier and keep significant and render a service.The oral cavity acceptable carrier can comprise various other conventional active component well known by persons skilled in the art, comprises antitartar agents, caries preventive agent and sensitive agent etc.Preferably, carrier can not reduce basically the effectiveness of the anti-inflammatory activity composition be made up of extract of magnolia basically.
Suitable vehicle or carrier comprise that one or more are suitable for suitable solid-state or liquid fillers, diluent, excipient or encapsulating substance to the administration of oral cavity tissue surface local.Preferably the oral cavity acceptable carrier can not cause stimulation, swelling or pain and generally not produce allergy or untoward reaction, for example stomach discomfort, nauseating or dizzy.Desired product form is depended in the selection of concrete carrier component, comprises dentifrice, toothpaste, dentifrice, prophylaxis pastes, collutory, lozenge, chewing gum, gel and varnish etc.
In numerous embodiments, the acceptable dentifrice carrier in oral cavity that is used to prepare composition for oral cavity comprises water.Just as recognized by those skilled in the art, composition for oral cavity of the present invention randomly comprises other material, for example, viscosity modifier, diluent, surfactant, for example surfactant, emulsifying agent and foam modifier, pH modifier, abrasive material, wetting agent, taste agent, sweeting agent, flavoring agent, coloring agent, antiseptic and combination thereof.Certainly, though the general features of every kind of above-mentioned classification material can be different, they may have some common features, and arbitrary given material can be realized multiple purpose within the material of two or more above-mentioned classifications.Preferably, select to have compatible carrier material with other composition of anion antibacterial magnolia active component and compositions.
Term " mouthwass " is meant and is the composition for oral cavity of liquid, for example collutory, spraying or lotion in nature substantially in the present invention.The oral cavity acceptable carrier generally has the water of the mixture that comprises water or water and alcohol in such goods.Further, in numerous embodiments, oral carrier has wetting agent as described below and surfactant.Usually, the weight ratio of water and alcohol about 1: 1 in the scope of about 20: 1 amount, preferred about 3: 1 to 10: 1 and more preferably from about 4: 1 to about 6: 1.The total amount of water-alcohol mixture generally accounts for about 70 to about 99.9% of goods in this based article.In numerous embodiments, alcohol generally is ethanol or isopropyl alcohol.
The liquid that the present invention is such and the pH of other goods are generally about 4.5 to about 10.This pH can use acid (for example, citric acid or benzoic acid) or alkali (for example, sodium hydroxide) or buffer agent (for example, with sodium citrate, benzoate, carbonate or heavy carbonate, disodium bicarbonate or carbonic acid sodium dihydrogen) to control.
In numerous embodiments, aqueous oral composition (for example, mouthwass) contains wetting agent.This wetting agent is for example glycerol and sorbitol of wetting agent normally, with the polyhydric alcohol mixture of propylene glycol, butanediol, hexanediol, Polyethylene Glycol for example.The content of wetting agent is about 5 to about 40%, and preferred about 10 in about 30% scope.Effectively surfactant comprises anion, nonionic and zwitterionic surfactant in embodiments of the present invention.Surfactant is with about 0.01% to about 5% amount, preferably is present in the aqueous oral composition of the present invention with about 0.5% to about 2.5% amount.
Term used herein " confectionery composition " comprises chewing gum and mouth-soluble tablet, beadlet and lozenge.Saliva dissolves lozenge or chewing gum product; and promoted to contact, thereby guarantee when using product the active component of sufficient dosage is delivered to oral surfaces so that send antibacterial and anti-tartar system in lozenge tablet, beadlet or the gum formats with the prolongation of oral surfaces.
In the present embodiment, the oral cavity acceptable carrier is the form of lozenge, beadlet, tablet or chewing gum or other similar solid delivery system.Such delivery system is well known to a person skilled in the art, and active antibacterial and antitartar agents need be stirred in the warm base material with flavoring agent and Fei Sheng dental caries sweeting agent usually.
Acceptable vehicle in oral cavity in lozenge, beadlet or the tablet and carrier are non-living dental caries, the soluble polyhydroxy-alcohol of hard water (polyhydric alcohol); for example mannitol, xylitol, Sorbitol, maltose alcohol, hydrogenated starch hydrolysate, hydrogenated glucose, hydrogenation disaccharide or hydrogenation polysaccharide, it is to exist with about 85 to about 95% the amount that accounts for total composition.Emulsifying agent for example glycerol and tablet lubricants can mix in tablet, beadlet or the lozenge preparation to improve the preparation of tablet, beadlet and lozenge with about 0.1 to 5% less amount.Examples of suitable lubricants comprises for example Oleum Cocois of vegetable oil, magnesium stearate, aluminium stearate, Talcum, starch and carbowax (CARBOWAX).Suitable non-living dental caries natural gum comprises kappa carrageenan (kappa carrageenan), carboxymethyl cellulose and hydroxyethyl-cellulose etc.
Lozenge, beadlet or tablet can be randomly with clad material wax for example, Lac, carboxymethyl cellulose, polyethylene/copolymer-maleic anhydride or kappa carrageenan are coated with further increase tablet or lozenge in the orally-dissolvable time that spends.Tablet of Bao Fuing or lozenge slowly do not dissolve, and provide about 3 to 5 minutes active component to continue rate of release.Therefore, the solid dose tablet of this embodiment, beadlet and lozenge composition have given relatively than the contact cycle of tooth in the long oral cavity with anti-inflammatory activity composition of the present invention.
Chewing gum of the present invention preferably contains antibacterial and the not sacchariferous chewing gum anti-tartar chemical compound.Chewing-gum preparation generally also contains one or more plasticizers, at least a sweeting agent and at least a flavoring agent except that the chewing gum base material.
The gum base materials that is suitable in the invention process is well known in the art, comprises natural or synthetic gum base materials or its mixture.Representational natural gum or elastomer comprise tunny gum, natural rubber, gelutong, balata, gutta-percha, come Jaan Kikkas hide glue (lechi caspi), tonkabean milk (sorva), guttakay, hat glue, perillo, or its mixture.Representational paragutta or elastomer comprise BS, polyisobutylene and isobutene .-isoprene copolymers.Gum base materials is mixed in the chewing gum product to about 35% concentration to about 40%, preferred about 20 with about 10.
Plasticizer/the softening agent that is usually used in the chewing gum compositions all is suitable for using in the present invention, comprises that content is about 0.1 to about 5% gelatin, wax and composition thereof.Be used for sweetener component of the invention process and can be selected from many materials, comprise with the preparation tablet, beadlet and lozenge in used identical artificial sweetener and polyhydric alcohol sweeting agent.The polyhydric alcohol sweeting agent for example is Sorbitol and maltose alcohol, and the amount with about 40 to about 80% and preferred about 50 to about 75% is present in the chewing gum compositions of the present invention.Artificial sweetener is present in the chewing gum compositions of the present invention with about 0.1% to about 2% and preferred about 0.3 to about 1% amount.
In some other desirable form of the present invention, composition for oral cavity can be a dentifrice.Here " dentifrice " of indication is the compositions that is used for the oral surfaces of cleaning oral cavity.Such dentifrice comprises dentifrice, dental tablet, toothpaste (dental cream) or gel.In toothpaste dentifrice, the oral cavity acceptable carrier can comprise water and wetting agent, and it generally accounts for about 10% to about 80% of composition for oral cavity.
In numerous embodiments of the present invention, glycerol, propylene glycol, Sorbitol, polypropylene glycol and/or Polyethylene Glycol (400-600) are suitable wetting agent/carriers for example.The liquid mixture of water, glycerol and Sorbitol also is favourable.At carrier is that clear gel and refractive index are in those embodiments of key factor, and compositions comprises about 3 to about 30% water, 0 to about 70% glycerol and the Sorbitol of about 20-80%.
In numerous embodiments, for example for toothpaste, emulsifiable paste and gel, described composition for oral cavity contains natural or synthetic thickening agent or gellant, and it is not a silicon dioxide thickening agents, but comprises natural and synthetic natural gum and colloid.Such suitable thickening comprises naturally occurring polymer for example carrageenin, xanthan gum, the different Polyethylene Glycol of molecular weight that synthetic thickening agent is for example sold with trade name POLYOX, and cellulosic polymer for example hydroxyethyl-cellulose and hydroxypropyl cellulose.Other inorganic thickening agent comprises natural and synthetic clay for example HECTABRITE DP, Lithium metasilicate magnesium (LAPONITE) and aluminium-magnesium silicate.Other suitable thickening is synthetic li-montmorillonite, synthetic colloidal substance magnesium alkali metal silicate compound clay, and obtainable for example is the Laponite (for example, CP, SP2002, or D) that is sold by LaporteIndustries Limited.LaponiteD analyzes demonstration, approximately is 58.00%SiO
2, 25.40%MgO, 3.05%Na
2O, 0.98%Li
2The metal of O and some water and trace, its real proportion is 2.53, ABD is 1.0 (g/mL is under 8% humidity).In some embodiments, thickening agent is with about 0.1 to about 10%, and preferred about 0.5 to about 5.0% amount is present in the Dentrifice composition.
Other suitable thickening comprises for example Syloid of fine gtinding (for example 244) of Irish moss, gum tragacanth, starch, polyvinylpyrrolidone, ethoxy propyl cellulose, hydroxy butyl methyl cellulose, hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, sodium carboxymethyl cellulose and cabosil.
Also comprise surfactant in the numerous embodiments of the present invention, it can play the effect of surfactant, emulsifying agent and/or foam modifier.Surfactant generally can obtain enhanced preventive effect by active component fully is distributed in the whole oral cavity.Suitable emulsifying agent be those quite stables and in the whole scope of pH widely all blistered emulsifying agent, it comprises non-soap anionic, non-ionic, zwitterionic and amphoteric synthetic organic detergent.Further, surface active ingredient preferably makes quick-dissolving compositions can accept on cosmetics more.Organic surface active material preferably is anionic, non-ionic or amphoteric in essence, and preferably gives the detergent material of compositions with cleaning and foam characteristics.In some embodiments, one or more surfactants are with about 0.1% to about 5% amount, preferably are present in the composition for oral cavity of the present invention with about 0.6% to about 2.0% amount.
The effective ionic surfactant pack of the present composition is drawn together the chemical compound that is prepared with organic hydrophobic compound condensation by alkylene oxide (especially oxirane), and it can be aliphatic or aralkyl family in essence.One group of surfactant is called as that " ethoxy mix monomer "--they are products of oxirane and the condensations such as (for example, monostearate sorbitan esters) of fatty acid, aliphatic alcohol, fatty acid amide and polyhydric alcohol." polysorbate " is the title of a class non-ionic surface active agent, and it is to prepare by the free hydroxyl group ethoxylation with sorbitan-fatty acid ester.They are commercially available acquisitions, for example with the TWEEEN of ICI
Surfactant obtains.The example of indefiniteness comprises Polysorbate 20 (polyethylene glycol oxide 20 mono laurate sorbitan esters, TWEEN
20) and Polysorbate 80 (polyethylene glycol oxide 20 single oleic acid sorbitan esters, TWEEN
80).Preferred polysorbate comprises that those every mole sorbitan ester has the polysorbate of about 20 to 60 moles of ethylene oxide.
Other suitable ionic surfactant pack is drawn together poly-(oxirane)-poly-(expoxy propane) block copolymer, especially has such three sections copolymers of two sections poly-(oxirane) and a section poly-(expoxy propane).Such copolymer commercial known, is used in combination this title the independent sign that indicates each copolymer by non-proprietary name poloxamer with numeric suffix.The content of oxirane and expoxy propane can change in the poloxamer, thereby has produced a large amount of chemical constitutions and molecular weight.A kind of preferred poloxamer is a poloxamer 407.It can be obtained widely, for example with the commodity of BASF AG PLURONIC by name
127 product obtains.
Other indefiniteness example of suitable non-ionic surface active agent comprises the product that is obtained by the product condensation of oxirane and expoxy propane and ethylenediamine, long chain tertiary amine oxide, long chain tertiary phosphine oxide and long-chain dihydroxy sulfoxide etc.
Other surfactant useful to numerous embodiments of the present invention comprises the amphion synthetic surfactant.Part in these can broadly be described as aliphatic quaternary ammonium, and sulfonium compound, wherein fat-based can be a straight or branched, in the aliphatic substituent group one is contained 8 to 18 carbon atoms and one and is contained the anionic water solubilization radical, for example carboxyl, sulfonate radical, sulfate radical, phosphate radical or phosphonate radical.The example of a suitable zwitterionic surfactant is 4-(N, N-two (2-ethoxy)-N-octadecane ammonium)-butane-1-carboxylate.
Other suitable zwitterionic surfactant comprises beet alkali surface activator, and for example United States Patent (USP) 5,180, those disclosed in 577.Typical alkyl dimethyl betanin comprises decyl betaine 2-(N-decyl-N, N-dimethylammonio) acetic acid, cocoa betanin, myristyl betanin, palmityl betaine, lauryl betaine, cetyl betaine and stearyl betaine etc.The example of amido betaine is cocoa amino-ethyl betanin, cocoa aminopropyl betanin and dodecanamide propyl betanin etc.Useful especially beet alkali surface activator comprises cocoa aminopropyl betanin and dodecanamide propyl betanin.
Suitable examples of anionic surfactants is the water soluble salt of higher fatty acids monoglyceride Monosulfate; the sodium salt of the hydrogenated coconut fatty acid oil monoglyceride of sulfate mono esterification for example; higher alkyl sulfates is sodium lauryl sulphate for example; alkylaryl sulfonates is dodecylbenzene sodium sulfonate for example; higher alkyl sulfoacetates; 1; the high-grade aliphatic ester of 2-dihydroxypropyl sulfonate; and the saturated basically senior aliphatic amide of lower aliphatic amino carboxylic acid compounds, for example those are at fatty acid; have 12 to 16 carbon in alkyl or the acyl group etc.The example of last-mentioned amide is sodium, potassium and the ethanolamine salt of N-Hamposyl L and N-lauroyl, N-myristoyl or N-palmitoyl sarcosine, wherein preferably is substantially free of the higher fatty acids material of soap or analog.
The carrier of oral care composition is in the numerous embodiments of the present invention of solid or mastic therein, and composition for oral cavity preferably comprises the acceptable abrasive material of tooth, and it can be used for polishing enamel or whitening effect being provided.In the preparation of Dentrifice composition, can be used for implementing abrasive material of the present invention and comprise abrasive silica, for example the highest precipitated silica that is about 20 microns of particle mean size, for example ZEODENT that sells by J.M.Huber
115.A kind of effective abrasive material is the commodity ZEODENT by name that is sold by J.M Huber Co
105 material, it has low abrasiveness to enamel, and is that diameter is about 7 to about 10 microns precipitated silica, and the BET surface area of silicon dioxide is 390m
2/ g, and the oil absorption of silicon dioxide is less than 70cm
3/ 100g.Other effective dentifrice abrasives comprises Polymeric sodium metaphosphate., potassium metaphosphate, tricalcium phosphate, Tri-Compress, aluminium silicate, calcined alumina, Bentonite or other silicate material or its combination.
In other embodiment of the present invention, the effective abrasive material that is used to prepare Dentrifice composition comprises that oil factor is less than 100cm
3/ 100g silicon dioxide and preferred oil factor are about 45cm
3/ 100g arrives less than about 70cm
3The silica gel of the amount of/100g silicon dioxide and precipitation amorphous silica.Oil factor is to use ASTA Rub-Out Method D281 to measure.When measuring with 5% slurry, these silicon dioxide be particle mean size at about 3 microns to about 12 microns, more preferably from about 5 in about 10 micrometer ranges, the pH scope is about 4 to 10, preferably about colloidal particles of 6 to 9.
To the effective more suitable abrasive material of numerous embodiments of the present invention is that low oil absorption silica abrasives is for example by Davison Chemical Division of W.R.Grace﹠amp; Co., Maryland, USA Baltimore, the commodity of sale are called SYLODENT
XWA or SYLODENT
Those abrasive materials of 783.SYLODENT
XWA 650, a kind of silica hydrogel of being made up of following cabosil microgranule is to implementing the effectively preferred embodiment of low oil suction abrasive silica of the present invention, the water content of described cabosil microgranule is 29%, diameter average out to about 7 to about 10 microns and oil factor less than 70cm
3/ 100g silicon dioxide.Abrasive material is with about 10 to about 40%, and preferred about 15 to about 30% concentration is present in the Dentrifice composition of the present invention.
Other suitable polishing material comprises particulate heat reactive resin, for example tripolycyanamide, phenols and carbamide-formaldehyde, and crosslinked polyepoxide and polyester.Preferred polishing material comprise granularity be up to about 5 microns, particle mean size be up to about 1.1 microns and surface area be up to about 50,000cm
2The crystalline silica of/g, silica gel or cabosil and compound amorphous alkali metal aluminosilicate.
At dentifrice is in the embodiment of clarification or clear gel, the cabosil polishing agent, and for example those are with trade mark SYLOID
Or with trade mark SANTOCEL
The alkali metal aluminosilicate complex of selling is effective especially, because their refractive index approaches to be usually used in the refractive index of gellant-liquid (comprising water and/or the wetting agent) system in the dentifrice.
The polishing material of many so-called " water insoluble " be in nature anionic property and also comprise a spot of soluble substance.Therefore, the example of the polishing material that is fit to is insoluble Polymeric sodium metaphosphate., and it also is known as horse Dreyer salt (Madrell ' s salt) and Ku Luoer salt (Kurrol ' s salt).These metaphosphates only show small dissolubility in water, therefore be commonly called insoluble metaphosphate (IMP).Such IMPs contains a spot of usually, and the soluble phosphoric acid salt material that is generally several percentage ratios (for example,＜4%) is as impurity.Part in these impurity can be removed by the described material of pre-wash.Insoluble alkali metal metaphosphate generally is used as the powder type with following granularity, makes to be no more than 1% material greater than 37 microns.
In some embodiments, abrasive material can also comprise the abrasive grain of giving white, and it for example comprises, metal-oxide.Described metal-oxide can comprise any metal-oxide that white colour can be provided, for example, and titanium dioxide, aluminium oxide, stannum oxide, calcium oxide, magnesium oxide, Barium monoxide or its combination.Some abrasive material of giving white also can be the particle of pearl-like, and it comprises single mineral or chemical substance, and for example, silicate is such as Muscovitum or bismuth oxychloride.The meaning of " Muscovitum " is to have in lamellar morphology and the rimose silicate hydrate aluminium mineral of perfect base portion (micaceous) group any one.For example, Muscovitum can be sheet mica, fragment Muscovitum or scale Muscovitum, for instance as white mica, biotite or phlogopite type Muscovitum.In some embodiments, the pearl-like particle can comprise complex, and described complex comprises and surpasses a kind of mineral or chemical substance, for example is coated with for example Muscovitum of titanium dioxide of metal-oxide.
At dentifrice is in the embodiment of solid or cream form, and abrasive material exists with about 10% to about 99% the amount that accounts for composition for oral cavity usually.In some embodiments, polishing material is present in the toothpaste with about 10% to about 75% amount, and the amount with about 70% to about 99% is present in the dentifrice.
As mentioned above, in numerous embodiments of the present invention, water also may reside in the composition for oral cavity.Be used to prepare the water that is suitable for commercial toothpaste, gel and collutory and should preferably deionized and do not contain organic impurities.Here, the content of water accounts for the about 10% to 50% of dentifrice composition usually, preferably accounts for about 20% to 40%.The water that is added into is free water, and water can also be introduced into other material in addition, for example is added into Sorbitol.
In numerous embodiments, oral care composition of the present invention contains flavoring agent.Be used to implement flavoring agent of the present invention and comprise quintessence oil and multiple seasoning aldehyde, ester, pure and mild similar material.Any suitable seasoning or sweet material can be used.The example of suitable flavoring ingredient is flavored oils and methyl salicylate, and described flavored oils for example is the oil of Mentha viridis L, Mentha arvensis L. syn.M.haplocalyxBrig, Herba pyrolae japonicae, Radix sassafratis, Flos Caryophylli, Salvia farinacea, Eucalyptus, Origanum majorana L., Cortex Cinnamomi, Fructus Citri Limoniae, Citrus aurantium Linn., Fructus Citri junoris, Fructus Citri grandis.Chemicals as menthol, carvone and anethole also is effective.Suitable sweeting agent comprises sucrose, lactose, maltose, Sorbitol, xylitol, cyclamate, perillartine, AMP (aspartyl phenylalanine, methyl ester) and glucide etc.Seasoning and sweeting agent can be respectively or are incorporated in the composition for oral cavity with about 0.001 to about 5% and preferred about 0.5 to about 2.0% concentration jointly.
In some embodiments of the present invention, composition for oral cavity can be the form of non-abrasive medicament gel.The meaning of " medicine " be with cure or improve disadvantageous state or disease be purpose be that pharmacotherapy or treatment provide described gel.Present embodiment is not used for limiting those as the medicine effective composition, and the form of composition for oral cavity described above also is suitable for as medicine.But, effective especially with the composition for oral cavity that non-abrasive gel or ointment form provide for topical therapeutic, and can use with wound dressing, gauze and thin film etc.Such gel can comprise moisture and anhydrous gel the two, and comprise those preparations of before describing in the above.
Some aqueous gel is particularly suitable for being applied to gingival sulcus or gingival edge, and is suitable for using under gum.Such aqueous gel comprises the water of sweeting agent, optional colorant (amount with about 0.01 to about 0.5%) and surplus of flavoring agent, about 0.1 to about 3% the amount of wetting agent, about 0.01 to about 2% the amount of thickening agent, about 10 to about 55% the amount of about 0.1 to about 20% amount usually.Gel can comprise polymer support, and described carrier comprises the polymer that is selected from polylactic acid, polyglycolic acid, poly-lactyl-co-glycolic acid, for example poly-aspartyl-phenylalanine methyl ester of polyamino acid, chitosan, collagen, poly-albumin, gelatin and hydrolyzed animal protein, polyvinyl pyrrolidone, xanthan gum and other water-soluble gum, polyanhydride and poe.In some embodiments, gel comprises the polymer and the copolymer of polylactic acid, polyglycolic acid and poly-lactyl-co-glycolic acid.In other embodiments, gel comprises the copolymer of lactide and glycolide monomer, wherein based on mole, the content of lactide is about 15% to about 85%, 35 to about 65% amount most preferably from about, the content of glycolide monomer class are about 15% to about 85%, preferred about 35% to about 65%.
Long ago just known by chewing (for example, chewing bone) and scraped off of the prevention of the hard relatively surface of house pet tooth with the odontopathy of promotion house pet, especially Canis familiaris L., cat and horse.The accidental contact active component relevant with animal product further promoted the oral health of animal.Therefore, in some embodiments, active component of the present invention can be mixed in animal feed product, enriching substance product (for example, pet treat agent) and the chaw etc.
Just as known to those skilled in the art, chew article or toy can be made into various styles and size, and preferably provide physics certain level and tooth and gingival surface to interact, to promote the release of gingival irritation and/or Asia-gingival particle.The example of such toy can be bone, ball and rope.Further, preferred chew toys can the supported active composition, for example by inner memorizer, and by immersing described material, or in the surface applied of toy.The chew article of present embodiment is preferably formed by nontoxic edible material, comprises, for example, greenhide or polymer be polyester or polyisoprene for example.
Feed product of animal and enriching substance are known in the art and are preferably made by any suitable dough/pasta.Food supplement dough comprises at least a flour, coarse powder, fat, water and optional granular protein granule (for systematism) and flavoring agent usually.For example, when the product that requires is cookies, can use conventional dough/pasta, randomly contain the granule or the pulverulent material of discrete meat and/or meat by-products.The example that is used to produce the suitable dough/pasta of hard and soft (comprising the wetting agent that is used to control water) animal crackers is disclosed in U.S. Patent number 5,405,836; 5,000,943; 4,454,163; In 4,454,164, wherein the content of each piece all is hereby incorporated by.Preferably such compositions is cured.Can add flavoring agent in active component, it is included in the internal storage with soft center or by dipping or spraying and is applied on the surface of curing food supplement.Well known by persons skilled in the art being used for also all can expect by the present invention to any other suitable method of animal delivering active ingredients.
Except the anti-inflammatory activity composition of forming by extract of magnolia basically, also randomly comprise active substance arbitrarily according to compositions used in the present invention, it can prevent or treat the state or the obstacle of the hard or soft tissue in oral cavity, prevention or treatment disorder or state perhaps provide dressing effect.In such embodiment, one or more additional active component do not suppress the effectiveness of previously described anti-inflammatory component, and such supplementary element is not have anti-inflammatory property usually.
The effective additional activity material of compositions as described herein is disclosed in, and for example U.S. Patent number 6,290,933 and United States Patent (USP) 6,685,921 in, wherein the content of each piece all is hereby incorporated by.
Composition for oral cavity of the present invention can contain caries preventive agent, for example fluoride ion source or the component of fluorine is provided.In numerous embodiments, fluoride based anticaries agent is to be enough to provide about 25ppm to 5, and the amount of 000ppm fluorion exists.Effectively caries preventive agent comprises inorganic fluoride salts, for example soluble alkali metal salts.For example, effective preferred fluorinated thing source is a sodium fluoride in compositions; Potassium fluoride; Prodan; Ammonium fluosilicate; Amine fluoride; Comprise olafur (N '-octadecane trimethylene diamidogen-N, N, N '-three (2-ethanol)-dihydrofluoride); And stannic fluoride, for example stannous fluoride and stannous chloride.
In numerous embodiments, composition for oral cavity of the present invention comprises the formation of antitartar agents with prevention and/or minimize calculus.Can there be one or more such materials.
Suitable antitartar agents includes but not limited to: phosphate and Quadrafos.Phosphate and Quadrafos use with their form of all or part of neutral water-soluble cationic material (for example, potassium, sodium or ammonium salt, and mixture arbitrarily) usually.Therefore, effectively inorganic phosphate and Quadrafos exemplarily comprise an alkali valency, bibasic and the phosphatic monovalent cation of three alkali valencys; Tripolyphosphate and four Quadrafos; Single-, two-, three-and four-pyrophosphate; And PC (this area is also referred to as " metaphosphate " usually).For example, so phosphatic effective monovalent cation comprises hydrogen, monovalence metal, comprises alkali metal and ammonium.
In addition, numerous embodiments of the present invention comprises the anti-tartar system, and described anti-tartar system further comprises the linear polycarboxylate polymer of synthetic anionic property.The linear polycarboxylate of described anionic property normally contains the alkene of the two keys of activatory carbon-to-carbon alkene and at least one carboxyl or ethylene unsaturated carboxylic acid by use and synthetic.Described acid contains olefinic double bond, and it plays a role in polymerization easily, because with respect to carboxyl or as the methylene group of end group part, the described pair of key is present in α or the β position in the monomer molecule.The example of such acid is the acid and the anhydride of acrylic acid, methacrylic acid, ethylacrylic acid, α-Lv Daibingxisuan, butenoic acid, β-acryloxy propionic, sorbic acid, alpha-chloro sorbic acid, cinnamic acid, β-styrene acrylic, sticking furancarboxylic acid, itaconic acid, citraconic acid, mesaconic acid, glutaconate, equisetic acid, atropic acid, 2-benzyl acrylic acid, 2-cyclohexyl acrylic acid, angelic acid, umbellic acid, fumaric acid, maleic acid.Can comprise vinyl acetate base ester, vinyl chloride and dimethyl maleate etc. with other alkenyl monomer of such carboxylic monomer copolymerization.Synthetic anion linear polymerization polycarboxylate component mainly is the hydrocarbon that has optional halogen and contain the O substituent group and be present in the linking group in for example ester, ether and the OH group.For water solublity, copolymer preferably contains enough carboxylate groups.Term " synthetic " and " line style " do not comprise known thickeners or the gel that contains carboxymethyl cellulose and other cellulose and natural gum derivant, do not contain the deliquescent carbopol that has reduction owing to crosslinked yet.
In composition for oral cavity of the present invention, can comprise multiple optional oral care active, comprise above-mentioned those, for example (its prevention bacterial plaque is adhered to enamel surface for antibacterial (for example, plant extract or galenical reactive compound), ascoxal, antitack agent, for example, N
α-acyl amino acid alkyl ester comprises N
α-lauroyl-L-arginine ethyl ester hydrochlorate), antioxidant (for example; vitamin E or coenzyme Q10), caries preventive agent, desensitizer (for example; potassium citrate, Soluble tartar., potassium chloride, potassium sulfate and potassium nitrate), brightening agent (for example, urea peroxide, SODIUM PERCARBONATE, sodium perborate and polyvinylpyrrolidone-H
2O
2), suitable enzyme, tartar controlling agent, periodontal actives, chlorophyll compound, nutrient (for example, vitamin, mineral and aminoacid, lipophilic thing (lipotropics), fish oil and coenzyme etc.), abrasive material, breath freshening/the stink controlling agent (for example, zinc salt, as zinc gluconate, zinc citrate, zinc chlorite and α-Zi Luolantong) and saliva stimulus object (for example, citric acid, lactic acid, malic acid, succinic acid, ascorbic acid, adipic acid, fumaric acid and tartaric acid); And any other proper composition that is used for mouth care well known by persons skilled in the art.When existing, these additives mix in the composition for oral cavity with basically can the negative effect not desired characteristic and the amount of feature, and its concentration is about 0.001 to about 10% usually.
Multiple other material also can be impregnated in the composition for oral cavity of the present invention, comprises for example antiseptic, for example sodium benzoate, and siloxanes.When existing, these auxiliary agents are impregnated in the compositions with basically can the negative effect not desired characteristic and the amount of feature.
Example I
Prepare Dentrifice composition by the following method with Table I ingredients listed.Separate the extract of magnolia that obtains by HFA-13A and have the honokiol of about 15% weight and the magnolol of 37% weight.
With saccharin sodium, sodium fluoride and arbitrarily other salt be dispersed in the water and in the blender of routine and mix.Under agitation for example glycerol and Sorbitol add in the aqueous mixtures with wetting agent.Add organic thickening agent then, for example carrageenin and CMC, and polymer arbitrarily.The mixture that stirs gained is until forming uniform gel phase.Mixture is changed in the high-speed vacuum blender then; In blender, add SYLODENT XWA 650 and SYLODENT 783 abrasive materials and silicon dioxide thickening agents ZEODENT 165.Then about 20 to the 50mm mercury column, under the vacuum of preferably about 30mm mercury column, with mixture mixed at high speed 5 to 30 minutes.Weigh up flavored oils, then Drymotaenium miyoshianum (Mak.) Mak. is mixed in the flavored oils.The mixture of flavored oils and Drymotaenium miyoshianum (Mak.) Mak. is mixed in the described mixture.At last, with surfactant, for example sodium lauryl sulphate (SLS) adds in the blender.Products obtained therefrom is uniform, semisolid, squeezable cream or gel products.
| Table I |
| Composition Wt.% |
| Drymotaenium miyoshianum (Mak.) Mak. cortex extract 0.3 |
| Sorbitol (70% aqueous solution) 26.7 |
| Glycerol 12.0 |
| Sodium fluoride 0.3 |
| Saccharin sodium 0.5 |
| Sodium hydroxide (50% aqueous solution) 2.0 |
| CMS 2000S 0.8 |
| Carrageenin (LB 9505) 0.4 |
| Sylodent 783 11.0 |
| Sylodent XWA 650 10.0 |
| Zeodent 165 3.5 |
| Sodium lauryl sulphate (30% taper) 4.0 |
| TiO 2The Muscovitum 0.1 of coating |
| Flavoring agent (89-332) 1.0 |
| Blue color solution 0.05 |
| Water Q.S. |
Embodiment as described herein and other embodiment are exemplary, rather than are used for limiting the four corner of describing the present composition and method.The equivalence that can carry out the specific embodiment, material, compositions and method within the scope of the invention changes, improves and develops, and these all have similar basically result.
Claims (25)
1. a treatment suffers from the method for the mammalian object of oral tissue inflammation, this method comprises makes described tissue contact with composition for oral cavity, described composition for oral cavity comprises anti-inflammatory activity composition and the oral cavity acceptable carrier of being made up of extract of magnolia basically, and wherein said composition for oral cavity is by reducing the inflammation that one or more inflammatory mediators reduce oral cavity tissue.
2. method according to claim 1, wherein at period of contact, described composition for oral cavity provides analgesic effect further for described tissue, has therefore reduced the pain and the sensitivity of oral cavity tissue in the mammalian object.
3. method according to claim 1, wherein the concentration of extract of magnolia is less than 0.5%.
4. method according to claim 1, wherein the concentration of extract of magnolia is less than 0.3%.
5. method according to claim 1, wherein extract of magnolia comprises the reactive compound that is selected from magnolol, honokiol, tetrahydrochysene magnolol, tetrahydrochysene honokiol and composition thereof.
6. method according to claim 1, wherein extract of magnolia comprises about 2% to about 95% the reactive compound that is selected from magnolol, honokiol or its mixture.
7. method according to claim 1, wherein the oral cavity acceptable carrier comprises one or more orally active compositions that is selected from antitartar agents, antibacterial, caries preventive agent, brightening agent, desensitizer, vitamin, suitable enzyme, flavorants, deodorant and combination thereof.
8. method according to claim 1, wherein the oral cavity acceptable carrier comprises one or more components that is selected from viscosity modifier, diluent, surfactant, pH modifier, abrasive material, wetting agent, taste agent, sweeting agent, flavoring agent, coloring agent, antiseptic and combination thereof.
9. according to the described method of claim 1, wherein the oral tissue inflammation in the mammalian object infects relevant with chronic disease originality.
10. method according to claim 1, wherein oral tissue inflammation is relevant with following state, and described state is selected from: disease that injury of teeth, oral cavity wound, dental pulp disease, stomatitis, alveolus atrophic debility of bones are molten, pathological changes, gingivitis, periodontitis, Nicotiana tabacum L. cause and their combination.
11. method according to claim 1, wherein one or more inflammatory mediators are cytokines.
12. method according to claim 1, wherein one or more inflammatory mediators are prostaglandins.
13. method according to claim 1, wherein said contact are repeated many days to reduce inflammation.
14. method according to claim 1, wherein oral care composition is the form that is selected from mouthwass, dentifrice, animal product, drug gel and dentifrice.
15. method that reduces oral tissue inflammation in the mammalian object, this method comprises described tissue is contacted with composition for oral cavity, described composition for oral cavity comprises the anti-inflammatory activity composition and the oral cavity acceptable carrier be made up of extract of magnolia basically of non-quantity of stimulus, and wherein said composition for oral cavity does not stimulate oral cavity tissue and further reduced the inflammation of oral cavity tissue by reducing one or more inflammatory mediators.
16. method according to claim 15, wherein after contact, the composition for oral cavity of non-quantity of stimulus relates to one or more active component that are present near the extract of magnolia the oral cavity tissue with the concentration less than 20 μ g/mL.
17. method according to claim 15, wherein after contact, the composition for oral cavity of non-quantity of stimulus relates to one or more active component that are present near the extract of magnolia the oral cavity tissue with the concentration less than 10 μ g/mL.
18. method according to claim 15, wherein at period of contact, described composition for oral cavity provides analgesic effect further for described tissue, has therefore reduced the pain and the sensitivity of oral cavity tissue in the mammalian object.
19. method according to claim 15, wherein the concentration of extract of magnolia is less than or equal to 0.3% in composition for oral cavity.
20. method according to claim 15, wherein extract of magnolia comprises about 2% to about 95% the reactive compound that is selected from magnolol, honokiol or its mixture.
21. method according to claim 15, wherein the oral cavity acceptable carrier comprises one or more orally active compositions that is selected from antitartar agents, antibacterial, caries preventive agent, brightening agent, desensitizer, vitamin, suitable enzyme, flavorants, deodorant and combination thereof.
22. method according to claim 15, wherein the oral cavity acceptable carrier comprises one or more components that is selected from viscosity modifier, diluent, surfactant, pH modifier, abrasive material, wetting agent, taste agent, sweeting agent, flavoring agent, coloring agent, antiseptic and combination thereof.
23. method according to claim 15, wherein one or more inflammatory mediators are cytokines.
24. a treatment suffers from the method for the mammalian object of oral tissue inflammation, this method comprises that the oral cavity tissue that makes inflammation contacts with composition for oral cavity, the anti-inflammatory activity composition that described composition for oral cavity comprises the oral cavity acceptable carrier and is made up of extract of magnolia basically, wherein said composition for oral cavity reduces inflammation by reducing one or more inflammatory mediators, and wherein the oral cavity acceptable carrier comprises one or more and is selected from antitartar agents, antibacterial, caries preventive agent, brightening agent, desensitizer, vitamin, suitable enzyme, flavorants, the active component of deodorant and combination thereof.
25. method according to claim 24, wherein the oral cavity acceptable carrier further comprises one or more components that is selected from viscosity modifier, diluent, surfactant, pH modifier, abrasive material, wetting agent, taste agent, sweeting agent, flavoring agent, coloring agent, antiseptic and combination thereof.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64016104P | 2004-12-29 | 2004-12-29 | |
| US60/640,161 | 2004-12-29 | ||
| US11/285,809 | 2005-11-23 |
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| CN101132806A true CN101132806A (en) | 2008-02-27 |
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| CNA2005800487933A Pending CN101132806A (en) | 2004-12-29 | 2005-12-21 | Method of reducing oral tissue inflammation using magnolia extract |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102762219A (en) * | 2010-02-24 | 2012-10-31 | 高露洁-棕榄公司 | Oral care compositions |
| CN103025305A (en) * | 2010-02-24 | 2013-04-03 | 高露洁-棕榄公司 | Oral care compositions comprising magnolia bark extract or a synthetic analog thereof |
| CN104473822A (en) * | 2014-12-02 | 2015-04-01 | 东莞市荷花食品有限公司 | Mouthwash tablet containing plant extract and preparation method of mouthwash tablet |
| CN108135814A (en) * | 2015-09-11 | 2018-06-08 | Wm.雷格利Jr.公司 | Lily magnolia bark extract and L-arginine NαLauroyl ethyl ester is to the synergetic antibacterial effect of saliva bacterium |
| CN110668981A (en) * | 2019-09-20 | 2020-01-10 | 广东省禾基生物科技有限公司 | Magnolol derivative and preparation method and application thereof |
| CN111743835A (en) * | 2020-07-07 | 2020-10-09 | 福建维真园医药科技有限公司 | Composition of mucosa repair antibacterial liquid and application |
| CN108135876B (en) * | 2015-09-11 | 2020-10-09 | Wm.雷格利Jr.公司 | Magnolia bark extract and L-arginine NαSynergistic antibacterial effect of lauroyl ethyl ester on plaque biofilm |
-
2005
- 2005-12-21 CN CNA2005800487933A patent/CN101132806A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102762219A (en) * | 2010-02-24 | 2012-10-31 | 高露洁-棕榄公司 | Oral care compositions |
| CN103025305A (en) * | 2010-02-24 | 2013-04-03 | 高露洁-棕榄公司 | Oral care compositions comprising magnolia bark extract or a synthetic analog thereof |
| CN104473822A (en) * | 2014-12-02 | 2015-04-01 | 东莞市荷花食品有限公司 | Mouthwash tablet containing plant extract and preparation method of mouthwash tablet |
| CN108135814A (en) * | 2015-09-11 | 2018-06-08 | Wm.雷格利Jr.公司 | Lily magnolia bark extract and L-arginine NαLauroyl ethyl ester is to the synergetic antibacterial effect of saliva bacterium |
| CN108135876B (en) * | 2015-09-11 | 2020-10-09 | Wm.雷格利Jr.公司 | Magnolia bark extract and L-arginine NαSynergistic antibacterial effect of lauroyl ethyl ester on plaque biofilm |
| CN108135814B (en) * | 2015-09-11 | 2021-05-25 | Wm.雷格利Jr.公司 | Magnolia bark extract and L-arginine NαSynergistic antibacterial action of lauroyl ethyl ester against salivary bacteria |
| CN110668981A (en) * | 2019-09-20 | 2020-01-10 | 广东省禾基生物科技有限公司 | Magnolol derivative and preparation method and application thereof |
| CN111743835A (en) * | 2020-07-07 | 2020-10-09 | 福建维真园医药科技有限公司 | Composition of mucosa repair antibacterial liquid and application |
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