CN1250368A - Mouthwash composition - Google Patents

Abstract

A two phase mouthwash composition is described comprising chlorhexidine and polyvinyl pyrrolidone.

Description

Mouthwash composition

The present invention relates to mouthwash composition, particularly the compositions of cation antibacterial hibitane.

WO93/16681 discloses a kind of oral hygiene composition, comprises cation antibacterial such as hibitane and detergent polyvinyl pyrrolidone (PVP).

Have now found that the biphase hibitane/PVP collutory with specific pH scope demonstrates enhanced hibitane effect.

Therefore, first aspect the invention provides and comprises biphase mouthwash composition; First comprises on hibitane or its a kind of stomatology acceptable carrier or excipient on the acceptable acid-addition salts and a kind of stomatology mutually, and second comprises acceptable carrier or excipient on PVP and a kind of stomatology mutually; The biphase maintenance before use separately, mix the back they pH is provided is 6 to 10 single-phase composite.

Using preceding separately is useful with hibitane with PVP mutually, can be lowered because have been found that hibitane its effect after the PVP long term store.

Hibitane mutually and PVP pH scope mutually should be after mixing, obtain 6.0-10.0, preferably 6.0-9.0, more preferably 6.0-7.0 is as 6.2 pH.

Can will wait the hibitane of weight to be mixed mutually easily before using with PVP.

The initial pH of hibitane phase is fit to be not more than 6, and this has the advantage of the extended storage stability that improves hibitane.

The initial pH of preferred hibitane phase is 3.0-6.0,5.0-5.9 5.5-5.9 for example more preferably.

The matched pH of PVP is 6.0-10.0, be preferably 6.0-9.0,6.0-8.0 more preferably.

Thereby preferred described PVP comprises acceptable buffer on a kind of stomatology or pH regulator agent mutually obtains required pH mixing the back mutually with hibitane.

The example of acceptable buffer agent and pH regulator agent comprises a kind of alkali such as sodium hydroxide or a kind of acid such as acetic acid, gluconic acid, tartaric acid, citric acid, lactic acid or phosphoric acid or a kind of its soluble-salt on the stomatology.These materials can use separately, also can mix use.A kind of preferred buffer is a sodium acetate.

For required buffering effect is provided, described buffer or pH regulator agent should exist with enough amounts, and the scope that is fit to is the 0.01-10% of described composition weight, preferred 0.1-2%.

Compositions of the present invention can be packaged in the container such as bottle or pipe with two chambers that separate described each phase, and described container has a dispersing nozzle to be disperseed for the control of described each phase before using and compatibly mix.Perhaps described compositions can be packaged in the bag (sachet) with two Room, and two Room separate by a brittle sealing material, before using seal dissepiment is broken to allow biphasely to mix in bag.

Perhaps also can be packaged in the independent container biphase, desirable aequum is respectively disperseed mutually before mixing and the use.

Be used for that polyvinyl pyrrolidone of the present invention is fit to have at least 5000, the mean molecule quantity of for example 5000-100000, preferably have the mean molecule quantity of 5000-50000.Having mean molecule quantity and be 10000,30000 and 40000 polyvinyl pyrrolidone can be respectively available from Sigma Chemical Co., GAF Corporation and Sigma ChemicalCo..The suitable amount of polyvinyl pyrrolidone be described composition weight at least 0.5%, be preferably 0.5-30%, 0.5-25% more preferably, favourable scope is 1-15%.

On hibitane or a kind of its stomatology the suitable amount of acceptable acid-addition salts be described composition weight 0.005-10%, be preferably 0.01-5%, 0.01-2% more preferably.

The salt of the hibitane that is suitable for is included in 20 ℃ of salt with the dissolubility of at least 0.005% (weight/volume), comprises digluconate, diformate, diacetin, dipropionate, two hydriodates, nicotinium dihydrochloride, lactyl-lactic acid salt, dinitrate, sulfate and tartrate.Wherein digluconate, diacetin and nicotinium dihydrochloride are preferred.

Compositions of the present invention also can usefully comprise a kind of ion fluorochemical.The ion fluorochemical that is suitable for for example comprises that fluoride salt such as amine fluoride and alkali metal fluoride salt such as sodium fluoride and mono-fluor phosphate are such as alkali metal mono-fluor phosphate such as sodium monofluorophosphate.Described ion fluorochemical suitably is blended in the described compositions, so that the fluorion of 50-2000ppm, preferred 100-500ppm to be provided.

Compositions of the present invention is suitable for preferably comprising in a kind of aqueous solution or a kind of water/alcoholic solution as a kind of surfactant of carrier component and the wetting agent of choosing any one kind of them.

It will be understood by those skilled in the art that the antibacterial activity in order to ensure hibitane is not reduced by reality, can select compatible component to be included on the stomatology in acceptable carrier or the excipient.Therefore, should preferably avoid required anionic species, because this material can cause its inactivation by forming insoluble precipitation with hibitane.Therefore, anion surfactant and anionic wetting agent preferably need not and agree with using non-anion homologue such as nonionic, cation or amphoteric surfactant and nonionic wetting agent.

The ionic surfactant pack that is suitable for for example draw together polyethoxylated sorbitol ester, particularly polyethoxylated sorbitol one ester such as PEG (40) two isostearic acid Isosorbide Dinitrates and by ICI with commodity ' Tween ' product sold by name; The condensation polymer of oxirane and expoxy propane (poloxamers) such as BASF-Wyandotte is with commodity ' Pluronic ' product sold by name; The condensation substance of propylene glycol; Polyethoxylated hydrogenated castor such as cremophors; And fatty acid esters of sorbitan.

The amphoteric surfactant that is suitable for comprises that for example the long-chain imidazolidine derivatives is such as being called ' Miranol C2M ' product sold by Miranol with commodity; Long-chain alkyl lycine is such as being called ' Empigen BB ' product sold and chain alkyl amido alkyl betanin such as cocamidopropyl betaine and its mixture by Albright+Wilson with commodity.

The cationic surfactant that is fit to comprises the D with the ethyl-N-cocoyl-L-arginine ester of commodity CAE sale by name by Ajinomoto Co.Inc., L-2-pyrrolidone-5-carboxylic acid salt.

Preferred surfactants comprises non-ionic poloxamers and many ethoxylated hydrogenated castor oils.

Have been found that if the pH of mixed phase at 6-10, preferably at 6-8, the compatibility of so this surfactant and hibitane further strengthens.

The amount of described surfactant be preferably described composition weight 0.005-5%, be preferably 0.005-1%, 0.01-0.5% more preferably.

Be applicable to that the wetting agent in the compositions of the present invention comprises for example glycerol, sorbitol, propylene glycol or Polyethylene Glycol or its mixture.The amount of described wetting agent can be described composition weight 5-70%, be preferably 5-30%, 5-20% more preferably.

Other material that can join if desired in the described compositions has for example sweeting agent, fumet, coloring agent, preservative agent and emulsifying agent.

Described PVP fit comprises a kind of sweeting agent such as saccharin sodium, preferably itself and hibitane is kept separating mutually the unnecessary precipitation of hibitane when preventing long term store according to this/glucide coordination compound.

Can be according to preparation of compositions of the present invention by its each component is mixed and when needed its pH regulator carried out to desirable value then in required ratio and by any order easily.

Can be used for reducing or eliminating the stain that normally is accompanied by the appearance of use hibitane according to compositions of the present invention.

Therefore, on the other hand, the invention provides the defined mouthwash composition that is used for the treatment of of a kind of preamble, especially for the treatment of anti-speckle, preventing decayed tooth, anti-calculus and/or periodontal disease (comprising anti-gingivitis).

The present invention now illustrates with reference to the following example.

Embodiment 1 hibitane collutory

Composition %w/w	Hibitane phase %w/w	PVP phase %w/w
			PVP	-	15.000
Saccharin sodium	-	0.104
			Sodium acetate	-	1.400
The hibitane gluconate	0.400	-
			Glycerol	10.000	-
Dye solution	0.100	0.100
			Ethanol	5.000	8.000

Cremophor?RH60 *	0.200	0.250
			Flavored oils	0.120	0.120
Deionized water	84.180	75.026
			Altogether	100.00	100.00
Mixing back pH is 6.20	Initial pH is 5.90	Initial pH is 6.30

^*Cremophor RH60 is a kind of polyethoxylated hydrogenated castor that contains average 60 ethoxy units in the polyethoxylated chain.

Embodiment 2 pH are to from the bonded influence to the hydroxyapatite disk of coating saliva of the hibitane of collutory

It is active efficiency index in the oral cavity to the combination of hydroxyapatite that those skilled in the art know hibitane, because the effect of hibitane is attached to the ability of oral surfaces just because of it.

Following test method be used in the external test hibitane to hydroxyapatite in conjunction with level:

A) with the hydroxyapatite disk of known surface area under 37 ℃ in soaked overnight in sterifiltered blended people's saliva;

B) then disk was cleaned 15 seconds in 25 ml deionized water;

C) then every disk is soaked 60 seconds in 5 milliliters of test solutions after, washing 3 times (each 60 second time) in the deionized water of 25 milliliters of equal portions;

D) extract bonded hibitane and pass through high performance liquid chromatography (HPLC) analysis from disk then.

In order to estimate pH, contrast solution shown in table 1 and 2 and collutory have been prepared to the influence of hibitane in conjunction with level.Then product is estimated the hibitane associativity with listed method.What obtain the results are shown in Table 3.

Table 1

	Standard %w/w
					Collutory :-	1	2	3	4
The hibitane gluconate	0.00	0.03	0.06	0.09
					0.1M sodium acetate buffer	To 100.00	To 100.00	To 100.00	To 100.00

pH

?7.0

?7.0

?7.0

?7.0

Table 2

	Test collutory %w/w
							Collutory :-	???5	???6	???7	???8	???9	???10
The hibitane gluconate	???0.06	???0.06	???0.06	???0.06	???0.06	???0.06
							Cremaphor?RH60	???0.225	???0.225	???0.225	???0.225	???0.225	???0.225
Flavored oils	???0.12	???0.12	???0.12	???0.12	???0.12	???0.12
							Ethanol 96	???6.50	???6.50	???6.50	???6.50	???6.50	???6.50
Blue dyes solution	???0.10	???0.10	???0.10	???0.10	???0.10	???0.10
							Glycerol	???5.00	???5.00	???5.00	???5.00	???5.00	???5.00
PVP	???5.00	???5.00	???5.00	???5.00	???5.00	???5.00
							Sodium acetate	???0.70	???0.70	???0.70	???0.70	???0.70	???0.70
Sodium fluoride	???0.05	???0.05	???0.05	???0.05	???0.05	???0.05
							Saccharin sodium	???0.052	???0.052	???0.052	???0.052	???0.052	???0.052
Acetic acid solution 50%w/w	???0.625	???-	???-	???-	???-	???-
							NaOH solution 10.2%w/w	???-	???-	???0.073	???0.083	???0.128	???0.1625
Deionized water	To 100.00	To 100.00	To 100.00	To 100.00	To 100.00	To 100.00
							pH	???5.6	??6.2	???7.5	???8.2	???8.9	???9.5

Table 3

Product	pH	Number of repetition	On average in conjunction with horizontal μ g/cm
				1 (standard)	7.0	10	0.32
2 (standards)	7.0	10	4.67
				3 (standards)	7.0	8	8.18

4 (standards)	7.0	?10	?9.37
				5 (collutory)	5.6	?10	?4.76
6 (collutory)	6.2	?8	?6.51
				7 (collutory)	7.5	?10	?5.66
8 (collutory)	8.2	?10	?6.23
				9 (collutory)	8.9	?9	?6.83
10 (collutory)	9.5	?10	?6.25

The result shows in conjunction with level and significantly improves to 6.2 (collutory 6) from 5.6 (collutory 5) with pH.But, do not observe that there were significant differences between the product along with pH rises to 9.5 (collutory 6-10) from 6.2.

If this experimental results show that the pH that makes collutory just can obtain enhanced in conjunction with level greater than 6.

Claims (8)

1. a mouthwash composition comprises biphase; First comprises on hibitane or a kind of stomatology acceptable carrier or excipient on acceptable its acid-addition salts and a kind of stomatology mutually, and second comprises acceptable carrier or excipient on polyvinyl pyrrolidone (PVP) and a kind of stomatology mutually; Described biphasely separately deposit before use, they provide pH single-phase between 6-10 to mix the back.

2. according to the compositions of claim 1, wherein hibitane obtains the pH that scope is 6.0-8.0 mutually with after PVP mixes mutually.

3. according to the compositions of claim 1 or 2, the pH of wherein said hibitane phase is not more than 6.

4. according to each compositions in claim 1 or 3, wherein the pH of PVP phase is 6.0-10.0.

5. according to the compositions of claim 4, thereby wherein said PVP comprises mutually on a kind of stomatology and to obtain required pH after acceptable buffer or pH regulator agent make it and hibitane mixes mutually.

6. according to each compositions in claim 1 or 5, wherein said PVP is at least 0.5% of described composition weight.

7. according to each compositions among the claim 1-6, also comprise a kind of ion and contain fluoride mixture.

8. according to each compositions among the claim 1-7, comprise a kind of nonionic, both sexes or cationic surfactant.