Micellar solution for endodontic and / or oral cleaning

Abstract

The invention pertains to a micellar solution for endodontic and / or oral cleaning, in particular for endodontic and / or oral disinfection, comprising a phospholipid; and a chelating agent. Such micellar solutions are essentially non-toxic, non-antigenic, non-carcinogenic and the smear layer is completely removed. Further, such micellar solutions require no further irrigation solutions to prevent endodontic reinfection. In addition, no detrimental precipitates are formed and no dentine discoloration occurs.

Description

[0001] Micellar solution for endodontic and / or oral cleaning

[0002] The invention relates to a micellar solution for endodontic and / or oral cleaning, in particular endodontic and / or oral disinfection, according to the independent claim .

[0003] In endodontic treatments , the obj ective of any chemical cleaning of the root canal is to heal and prevent endodontic infections caused by planktonic bacteria and biofilm . A biofilm is formed by thin-layered condensations of microorganisms as for example , bacteria, fungi , protozoa, that naturally colonise various surface structures . The microorganisms aggregate to form a colony with a complex structure that adheres to a surface with a smear layer that protects the microorganisms from harmful exogenous influences such as antimicrobial agents and a variety of disinfectants used in the treatment of endodontic infections . The smear layer is a porous layer of amorphous structures of organic particles consisting of coagulated proteins , necrotic and pulpal tissue debris , microorganisms and inorganic particles of minerals from dentine structure . For success ful treatment of endodontic diseases the whole biofilm and bacteria should ideally be removed in order to prevent reinfection .

[0004] In the prior art the removal of this biofilm is achieved by mechanical debridement and chemical cleaning . The chemical cleaning has so far only been achieved by applying a number of di fferent irrigation solutions which is time consuming . Current endodontic solutions like sodium hypochlorite and chlorhexidine are associated with certain toxicity potential . Sodium hypochlorite for example can cause serious inj uries to the patient i f extruded into the periodontium . Further, the combination of di f ferent irrigation solutions has led to undesirable interactions, which have resulted in, for example, precipitation of carcinogenic para-chloroaniline or a reduction in efficacy.

[0005] It is thus an object of the present invention to overcome at least some of the drawbacks outlined above, e.g. to provide a micellar solution for endodontic and / oral cleaning, in particular for endodontic and / or oral disinfection, that is easy to use, and / or has less toxicity potential. This objective is solved by a micellar solution for endodontic and oral uses according to the independent claims. Preferred embodiments are defined in the dependent claims and throughout this specification.

[0006] Pursuant to the invention, a micellar solution for endodontic and / or oral cleaning, in particular for endodontic and / or oral disinfection, comprises a phospholipid (i.e., at least one phospholipid) and a chelating agent (i.e., at least one chelating agent) . Such micellar solutions are essentially non-toxic, non- antigenic, non-carcinogenic and the smear layer is completely removed. Further, it has surprisingly been found that such micellar solutions require no further irrigation solutions to prevent endodontic reinfection. In addition, no detrimental precipitates are formed and no dentine discoloration occurs.

[0007] As understood herein, a micellar solution is a dispersion of micelles in water. Micelles are formed due to the presence of the phospholipids, due to their amphiphilic characteristics.

[0008] In preferred embodiments the micellar solution has a pH between 1.5 to 6.5. The carefully selected pH range has the advantage of stabilising the solution, being non-corrosive, non-irritating and still possesses the property of bacterial and biofilm removal and therefore amenable for use as mouth washer and / or antiseptics. In further preferred embodiments , the phospholipid is a quaternary ammonium salt , preferably selected from the group consisting of myristamidopropyl PG-dimonium chloride phosphate , linole- amidopropyl PG-dimonium chloride phosphate , cocoamidopropyl PG- dimonium chloride phosphate , sodium coco PG-dimonium chloride phosphate , and combinations thereof . These quaternary ammonium salts , in particular the aforementioned PG-dimonium chloride phosphates , are particularly advantageous due to their foaming behaviour, which can be further enhanced to produce microstreaming, for example through ultrasonic agitation . Further, they reduce the surface tension, which allows the micellar solution to reach even the smallest side channels of the root canal to remove the biofilm and avoid reinfections . In addition, they aid in the incorporation of di f ficult to dissolve chemical substances present in the irrigation solution . This prevents phase separation and provides a physically stable micellar solution . Moreover, they make the solution mild and non-corrosive . As a result , the periodontal tissue is not damaged .

[0009] Myristamidopropyl PG-dimonium chloride phosphate , which is particularly preferred, is also referred to as [ 3-bis [ 3- [ dimethyl- [ 3- ( tetrade canoylamino ) propyl ] azaniumyl ] - 2 -hydroxypropoxy ] phosphor yloxy- 2 -hydroxypropyl ] -dimethyl- [ 3- ( tetrade canoylamino ) propyl ] azanium; trichloride . In particular in the preferred concentration range ( cf . below) , it completely, ef fectively and gently removes the biofilm without irritating the soft tissue . It further provides advantageous viscosity and good surface tension reduction, allowing the micellar solution to penetrate deeper into the accessory canals , lateral canal , and isthmus .

[0010] In further preferred embodiments , the phospholipid ( s ) is / are comprised in a concentration between 0 . 01 - 30% by weight , preferably in a concentration between 0 . 1 - 15% by weight , more preferably in a concentration of about 2 . 5 % . In this range of concentrations , the physical and functional integrity of the solution is not compromised, which could otherwise render the solution unusable for its intended application .

[0011] In further preferred embodiments , the chelating agent ( s ) is / are selected from the group consisting of glycolic acid; lactic acid; gluconic acid; carboxylic acids with two or more carboxylic acid groups , in particular a tricarboxylic acid, preferably citric acid; N- ( 2-hydroxyethyl ) iminodiacetic acid (HEIDA) ; aminopolycarboxlic acids , preferably ethylenediaminetetraacetic acid (EDTA) ; hydroxyethylethylenediaminetriacetic acid (HEDTA) ; methylglycinediacetic acid (MGDA; , L-glutamic acid, N, N-diace- tic acid ( GLDA) ; and combinations and salts thereof . Citric acid ( and its salts , respectively) is particularly preferred because it very ef fectively destroys the smear layer and does not lead to undesirable precipitations . In addition, citric acid is low in toxicity . Aminopolycarboxlic acids , preferably ethylenediaminetetraacetic acid (EDTA) ( and salts thereof , respectively) , are advantageous because they show a microbial ef fect that avoids reinfections of the endodontic area .

[0012] In further preferred embodiments , the chelating agent ( s ) , preferably the tricarboxylic acid or a salt thereof , is / are comprised in a concentration between 1 . 0 to 45% by weight , preferably in a concentration between 5 to 25% by weight , more preferably in a concentration of about 10% by weight . It has been found that this range of concentrations is advantageous for ef fective removal of the smear layer without compromising the integrity of the dentine . For example , higher concentrations were found to cause demineralisation of the dentin, resulting in microcracks and tooth fracture over time . In further preferred embodiments, the chelating agent (s) is / are selected from the group consisting of ethylenediaminetetraacetic acid (EDTA) and citric acid and a combination thereof. In these embodiments, it is preferred that the ethylenediamintetraacetat and / or citric acid or the salt thereof is comprised in the micellar solution in a concentration between 1 - 25% by weight, preferably in a concentration between 5 - 20% by weight, more preferably in a concentration of about 17% by weight.

[0013] In some embodiments, the micellar solution further comprises a surfactant which is not a phospholipid.

[0014] In preferred embodiments, the surfactant that is not a phospholipid is comprised in the micellar solution in a concentration between 0.01 - 15.0% by weight, preferably in a concentration between 0.1 - 10.0% by weight, more preferably in a concentration of about 0.65 % by weight.

[0015] In preferred embodiments, the surfactant that is not a phospholipid is polyglycerol; or an ester of polyglycerol and caprylic acid. A preferred surfactant that is not a phospholipid is poly- glyceryl-10 caprylate. Polyglyceryl-10 Caprylate, in particular in the aforementioned concentration ranges, is mild and shows excellent foaming properties. It aids in creating a flash foam and supports a more stable foam structure for the micellar solution. Further, and in particular in the aforementioned concentration ranges, the surface tension and viscosity of the solution allow for a better flow so that necrotic tissues and dentinal debris are better removed from the canal ramification.

[0016] In preferred embodiments, the micellar solution further comprises a preservative, to increase the lifetime of the micellar solution . In further preferred embodiments, the preservative is comprised in a concentration between 0.01 - 2.0% by weight, preferably in a concentration between 0.1 - 1.5% by weight, more preferably in a concentration of about 1.0% by weight.

[0017] In further preferred embodiments, the preservative is 2-phenoxy- ethanol. It has been found to very effectively preserve the solution from degradation and to prolong the shelf life. In addition, it enhances the antimicrobial properties of the solution.

[0018] In the following the invention is exemplified in more detail with a specific example, without restricting the object of the invention to this embodiment.

[0019] The composition of a micellar solution according to the specific example is as follows (amounts are given in % by weight) :

[0020] Component %

[0021] Myristamidopropyl PG-dimonium chloride phosphate (phospholipid) 2.5

[0022] Citric acid (chelating agent) 6.80

[0023] Tri-sodium citrate dihydrate (chelating agent) 3.30

[0024] 2-Phenoxyethanol (preservative) 1.00

[0025] Polyglyceryl-10 caprylate (surfactant) 0.65

[0026] Distilled water (matrix) 85.75

[0027] Figure 1: Scanning electron microscope (SEM) images showing the effect of the exemplary micellar solution on a human dentine disc-surface

[0028] As shown in Fig. 1, the effect of an exemplary micellar solution on the smear layer is striking.

[0029] The smear layer removal was evaluated by soaking dentine discs in the micellar solution for 5 min. Afterwards the dentine discs were analysed by scanning electron microscope ( SEM) . The dentine discs were obtained by sectioning human teeth hori zontally with a disc si ze of 2mm . The discs were rinsed with deionised water and dried with filter paper . An initial scanning electron micro- scope analysis has been performed . After soaking the dentine discs of 5 minutes in the micellar solution, the dentine discs were rinsed again with deionised water to terminate further chemical activity of the solution on the dentine discs . The dentine discs were dried again with filter paper . Finally, a scan- ning electron microscope analysis ( SEM) was carried out .

[0030] The result of the SEM shows that the smear layer covering the canal surfaces after sectioning of the teeth were signi ficantly removed after treating the dentine discs with the exemplary micellar solution . The dentine tubuli are clearly visible .

Claims

Claims1. A micellar solution for endodontic and / or oral cleaning, in particular for endodontic and / or oral disinfection, comprising- a phospholipid; and- a chelating agent.

2. A micellar solution according to claim 1, wherein the pH is between 1.5 and 6.5.

3. A micellar solution according to claim 1 or 2 wherein the phospholipid ( s ) is / are a quaternary ammonium salt; preferably selected from the group consisting of myristamidopropyl PG-dimonium chloride phosphate, linoleamidopropyl PG-dimo- nium chloride phosphate, cocoamidopropyl PG-dimonium chloride phosphate, sodium coco PG-dimonium chloride phosphate, and combinations thereof.

4. A micellar solution according to any of claims 1 to 3, wherein the phospholipid ( s ) is / are comprised in a concentration between 0.01 - 30% by weight, preferably in a concentration between 0.1 - 15% by weight, more preferably in a concentration of about 2.5 %.

5. A micellar solution according to any of claims 1 to 4 wherein the chelating agent (s) is / are selected from the group consisting of glycolic acid; lactic acid; gluconic acid; carboxylic acids with two or more carboxylic acid groups, in particular a tricarboxylic acid, preferably citric acid; N- ( 2-hydroxyethyl ) iminodiacetic acid (HEIDA) ; aminopolycarboxlic acids, preferably ethylenediaminetetraacetic acid (EDTA) ; hydroxyethylethylenediaminetriaceticacid (HEDTA) ; methylglycinediacetic acid (MGDA; , L-glutamic acid, N, N-diacetic acid (GLDA) ; and combinations and salts thereof .

6. A micellar solution according to any of claims 1 to 5 wherein the chelating agent (s) , preferably the tricarboxylic acid or a salt thereof, is / are comprised in a concentration between 1.0 to 45% by weight, preferably in a concentration between 5 to 25% by weight, more preferably in a concentration of about 10% by weight.

7. A micellar solution according to any of claims 1 to 6 wherein the chelating agent (s) is / are selected from the group consisting of ethylenediaminetetraacetic acid (EDTA) and citric acid and a combination thereof.

8. A micellar solution according to claim 7, wherein the eth- ylenediamintetraacetat and / or citric acid or the salt thereof is comprised in a concentration between 1 - 25% by weight, preferably in a concentration between 5 - 20% by weight, more preferably in a concentration of about 17% by weight .

9. A micellar solution according to any of claims 1 to 8, wherein the micellar solution further comprises a surfactant which is not a phospholipid.

10. A micellar solution according to claim 9, wherein the surfactant is comprised in a concentration between 0.01 - 15.0% by weight, preferably in a concentration between 0.1 - 10.0% by weight, more preferably in a concentration of about 0.65% by weight.

11. A micellar solution according to claim 9 or 10, wherein the surfactant is polyglycerol; or an ester of polyglycerol and caprylic acid.

12. A micellar solution according to any of claims 1 to 11, wherein the micellar solution further comprises a preservative .

13. A micellar solution according to claim 12, wherein the pre- servative is comprised in a concentration between 0.01 -2.0% by weight, preferably in a concentration between 0.1 - 1.5% by weight, more preferably in a concentration of about 1.0% by weight .

14. A micellar solution according to claim 12 or 13, wherein the preservative is 2-phenoxyethanol .

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