CN1082806C - Packaged antibacterial antiplaque oral composition - Google Patents

Packaged antibacterial antiplaque oral composition Download PDF

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Publication number
CN1082806C
CN1082806C CN89106899A CN89106899A CN1082806C CN 1082806 C CN1082806 C CN 1082806C CN 89106899 A CN89106899 A CN 89106899A CN 89106899 A CN89106899 A CN 89106899A CN 1082806 C CN1082806 C CN 1082806C
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China
Prior art keywords
compositions
antiplaque
dentifrice
agent
oral cavity
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CN89106899A
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CN1044223A (en
Inventor
努兰·纳比
阿布尔·加发
约翰·阿弗雷托
奥鲁姆·斯特林格
迈克尔·普伦辛波
理查德·S·鲁比森
杰弗里·米勒
奇姆皮拉玛·波蒂诺
迈克尔·阿伦·科林斯
特里萨·加布里埃尔·沙克尔
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Russell Energy
Colgate Palmolive Co
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Russell Energy
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Priority claimed from US07/291,712 external-priority patent/US4894220A/en
Priority claimed from US07/398,566 external-priority patent/US5032386A/en
Priority claimed from US07/398,592 external-priority patent/US5188821A/en
Priority claimed from US07/427,660 external-priority patent/US5135738A/en
Application filed by Russell Energy filed Critical Russell Energy
Publication of CN1044223A publication Critical patent/CN1044223A/en
Application granted granted Critical
Publication of CN1082806C publication Critical patent/CN1082806C/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8164—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical, and containing at least one other carboxyl radical in the molecule, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers, e.g. poly (methyl vinyl ether-co-maleic anhydride)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/0005—Components or details
    • B05B11/0037—Containers
    • B05B11/0039—Containers associated with means for compensating the pressure difference between the ambient pressure and the pressure inside the container, e.g. pressure relief means
    • B05B11/0044—Containers associated with means for compensating the pressure difference between the ambient pressure and the pressure inside the container, e.g. pressure relief means compensating underpressure by ingress of atmospheric air into the container, i.e. with venting means
    • B05B11/00446—Containers associated with means for compensating the pressure difference between the ambient pressure and the pressure inside the container, e.g. pressure relief means compensating underpressure by ingress of atmospheric air into the container, i.e. with venting means the means being located at the bottom of the container or of an enclosure surrounding the container
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/1042—Components or details
    • B05B11/1052—Actuation means
    • B05B11/1053—Actuation means combined with means, other than pressure, for automatically opening a valve during actuation; combined with means for automatically removing closures or covers from the discharge nozzle during actuation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/87—Application Devices; Containers; Packaging

Abstract

An oral composition, such as a paste or gel dentifrice or a liquid mouthwash, containing a substantially water insoluble non-cationic antibacterial agent, such as triclosan, which, when used to clean the teeth or rinse the mouth, acts to decrease plaque on the teeth, is packaged in a dispensing container or bottle which includes a solid polymeric material, such as polyfluoroethylene, which is compatible with the antibacterial agent. Also described is a method for inhibiting development of plaque on teeth.

Description

The antibacterial antiplaque oral compositions of encapsulation
The invention relates to the antibacterial that contains antiplaque, as 2 ', 4,4 '-three chloro-2-hydroxyl-diphenyl ether (THDE) are as the encapsulation antibacterial antiplaque oral composition of antiplaque effective ingredient, in the container that said composition is encapsulated in is that contact with oral cavity composition, that be suitable for antibacterial in the compositions, made by polymer plastic.Though multiple plastics can reduce the antiplaque effect of above-mentioned antibacterial, but have been found that some plastics, be suitable for THDE as polyvinyl fluoride and polrvinyl chloride, under room temperature or high temperature, they can not cause the antibiotic and active excessive loss of antiplaque in the oral cavity composition of storage in the concurrent present storage.Even when the not intact gold of the parts of plastics that contacts with container itself is suitable for antimicrobial compound, in oral cavity composition, add certain proportion has Stabilization to antimicrobial compound stabilizing agent, for example terpenes (as limonene) or essential oil (natural or synthetic), they may reside in the aromatic substance of oral cavity composition, and fitness can be improved so.The aforementioned stable agent exists with enough ratios, so that make the oral cavity composition of encapsulation and supply become effective antiplaque compositions, their production is purpose of the present invention.Make oral surfaces and the method that the oral cavity composition that contains effective ratio ascoxal contacts, comprise within the scope of the invention.On bristle, have the toothbrush of the antiplaque dentifrice of effective ratio, be also included within the scope of the present invention.
Bacterial plaque on the tooth is considered to the paathogenic factor of negative periodontal membrane (negative period-ontal) disease, and dental plaque is the precursor of tartar.Bacterial plaque can form in any part (comprising the gum edge) of dental surface.Bacterial plaque makes tooth seem matt, and impels the tartar development, and it is also relevant with the generation of gingivitis.Therefore, containing the oral cavity composition antiplaque composition, that can give bacterial plaque development on anti-or the inhibition tooth is the important medicament that takes care of one's teeth.
Though the antibacterial in the known oral cavity composition can reduce bacterial plaque (with other materials and with often effective especially), various antimicrobial compound all has their shortcomings of using of certain obstruction in oral cavity composition.Cationic antibacterial agent for example, tend to make tooth discoloration as quaternary ammonium halide, but in oral cavity composition,, cationic antibacterial agent is lost activity owing to there is anionic species (often needs are used anion surfactant or detergent in oral cavity composition).
Basically water-insoluble halo (or hydroxylating) diphenyl ether, as THDE (triclosan) and 2,2 '-dihydroxy-5,5 '-two bromo-diphenyl ether (DDDE) are effective antiplaque antibacterial, but as what the applicant found, they can lose activity owing to the existence of non-ionic surface active agent and many plastics.Therefore, the objective of the invention is in oral cavity composition, to add antimicrobial ascoxal, as halogenated diphenyl ether, especially THDE and DDD and similarly ascoxal, so that when using when storing before application and from packing or container, antibacterial can not lost its activity egregiously.The triclosan dentifrice that is provided by the pharmacists in prior art was used 1 time or 2 times when every day, used 1.5g at every turn, brushed teeth (this is considered to roughly brush teeth normally operation) 1 minute the time, and the triclosan quantity delivered is not enough to reduce effectively bacterial plaque.With regard to effect, cause after using for 3 weeks as stated above bacterial plaque to reduce 25% at least, this is equivalent to by the result who uses contrast 3 weeks of toothpaste with quadrat method.
Best antiplaque composition is THDE in the oral cavity composition of encapsulation at present, and it also is referred to as triclosan.Triclosan is as antibacterial and anticalculus agent (zinc ion is provided) and usefulness, and this is at United States Patent (USP) 4,022, and is open in 880; With copper compound and usefulness, open in German patent specification (OLS) 3532860.Triclosan is that the aromatic of substrate is used as dentifrice with Polyethylene Glycol with oil, and is open in european patent application 0161898,0161899 and 0220890.
Known have various oral cavity composition or a dental formulations, comprising the dentifrice of paste, gel, powder, liquid preparation, tablet, lozenge, sachet agent and encapsulation, and liquid and flaky collutory; The dental procedure agent that the professional uses (for example tooth hardening composition, as fluoride aqueous solution).Above-mentioned product is encapsulated in deformable tube, sucking type feeder, forced feed pipe, bag, bottle, jar or other containers.Though deformable or flexible pipe is to be made by metal (as lead and aluminum) at first, bottle is to use the glass manufacturing, and these containers are normally made with synthetic organic polymer plastics in recent years, or the laminate of above-mentioned plastics.It is known reacting to each other between container material and the oral cavity composition adorned, for example responds between toothpaste and the aluminium vessel, and in order to prevent this reaction, container should be handled specially, perhaps uses different container materials.But, many applicants do not believe that some plastic package materials of narrating in the prior art (are encapsulated in the container oral cavity composition before invention, and contact with above-mentioned plastics) in the antiplaque effect meeting of halogenated diphenyl ethers antimicrobial compound exert an adverse impact, do not believe yet and had been found that some plastics can be used for said vesse and not cause the active loss of halogenated diphenyl ethers antiplaque, do not believe that perhaps the above-mentioned loss of activity with the oral cavity composition of the plastics of " reactivity " (owing to absorb or opposite effect, making active reduction of antiplaque of oral cavity composition) contact can be by adding terpenes (as limonene) yet, other aromatic compositions of oral preparation and obtain stoping or giving anti-.
According to some content of the present invention, the present invention relates to be encapsulated in oral cavity composition in the supply container, that contain effective bacterial plaque feature, said composition preparation the time be actually water-fast non--cationic antibacterial agent, supply container comprises the solid polymerization material that contacts with oral cavity composition, as synthetic organic polymer plastics, this solid polymerization material is applicable to the antibacterial in the oral cavity composition, and being stored in the container (as storing several weeks in 20 ℃～40 ℃, preferably to more than 1 year or 1 year) can not cause the antibiotic and active loss of antiplaque of oral cavity composition.The oral cavity composition of this encapsulation normally is contained in toothpaste, gel dentifrice or the collutory in deformable supply pipe, sucking type feeder or the bottle respectively, the parts of plastics of used container (is preferably halogenated diphenyl ether to antibacterial, as triclosan) the antiplaque effect can not exert an adverse impact, the composition that perhaps in oral cavity composition, contains any harmful " reaction " between the parts of plastics that can suppress or stop antibacterial and container, otherwise container exerts an adverse impact to the antiplaque effect meeting of compositions.
From the narration of the present patent application description and in conjunction with diagram, can easily understand the present invention, in the diagram of the present invention
Fig. 1 is the perspective view of dentifrice tube and departing block thereof, and toothpaste is extruded on the toothbrush from pipe;
Fig. 2 is the amplification profile of compressible tube thin layer wall, as shown in Figure 1;
Fig. 3 is for being equipped with the vertical cross section of the sucking type feeder of toothpaste or dentifrice gel as required;
Fig. 4 contains the sachet of heat-sealing mouth of ampoule toothpaste or the side view of pouch;
Fig. 5 is the vertical cross section of the band medicated cap bottle of dress collutory.
In Fig. 1, the anti dental plaque tooth paste commodity 11 of encapsulation comprise deformable dentifrice tube 13, Contain anti dental plaque tooth paste 15 in the dentifrice tube, by pushing take unit quantity (as 0.8～2 G) be distributed on the toothbrush 17. Pipe 13 is opaque, is moulded by synthetic organic polymer Material is made such as polyvinyl fluoride, perhaps makes lining with the thin slice of above-mentioned plastics, and used plastics are in storage Antiplaque activity to toothpaste in depositing does not have bad impact. On the other hand, pipe 13 also can There is adverse effect (to reduce and have antibiotic in the toothpaste and the antiplaque work with the antiplaque effect to toothpaste With the antiplaque effect of halogenated diphenyl ether composition) the plastics manufacturing, perhaps make lining with it, But in this case, can be by being present in stablizing in the denfifrice to the adverse effect of antiplaque Agent stops or suppresses, and stabilizing agent can be terpenes, and such as limonene, or other are effectively fragrant The material composition. Preferably dentifrice tube, toothpaste pipe cap 19, the dentifrice tube that contacts with toothpaste is any Miscellaneous part (such as the cap liner) also need not all without copolyester/polyether elastic material manufacturing Even having the antiplaque that in fact still can reduce in the oral preparation of the stabilizing agent of antiplaque composition does With other plastics make. Also require to have avoided other elastomeric materials (such as isobutyl diene, neoprene Rubber, butadiene rubber and acrylonitrile-butadiene rubber) exist, they can react with THDE, perhaps Absorb THDE. What meet the requirements is that above-mentioned part is by the antiplaque activity is not had bad shadow The plastics manufacturing that rings, even in denfifrice, do not have terpenes or its that stabilizing agent to have above-mentioned moulding Material does not still have harmful effect to the antiplaque activity, but when the aforementioned stable agent be present in the toothpaste with When reducing the deactivation of plastics, it is (just best to use above-mentioned other unsettled plastics Avoid using elasticity copolyester/polyethers and other disadvantageous elastomeric materials).
In Fig. 2,21 is the polyoxyethylene thin layer, and 23 is aluminium flake, and 25 is polyethylene Film, polyvinyl fluoride are on inner pipe wall, here contact with toothpaste. Among the figure cap 19 in Lining does not draw, and it also can be polyvinyl fluoride, and like this, all contact with toothpaste during storage The surface all is suitable for halogenated diphenyl ether antimicrobial component in the toothpaste, and can not promote it when storing The active excessive loss of antiplaque. Can replace polyvinyl fluoride thin layer inwall with polyethylene 21, inwall 21 can be polyethylene or other suitable polymer.
Sucking type toothpaste feeder is the pattern that gondola Guala S.P.A sells in Fig. 3, and it is a United States Patent (USP) 4,776,496 content.When prepare using, at the compartment 29 of sucking type feeder 27 toothpaste is housed, compartment 29 is limited by diapire 31 and film 33.Extruding drive rod 35 can make film 33 move down, and forces toothpaste to pass through conduit 37, and comes out from carrier pipe 39.When the pressure on drive rod 35 was removed, elastic film 33 recovered original shape, and conduit 37 and bar 35 are got back to original position.Atmospheric pressure upwards promotes the end 31 simultaneously.Its inner each several part of the sucking type feeder that contacts with toothpaste preferably can not make the plastics material of halogenated diphenyl ether ascoxal inactivation.Yet, have required physical property and be applicable to that still the plastics of ascoxal are impossible in different contact portion tools application, therefore can use other plastics, condition is that dentifrice composition (or gel dentifrice) contains stabilizing agent, as limonene or other effective terpenes or fragrance component.But, preferably avoid using copolyester/polyether elastic material, especially for pumping diaphragm 33, in the oral cavity composition of described type, pumping diaphragm 33 used plastics stop the activity of THDE seemingly positive especially.
In Fig. 4, sachet or not the bag 41 for the heat-sealing mouthful; Heated sealant three limits are with numeral 43 and 45 expressions.Just self turning back in the 4th limit 47, need not heat and seal.Being enclosed in the bag is oral cavity composition, and as the toothpaste (not shown), the plastics on the inner surface of sachet can not promote the antiplaque effect of antimicrobial compound in the oral cavity composition too to reduce.Other containers for antibacterial antiplaque oral composition, can use its internal layer antibacterial is not had dysgenic plastic layer, if perhaps plastics have above-mentioned side effect, can eliminate with the suitable stabilizers that is present in the oral cavity composition, stabilizing agent preferably also can be used as aromatic.
In Fig. 5, the 49th, opaque bottle, the 51st, seal medicated cap.The packing ring (not shown) of sealing in bottle and the valve protection cap is the plastics that are applicable to THDE, and THDE is the antiplaque composition of collutory 53 in the bottle.As in other known embodiment,, in collutory, suitable stabilizers need be arranged so, so that prevent the excessive reduction of antiplaque effect of THDE or other halogenated diphenyl ether if use " reactive " plastics as bottle or seal the material of medicated cap inside.
Be present in compositions in the described packing container except gel dentifrice and thick liquid ((rather than toothpaste), the compositions that can also add the dental treatments that is applicable to that the professional uses, as the tooth hardening composition, it can comprise chloride and phosphate, compound antibacterial, indicate dye solution and other suitable oral cavity compositions of bacterial plaque.Equally, the pressurization or the aerosol composition that contain above-mentioned antiplaque chemical compound can be encapsulated in the pressure vessel (using nitrogen pressure usually), and condition is that the parts of plastics of contacting container should be the excessive material that reduces of antiplaque effect that does not cause ascoxal in contained toothpaste or other oral cavity compositions.
In above figure the listed various container, can also use squeeze bottle, capsule, jar, resemble the supply container of spongioid medium and dissimilar machine-building.Because some halogenated diphenyl ether antimicrobial compounds are to photaesthesia, therefore often need to use the container of being made up of coating or laminate that can cover chemistry or physics light, known have many such materials so that prevention can cause the irradiation of the light (as ultraviolet) of inactivation.Equally, wish that said vesse is opaque, stoping photochemical irradiation, thereby avoid the antiplaque composition inactivation of oral preparation (for example toothpaste).
Plastics cause the THDE that has the antiplaque effect in the oral cavity composition and other in fact the reason of non-cationic antimicrobial agent inactivation it be unclear that.So far research determines to reduce required active mechanism as yet, and this result is owing to chemical reaction or because Physical Absorption is still undetermined so far.Containing the basic collutory of THDE or the test of oral cavity cleaning formula of liquid shows, in container under room temperature, 38 ℃ and 49 ℃, when above-mentioned collutory or mouth cleaning solution when 12 weeks, the back was aging, perhaps when the oral cavity cleaning solution contacts with parts with the chamber wall of low-density polyethylene, highdensity polyethylene, polyethylene terephthalate, polypropylene, nylon, polyallomer and polymethylpentene, the loss (THDE begins more than 25% of concentration) of " excessive " is arranged.Equally, when be stored in copolyester/polyether elastic material as the container of inwall or parts in the time, in the Guala pumping diaphragm, serious loss can take place as aforementioned applications.Have been found that polyvinyl-fluoride (as politef), polyethylene chlorine class, polycarbonate-based and polysulfones not with the THDE reaction of extra proportion, do not absorb it yet.But Merlon and polysulfones are brittle, therefore normally are unsuitable for the parts as supply container.Polrvinyl chloride is often given oral cavity composition (as toothpaste) with external taste, therefore generally avoids as container material, unless this external taste is consistent with the taste of applied toothpaste aromatic.Therefore, in all useful polymer plastics, polyvinyl fluoride especially is suitable for as deformable container or packaging material, and it can not reduce the antiplaque activity of ascoxal significantly.But, as described in the past, in oral cavity composition, add and make the stable chemical compound of ascoxal, as terpenes (it is representative wherein storing alkene), essential oil (containing terpenes usually) with have its fragrance component of similar Stabilization, when container of making when compositions and the above-mentioned various different polymer plastics that make the active undue loss of antiplaque or container parts contact, the aforementioned stable agent can reduce the loss of activity of ascoxal.Therefore, if when also containing the terpenes of Stabilization or other suitable " stabilizing agents " in the oral cavity composition, people need not rely on polyvinyl fluoride as container material.When the aforementioned stable agent is present in the oral cavity composition or when polyvinyl fluoride (or polrvinyl chloride, Merlon, polysulfones) is polymer plastic unique and that oral cavity composition contacts, even store several weeks until more than 1 year or 1 year in ambient temperature or higher temperature (as 20 °～40 ℃), the active loss of storing of antiplaque is less than 25%, being preferably less than 10% the most stable oral cavity composition is comprising the terpenes with Stabilization or other suitable stabilizers, and only is made of polyvinyl fluoride (or plastics of any other non-activity) by the container of contact.According to the present invention, though terpenes and essential oil are main stabilizing agents, other fragrance components also can be used as the material of stablizing antiplaque, they or suppress the absorption of plastics to halogenated diphenyl ether, perhaps disturb unsettled reaction, or pass through the mechanism of other the unknowns.Therefore, can reasoning, can dissolve some composition of the oral cavity composition of THDE, can hold it in the oral cavity composition, and be used for suppressing or stop THDE to move into plastics.On the other hand, all right reasoning, above-mentioned dissolution can promote dissolved THDE to transfer in the plastics.Because above-mentioned arguement is also unresolved, so the applicant is not subjected to the constraint of above arbitrary theory.In addition, though wish that terpenes and other stabilizing agents also are fragrance components, this is optional, and stabilizing agent can only be used for stablizing purpose.
Though inwall that packing container of the present invention is preferably made with synthetic organic solid polymer plastic (contacting) or lining with compositions, but use other solids (and/or form membrane) polymeric material (no matter they are synthetic, organic or even plastic cement), this also belongs to content of the present invention.Therefore also can use Polyethylene Glycol and methoxy poly (ethylene glycol), for example " Polyethylene Glycol " type as Polyethylene Glycol 4,000 and Polyethylene Glycol 6,000, is used their lining materials as described compositions packing container usually.Inorganic silicon polymer (as silica silicon) and the film forming material of nonsynthetic organic shape (resin for example is as carrageenin, yellow glue, karaya) also can be used as the lining of container.In addition, solid polymeric material, for example cellulose and starch and their derivant also can be used as with the oral cavity composition that encapsulates in the container material that contacts with the antiplaque composition of antibacterial.
In the oral cavity compositions of the various different encapsulation of the present invention the form of normal preparation be toothpaste, dentifrice gel and collutory (often being called mouth cleaning solution).Preceding two kinds are referred to as dentifrice here, last a kind of collutory that is referred to as usually.Dentifrice comprises three kinds of major ingredients, carrier, polishing material and surfactant (or detergent).Antibacterial (for example halogenated diphenyl ether) generally is present in the carrier, and carrier accounts for 10～80% (content is all based on final compositions) of dentifrice usually.About 3～40% is water in the carrier, about 7～77% is wetting agent (as glycerol, sorbitol, propylene glycol or their mixture), and 0.5%～10% is gellant (for example sodium carboxymethyl cellulose, Irish moss, small carrageenin or hydroxyethyl-cellulose and their mixture).In gel dentifrice or toothpaste, polishing material generally accounts for 10～75% of dentifrice, perhaps being generally 50～99% these polishing materials in powder can be colloidal silica, sedimentation silicon dioxide, silicate aluminum sodium, insoluble Polymeric sodium metaphosphate., hydrated alumina, baked aluminium oxide, dicalcium phosphate dihydrate, anhydrous dicalcium phosphate or calcium carbonate, other known substances or their mixture.Surfactant comprises anionic, nonionic, cationic and amphoteric ionic surfactant, but avoid using nonionic surfactant usually, because it (has bad influence as THDE to antimicrobial component, and also avoid usually using cationic and amphoteric ionic surfactant, because they can make tooth staining or deepening.Therefore, organically synthetic anion surface active agent (they also are detergents) is the cleaning agent of preferentially selecting for use in dentifrice, sodium lauryl sulphate and at moieties the higher alkyl sodium sulfate of 10～18 carbon atoms to be arranged be preferably wherein, but also can replace them, can partly replace them at least with other known sulphations or sulfonated detergent.Other effective compositions also can be arranged, as the chemical compound of fluoride is provided, for example sodium fluoride or sodium monofluorophosphate exist, so that tooth sclerosis, the amount of fluoride is generally 0.001～1% of compositions, also can use adjuvant (as aromatic and sweeting agent), and its consumption is 0.1～10%.In addition, wish to use poly-carboxylate, for example polyvinyl methyl ether maleic anhydride (PVM/MA) copolymer (Gantrez *) its consumption is equivalent to 0.5～4% of dentifrice.Found that above-mentioned poly-carboxylate can improve the antiplaque effect of antimicrobial compound in fact.In oral cavity composition, use poly-carboxylate at United States Patent (USP) 4,627, narration in 977, with its incorporate into own forces in this application as a reference,
In collutory, its vehicle is water and alcohol (as ethanol or isopropyl alcohol) preferably.Vehicle generally accounts for 90～99.9% of compositions, and wherein ethanol accounts for 5～30% of compositions, and propylene glycol accounts for 2～10% (calculating according to end product) usually.The remainder of compositions accounts for 0.1～10%, and by concrete purpose, they can comprise spice, surfactant, sweeting agent, coloring agent, ascoxal and other adjuvant.In dentifrice and collutory compositions, antimicrobial antiplaque chemical compound effective dose is generally 0.02～0.2%, be 0.03～0.1% better in collutory, in dentifrice, be generally 0.25～1%, be 0.25～0.5 or 0.6% better, the scope of THDE is no more than 0.8% in toothpaste, and THDE is no more than 0.2% (because may be numb at the higher concentration end opening) in collutory, invalid for fear of antiplaque under low concentration, THDE should not be lower than described percentage ratio.Ascoxal that compositions contains and the amount of THDE better, if still it begins concentration in given scope, are acceptables until loss 25% in described scope so, and such compositions surely within the scope of the invention.
In order to make the oral cavity composition stable (wherein used plastics and antimicrobial compound is " reactive ") that is encapsulated in the container (plastic wall or miscellaneous part are arranged), in oral cavity composition, need 0.01～2% terpenes or stabilizing agent, with 0.05～1% better, be 0.1～0.5% better.Such stabilizing agent may reside in the suitable fragrance of dentifrice, (normally needs) if desired, has 5% spice at least, and is better with 10% at least, is 25% better, preferably is at least 50%.
Though with above-mentioned described mainly be about dentifrice and collutory, other oral cavity compositions of the present invention (for example chewing gum) can contain the composition of same ratio, (for example content is lower in mouth cleaning solution according to the form of compositions, content is higher in thicker compositions toothpaste), usually add specific composition, so that reach the purpose of above-mentioned composition.Therefore, the compositions of sclerosis tooth can comprise fluoride and phosphate in dentifrice or collutory, for example sodium fluoride, potassium fluoride and sodium fluorophosphate, and its consumption is generally 1～5%.Bacterial plaque indication staining solution can comprise suitable dyestuff (redness obviously is the most satisfied color of this series products), and its concentration is generally 0.001～0.1% in collutory.Therefore, other product compositions, those of ordinary skill in the art can suitably adjust.
Antibacterial be the insoluble or water-insoluble basically non-cationic material of water (in 25 ℃ of dissolubility in water less than 10g/l, sometimes less than 1 or 0.1g/l).Such material can dissolve or be dispersed in the dentifrice vehicle that contains glycerol, sorbitol and/or propylene glycol, obtains the above end product of giving an account of matter for the basis.They also can dissolve or be dispersed in the rare pure medium of collutory.
In antibacterial, halogenated diphenyl ether contains bromine and/or chlorine usually, and is wherein better with chlorine.In halogenated diphenyl ether, there are 1～3 hydroxyl and 1～4 halogen atom to replace better, there are 1 or 2 hydroxyl and 2 or 3 halogens to replace better, being preferably on each ring respectively has 2 substituent groups always to have 4 substituent groups.In the above chemical compound, with 2,2 '-hydroxyl-5,5 '-two bromo-diphenyl ethers and 2 ', 4,4 '-three chloro-2-hydroxyl-diphenyl ether are better, and a back chemical compound (THDE) is best.The water-insoluble in fact various different halogenated phenols that replace, non--positive antimicrobial antiplaque chemical compound is at S.N number of patent application 07/398, describe in detail in 566 (Augusts 25 1989 date of application), this application is incorporated into own forces in this application as a reference, if see fit, can substitute the halogenated diphenyl 2, 2-Oxydiphenol with above-claimed cpd whole or in part.
Term terpenes used in the present specification comprises terpene hydrocarbon and oxidized derivatives thereof, and the chemical compound that comprises has for example dl-limonene, menthol, diterpene, polyterpene and derivant thereof, and it is found in different essential oil or other spice wherein having many.Except the stabilizing agent that is used as halogenated diphenyl ether, they are usually also as the spice of oral cavity composition of the present invention.In terpenes and the derivant thereof, though also can for example contain the aromatic and the emulsible lipotropy essential oil of stabilizer element with other terpenes (comprising the terpenes that does not belong to spice), limonene is considered to meet most above requirement.
Is because the chemical property of these plastics and the situation of polymerization are known with previous described various different plastics as the composition of container and/or container parts, in the application's explanation, need not to be described in detail again like this, further if desired details, can be with reference to ModernPlastics Ency Clopedia, this book is published by MCGraw-Hill company (New York) every year.
As described in the S.N.07/398566 that incorporates into own forces, compositions of the present invention can contain in the oral cavity can provide 25～5, and the fluoride ion source of 000ppm fluoride ion can provide 300～2, and 000ppm is better, preferably provides 800～1,500ppm.About the further details of suitable fluoride, ratio and preparation aspect, can be referring to United States Patent (USP) 4,627,977.Chloride mainly can be used as tooth hardener, also can be used to make the polyphosphate anti-calculus chemical compound of existence stable.Described polyphosphate is preferably the mixture of tetrasodium pyrophosphate and potassium, also can make it stable with polyvinyl methyl ether maleic anhydride copolymers (Gautrez-S97).Used proportion is seen U.S.S.N.07/398605 (August 25 1989 date of application), United States Patent (USP) 4,627,977 and 4,806,340, and they are all incorporated into own forces in this application as a reference.
About other details of prescription, composition, adjuvant, preparation and application, please refer to above-described patent, description or application among the application, they are all incorporated into own forces in this application as a reference.
Can prepare the above all kinds of oral cavity composition with various general technology.For for simplicity, can be with reference to concrete example.THDE is disperseed and/or be dissolved in the vehicle of dentifrice, terpenes is present in the aromatic.In order to prepare dentifrice, preparation contains the vehicle of glycerol, sorbitol and propylene glycol, and gel, suitable adjuvant (are comprised Gautrez S-97 and triclosan), vehicle, anionic detergent (is preferably sodium lauryl sulphate, or be the mixture of sodium lauryl sulphate and Sodium methylCocoyl taurate) aqueous solution, then mix with premix and buffing compound composition, and mixing.Last be dissolved in ethanol in aromatic (comprising terpenes) mix and adjusting PH.In order to prepare collutory, various composition is mixed in alcohol or the enol medium, stir, until dissolving.Preferably use the anion surfactant composition of the mixture (its proportion is 1: 4～4: 1) of sodium lauryl sulphate (SLS) and Sodium methyl Cocoyl taurate as collutory, as have taurate, can allow SLS content quite to reduce.Can prepare other oral cavity compositions by method like the related genera.
Oral cavity composition is encapsulated in the supply container, requirement avoids compositions to contact with the plastics of its poly-polyester/polyether elastic material, and requiring to avoid any compositions that does not contain stabilizing agent (as terpenes or contain terpenic spice) to contact with above-described plastics in the application's book, these plastics can react with THDE, other above-mentioned antibiotic and antiplaque chemical compounds.The short time is stored in bucket, any other container, pipe, pump or the equipment made from described plastics for a long time or at elevated temperatures particularly importantly to avoid making oral cavity composition.
Even when preparing the compositions of the present invention's encapsulation, with when the oral cavity composition that contains THDE or other halogenated diphenyl ether antibacterial with have reactive plastics when avoiding contacting, also require to make the compositions of encapsulation to reduce to minimum, found that heat and light can promote the active loss of antiplaque with contacting of light and heat.Therefore, compositions of the present invention is better than 10 ℃～38 ℃ storages most and is encapsulated in opaque container and the feeder.In addition, the compositions of encapsulation can store and use by common mode.Can obtain needed antiplaque effect like this.The antiplaque effect effect that test the chamber and aspiration experimenter group tooth is tested by experiment proves that the experimenter has used various encapsulating composition, and establishes matched group relatively.Compare with the encapsulating composition of contrast, observed the remarkable effect of encapsulating composition of the present invention aspect antiplaque, in the encapsulating composition of contrast, the plastics of packaging container are to have reactively with the halogenated diphenyl ether antimicrobial compound, and do not contain stabilizing agent in oral cavity composition.When the packaging container of using is made by " active " plastics (but not being copolyester/polyether elastic material), and when containing terpenic oral cavity composition and contact, with the contrast oral cavity composition contrast that does not contain terpenes and aromatic, find the active obviously improvement of antiplaque equally.
Be described in detail the present invention with following example, but be not restriction the present invention.Except as otherwise noted, percentage ratio and ratios all in example, application specification and the appended claims all are by weight calculation, and the temperature that is not had for degree centigrade.
Example 1 composition % deionized water, 47.84 sorbitol (70% aqueous solution) 20.00 ethanol (95% aqueous solution) 12.50 glycerol 10.00 propylene glycol 7.00 *Gantrez S-97 (13% solution) 1.92 sodium hydroxide (50% aqueous solution) 0.12 sodium lauryl sulphate 0.25 *Tauranol WSHP 0.20 * *Spice mixt 0.12 * * *Triclosan (Irgasan RDP.300,0.05
CIBAGEIGY produces)
100.0 *Polyvinyl methyl ether/maleic anhydride copolymers *Sodium methyl Cocoyl taurate * *Contain at least 25% terpenes, comprise at least 25% limonene * * *THDE (2 ', 4,4 '-three chloro-2-hydroxyl-diphenyl ether)
According to standard method, the various compositions listed are mixed by the order of any appropriate make mouth cleaning solution of the present invention (or collutory), but preferably at first triclosan is dissolved in glycerol and the alcohol mixeding liquid, then itself and sorbitol aqueous solution, glycerol and anion surfactant are mixed, add spice mixt at last.With in the sodium hydroxide solution and the acidic mixture of gained, be neutralized to pH6.84 (is optimal at product neutral or that make during near neutral pH).
The mouth cleaning solution that makes has the stability and the acceptable fragrance of good cosmetics, and spice and triclosan are dissolved well, and this is at least in part owing to the existence of TauranolWSHP.When only using 0.25%SLS as anion surfactant, the dissolution of aromatic and triclosan is not satisfied.Can increase this dissolution though use more SLS, the acceptable maximum of this chemical compound is limited the quantity of and is about 0.25% usually in cleaning agent for mouth cavity, and Tauranol RWSHP and SLS are safe and acceptable in the ratio of using.The bioavaliability of triclosan under more following two kinds of situations: a kind of situation is for omitting the oral cavity cleaning formula of liquid of Tauranol WSHP; Another kind of situation is the oral cavity cleaning formula of liquid that the non-ionic surface active agent (PluronicF-127) with half amount replaces Tauranol WSHP, and described oral cavity cleaning formula of liquid is carried out in vitro tests.Scribbled the degree of absorption of the hydroxyapatite garden sheet of saliva with the measurement triclosan by the absorption test of triclosan, simultaneously by the test of " inhibition zone " protein adsorption, discovery is compared with the bioavaliability of the prescription that only contains SLS, the existence of blended anion surface active, can make triclosan have similar bioavaliability, its bioavaliability of prescription that does not contain the nonionic washing is higher than the prescription that wherein contains nonionic detergent (PluronicR F-127) significantly.
The mouth cleaning solution prescription of this example is aging in 3～5 weeks when high temperature (41 ℃), actual degree of aging at least about 6 months and 1 year under this result and the room temperature is suitable, and this degradation is carried out in the supply container made from glass, polrvinyl chloride and polyethylene terephthalate (or using the plastic substance lining).When container is glass, do not find the triclosan loss though after above-mentioned aging period, mouth cleaning solution is carried out chemical analysis, but when container is polyethylene terephthalate or polrvinyl chloride product, triclosan in the mouth cleaning solution has loss, but the amount of loss obviously is less than 25% (original content) of allowing, is below 5% or 10%.
With 0.1,0.2 and 0.4%dl limonene when replacing spice mixt, can make that triclosan has better stability in the dentifrice of the above-mentioned packing of the present invention, deposit when levying with similar ratio when other terpenes that from various different essential oil any, obtain and aromatic, also can obtain this Stabilization.If container material or container lining are polymethylpentene, polyallomer, polypropylene, height and low density polyethylene (LDPE) and nylon, when though these materials are stored in the presence of not at spice mixt (with the terpenes that contains), can cause that triclosan obviously and greatly loses (especially under the elevated temperature situation) in the mouth cleaning solution, but also can obtain above-mentioned good stable result.
Example 2 composition % deionized waters 84.42 ethanol (95%) 10.0 propylene glycol 5.0 sodium lauryl sulphates 0.50 triclosan 0.06 saccharin sodium 0.02
100.00
The mouth cleaning solution of above-mentioned prescription with various plastics manufacturings or with the supply container of its lining in test after storing for 3 weeks, to determine the effective degree of triclosan.Test is in room temperature, carries out under 38 ℃ and 49 ℃, stores with heating up with the long period of storage of simulation (until at room temperature storing 1 year or the longer time).When being polymethylpentene, polyallomer, polypropylene, height and low density polyethylene (LDPE) and nylon as container material, the loss of triclosan surpasses 25% in the mouth cleaning solution of storing, when container material is polypropylene, polyethylene and nylon, obtained unacceptable result (excessive loss) (the poorest) with nylon
When container material or lining are that polrvinyl chloride, Merlon, polysulfones or polyvinyl fluoride are (as politef or Teflon R) time, triclosan is not loss basically.Press example 1 described identical method, limonene, another terpenes or essential oil (wherein they can exist) are added in the mouth cleaning solution, terpenes ratio preferably is at least 0.1%, preferably more some more, as be 0.2% or 0.4% (based on final composition), be stored in so with the container of above-mentioned polymer (polymethylpentene etc.) manufacturing or the loss of its triclosan of mouth cleaning solution in its lining and can reduce.In this case, even use and not contain the terpenic fragrance material of any obvious ratio and also can produce positive effect, but this effect do not resemble contain in the prescription phase that terpenes gives good.
Example 3 composition % propylene glycol 10.00 small carrageenin 0.75 sodium fluoride 0.33 sorbitol (70%) 30.00 saccharin sodium 0.30 titanium dioxide, 0.50 sodium hydroxide (50% aqueous solution) 0.80 deionized water 27.71+Luviform TM(35% solution) 4.76++Zeodent TM113 20.00+++Sident TM22S 2.00 sodium lauryl sulphates (94% activity) 1.60 spice 0.95 triclosan 0.30
100.00+ polyvinyl methyl ether/maleic anhydride copolymers (BASF AG) ++ silicon dioxide buffing compound (J.M.Huber company) +++silicon dioxide thickening agents (Degussa company)
The dentifrice for preparing above-mentioned prescription by common method, above-mentioned dentifrice is stored in the supply container, and by this supply container administration, and used container or parts system are by various different plastics manufacturings, if when containing the dentifrice of triclosan and contacting, use the medium of dentifrice as test triclosan stability with them.The plastics of test usefulness are the Pibiflex that is produced by Inmont TM46, by the Arnitel of AKZO production TM460EM makes the flexible pipe (as shown in Figure 3) of thin film or sucking type feeder with them.Test 6 plastic samples, respectively make 3 with above-mentioned plastics, per 1 in 3 has dissimilar releasing agents, tests (whether relevant with the kind of releasing agent to determine the triclosan stability that lay up period contacts with plastics) then.This releasing agent is respectively SiliconeMaster TM(5% silicone oil and 95% polypropylene), SiliconeMaster add silicone oil (with other silicone oil) and ArmidoMaster TM(5% oleamide and 95% polypropylene).The test specimen that contacts with dentifrice takes out dentifrice from plastic containers after different temperatures (room temperature, 38 ℃ and 49 ℃) stored for 2 weeks, plastics wash with water and immerse in the methanol, to be dissolved in the triclosan that lay up period is absorbed by them.Merge methanol wash liquid, and use efficient liquid phase chromatographic analysis.Find that different thin-film materials is substantially the same for the Absorption of triclosan, though variant between the Absorption, this species diversity is often relevant with used releasing agent, and this result is identical in all cases basically.Find that copolyester/polyether elastic material is remarkable to the living percent absorption of three nitrogen in the dentifrice, when copolyester/polyether elastic material was used as the hose material of the sucking type feeder that the described dentifrice of the scope of the invention and other dentifrice are housed, The above results was determined.Therefore, comprise the terpenes aromatic substance of (being present in the spice of dentifrice prescription) (be at least dentifrice 0.1%), also do not wish to use copolyester/polyether elastic material and contact with dentifrice of the present invention or collutory even dentifrice and collutory contain.
When repeated trials, use Arnitel TMCopolyester/polyether elastic material thin film make existing Guala sucking type feeder as the dentifrice container, the loss of triclosan also is unacceptable, if but with other acceptable plastics, when replacing copolyester/polyether elastic material as polyvinyl fluoride, the activity of triclosan improves, and reaches acceptable limit.In addition, do not find that other parts of plastics (as the polypropylene inwall) of above-mentioned sucking type feeder can absorb triclosan excessively, therefore, the antiplaque activity of dentifrice can significantly not reduce, and obviously this is to have terpenic reason in the aromatic owing to dentifrice.
Carry out group experiment, comprise at least that wherein 10 people application is contained in this example dentifrice that scribbles in polyethylene terephthalate and the polyethylene-lined pipe, brush teeth 2 every day in one month, carries out sequence during this period and observe, and experimenter's dental plaque is estimated.Result of the test proves that the dentifrice composition of this example has sure antiplaque activity, its effect is with to test viewed result with the mouth cleaning solution of example 1 and 2 similar, confirmed that also triclosan does not have underproof inactivation activity, triclosan still has the ratio of effectively antibiotic and antiplaque in dentifrice.
Example 4 composition % glycerol 7.00 propylene glycol 3.00 small carrageenin 0.75 sorbitol (70%) 30.00 saccharin sodium 0.30 sodium fluoride 0.33 titanium dioxide 0.50Gantrez RS-97 (13% solution) 15.00 deionized waters, 16.07 sodium hydroxide (50% aqueous solution) 0.80Zecdent R113 (J.M.Huber company) 20.00Sylodent R15 (silicon thickening agents; W.R.
Grace company) 3.00 aromatic, 0.95 sodium lauryl sulphate, 2.00 triclosans 0.30
100.00
By above-mentioned formulated toothpaste, and be stored in the sucking type feeder flexible pipe of Arnitel type thin film.This dentifrice is enclosed in the thin slice pipe that thin slice inside scribbles polyethylene terephthalate, and inside pipe wall contacts with dentifrice.With this dentifrice in 5 ℃, 25 ℃ and 39 ℃ of degradations of carrying out for 2,4 and 6 weeks.Behind aging period, 1.5g supplies with this dentifrice with about every day, at interval the content of triclosan in the dentifrice supplied with of all assay determinations.Under the situation of Guala sucking type feeder, the dentifrice of being supplied with is loss 27% triclosan approximately, loses excessively, and is inappropriate.This loss constant, and irrelevant with storage temperature or period of storage, this phenomenon can be explained from birth with sucking type film absorption trichlorine, because just produced contact before supplying with.This damp film is made by copolyester/polyether elastic material, should avoid with this class plastics as the container that contains triclosan dentifrice or supply container or as their parts.If but with previously mentioned any plastics of accepting, when for example the thin film made of polyethylene terephthalate replaces elastic copolyester/polyethers thin film, the thin-film material that it can be used as improved sucking type feeder (replenishes this kind plastics of different proportion, improve) can improve the stability of triclosan, it is satisfied and effectively that said composition is used as anti dental plaque tooth paste.
After storage and in supplying with, the stability of the triclosan of the gel dentifrice prescription of above-mentioned packing has similar situation.
In the similar test,, show terpenes (compositions 0.1% or more), the limonene of (or aromatic itself) existence in the aromatic, can prevent loss or its inactivation of triclosan with the loss little (＜5%) of its triclosan of polyethylene terephthalate lining pipe.If use polyvinyl fluoride lining pipe, even save aromatic in the dentifrice composition, the loss of triclosan is also little, when the application polrvinyl chloride contacts with dentifrice as lining material, or when using polysulfones or Merlon and contacting with dentifrice, also be same situation as package member.Yet, do not use the plastic of back 3 kinds of titles usually as above-mentioned showing.
In the test of being reported, wherein adjust container allotment dentifrice with Guala, with 4.76 parts of Luviform (35%) replacement Gantrez S-97, and when preparing, aspect triclosan stable, do not find tangible difference between 2 prescriptions with deionized water.
Polishing material is a siliceous material rather than based on the material of aluminium oxide in the above-mentioned prescription.When buffing compound changed over aluminium oxide, the problem of more above-mentioned plastics can reduce, but still existed.In addition, the terpenic stability that is beneficial to triclosan that has in the dentifrice, with regard to this point, similarly the existence of siliceous buffing compound also helps the stable of triclosan in the dentifrice composition.
Example 5
In the mouth cleaning solution of above-mentioned example and the dentifrice each composition in compositions proportion can ± 10% and ± 25% scope in change, condition is that this percentage ratio can not surpass the scope that provides elsewhere in this description, can obtain the product of effectively antibiotic and antiplaque like this, like this, product can be supplied with the effective state of antiplaque from the above-mentioned supply container of plastics manufacturing applicatory.The dentifrice gel of being mentioned above above-mentioned product can also being become in this description, oral cavity gel, paste, liquid agent, lozenge, capsule, tablet and little sachet agent.At polyvinyl fluoride, polrvinyl chloride, the material of Merlon and polysulfones packaging material or packing composition exists down, even when not having aromatic and terpenes in the Orally administered composition, the above-mentioned product that contains triclosan or other halogenated diphenyl ether or antimicrobial ascoxal still can be very stable by the same manner, in addition, when polyethylene as packaging material or packing composition material, the polypropylene polyethylene terephthalate, polyallomer, when nylon and polymethylpentene exist, as long as the fragrance component of a terpenes (as limonene) or a Stabilization is present in the Orally administered composition, then this product also is stable.Situation as other dentifrice previously discussed and collutory is the same, because copolyester/polyethers and other elastomeric materials have excessive Absorption or other detrimental effects to triclosan, therefore preferably avoids using this class material.
Example 6
The dentifrice of preparation example 3 and 4 prescriptions, in 30 ℃ in (another kind of situation) soft dentifrice tube of polyethylene-lined (a kind of situation) and polyethylene terephthalate lining storage use by shown in Figure 1 squeezing on the bristle toothbrush after 1 month.Squeeze in the amount of paste on the toothbrush in 0.8～2.0g scope, better with 1～1.5g.When using 1.5g toothpaste, effective triclosan is about 4mg (only having 10% triclosan to lose activity) in the dentifrice on toothbrush.When storing under long period or higher temperature, perhaps the more unsettled plastic of lay up period contacts with dentifrice, can contain about 3mg triclosan in the compositions of the 1.5g encapsulation of using on toothbrush.Therefore on the toothbrush during with 1g dentifrice the amount of triclosan be about 2.7mg and 2mg respectively.For the dentifrice that contains 0.25%～0.6% triclosan, be in 10%～25% scope if triclosan loses activity, then triclosan is 2.2～8mg, if there is not triclosan to lose activity, then triclosan can reach about 9mg.
The dentifrice of above-mentioned encapsulation is applied on the toothbrush brushes teeth the about 0.8～2g of general each usefulness.Brush teeth every day 2 times, morning and evening each 1 time, each 1 minute, carried out for 4 weeks, to compare with the contrast dentifrice that does not contain triclosan, the back antiplaque effect of 4 weeks improves significantly.Be packaged in polyethylene and polyethylene terephthalate lining pipe in contain triclosan and the matched group that do not contain spice (not containing terpenes) is compared, the antiplaque effect also is improved.
The present invention has narrated relevant instantiation, but the present invention is not subjected to their restriction, and obviously, those skilled in the art that can utilize substitute or suitable thing before this explanation, and can not break away from spirit of the present invention.

Claims (9)

1. antiplaque anti-calculus composition for oral cavity, it comprises a kind of carrier for oral cavity of being stored in the supply container and a kind of water-fast non-cationic halogenated diphenyl ether antibacterial antiplaque speckle agent of effective 0.02%-1% antiplaque amount, described supply container has the solid polymer that contacts with the agent of described antibacterial antiplaque speckle and compatible with it, so that store described compositions does not cause described ascoxal after 12 weeks the active loss of at least 25% antiplaque in the described container of room temperature, it is characterized in that described loss suppresses by following measure:
A. use politef or polrvinyl chloride as polymeric material, this class material is compatible with the agent of described antibacterial antiplaque speckle, and/or
B. when this class polymeric material is selected from not compatible with the agent of described antibacterial antiplaque speckle polyethylene or polypropylene, Merlon, polymethylpentene, polyallomer and nylon, the terpenes stabilizing agent that comprises a kind of 0.01%-2% in described compositions is so that this polymer is compatible with the agent of described antibacterial antiplaque speckle.
2. according to the compositions of claim 1, wherein said ascoxal comprises triclosan.
3. according to the compositions of claim 1 or 2, wherein said polymeric material comprises that polyethylene and described compositions contain the stabilizing agent of a kind of claim 1 (b) definition.
4. according to the compositions of claim 1 or 2, wherein said polymeric material comprises that polyethylene terephthalate and described compositions contain the stabilizing agent of a kind of claim 1 (b) definition.
5. according to the compositions of claim 1 or 2, wherein said stabilizing agent comprises limonene.
6. according to the compositions of claim 1 or 2, wherein said ascoxal comprises the mixture of tetrasodium pyrophosphate or potassium.
7. according to the compositions of claim 1 or 2, further contain fluoride sources.
8. according to claim 1 or 2 compositionss, further contain the polyvinyl methyl ether maleic anhydride copolymers.
9. according to the compositions of claim 1 or 2, wherein said container is opaque.
CN89106899A 1988-12-29 1989-12-28 Packaged antibacterial antiplaque oral composition Expired - Lifetime CN1082806C (en)

Applications Claiming Priority (16)

Application Number Priority Date Filing Date Title
US07/291,712 US4894220A (en) 1987-01-30 1988-12-29 Antibacterial antiplaque oral composition
US219,712 1988-12-29
US39860689A 1989-08-25 1989-08-25
US39860589A 1989-08-25 1989-08-25
US39966989A 1989-08-25 1989-08-25
US399,669 1989-08-25
US398,605 1989-08-25
US398,606 1989-08-25
US398,592 1989-08-25
US398,566 1989-08-25
US07/398,566 US5032386A (en) 1988-12-29 1989-08-25 Antiplaque antibacterial oral composition
US07/398,592 US5188821A (en) 1987-01-30 1989-08-25 Antibacterial antiplaque oral composition mouthwash or liquid dentifrice
US41068289A 1989-09-21 1989-09-21
US410,682 1989-09-21
US07/427,660 US5135738A (en) 1988-12-29 1989-10-26 Article comprising a dispensing container of polymeric material in contact with an antiplaque oral composition with which it is compatible
US427,660 1989-10-26

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US4418841A (en) * 1982-11-23 1983-12-06 American Can Company Multiple layer flexible sheet structure
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CA2006713C (en) 2001-02-13
NO178953B (en) 1996-04-01
OA09256A (en) 1992-08-31
SE8904179D0 (en) 1989-12-12
IL92691A0 (en) 1990-09-17
FI98121C (en) 1997-04-25
DE3942642A1 (en) 1990-08-30
PT92736A (en) 1990-06-29
FR2641187B1 (en) 1994-06-10
HU896809D0 (en) 1990-03-28
SE8904179L (en) 1990-06-30
SK281207B6 (en) 2001-01-18
NL8903186A (en) 1990-07-16
FI896317A0 (en) 1989-12-28
CH679741A5 (en) 1992-04-15
IE63176B1 (en) 1995-03-22
FI98121B (en) 1997-01-15
NZ231814A (en) 1992-05-26
FR2641187A1 (en) 1990-07-06
CN1044223A (en) 1990-08-01
HUT52695A (en) 1990-08-28
NO895309D0 (en) 1989-12-28
AU4676889A (en) 1990-07-05
AT398034B (en) 1994-08-25
CA2006713A1 (en) 1990-06-29
BR8906850A (en) 1990-10-02
RU2103990C1 (en) 1998-02-10
IE894194L (en) 1990-06-29
CZ286156B6 (en) 2000-01-12
MY105787A (en) 1995-01-30
GB8928964D0 (en) 1990-02-28
GB2227661B (en) 1992-12-02
PT92736B (en) 1997-03-31
MA21713A1 (en) 1990-07-01
GB2227661A (en) 1990-08-08
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HK172095A (en) 1995-11-17
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NO178953C (en) 1996-07-10
DK671089A (en) 1990-06-30
LU87652A1 (en) 1990-05-15
CZ751089A3 (en) 1999-08-11
HU206971B (en) 1993-03-01
NO895309L (en) 1990-07-02
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UA55363C2 (en) 2003-04-15
SK751089A3 (en) 2001-01-18

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