WO1993023007A1

WO1993023007A1 - Oral care compositions containing silica based materials with improved compatibility

Info

Publication number: WO1993023007A1
Application number: PCT/US1993/004716
Authority: WO
Inventors: James Neil Pryor
Original assignee: W.R. Grace & Co.-Conn.
Priority date: 1992-05-19
Filing date: 1993-05-17
Publication date: 1993-11-25
Also published as: JPH08502034A; AU4251693A; EP0641191A1; EP0641191A4

Abstract

The compatibility of silicas with therapeutic agents in oral care compositions is improved by dehydroxylating the silica by a) thermal treatment and/or b) chemical reaction with a dehydroxylation agent selected from the group consisting of alcohols, silanes, and organosilanes. The invention provides especially beneficial improvement in compatibility between silica and non-fluoride therapeutic agents used in dentifrice and other oral care compositions.

Description

ORAL CARE COMPOSITIONS CONTAINING SILICA BASED MATERIALS WITH IMPROVED COMPATIBILITY

Background of the Invention

Commercial oral care compositions, such as dentifrices, lozenges, chewing gums, etc., generally contain a variety of constituents. These constituents (such as therapeutic agents, carrier fluids, humectants, abrasives, thickeners, flavorings, fragrances, etc.) are typically selected based on various criteria such as cost, efficacy and compatibility.

Compatibility refers to the interaction between the various constituents when they are put together into a single composition. Compatibility is concerned with how any interaction between the various constituents may affect the efficacy of the individual constituents. While there may be situations where the efficacy of constituents is enhanced by combination in' a single composition, the goal often is to find combinations of constituents which have a minimum adverse interaction. Since the performance of the therapeutic agent(s) is generally most important for the overall performance of the dentifrice composition, the other constituents are often chosen based on their compatibility with the therapeutic agent(s) to be used.

A wide variety of therapeutic agents for oral care compositions have been developed over the years. Fluoride-based agents are most widely known and used for their proven anti-caries effects, however there are numerous other therapeutic agents which have been developed to address other oral care objectives such as fighting calculus, plaque, bacteria, etc. U.S. Patent 5,015,467 (Smitherman) gives a good review and discussion of therapeutic agents for oral care. Examples of non- fluoride agents include pyridinium salts such as cetyl pyridinium chloride (CPC) , guanidines such as chlorhexadine, triclosan, sanguinaria, zinc salts, copper salts, etc. Silica particles have been widely used in oral care compositions as abrasives and/or thickeners, silica particles are generally porous, amorphous silicas having fine particle size. Typical silica particles have surface areas of about 50-800 m²/g. Silica particles used as abrasives generally have pore volumes of about 0.3-1.0 cc/g whereas silica particles used as thickeners may have pore higher pore volumes up to or greater than 1.5 cc/g. Conventional silicas generally have surface hydroxyl groups which are bonded to silicon atoms on the silica surface as SiOH (silanol) groups. Silicas used in dentifrice compositions generally have about 4-8 SiOH groups per nanometer squared.

Silica particles are known to exhibit good compatibility fluoride-based therapeutic agents. Although the silica particles have relatively large surface area, only a small amount of the fluoride species is adsorbed on the silica. Thus, most of the fluoride species in the composition remains available in the oral care composition to perform its therapeutic function in the oral cavity.

Unfortunately, with the increasing use of non- fluoride therapeutic agents in oral care compositions, it has become apparent that conventional silica particles are often not very compatible with non-fluoride therapeutic agents. Non-fluoride therapeutic agents often contain nonionic or cationic species which tend to be adsorbed onto the silica surface. Thus, less of the therapeutic agent is available to perform its therapeutic function in the oral cavity. The problem is especially acute for high surface area/pore volume silicas which are used as thickeners.

Poor compatibility between silica and non-fluoride therapeutic agents has necessitated overloading of the non-fluoride therapeutic agent and/or substituting alternative materials for the silica. Both these solutions to the problem generally involve increased cost and/or unsatisfactory performance. Moreover, substitutes for silica often have less compatibility with fluoride species which are usually used in conjunction with the non-fluoride therapeutic agents in oral care compositions.

U.S. Patent 3,862,307 (DiGiulio) proposed to improve compatibility by reacting the silica with hydrofluoric acid and maintaining the pH of the oral care composition (dentifrice) at less than 5. Use of such low pH in oral care compositions is considered unacceptable both from commerical and physiological perspectives. Accordingly, there remains a need for a viable solution to the silica agent compatibility problem.

Summary of the Invention

The present invention solves the compatibility problem between silica and therapeutic agents, especially non-fluoride therapeutic agents. The invention involves the modification of conventional silica and use of the modified silica in oral care compositions containing therapeutic agents. In one aspect, the invention encompasses oral care compositions containing silica particles and at least one therapeutic agent wherein the improvement comprises using silica particles which have been at least partially

SUBSTT dehydroxylated by thermal treatment.

The thermal treatment embodiment involves heating the silica particles to cause dehydroxylation. The heating is preferably performed at about 350°-850°C for a time sufficient to produce some increase in compatibility.

In another aspect, the invention encompasses oral care compositions containing silica particles and at least one therapeutic agent wherein the improvement comprises using silica particles which have been at least partially dehydroxylated by reacting the silica with a dehydroxylating agent selected from the group consisting of alcohols, silanes, and organosilanes.

Alternatively, the silica may be subjected to a combination of the thermal and chemical dehydroxylation treatments. While the two treatments may be carried out in any order, preferably the thermal treatment is performed prior to the chemical treatment.

The modified silicas of the invention provide significantly improved compatibility with therapeutic agents, especially non-fluoride therapeutic agents. The improved compatibility of the invention does not require highly acidic pH.

These and other aspects of the invention will be explained in further detail below.

Detailed Description of the Invention

The invention involves the modification of conventional silicas used in oral care compositions by thermal and/or chemical treatment to improve the compatibility between the silica and therapeutic agents.

The thermal treatment may be performed by simply heating the silica to cause dehydroxylation. Preferably, the heating is performed at about 300°-850°C for about 1 - 3 hours. The heating may be performed in air or any other suitable atmosphere. The heating may be performed at reduced pressure to facilitate removal of gases evolving from the dehydroxylation (i.e. H0) .

The extent of thermal dehydroxylation can be measured by determining the loss on ignition (LOI) for the silica. As referred to in this application, the LOI is determined by first predrying the sample at 130°C for about four hours. The predried sample is then calcined for two hours at about 960°C. The LOI is the % weight loss of the calcined sample compared to the weight of the predried sample. Preferably, the thermal dehydroxylation is performed to achieve silica having a loss on ignition of about 2% or less, more preferably about 1% or less. Thermal dehydroxylation may be accompanied by reduction in porosity and surface area. Preferably, the thermal treatment is not performed to such an extent as to result in a loss of all porosity. Preferably, the thermally treated particles have a pore volume of at least about 0.3-1.5 cc/g. The extent of thermal treatment which the silica particles can withstand may be partly a function of the porosity in the untreated particles. Chemical treatment to dehydroxylate the silica may be used instead of or in addition to thermal dehy¬ droxylation. Chemical dehydroxylation involves reacting surface hydroxyl groups on the silica with a dehydroxy¬ lation agent selected from the group consisting of alcohols, silanes, and organosilanes. Preferred alcohols are methanol, ethanol, propanol, butanol and glycerol. Glycerol is most preferred since it is non-toxic and is widely used in commercial dentifrice formulae. Chemical dehydroxylation may be performed by combining the silica with an excess amount of the dehydroxylation agent, preferably in the absence of water. The mixture is then reacted whereby some or all of the surface hydroxyl groups on the silica are replaced with a radical from the dehydroxylation agent. In the case of alcohols, an ester of the alcohol would be formed at the site where a hydroxyl group was located. The mixture may be heated to promote the reaction. Once the dehydroxylation reaction has occurred, the dehydroxylated silica may be recovered by filtration. The silica is then preferably dried or otherwise treated to remove unreacted dehydroxylation agent. If glycerol is used as the dehydroxylation agent, excess glycerol need not be removed from the silica surface assuming glycerol is to be used in the oral care composition.

The chemical dehydroxylation is preferably carried out enough to achieve at least some improvement in silica-therapeutic agent compatibility, more preferably at least some improvement in silica-non-fluoride thera¬ peutic agent compatibility. If desired, the dehydroxy¬ lation reaction may be carried out to virtual completion. Unlike thermal dehydroxylation, chemical dehydroxylation generally does not result in loss of porosity. It may be advantageous to use a combination of the dehydroxylation treatments. For example, if substantially complete dehydroxylation is desired with some decrease in porosity, then a combination of thermal dehydroxylation followed by chemical dehydroxylation would be appropriate. Combinations of thermal treatments or combinations of chemical treatments can also be employed if desired. In general, chemical treatment is believed to provide better dehydroxylation of isolated surface hydroxyl groups whereas thermal dehydroxylation may provide more permanent dehydroxylation of adjacent hydroxyl pairs.

The measurement of extent of chemical dehydroxy- lation by measurement of LOI values may not be accurate because the radicals left at the former hydroxyl sites may also be volatilized during heating to determine LOI.

The compatibility of the silica with a particular therapeutic agent can be measured by comparing the availability or concentration of the therapeutic agent in a mixture at a reference pH before and after contact with the silica. The compatibility of the silica may be expressed as the percentage ratio of concentration of the agent in the mixture after contact with the silica to the concentration of the agent in the mixture before silica addition. The pH of the silica-containing mixture is preferably adjusted to the reference pH on addition of the silica. The concentration after contact with silica is preferably measured after separation of the silica from the mixture. The method of determining the concentration of the therapeutic agent may be any conventional method suitable for the particular agent (e.g. ultraviolet light absorption) .

The improvement in compatibility would simply in- volve comparison of the compatibility values for the untreated and treated silicas. The compatibility test may be applied to all dehydroxylated silicas regardless of method of dehydroxylation. While any degree of im¬ provement in compatibility would be encompassed by the invention, preferably the thermal and/or chemical treat¬ ment of the invention results in at least about 5% improvement in compatibility in comparison with the untreated silica. The silica treated in accordance with the invention may be any silica conventionally used in dentifrices or other oral care compositions. Preferably, the silica is an amorphous silica gel (e.g. a xerogel) or an amorphous precipitated silica. Amorphous silica gels and precipitated silicas are typically used in dentifrices or other oral care compositions as abrasives and/or thickeners.

The treatments of the invention provide improved compatibility of the silica with therapeutic agents in general at pH values commonly used in dentifrice and other oral care compositions (e.g. about 6-7) . The treatments also result in improved compatibility at more acidic or basic pH levels. The invention is further illustrated by the following examples. The invention is not limited to the details of the examples.

Example 1 A 200g sample of silica xerogel (620 m²/g surface area, 0.35 cc/g pore volume, 8μ median particle size) was thermally treated for two hours in a muffle furnace at 760°C. Loss on ignition (LOI) , defined as the % weight loss during a two hour, 960°C calcination of a predried sample (130°C) , was used to estimate the extent of dehydroxylation of the silica gel. The LOI value dropped from approximately 7% for the untreated silica to less than 2% for the 760°C treated sample indicating substantial dehydroxylation. The thermally treated sample was then compared to the silica xerogel starting material for CPC compatibility (availability) using the following procedure: o A stock solution of 1.2 wt.% CPC in deionized water was prepared. o Two 1.75 gram samples of the thermally treated and of untreated silica gel were slurried (i.e. four slurries total) into 42 ml aliquots of the stock solution. o The pH of one thermally treated silica gel slurry and one untreated silica gel slurry was adjusted to 6 pH using a small amount of 10% NaOH solution. Correspondingly, the pH of the remaining two slurries was adjusted to 7 pH using the same NaOH solution. o The samples were shaken well then allowed to age overnight (approximately 16 hours at room temperature) . o The slurry samples were then centrifuged and the supernatant liquid from each settled slurry was filtered through a 0.4/t polycarbonate filter to remove any remaining suspended silica gel. o The percentage of CPC remaining in solution

(i.e. available) was determined by measuring ultraviolet light absorbance (at 259.5 nm) of the supernatant and the stock solution and using the following formula:

% CPC Remaining = Abs. of Sample Solution x 100

Abs. of Stock Solution o The pH of the filtered supernatant solutions was then measured. o Because minor shifts in solution pH occurred during aging, linear interpolation/ extrapolation was used to estimate the % CPC remaining for both silica types at exactly 6.0 and 7.0 pH. The measured results as well as the interpolated/ extrapolated values are given in the following table. Significant improvement in availability results from the thermal treatment.

CPC Availability

Measured Values Interpolated Values % CPC % CPC pH Avail. pH Avail.

Starting Material -

Silica Xerogel 5.98 23 6.0 23

7.05 1 7.0

Example 2 A thermally treated xerogel similar to that described in Example 1 except calcined at 800°C was evaluated for chlorhexidine (ChlX) availability. The testing procedure was analogous to that used for determination of CPC availability except that the stock solution consisted of a 1.0 wt.% chlorhexidine digluconate in deionized water, and the UV absorbance measurement used for to determine % ChlX remaining was performed using 254 nm wavelength radiation.

Results, given in the table below, again show the improved compatibility of the thermally treated silica.

ChlX Availability

(Interpolated Values) PH 6 pH 7

Starting Material-Silica Xerogel 55 7

Thermally Treated Xerogel (800°C) 77 62 Example 3 A glycerol-reacted silica xerogel was prepared by slurrying 100 grams of the same xerogel starting material as Example 1 into 350 mis of glycerol and boiling the slurry under vacuum for 2 hours during which time the temperature of the slurry rose to approximately 200°C. 600 mis of anhydrous roethanol were then added to the viscous slurry, and the reacted silica was removed by centrifugation and decantation. The reacted silica was then reslurried in another 600 is of anhydrous methanol, to further wash the product free of unreacted glycerol, and then filtered. The reacted silica product was then dried in a vacuum oven for 16 hours at 165°C in order to remove any remaining methanol solvent. An LOI value of 24.5% confirmed the substantial reaction of glycerol with the silica xerogel surface.

The reacted silica sample was evaluated for CPC availability using the method described in Example 1. Results, given in the following table, show improved CPC availability with the glycerol-reacted silica xerogel compared to the unreacted xerogel from which it was prepared.

CPC Availability

(Interpolated/Extrapolated Values) PH 6 pH 7

Starting Material- Silica Xerogel 23 2

Glycerol Reacted Xerogel 46 29 Example 4 A sample of the glycerol-reacted silica xerogel prepared according to Example 3 was also evaluated for ChlX availability using the method given in Example 2. Results given in the table below again show a superior availability with the glycerol-reacted silica gel compared to the untreated silica gel from which it was prepared.

ChlX Availability

(Interpolated/Extrapolated Values) PH 6 PH 7

Starting Material- Silica Xerogel 55 7

Glycerol Reacted Xerogel 76 42

Example 5

A sample of the same silica xerogel starting material of Example 1 was treated by thermal dehydroxylation followed by glycerol reaction. The thermal treatment was identical to that described in Example 1 except that the temperature of the treatment was 705°C. It was followed by a glycerol reaction step identical to that described in Example 3. The resulting sample was tested for ChlX availability using the method described in Example 2.

ChlX Availability (Interpolated/Extrapolated Values) PH 6 PH 7

Starting Material- Silica Xerogel 55

Combined Thermal Treatment Plus Glycerol Reaction 83 74

Claims

WHAT IS CLAIMED IS:

1. In an oral care composition containing silica particles and at least one therapeutic agent, the improvement comprising said silica particles being at least partially dehydroxylated by thermal treatment.

2. The composition of Claim 1 wherein said thermal treatment comprises heating said silica particles to about 300-850°C.

3. The composition of Claim 2 wherein said heating is conducted for a time sufficient to improve compatibility of said silica with said therapeutic agent.

4. The composition of Claim 3 wherein said heating lasts about 1-3 hours.

5. The composition of Claim 4 wherein said thermally treated particles have a pore volume of at least about 0.3-1.5 cc/g.

6. The composition of Claim 3 wherein said therapeutic agent comprises at least one non-fluoride therapeutic agent.

7. The composition of Claim 6 wherein said non- fluoride therapeutic agent is selected from the group consisting of pyridinium salts, guanidines, triclosan, sanguinaria, zinc salts, and copper salts.

8. The composition of Claim 6 wherein said non- fluoride therapeutic agent is selected from the group consisting of antibacterial agents, antiplaque agents, and anticalculus agents.

9. The composition of Claim 3 wherein said therapeutic agent comprises a cationic or nonionic species.

10. The composition of Claim 3 wherein said compatibility is increased by at least about 5% by said thermal treatment.

11. The composition of Claim 1 wherein the improvement further comprises chemically dehydroxylating said thermally treated silica by reacting said thermally treated silica with a dehydroxylating agent selected from the group consisting of alcohols, silanes and organosilanes.

12. The composition of Claim 11 wherein said thermal and chemical treatments result in improved compatibility between said silica and said therapeutic agent.

13. The composition of Claim 1 wherein said composition comprises a fluoride.

14. The composition of Claim 1 wherein said silica particles are selected from the group consisting of silica gels, precipitated silicas and mixtures thereof.

15. The composition of Claim 14 wherein said oral care composition is a dentifrice.

16. The composition of Claim 1 having a pH of about 6-7.

17. In an oral care composition containing silica particles and at least one therapeutic agent, the improvement comprising said silica being at least partially dehydroxylated by reacting said silica with a dehydroxylating agent is selected from the group consisting of alcohols, silanes and organosilanes.

18. The composition of Claim 17 wherein said reacting is performed to an extent sufficient to improve compatibility of said silica with said therapeutic agent.

19. The composition of Claim 18 wherein said compatibility is increased by at least about 5% by said reacting.

20. The composition of Claim 17 wherein said therapeutic agent comprises a non-fluoride therapeutic agent.

21. The composition of Claim 20 wherein said non- fluoride therapeutic agent is selected from the group consisting of pyridinium salts, guanidines, triclosan, sanguinaria, zinc salts, and copper salts.

22. The composition of Claim 17 wherein said dehydroxylated silica particles have a pore volume of at least about 0.3-1.5 cc/g.

23. The composition of Claim 22 wherein said pore volume is at least 1.5 cc/g.

24. The composition of Claim 17 wherein said composition comprises a fluoride.

25. The composition of Claim 17 wherein said dehydroxylating agent is an alcohol selected from the group consisting of methanol, ethanol, propanol, butanol and glycerol.

26. The composition of Claim 17 wherein said reacting is performed at elevated temperature.

27. The composition of Claim 17 wherein said silica is selected from the group consisting of silica gels, precipitated silicas and mixtures thereof.

28. The composition of Claim 27 wherein said oral care composition is a dentifrice.

29. The composition of Claim 17 having a pH of about 6-7.