CN1173323A - Composition for enhancing oral hygiene - Google Patents

Abstract

The present invention relates to a composition for enhancing oral hygiene which can effectively prevent and treat periodontal diseases and dental caries, characterized in that it contains as an effective component one or more component selected from ursodesoxycholic acid and chenodesoxycholic acid having a good inhibiting effect on collagenase, which is known as the inducer of gingivitis.

Description

Be used to promote the compositions of oral hygiene

The present invention relates to a kind of compositions that is used to promote oral hygiene, it can prevent and treat periodontal and caries prevention effectively.The present invention be more particularly directed to a kind of compositions that is used to promote oral hygiene, it can prevent and treat periodontal and dental caries effectively, it is characterized in that it contains one or more components as effective ingredient, this component is selected from has good inhibiting ursodesoxycholic acid and chenocholic acid to collagenase activity.

The multiple oral disease that occurs in the oral cavity tissue is to be caused by the dental plaque that a large amount of microbial actions that exist in the oral cavity form.They are widely studied in the value aspect clinical and the pathology, and are also found by many research worker, comprising Alcxander (A1exander A.G., J.Periodent, 42,21-2,1971), Ash (Ash, M.M., J.Periodontol, 35,424,1964). etc.

Saliva is a kind of special mixture, and it contains electrolyte and other component, for safeguarding that oral health and digestion have important function.Contain various enzymes in the saliva, comprising some enzymes such as metalloproteases, they can strengthen the patient's who suffers from periodontal enzymatic activity.Therefore, ptyalin is the important object of control periodontal research.It is salivary gland, serum, leukocyte, epithelial cell that known and such ptyalin form relevant, oral microorganism etc.

Collagenase belongs to one of metalloproteases, has remarkable effect for the decomposition of connective tissue, and it is present in healthy mouth with the inactivation form, and is present in activated form in periodontal patient's the oral cavity.Therefore, in view of the deactivation of collagenase remarkable contribution, need exploitation have the inhibiting material of collagenase to the treatment periodontal.

Known, fel tauri (gallbladder of cattle) and fel ursi (gallbladder of Bears) are the natural drugs of taking from medicinal animal, and knownly have effects such as pain relieving, function of gallbladder promoting, calmness, spasmolytic and antiinflammatory action, treatment chronic hepatitis, chest (lhoraetic) tumor.In addition, open 93-11992 of Korean Patent and 93-11993 have disclosed by mixing fel

The cleaning agent for mouth cavity that tauri salt is made, it is that Fel Bovis seu Bubali and salt are mixed, and heating at high temperature makes, and contains glycocholic acid, taurocholic acid etc. and salt in the Fel Bovis seu Bubali, has through this mixture of heating and suppresses that dental plaque forms and the effect of control periodontal.But fel tauri and felursi take from the natural drug of medicinal animal, also have some problem, promptly they contained multicomponent, poor stability, this natural material degeneration voluntarily under storage requirement when being used for medicine, and it be difficult to keep constant drug effect.

Therefore, the inventor has improved the above-mentioned problems in the prior art by research, thereby and develops a kind of medicine that can eliminate periodontal because of prevention of periodontal disease outbreak substantially.The result, we have found a kind of compositions that contains one or more components, this component is selected from ursodesoxycholic acid and chenocholic acid, they all are main components of fel ursi, they can suppress the activity of collagenase effectively as active ingredient, and collagenase is the material that causes periodontal, and said composition has improved bin stability, and compare human patients with the compositions that contains fel tauri or fel ursi itself and have improved safety, thereby finished the present invention.

Therefore, the purpose of this invention is to provide a kind of compositions that is used to promote oral hygiene, it contains one or more components as active component, and this component is selected from ursodesoxycholic acid and chenocholic acid.

In addition, another object of the present invention provides a kind of compositions that is used to promote oral hygiene, it contains one or more components as active component, and this component is selected from ursodesoxycholic acid and chenocholic acid, and the good inhibitory action of triclosan to provide dental plaque to form also is provided said composition in addition.

Above Description of content relevant purpose of the present invention.It only is to some explanation about characteristics and application of the present invention that these purposes should be considered to.Can obtain many other useful results by using content disclosed by the invention by different way or in scope disclosed by the invention, improving the present invention.Therefore except that the content of the present invention that the right claim is limited, can more at large understand other purpose of the present invention and content with reference to disclosure of the present invention.

The present invention relates to a kind of compositions that is used to promote oral hygiene, it contains one or more components as active component, and this component is selected from ursodesoxycholic acid and chenocholic acid.

In compositions of the present invention, as the ursodesoxycholic acid of effective ingredient with chenocholic acid can use separately or use with the form of mixture.When the mixture with ursodesoxycholic acid and chenocholic acid is used for compositions of the present invention, because ursodesoxycholic acid and chenocholic acid can correspondingly be replaced the therefore non-strict restriction of the mixing ratio of described two components.The mixing ratio of ursodesoxycholic acid and chenocholic acid generally is 100: 1 to 1: 100 (weight).

In the compositions of the present invention, the ursodesoxycholic acid that uses respectively or use with form of mixtures and the content of chenocholic acid account for 0.02 to 1.0% (weight) of composition total weight, are preferably 0.02-0.6% (weight).When adopt be the mixture of ursodesoxycholic acid and chenocholic acid the time, the effect of gained was similar substantially when the consumption of mixture should be with a kind of composition of independent use same amount.If the consumption of effective ingredient is lower than 0.02% (weight), the effect of said composition prevention of gingivitis will be reduced to and can't reach required purpose, if the consumption of effective ingredient surpasses 1.00% (weight), then also not preferred, because the increase of required drug effect is not directly proportional with the increase of active constituent content.

As needs, compositions of the present invention also can contain triclosan, and it has good bactericidal effect, and has the effect of eliminating dental plaque and control periodontal, suppresses the potentiation that dental plaque formed and alleviated gingivitis thereby provide.When comprising triclosan in the present composition, contain the 0.01-1.0% (weight) that accounts for composition total weight, ursodesoxycholic acid or the chenocholic acid of preferred 0.02-0.6% (weight) in the compositions, or its mixture, and the triclosan of 0.001%-1.0% (weight), particularly 0.001-0.300% (weight).If the addition of triclosan is lower than 0.0001% (weight), then required synergism a little less than, then also not preferred if the addition of triclosan surpasses 1.000% (weight), because of synergism can not strengthen because of the increase of triclosan.

As needs, according to prepared compositions kind, compositions of the present invention also can comprise one or more materials that is suitable for, they are selected from: fluoride such as sodium fluoride, sodium fluorophosphate, amine fluoride, stannic fluoride etc.,  hold salt (bamboo salt), hibitane, tranamic acid, allantoin, caproic acid, enzyme and herb extracts such as bark of amur corktree, Radix Platycodonis root, Herba Schizonepetae herb, Fructus Gardeniae fruit, licorice, Radix Sanguisorbae root etc. as auxiliary effective ingredient.Especially preferably will assist effective ingredient  to hold salt, bark of amur corktree extract, Radix Platycodonis root extract, Herba Schizonepetae herb extract and fluoride is used in combination by a certain percentage.Be the 1.0-5.0% (weight) that consumption that  holds salt accounts for composition total weight, the gross weight of three kinds of herb extracts can be 0.01-5.0% (weight), and the consumption of fluoride is a conventional dosage, particularly 0.1-1.0% (weight) in the art.If the consumption of auxiliary effective ingredient is lower than preferable amount, then inaccessible required effect, and if the consumption of auxiliary effective ingredient surpasses preferable amount, then be unfavorable for the character of final products such as toothpaste.

The compositions that is used to strengthen oral hygiene of the present invention can be made into toothpaste, collutory, chewing gum, oral cavity massage cream etc., according to application aims, the conventional additives that is adopted comprises abrasive material, wetting agent, binding agent, foaming agent, sweeting agent, antiseptic, medicinal ingredient, essence, acid regulator, brightening agent etc.

When preparation of compositions of the present invention becomes toothpaste form, this dentifrice composition is except that comprising above-mentioned effective ingredient, also comprise additive commonly used in the toothpaste preparation, for example, abrasive material, wetting agent, binding agent, foaming agent, sweeting agent, essence, acid regulator, brightening agent etc.

One or more materials as abrasive material are selected from calcium hydrogen phosphate, silica precipitate, calcium carbonate, hydrated alumina, Kaolin and sodium bicarbonate (NaHCO ₃), consumption is the 20-60% (weight) of composition total weight.

One or more materials as wetting agent are selected from glycerol, sorbitol, amorphism sorbitol solution, propylene glycol, Polyethylene Glycol and xylitol, and consumption is the 20-60% (weight) of composition total weight.The mixing ratio of glycerol or amorphism sorbitol solution and propylene glycol or Polyethylene Glycol mixture is preferably 10: 1 to 1: 1, and consumption is the 20-50% (weight) of composition total weight.

One or more materials as binding agent are selected from carrageenin, xanthene glue, sodium carboxymethyl cellulose, carboxyl ethylene polymer, sodium alginate, propolis and Laponite, its consumption accounts for the 0.1-3.0% (weight) of composition total weight, preferred 0.5-2.0% (weight).

One or more materials as foaming agent are selected from anion surfactant such as sodium lauryl sulphate, sarcosyl etc., and fatty acid sorbitol ester, polyoxyethylene hydrogenated Oleum Ricini and polyoxyethylene polyoxypropylene condensation polymer, consumption is the 0.5-5.0% (weight) that accounts for composition total weight, is preferably 0.5-3.5% (weight).

In addition, be selected from saccharin sodium, sweetener and glycyrrhizin as one or more materials of sweeting agent, consumption is the 0.05-0.5% (weight) that accounts for composition total weight, and one or more antiseptic are selected from p-Hydroxybenzoate and sodium benzoate.

Wait all by suitable mixed as the Herba Menthae quintessence oil of essence, spearmint essential oil, Mentholum, carbon oil (carbon).Preferably an amount of Oleum Anisi Stellati is added above-mentioned essence mixture by a certain mixing ratio.One or more materials as acid regulator are selected from phosphoric acid, sodium phosphate, citric acid, sodium citrate, succinic acid, sodium succinate, tartaric acid and sodium tartrate, are used for pH value is adjusted to 5-8.In addition, the consumption as the titanium oxide of brightening agent is composition total weight 0.1-2.0% (weight).

When compositions of the present invention is made the collutory form, preparation by the following method.

Mouthwash agent composition generally partly is made of alcohol moiety and pure water.Be that every kind of component all is dissolved in the part to its energy excellent dissolution, the two parts with gained are mixed with into mouthwash agent composition then.At this, ethanol is used to make collutory to have pure and fresh mouthfeel and dissolves those essence that is slightly soluble in water and antiseptic.Though the volatilization of essence is directly proportional with alcoholic acid content, because excess ethanol can cause bitterness also can stimulate oral mucosa, so consumption of ethanol generally accounts for the 1.0-30.0% (weight) of composition total weight, preferred 2.0 to 20% (weight).

The component that is mainly used in the preparation mouthwash agent composition comprises solubilizing agent, wetting agent, essence, sweeting agent, antiseptic etc., also comprises medicinal ingredient such as antibacterial, enzyme, the agent of anti-blood plasma enzyme etc.

Applicable antibacterial comprises antibacterial, cationic surfactant and quarternary ammonium salt compound.But, should do careful prechecking in use because antibacterial can cause allergy and the Drug resistance that causes microorganism.One or more materials as enzyme are selected from dextromase, and it is the main component of dental plaque; Glucoamylase, it can decompose the starch in the food debris and other polysaccharide material that adheres in the oral cavity; α-Dian Fenmei; Beta amylase, glucoseoxidase, it can make glucose oxidase, and (glucose can cause dental caries, its mechanism is: glucose is resolved into organic acid by the microorganism anaerobic in the oral cavity, it can corrode facing) the generation hydrogen peroxide, lysozyme, it is by directly effect destruction cell wall is to produce bactericidal activity, and the consumption of enzyme is a 0.1-100000 units/gram compositions.Adopt the agent of anti-blood plasma enzyme to be used to suppress gingivitis and hemorrhage, the prevention periodontal.Till, the consumption that is selected from one or more materials of tranamic acid, aminocaproic acid etc. is the 0.05-0.30% (weight) of composition total weight.

One or more materials as the solubilizing agent that makes essence solubilising in water are selected from anion surfactant such as sodium lauryl sulphate, sarcosyl etc., fatty acid sorbitol ester, polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene-polyoxypropylene condensation polymer, the polyoxyethylene deriv of senior alkyl acetas and fatty acid sorbitol ester, preferred one or more materials are selected from sodium lauryl sulphate, polyoxyethylene hydrogenated Oleum Ricini and polyoxyethylene-polyoxypropylene condensation polymer, its consumption is the 0.1-3.0% (weight) of composition total weight, is preferably 0.5-3.0% (weight).

Use wetting agent to make product have stability, sweet taste and certain viscosity.The wetting agent that can be used for this purpose can be enumerated glycerol, sorbitol solution, amorphism sorbitol solution, propylene glycol, Polyethylene Glycol and xylitol, preferably glycerine, amorphism sorbitol solution and xylitol.The consumption of wetting agent generally accounts for the 2.0-40.0% (weight) of composition total weight, and preferable amount is 3.0-20.0% (weight).

In addition, can adopt essence and the sweeting agent that improves the use mouthfeel.As Oleum menthae, spearmint essential oil, L-Mentholum, eucalyptus oil or the methyl salicylate of essence, its consumption is 0.1-1.0% (weight); And to adopt lactose sorbitol, sweetener, saccharin sodium etc. be sweeting agent.Particularly the consumption of saccharin sodium generally accounts for the 0.001-0.1% (weight) of composition total weight

One or more materials as antiseptic are selected from benzoic acid, sodium benzoate, p-Hydroxybenzoate, cresol and formalin, and its consumption accounts for the 0.05-0.15% (weight) of composition total weight.Preferred benzoic acid, sodium benzoate, methyl parahydroxybenzoate or the propyl ester of adopting is as antiseptic.

In addition, mouthwash agent composition of the present invention also can comprise buffer agent, coloring agent, sodium chloride etc.Wherein being used to regulate the tart buffer agent of this mouthwash agent composition is one or more materials that are selected from sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium phosphate, citric acid, sodium citrate, succinic acid, sodium succinate, tartaric acid and sodium tartrate.Preferred one or more materials that are selected from sodium dihydrogen phosphate and sodium phosphate that adopt.Coloring agent is used to improve the value of commodity, and is suitable for the application target of this mouthwash agent composition.Can adopt suitable edible coloring agent for this reason.The general sodium chloride that adopts alleviates gingivitis and generation antibacterial activity, and its consumption is the 3-35% (weight) of composition total weight.

To the present invention more at large be described by following examples and experiment.But it should be noted that these help the clear embodiment that understands the present invention and the technology of the present invention scope is not determinate to the present invention.Embodiment 1-6 and comparative example 1-4

The dentifrice composition of the dentifrice composition of embodiment 1-6 and comparative example 1-4 is the proportioning preparation of according to the form below 1 among the present invention.Powdered components should be comprised that specifically sodium carboxymethyl cellulose, saccharin sodium, p-Hydroxybenzoate etc. are scattered in the sorbitol solution and glycerol as the wetting agent component, and the dispersion liquid of gained is diluted with pure water, and in agitator, tentatively mix.In this mixture, add abrasive material and medicinal ingredient.Add foaming agent alkyl sodium sulfate, stabilizing agent and essence at last, and under vacuum condition, be mixed with the purpose dentifrice composition.

Table 1

Component	Embodiment 1	Embodiment 2	Embodiment 3	Embodiment 4	Embodiment 5	Embodiment 6	The comparative example 1	The comparative example 2	The comparative example 3	The comparative example 4
											Calcium hydrogen phosphate	40.00	40.00	20.00	?-	??-	?40.00	?40.00	?40.00	?40.00	?-
Calcium carbonate	?-	??-	20.00	?-	?38.00	???-	??-	?-	?-	?38.00
											The Silicon stone precipitated powder	?-	?-	?-	20.00	?-	???-	??-	?-	?-	-
Sorbitol	25.00	25.00	25.00	40.00	?25.00	???-	?30.00	?30.00	?-	-
											Glycerol	??-	-	?-	?-	??-	?25.00	???-	???-	?25.00	?25.00
Sodium lauryl sulphate	1.50	1.50	1.50	1.50	??1.50	??1.50	??1.50	??1.50	??1.50	??1.50
											Saccharin sodium	0.10	0.10	0.10	0.10	??0.10	??0.10	??0.10	??0.10	??0.10	??0.10
P-Hydroxybenzoate	0.10	0.10	0.10	0.10	??0.10	??0.10	??0.10	??0.10	??0.10	??0.10
											Sodium carboxymethyl cellulose	1.00	1.00	1.00	1.00	??1.00	???-	??1.00	??1.00	??-	??1.00
Carrageenin	?-	?-	?-	?-	???-	??0.90	??-	??-	??0.90	??-
											Ursodesoxycholic acid	0.02	0.20	0.60	1.00	??0.10	??0.02	??0.01	??2.00	??-	??-
Chenocholic acid	?-	?-	?-	??-	??0.10	??-	??-	??-	??-	??-
											 holds salt	?-	?-	?-	??-	??-	??3.00	??-	??-	??3.00	??-
The fluorophosphoric acid disodium	0.76	0.76	0.76	0.76	??0.76	??0.76	??0.76	??0.76	??0.76	??-
											The bark of amur corktree extract	??-	?-	?-	???-	??-	??0.10	??-	??-	??0.10	??-
The Radix Platycodonis root extract	??-	???-	?-	???-	??-	??0.10	??-	??-	??0.10	??-
											The Herba Schizonepetae herb extract	??-	???-	?-	?-	??-	??0.10	??-	??-	??0.10	??-
Pure water adds to	100.0	100.0	100.0	100.0	??100.0	?100.0	?100.0	?100.0	?100.0	?100.0

Annotate: unit-weight % (wt%)

Embodiment 7-12 and comparative example 5-8

The mouthwash agent composition of the mouthwash agent composition of embodiment of the invention 7-12 and comparative example 5-8 is through conventional method preparation according to the proportioning of following table 2.Specifically can be dissolved in alcoholic acid component and be dissolved in fully in the alcohol solvent, add essence then.Mixture is fully stirred, add the pure water part (wetting agent and other component are dissolved in the solution that makes in the pure water) for preparing in advance then, obtain initial soln, then gained solution is filtered, obtain required mouthwash agent composition through stirring.

Table 2

Component	Embodiment 7	Embodiment 8	Embodiment 9	Embodiment 10	Embodiment 11	Embodiment 12	The comparative example 5	The comparative example 6	The comparative example 7	The comparative example 8
											Ethanol (90%)	10.00	10.00	?10.00	??-	????-	?10.00	??10.00	?10.00	?10.00	???-
Glycerol	10.00	?-	?10.00	??-	????-	??-	????-	???-	????-	?38.00
											Sorbitol solution	?-	15.00		?15.00	????-	??-	????-	???-	????-	???-
Xylitol		??-	?-	??-	10.00	?10.00	????-	???-	????-	???-
											Sodium lauryl sulphate	?1.20	?1.20	???1.20	??1.20	???-	??1.20	????1.20	???1.20	????-	???-
Polyoxyethylene-polyoxypropylene copolymer (poloxamer 407)	??-	??-	???-	????-	?1.20	???-	?????-	??-	????1.20	???-
											Saccharin sodium	?0.50	?0.50	????0.50	??0.50	?0.50	??0.50	????0.50	???0.50	????0.50	???0.50
P-Hydroxybenzoate	?0.10	?0.10	????0.10	??0.10	?0.10	??0.10	????0.10	???0.10	????0.10	???0.10
											Ursodesoxycholic acid	?0.02	?0.20	????0.60	??1.00	?0.10	??0.02	????0.01	???2.00		???-
Chenocholic acid		??-	????-	???-	?0.10			????-	????-	??-
											 holds salt	???-	??-	????-	???-	??-	??3.00	???-	????-	????3.00	??-
The fluorophosphoric acid disodium	?0.76	?0.76	????0.76	??0.76	?0.76	??0.76	????0.76	????0.76	????0.76	??-
											The bark of amur corktree extract	?-	????-	???-	??-		??0.10		????-	????0.10
The Radix Platycodonis root extract	?-	??-	???-			??0.10		????-	????0.10	??-
											The Herba Schizonepetae herb extract	?-	??-	????-	??-	?-	??0.10	????-	????-	????0.10	??-
Essence	??1.00	?1.00	????1.00	??1.00	?1.00	??1.00	????1.00	????1.00	????1.00	??1.00
											Pure water adds to	??100.0	?100.0	???100.0	??100.0	?100.0	??100.0	???100.0	??100.0	??100.0	??100.0

Annotate: unit=weight % (wt%)

Embodiment 13-19 and comparative example 9-11

The toothpaste of the toothpaste of embodiment of the invention 13-19 and comparative example 9-11 is according to the preparation of the proportioning of following table 3.Specifically powdered components is comprised that sodium carboxymethyl cellulose, saccharin sodium, antiseptic p-Hydroxybenzoate etc. are scattered in the sorbitol solution and glycerol as the wetting agent component, and the dispersion liquid of gained diluted with pure water, and in blender, tentatively mix.In this mixture, add abrasive material and medicinal ingredient.Add alkyl sodium sulfate, stabilizing agent and essence at last, and under vacuum condition, be mixed with required dentifrice composition as foaming agent.

Table 3

Component	Embodiment 13	Embodiment 14	Embodiment 15	Embodiment 16	Embodiment 17	Embodiment 18	Embodiment 19	The comparative example 9	The comparative example 10	The comparative example 11
											Calcium hydrogen phosphate	??40.00	?40.00	?20.00	??-	???-	?40.00	?40?00	?40.00	?40.00	?-
Calcium carbonate		?-	?20.00	??-	???38.00	???-	?-	?-	??-	?38.00
											The Silicon stone precipitated powder		?-	?-	??20.00	???-	???-	?-	?-	??-	??-
Sorbitol	??25.00	?25.00	?25.00	??40.00	???25.00	???-	?30.00	?30.00	??-	??-
											Glycerol		??-	?-	??-	????-	?25.00	???-	????-	?25.00	?25.00
Sodium lauryl sulphate	????1.50	???1.50	???1.50	????1.50	????1.50	???1.50	???1.50	????1.50	???1.50	???1.50
											Saccharin sodium	????0.10	???0.10	???0.10	????0.10	????0.10	????0.10	????0.10	????0.10	????0.10	????0.10
P-Hydroxybenzoate	????0.10	???0.10	???0.10	????0.10	????0.10	????0.10	????0.10	????0.10	????0.10	????0.10
											Sodium carboxymethyl cellulose	????1.00	???1.00	???1.00	????1.00	????1.00	?????-	????1.00	????1.00	????1.00	????1.00
Carrageenin	?????-	???-	?????-		????-	????0.90		????-	????0.90	????-
											Ursodesoxycholic acid	????0.01	????0.02	????0.02	????0.20	????0.20	????0.01	????0.10	????0.001	???-	????1.50
Chenocholic acid	?????-	????-	????-	???-	????-	????0.01	????-	????-	????-	????-
											Triclosan	????0.0001	????0.0001	????0.0100	????0.1000	????0.3000	????0.0001	????1.0000	????0.0001	????0.0300	????1.5000
The fluorophosphoric acid disodium	????0.76	????0.76	????0.76	????0.76	????0.76	????0.76	????0.76	????0.76	????0.76	????0.76
											Pure water adds to	???100.0	???100.0	???100.0	???100.0	???100.0	???100.0	???100.0	???100.0	???100.0	???100.0

Annotate: the embodiment of unit-weight % (wt%) 20: chewing gum

Gum base 25.00%

Sorbitol 44.00%

Mannitol 12.00%

Glycerol 13.00%

Lecithin 0.50%

Sweetener 2.00%

Ursodesoxycholic acid 0.02%

Essence 1.00% embodiment 21: chamber rubbing frost (cream)

Glyceryl monolaurate 3.00%

Oleyl alcohol 5.00%

Polyethylene Glycol 15.00%

White vaseline 3.00%

N-cetyl monosodium glutamate 0.50%

Hydroxyethyl-cellulose 5.00%

Tocopherol acetate ester 0.10%

Ursodesoxycholic acid 0.20%

Sweetener 0.20%

Essence 0.30%

Pure water adds to 100.00%

The oral cavity massage cream of chewing gum of the foregoing description 20 and embodiment 21 all shows the good result that can alleviate gingivitis.Experiment 1

Logical main following method test and the various effective ingredient of the compositions that is used to promote oral hygiene more of the present invention to the inhibitory action of collagenase activity, wherein effective ingredient comprises ursodesoxycholic acid and chenocholic acid.1) measured matter

Ursodesoxycholic acid, chenocholic acid, fel tauri salt,  hold salt, ordinary salt, Machili skin, bark of amur corktree, Radix Platycodonis root, Herba Schizonepetae herb, licorice, Radix Angelicae Pubescentis root Chamomillae flower, Myrrha, Folium camelliae assamicae, Radix Taraxaci and herb, Flos Lonicerae, Rhizoma Cimicifugae rhizome.2) 1. method of testing adds the azoool solution of 100 μ l 2% in the test tube, adds 190 μ l buffer solution (0.05M Tris-HCl, 1mMCaCl then ₂, PH7.8).2. the various measured matters that in the above solution that makes, add following concentration :-adding ursodesoxycholic acid (10% alcoholic solution) or chenocholic acid (10% alcoholic solution), its ultimate density is 0.02%;-fel tauri salt,  are held salt or ordinary salt is dissolved in above-mentioned buffer solution, its ultimate density is 2.0%.-add 30% ethanol extraction of Machili skin, bark of amur corktree, Radix Platycodonis root, Herba Schizonepetae herb, licorice, Radix Angelicae Pubescentis root, Chamomillae flower, Myrha, Folium camelliae assamicae, Radix Taraxaci and herb, Flos Lonicerae or Rhizoma Cimicifugae rhizome, making its ultimate density is 0.1%.3. adding 100 μ l concentration is the collagenase of 100ppm, then this mixture is preserved 18 hours in 37 ℃ incubator.(make the standard activity curve by the collagenase of 10,100,200 μ l respectively.) 4. with centrifugal 5 minutes of test tube.5. supernatant is separated from test tube and is added in the cell.Adopt the trap at spectrophotometric determination 540nm place, go out tested group activity then by the standard activity curve determination.3) result

Table 4 measured matter is to the inhibitory action of collagenase activity

Project	Trap (540nm)	Inhibition (%) to enzymatic activity	Remarks
				Blank assay	????0.003		Do not contain collagenase
Contrast groups	????0.323	?????0.00	Contain collagenase
				Ursodesoxycholic acid	????0.243	????45.64
Chenocholic acid	????0.260	????39.23
				Feltauri salt	????0.330	????-6.15
Seat holds salt	????0.320	?????1.98
				Ordinary salt	????0.330	????-6.15
The Machili peel extract	????0.298	????17.74					Contain collagenase, 30% ethanol extraction
			The bark of amur corktree extract	????0.315	?????5.80
The Radix Platycodonis root extract	????0.325	????-2.01
			The Herba Schizonepetae herb extract	????0.320	?????1.98
Licorice root extract	????0.325	????-2.01
			The Radix Angelicae Pubescentis root extract	????0.325	????-2.01
The Chamomillae flower extract	????0.328	????-4.48
			The Myrrha extract	????0.310	?????9.48
Pu'er tea	????0.305	????13.02
			Radix Taraxaci and herb extract	????0.300	?????1.98
Flos Lonicerae extract	????0.328	????-4.48
			The dioicus stem extract	????0.330	????-6.15

Table 5 is the inhibitory action of enzyme to glue about the ursodesoxycholic acid and the chenocholic acid of content and mixing ratio.

Ursodesoxycholic acid content (%)	Chenocholic acid content (%)	Trap (540mm)	Inhibition (%) to enzymatic activity
				????0.001	??????-	????0.326	???-2.82
????0.010	??????-	????0.305	????13.02
				????0.020	????-	????0.243	????45.64
????0.050	????-	????0.215	????57.54
				????0.100	????-	????0.166	????71.26
????0.150	????-	????0.050	????88.60
				????0.200	????-	????0.005	????92.03
????0.600	????-	????0.002	????92.22
				????1.000	????-	????0.000	????92.34
????2.000	????-	????0.000	????92.34
				?????-	????0.001	????0.324	???-1.20
?????-	????0.010	????0.315	????6.55
				?????-	????0.020	????0.260	????39.23
?????-	????0.050	????0.230	????52.15
				?????-	????0.100	????0.180	????67.87
?????-	????0.150	????0.052	????88.41
				?????-	????0.200	????0.007	????91.91
?????-	????0.600	????0.002	????92.22
				?????-	????1.000	????0.002	????92.22
?????-	????2.000	????0.002	????92.22
				????0.005	????0.005	????0.310	????9.48
????0.025	????0.025	????0??220	????55.81
				????0.050	????0.050	????0.180	????67.87
????0.100	????0.100	????0.005	????92.03
				????0.500	????0.500	????0.002	????92.22

From above table 4 and table 5 as can be seen, compare with other herb extracts, ursodesoxycholic acid and chenocholic acid show stronger inhibitory action to collagenase.This effect is 0.01% beginning by concentration, and is to reach maximum at 0.6% o'clock in concentration.But after concentration surpassed 0.6%, this effect no longer included phenomenal growth.In addition, when using ursodesoxycholic acid and chenocholic acid mixture, similar to the effect of the every kind of effective ingredient gained that uses same amount separately by the effect of total content mixture gained.Experiment 2

Test by the following method and influence that the effective ingredient that is used for promoting the compositions of oral hygiene more of the present invention forms dental plaque, wherein effective ingredient comprises ursodesoxycholic acid, chenocholic acid and triclosan.1) measured matter ursodesoxycholic acid, chenocholic acid, triclosan.2) 1. method of testing cultivates tested Strep-tococcusmutans 10449 in brain-heart infusion agar culture medium, C type bacterial strain, then with the inoculation of being cultivated on THB (Todd Hewit meat soup), and cultivated 15 hours down at 37 ℃.2. little Glass rod is sterilized and weighed.3. Glass rod is inserted in the tested test tube, contain sucrose in the substrate in the test tube.The measured matter that adds given concentration in test tube adds the test microbial strains then.This test tube was cultivated 24 hours down at 37 ℃.4. after cultivating end, Glass rod is taken out from test tube carefully, and following dry one day at 37 ℃.Measure the final weight of Glass rod.Except that wherein not adding the measured matter, handle contrast groups according to the method identical with the test group.5. by measurement result, calculate the percentage ratio that dental plaque forms according to following equation:

3) result

Table 6

	Ursodesoxycholic acid	Chenocholic acid	Triclosan	Dental plaque forms (%)	????pH
						??1	??0.100	??-	????-	????100.0	????4.2
??2	??-	??0.100	????-	????100.0	????4.2
						??3	??-	??-	??0.0010	????100.0	????4.3
??4	??-	??-	??0.0050	????100.0	????4.3
						??5	??-	??-	??0.0100	????100.0	????4.3
??6	??-	??-	??0.0300	????50.0	????4.5
						??7	??-	??-	??0.0500	????0.0	????7.5
??8	??0.002	???-	??0.0001	????100.0	????4.5
						??9	??0.010		??0.0001	????80.0	????5.2
??10	??0.020	???-	??0.0001	????0.0	????6.8
						??11	????-	??0.002	??0.0001	????100.0	????4.5
??12	??-	??0.010	??0.001	????80.0	????5.1
						??13	??-	??0.020	??0.0001	????0.0	????6.8
??14	??0.010	??0.010	??0.0001	????0.0	????6.8

By the result shown in the last table 6 as can be seen, when ursodesoxycholic acid and/or chenocholic acid mixed with triclosan by a certain percentage, this mixture forms dental plaque had stronger inhibitory action.Experiment 3

Adopting the dentifrice composition of embodiment 1-6 in the table 1 and comparative example 1-4 to measure in accordance with the following methods forms and the inhibitory action of gingivitis dental plaque.The results are shown in following table 7 and 8.1) 1. method of testing selects tested object by the explanation that stomatology detects.2. with the tested object grouping, every kind of compositions group of embodiment and comparative example comprises 10 tested objects, teaches correct method for brushing teeth then.Measurand goes out dental plaque index (by the improved Quigley-Hein index of Turesky) and gingivitis indices (Gingival Blecding index, Loe-Silness index) through oral cavity medical science detection assay.3. before the test, all tested objects are all handled through odontexesis.4. used for two weeks comforted toothpaste (calcium hydrogen phosphate 40%, glycerol 25%, sodium lauryl sulphate 1.5%, saccharin sodium 0.1%, p-Hydroxybenzoate 0.1%, sodium carboxymethyl cellulose 1%, pure water add to 100%), and then measure dental plaque exponential sum gingivitis indices as initial value through oral cavity medical science.5. tested object was brushed teeth for 4 weeks by daily method three uses embodiment every day and comparative example's toothpaste.The 2nd the week and the 4th week to measure dental plaque exponential sum gingivitis indices through oral cavity medical science.6. value and the initial value that obtains after 4 weeks compared, and adopt the significance of T method of inspection test statistics.

Table 7 dental plaque numerical value

Test toothpaste	Initial index	Index after 2 weeks	Index after 4 weeks	Improve index
					Embodiment 1	?1.50±0.32	?1.30±0.27	?1.07±0.34	?0.43±0.28
Embodiment 2	?1.54±0.21	?1.30±0.25	?1.12±0.20	?0.42±0.22
					Embodiment 3	?1.54±0.19	?1.27±0.31	?1.08±0.28	?0.46±0.28
Embodiment 4	?1.47±0.32	?1.24±0.32	?0.98±0.30	?0.49±0.29
					Embodiment 5	?1.54±0.35	?1.17±0.32	?1.10±0.26	?0.44±0.32
Embodiment 6	?1.52±0.26	?1.08±0.19	?0.75±0.10	?0.77±0.13
					The comparative example 1	?1.53±0.28	?1.23±0.26	?1.13±0.32	?0.40±0.32
The comparative example 2	?1.52±0.31	?1.19±0.32	?0.96±0.17	?0.48±0.32
					The comparative example 3	?1.53±0.26	?1.10±0.19	?0.81±0.10	?0.72±0.13
The comparative example 4	?1.53±0.32	?1.37±0.32	?1.29±0.28	?0.24±0.35

The scoring of table 8 gingivitis indices

Test toothpaste	Initial index	Index after 2 weeks	Index after 4 weeks	Improve index
					Embodiment 1	?1.21±0.32	?1.05±0.38	?0.86±0.35	?0.35±0.18
Embodiment 2	?1.23±0.24	?0.95±0.27	?0.76±0.24	?0.47±0.17
					Embodiment 3	?1.23±0.27	?0.89±0.19	?0.63±0.18	?0.60±0.17
Embodiment 4	?1.22±0.23	?0.84±0.16	?0.57±0.12	?0.65±0.12
					Embodiment 5	?1.24±0.18	?0.96±0.30	?0.78±0.25	?0.42±0.23
Embodiment 6	?1.19±0.21	?0.60±0.20	?0.34±0.12	?0.85±0.09
					The comparative example 1	?1.23±0.23	?1.15±0.19	?1.01±0.15	?0.22±0.32
The comparative example 2	?1.18±0.33	?0.83±0.21	?0.55±0.18	?0.63±0.32
					The comparative example 3	?1.20±0.18	?0.84±0.19	?0.48±0.10	?0.72±0.13
The comparative example 4	?1.19±0.31	?1.12±0.32	?1.08±0.48	?0.11±0.32

By last table 7 as can be seen, use the dental plaque index significance test result of toothpaste after 4 weeks of embodiment 1-6 and comparative example 1-4 to show: the compositions of using embodiment 1-6 and comparative example 1-3 with use before compare, have the effect that significant inhibition dental plaque forms.But the effect of the compositions of embodiment 1-5 and comparative example 1-2 there is no marked difference to each other, and embodiment 6 compares with the effect of the compositions of comparative example 1-2 with embodiment 1-5 with comparative example 3 and shows marked difference.In addition, the compositions of embodiment 6 is compared with comparative example 3 compositions, does not show marked difference aspect effect.Therefore think that ursodesoxycholic acid and/or chenocholic acid form not significantly effect to dental plaque.Therefore illustrating that ursodesoxycholic acid and/or chenocholic acid are used in combination with other herb extracts does not show any synergism and antagonism.

Simultaneously, by last table 8 explanation, the compositions of using the dental plaque index significance test result of toothpaste after 4 weeks of embodiment 1-6 and comparative example 1-4 to show to use embodiment 1-6 and comparative example 2-3 with use before compare, have the remarkable effect that alleviates gingivitis, and the compositions of embodiment 6 is compared with comparative example 3 compositions and is had the effect that better alleviates tooth inflammation in age.In addition, also show: compare with the comparative example's 4 who does not contain ursodesoxycholic acid compositions, ursodesoxycholic acid begins to show the effect that alleviates gingivitis when concentration is 0.01% (weight); In concentration is 0.02% (weight) or when higher, shows remarkable effect; When concentration surpasses 1.0% (weight) (comparative example 2), the enhancing of effect is no longer increased proportional with concentration.Therefore think that ursodesoxycholic acid and/or chenocholic acid have the good result that alleviates gingivitis.For this reason, find when ursodesoxycholic acid and/or chenocholic acid holds salt with , when herb extracts is used in combination, its working concentration is 0.02-1.00% (weight), preferably shows the synergism that alleviates gingivitis during 0.02-0.6% (weight).Experiment 4

The inhibitory action that adopts the mouthwash agent composition of embodiment 7-12 described in the table 2 and comparative example 5-8 that dental plaque is formed according to the method test identical with embodiment 3.The results are shown in following table 9 and 10.

The scoring of table 9 dental plaque index

The test mouthwash agent composition	Initial index	Index after 2 weeks	Index after 4 weeks	Improve index
					Embodiment 7	?1.30±0.25	?1.12±0.23	?0.95±0.24	?0.35±0.24
Embodiment 8	?1.31±0.21	?1.08±0.26	?0.89±0.20	?0.42±0.22
					Embodiment 9	?1.30±0.19	?1.07±0.21	?0.85±0.28	?0.45±0.18
Embodiment 10	?1.30±0.22	?1.05±0.22	?0.82±0.30	?0.48±0.29
					Embodiment 11	?1.32±0.2?5	?1.10±0.22	?0.92±0.26	?0.40±0.25
Embodiment 12	?1.30±0.16	?0.95±0.15	?0.59±0.10	?0.71±0.13
					The comparative example 5	?1.29±0.28	?1.13±0.26	?0.99±0.22	?0.30±0.22
The comparative example 6	?1.32±0.11	?1.19±0.12	?0.84±0.12	?0.48±0.12
					The comparative example 7	?1.31±0.21	?1.00±0.19	?0.73±0.18	?0.58±0.13
The comparative example 8	?1.33±0.27	?1.25±0.22	?1.17±0.21	?0.16±0.20

The scoring of table 10 gingivitis indices

The test mouthwash agent composition	Initial index	Index after 2 weeks	Index after 4 weeks	Improve index
					Embodiment 7	?1.05±0.32	?0.87±0.25	?0.72±0.22	?0.33±0.23
Embodiment 8	?1.13±0.28	?0.91±0.23	?0.69±0.20	?0.44±0.19
					Embodiment 9	?1.10±0.20	?0.82±0.16	?0.50±0.28	?0.60±0.23
Embodiment 10	?1.02±0.23	?0.76±0.16	?0.37±0.12	?0.65±0.18
					Embodiment 11	?1.24±0.26	?0.96±0.22	?0.79±0.29	?0.45±0.23
Embodiment 12	?1.19±0.18	?0.65±0.15	?0.41±0.10	?0.78±0.19
					The comparative example 5	?1.20±0.21	?1.11±0.19	?0.99±0.15	?0.21±0.23
The comparative example 6	?1.02±0.31	?0.6?3±0.31	?0.34±0.19	?0.68±0.22
					The comparative example 7	?1.00±0.27	?0.74±0.19	?0.37±0.14	?0.63±0.23
The comparative example 8	?1.10±0.21	?1.05±0.22	?0.99±0.38	?0.11±0.31

From last table 9 and 10 as can be seen, use the dental plaque index significance test result of mouthwash agent composition after 4 weeks of embodiment 7-12 and comparative example 5-8 and coming to the same thing of use dentifrice composition gained.Therefore think still that ursodesoxycholic acid and/or chenocholic acid in the mouthwash agent composition form not significantly effect to dental plaque, but show the good result that alleviates gingivitis.The working concentration of ursodesoxycholic acid and/or chenocholic acid is 0.02-1.00% (weight) for this reason, is preferably 0.02-0.6% (weight).In addition, find when ursodesoxycholic acid and/or chenocholic acid and  hold salt, herb extracts etc. and be used in combination, to show the synergism that alleviates gingivitis.Experiment 5

According to adopting the dentifrice composition of embodiment 13-19 described in the table 3 and comparative example 9-11 that dental plaque is formed with the test of experiment 3 identical methods and the inhibitory action of gingivitis.The results are shown in following table 11 and 12.

The scoring of table 11 dental plaque index

Test toothpaste	Initial index	Index after 2 weeks	Index after 4 weeks	Improve index
					Embodiment 13	?1.72±0.22	?1.55±0.27	?1.39±0.24	?0.33±0.28
Embodiment 14	?1.73±0.19	?1.47±0.15	?1.26±0.20	?0.47±0.17
					Embodiment 15	?1.72±0.19	?1.40±0.18	?1.21±0.18	?0.51±0.28
Embodiment 16	?1.72±0.26	?1.35±0.25	?1.11±0.20	?0.61±0.29
					Embodiment 17	?1.73±0.15	?1.21±0.12	?0.91±0.11	?0.82±0.14
Embodiment 18	?1.74±0.26	?1.50±0.19	?1.30±0.15	?0.44±0.13
					Embodiment 19	?1.72±0.18	?1.18±0.16	?0.85±0.15	?0.87±0.15
The comparative example 9	?1.72±0.18	?1.60±0.17	?1.51±0.17	?0.21±0.22
					The comparative example 10	?1.73±0.26	?1.30±0.19	?1.09±0.19	?0.64±0.13
The comparative example 11	?1.74±0.22	?1.18±0.12	?0.85±0.21	?0.89±0.15

The scoring of table 12 gingivitis indices

Test toothpaste	Initial index	Index after 2 weeks	Index after 4 weeks	Improve index
					Embodiment 13	?1.32±0.22	?1.13±0.28	?0.95±0.25	?0.37±0.24
Embodiment 14	?1.32±0.24	?1.02±0.25	?0.79±0.24	?0.53±0.17
					Embodiment 15	?1.33±0.30	?0.96±0.29	?0.70±0.18	?0.63±0.19
Embodiment 16	?1.31±0.25	?0.95±0.26	?0.62±0.22	?0.69±0.17
					Embodiment 17	?1.32±0.25	?0.96±0.30	?0.52±0.25	?0.80±0.21
Embodiment 18	?1.31±0.24	?1.00±0.26	?0.81±0.23	?0.50±0.19
					Embodiment 19	?1.33±0.21	?0.86±0.19	?0.47±0.25	?0.86±0.22
The comparative example 9	?1.31±0.33	?1.23±0.21	?1.14±0.28	?0.19±0.23
					The comparative example 10	?1.31±0.28	?0.99±0.29	?0.67±0.23	?0.64±0.21
The comparative example 11	?1.31±0.30	?0.86±0.25	?0.43±0.28	?0.88±0.22

By last table 11 as can be seen, use the dental plaque index significance test result of toothpaste after 4 weeks of embodiment 13-19 and comparative example 9-11 to show: the compositions of using embodiment 13-19 and comparative example 9-111 with use before compare, have the effect that significant inhibition dental plaque forms.In addition, the toothpaste that contains 0.01-1.00% (weight) ursodesoxycholic acid and/or chenocholic acid and 0.0001-1.000% (weight) triclosan mixture shows the effect that better inhibition dental plaque forms.Particularly by embodiment 17 and comparative example 10 as can be seen, the toothpaste that contains blended by a certain percentage triclosan and ursodesoxycholic acid mixture shows the effect that better inhibition dental plaque forms than the toothpaste that only contains triclosan.

Simultaneously, the gingivitis indices significance testing result of toothpaste after 4 weeks by use embodiment 13-19 described in the last table 12 and comparative example 9-11 shows: the compositions of using embodiment 13-19 and comparative example 9-11 with use before compare, have the use that alleviates gingivitis significantly.In addition, the toothpaste that contains 0.01-1.00% (weight) ursodesoxycholic acid and/or chenocholic acid and 0.001-1.000% (weight) triclosan shows the effect that better alleviates gingivitis.Particularly by embodiment 17 and comparative example 10 as can be seen, the toothpaste that contains blended by a certain percentage triclosan and ursodesoxycholic acid mixture shows the effect that better inhibition dental plaque forms than the toothpaste that only contains triclosan.

Can think that deactivation has excellent activity to collagenase as the ursodesoxycholic acid of effective ingredient and chenocholic acid in the present invention, collagenase is the evocator of gingivitis.Therefore, when containing these compositions in toothpaste, collutory, chewing gum, the oral cavity massage cream etc., these compositionss can show the good mitigation to gingivitis.In addition, when also comprising known antibacterial triclosan in the compositions, said composition can show the effect of the alleviation gingivitis of effect that stronger inhibition dental plaque forms and enhancement.

In addition, because compositions the invention described above, that have good result, that be used to promote oral hygiene does not contain natural drug fel tauri and the fel ursi that takes from medicinal animal, said composition has some advantage, it is rotten promptly can not occur raw material substantially at lay up period, excellent storage stability, safe to human patients, therefore compositions of the present invention is easy to use.

Claims (13)

1 one kinds of compositionss that are used to promote oral hygiene, it contains one or more effective ingredient, and they are selected from ursodesoxycholic acid and chenocholic acid.

The compositions of 2 claim 1, the content that wherein is selected from one or more compositions of ursodesoxycholic acid and chenocholic acid accounts for the 0.02-1.0wt% of composition total weight.

The compositions of 3 claim 2, the content that wherein is selected from one or more compositions of ursodesoxycholic acid and chenocholic acid accounts for the 0.02-0.6wt% of composition total weight.

The compositions of 4 claim 1, effective ingredient wherein are the mixture of ursodesoxycholic acid and chenocholic acid, and its weight mixing ratio is 100: 1 to 1: 100.

The compositions of 5 claim 1, it also contains triclosan.

The compositions of 6 claim 5 wherein contains one or more of the 0.01-1.0wt% that accounts for composition weight, is selected from the composition of ursodesoxycholic acid and chenocholic acid, and the triclosan of 0.0001-1.0wt%.

The compositions of 7 claim 6, one or more that wherein contain the 0.02-0.6wt% that accounts for composition total weight are selected from the composition of ursodesoxycholic acid and chenocholic acid, and the triclosan of 0.001-0.3000wt%.

The compositions of 8 claim 1, wherein also contain one or more auxiliary effective ingredient, they are selected from sodium fluoride, sodium fluorophosphate, amine fluoride, stannic fluoride, hibitane,  and hold salt, tranamic acid, allantoin, caproic acid, enzyme and bark of amur corktree, Radix Platycodonis root, Herba Schizonepetae herb, Fructus Gardeniae fruit, licorice and Radix Sanguisorbae root extract.

The compositions of 9 claim 8 contains wherein that the  that accounts for composition total weight 1.0-5.0wt% holds salt, total amount is the fluoride of bark of amur corktree, Radix Platycodonis root and Herba Schizonepetae herb extract and the 0.1-1.00wt% of 0.01-5.0wt%.

The compositions of 10 claim 1, its form are toothpaste.

The compositions of 11 claim 1, its form are collutory.

The compositions of 12 claim 1, its form are chewing gum.

The compositions of 13 claim 1, its form are the oral cavity massage cream.