HK1075200B - Oral composition comprising fine ground natural chalk - Google Patents

Description

Oral composition containing fine ground natural chalk

The present invention relates to oral compositions comprising fine ground natural chalk.

Chalk is a commonly used abrasive in oral care formulations and such formulations have been sold worldwide for many years. One of the main advantages of this is that it is relatively inexpensive compared to other abrasives, such as silica. It is therefore quite common to choose chalk as the abrasive when producing toothpaste for developing or emerging markets.

Although chalk is available in many different forms, only one form is commonly used in the oral care market, namely Precipitated Calcium Carbonate (PCC).

PCC is typically produced by firing limestone or marble to form calcium oxide, which is then digested with water to form highly basic calcium hydroxide. Then bubble carbon dioxide in the thick slurry to form calcium carbonate (CaCO)₃). However, this production process is rarely completed completely, and always leaves traces of calcium hydroxide.

It should be noted that the use of the early term "chalk" in oral care is quite imprecise and refers to calcium carbonate such as PC, and in the present invention the term refers to Fine Ground Natural Chalk (FGNC) obtained from limestone or marble, which of course has been established for millions of years before grinding.

As mentioned above, virtually all oral care formulations containing chalk in the marketed prior art contain almost exclusively PCC.

In the literature, there are numerous references disclosing that any type of chalk, such as natural or precipitated, preferably precipitated chalk, can be used with equal effectiveness. Examples of such references include US3966863(Forward), which discloses that aragonite or calcite, or both, may be used, but preferably the chalk is synthetic precipitated chalk.

Further disclosed in WO 99/32074 (Unilihua) is an oral care formulation which may contain calcium carbonate having a particle size in the range of from 1 to 60 μm in diameter. It also states that ground marble can be used.

WO 00/10520 (Unitraz) discloses that it is common to use calcium carbonate particles having a particle size of 1-15 μm in diameter. It is also stated that the calcium carbonate may be natural or synthetic. However, it cannot be appreciated that chalk of natural origin is not a direct replacement for PCC. Furthermore it fails to disclose that certain natural chalks are preferred over others.

EP-A1-0517319 (Unitrawa) discloses naturally occurring chalk having a particle size of less than 10 μm for use in oral care compositions. It does not disclose the grade of FGNC required by the present invention.

US4844883(Patel) discloses a chalk based dentifrice containing wintergreen flavour. However, the type of FGNC required by the present invention is not taught.

EP-A2-0012008(Beecham) discloses that ground limestone or marble can be used in oral care compositions. However, the grades of FGNC claimed in the present application are not disclosed.

It should be understood that FGNC is a ground natural stone and therefore contains a wide variety of physically different substances. There are many different particle sizes, surface areas, which together can greatly affect their physical and chemical properties. While it is easy to make PCC into the desired grade, it is not so easy to predict what is effective for FGNC from this. The two are physically and chemically different. PCC and FGNC have different particle sizes, different surface areas, different densities, different reactivity, different absorption coefficients, etc. All of this affects how either can be used in an oral care composition. Thus, PCC becomes the chalk abrasive of choice in oral care.

We have now surprisingly found that certain grades of FGNC have significant, unexpected advantages over the prior art when used in oral care formulations.

These benefits include better sodium monofluorophosphate stability, greater triclosan efficacy and the ability to provide a wider formulation window since the pH of the compositions according to the invention can be lower than prior art pastes.

Accordingly, the present invention provides an oral composition comprising from 1 to 60% by weight of the total composition of Fine Ground Natural Chalk (FGNC), characterised in that the FGNC comprises a weight based median particle size of from 1 to 15 microns and a BET surface area of from 0.5 to 3m²Per gram of microparticulate material.

FGNC having these characteristics can be prepared using standard methods in the art, i.e., ball milling followed by sieving followed by selection of the desired characteristics. FGNC may also be chemically or physically modified by coating during milling or heat treatment after milling. Typical coatings include magnesium stearate or oleate. The morphology of FGNC may also be modified by milling processes using different milling methods, such as ball milling, air classification milling and spiral jet milling.

Fine ground natural chalk refers to chalk obtained by grinding limestone or marble deposits rather than synthetic precipitated chalk.

In a preferred embodiment, FGNC is the primary abrasive in the composition. However, the FGNC may also be used in conjunction with other abrasives to provide the composition with an improved abrasiveness profile. Typical such abrasives include PCC, dicalcium phosphate dihydrate (DCPD) or silica.

In an alternative embodiment, the composition of the invention comprises xylitol. Preferably, xylitol is present in an amount of from 0.1 to 20% by weight of the composition, more preferably from 1 to 15%, especially from 5 to 13%. Xylitol is a particularly preferred humectant for FGNC pastes of the present invention because of its anti-caries activity, and also because this effect can be enhanced by using a particular grade of FGNC as described herein.

In a preferred embodiment, the composition of the invention has a pH value below 10. Preferably the pH is below 9.5, more preferably below 9, especially below 8.5. Generally, chalk pastes have a high pH, typically above 10.5. The use of FGNC allows for a reduction in pH, thereby increasing the liberty of the present formulation, as many toothpaste ingredients cannot be used at such high pH values.

In an alternative embodiment, the composition of the invention comprises an alkali metal bicarbonate salt. Preferably the alkali metal bicarbonate is a sodium salt and is present in an amount of 1 to 30% by weight of the composition, more preferably 2 to 20%, especially 3 to 8%.

In a most preferred embodiment, FGNC comprises particles having a specific BET surface area to weight based median particle size ratio. This preferred operating range can be summarized by the following formula:

D＝(BET-3.4831)/A

wherein D is the weight-based median particle diameter (μm); BET is the BET surface area (m)²In g), and A is in the range from-0.17 to-0.23, preferably from-0.195 to-0.205, most preferably from-0.198 to-0.203.

FGNC particles falling within this range and having a weight-based median particle diameter and a BET surface area according to claim 1 are particularly suitable for the present invention. The benefits of using this type of FGNC can be attributed to the specific particle size and surface area combination of the chalk particles. When the particles have too large a surface area, they are too active and react with the perfume and other components, especially the ionic components of the composition. When the particle surface area is too low, it means that they are also large, very dense particles and give the user a gritty feel. These larger, dense particles also present problems in terms of rheological correction of the resulting paste, since they tend to interfere with the basic structure of the composition. The dense chalk particles settle during storage and thus produce an unattractive product.

In an alternative embodiment, the composition of the invention comprises an alkaline earth metal salt of phosphoglycerides. Preferably the alkaline earth metal salt of a phosphoglyceride is a calcium salt and is present in an amount of from 0.01 to 5 wt%, more preferably from 0.1 to 1 wt%, especially from 0.1 to 0.3 wt% of the composition.

In an alternative embodiment, the composition of the present invention comprises an anti-sensitive tooth agent. Preferably the anti-sensitive teeth agent is a potassium salt selected from potassium nitrate, potassium chloride, potassium citrate, potassium tartrate, potassium acetate, potassium ions being present in an amount of from 0.5 to 3% by weight of the composition, more preferably from 1 to 2.5% by weight, especially from 1.7 to 2.2% by weight. When the composition contains this concentration of anti-sensitive tooth agent, it is also preferred that the composition comprises less than 5 wt%, preferably less than 3 wt%, more preferably less than 1 wt% of a thickening agent. This is because these agents tend to produce thicker formulations when used in chalk pastes.

Typically, the BET surface area of FGNC may be from 0.5 to 3m²Per g, more preferably 0.9 to 2.5m²(ii) in terms of/g. The surface area is measured using the Brunauer-Emmett-teller (bet) method based on nitrogen adsorption at 77K. The BET surface area is calculated by using a so-called BET curve constructed using a relative pressure up to 0.3. In this part of the isotherm, a layer of nitrogen molecules (monolayer) is formed on the surface.

Preferably the total chalk content of the oral composition will comprise 35-100% FGNC, preferably 75-100%, especially 95-100% FGNC, with the balance being PCC. Typically, FGNC will comprise from 1 to 70 wt%, more preferably from 30 to 65 wt%, particularly preferably from 35 to 55%, most preferably from 40 to 55% of the oral composition. The FGNC content being around 50% means that no thickening silica is generally required in the oral composition, as FGNC itself may provide sufficient thickening. However, a reduction in FGNC concentration to about 40% often requires the addition of an additional 1-5%, preferably 2-4%, thickening silica to improve the texture of the paste.

FGNC contains particles having a weight-based median particle diameter of from 1 to 15 μm, preferably from 2 to 10 μm, in particular from 4 to 7 μm. Preferably, 90% of the particles will fall within 50%, preferably 30%, in particular 20% of the weight based median particle diameter value on either side of this weight based median particle diameter.

Particle size was measured using a Mastersizer Model X from malvern, version 1.2a, using the measurement methods listed in the instruction manual, using a 300 mm lens in the detector system. Reference to a weight-based median particle diameter in this specification means a particle diameter at which 50 wt% of the total amount of particles is greater than it and 50 wt% of the total amount of particles is less than it.

There is generally a wide range of particle sizes for commercially available FGNC and therefore a wide distribution despite having a low average particle size. This tends to mean that there is a significant amount of particles with a size greater than 15 μm. This gives the paste an unpleasant gritty feel.

In a most preferred embodiment, the composition according to FGNC comprises less than 10 wt%, more preferably less than 5 wt%, especially preferably less than 2 wt% of particles having a diameter of more than 15 μm.

In another embodiment of the present invention, the oral compositions of the present invention contain an alkaline labile ingredient. By base labile is meant that the ingredient is not stable at alkaline pH values, preferably at pH values above 8.5, preferably 9, more preferably 9.5, especially 10. Typically, the stability half-life of such ingredients will be longer than 6 months, preferably 3 months, especially 1 month.

Since chalk pastes are usually formulated at high pH values, it is not uncommon for ingredients common in e.g. silica pastes to be unable to transfer to the chalk process, as they are unstable at such alkaline pH values. Examples include any composition having an ester linkage. They are not commonly used in oral care formulations because the ester linkage is susceptible to hydrolysis at alkaline pH values. A typical such ingredient is wintergreen perfume oil, which is a very popular perfume ingredient in oral care compositions, having a substantially neutral pH. The wintergreen spice oil contains methyl salicylate and ester as main ingredients.

Thus, in a further embodiment of the invention, the oral composition contains a base-labile flavour, and it preferably contains an ester linkage. One such example is methyl salicylate.

In another embodiment of the invention, the oral composition contains a fluoride source as an anti-caries active. Preferably, the fluoride source is an alkali metal salt of monofluorophosphoric acid, preferably the sodium salt of monofluorophosphoric acid (SMFP).

Generally for chalk compositions, SMFP is the fluoride source of choice because its replacement sodium fluoride reacts with calcium carbonate to form insoluble calcium fluoride, which has limited anti-caries activity.

In another embodiment of the present invention, the oral compositions of the present invention contain a hydroxyl containing active. Examples of such active substances include triclosan. When the composition contains an active substance such as triclosan, it preferably also contains an agent to improve the delivery of triclosan to the oral surfaces. Such agents include the well-known delivery-improving polymer Gantrez^®。

In a further aspect of the invention, the oral composition comprises, in addition to FGNC having a weight-based median particle diameter of from 1 to 15 μm, a further particulate ingredient comprising particles having a weight-based median particle diameter of from 0.1 to 1.4 μm, preferably from 0.3 to 1.0 μm, particularly preferably from 0.5 to 0.9 μm. Such smaller particles may be silica, PCC or FGNC and, depending on the benefit to be obtained, constitute from 0.1 to 20% by weight, preferably from 1 to 15% by weight, particularly preferably from 2 to 8% by weight, of the composition according to the invention. For example, smaller particles at 1-5% by weight of the composition help to increase the viscosity of the composition and thereby reduce the need for thickening silica, while smaller particles help to neutralise plaque acid in the oral cavity when present at 5-15%, preferably 8-12% by weight of the total composition.

In a further aspect of the invention, the oral composition comprises, in addition to FGNC having a weight-based median particle diameter of from 1 to 15 μm, a further particulate component comprising particles having a weight-based median particle diameter of from 50 to 800 μm, preferably 100-. Such larger particles are preferably agglomerated particles and comprise silica, PCC or FGNC. Typical agglomerated particles are described in WO 96/09034 (Unitrawa), the contents of which in relation to agglomerated particles are incorporated herein by reference. The agglomerated particles will rapidly break down into smaller particles during brushing and therefore their action is short lived. Depending on the benefit to be achieved, they generally constitute from 0.1 to 20% by weight, preferably from 5 to 17% by weight, particularly preferably from 7 to 15% by weight, of the composition according to the invention. In principle, the benefit is sensory, i.e. the inclusion of larger particles helps to improve the whitening capacity of the composition, but it can also provide another sensory benefit, i.e. the crisping sound of the particles is often seen as an important use advantage, as they not only provide an attractive sensation in the mouth during brushing, but also tend to provide a motivation for increasing the number of brushings or prolonging the brushing time as the user attempts to crush each individual particle.

An important issue with chalk pastes is how to prevent bacterial growth during storage of the chalk slurry or paste. We have found that certain preservatives, such as the methyl, ethyl, butyl, propyl and isopropyl esters of p-hydroxybenzoic acid are particularly useful. Particularly preferred are mixtures containing methyl, ethyl, butyl and propyl parabens. The mixture can be surprisingly improved when combined with phenoxyethanol. Formaldehyde is another preferred preservative, in addition to dimethyldimethylhydantoin, in an amount of 0.05 to 0.8% by weight of the composition.

The oral compositions of the present invention also include other ingredients commonly used in the art, such as:

other antimicrobial agents, such as chlorhexidine, copper, zinc and tin salts, such as zinc citrate, zinc sulfate, zinc glycinate, sodium zinc citrate and stannous pyrophosphate, sanguinarine extract, metronidazole, quaternary ammonium compounds, such as cetylpyridinium chloride; biguanides, such as chlorhexidine digluconate, hexetidine, octenidine, alexidine; and halogenated bisphenol compounds such as 2, 2' -methylenebis- (4-chloro-6-bromophenol);

anti-inflammatory agents such as ibuprofen, flurbiprofen, aspirin, indomethacin, and the like;

other anti-caries agents such as sodium and stannous fluoride, amine fluorides, trisodium metaphosphate, and casein;

plaque buffers such as urea, calcium lactate, arginine, calcium glycerophosphate, and strontium polyacrylate;

vitamins such as vitamin A, C and E;

a plant extract;

desensitizing agents such as potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate, and strontium salts;

anticalculus agents such as alkali metal pyrophosphates, hypophosphite-containing polymers, organic phosphonates and phosphocitrates, polyphosphates, e.g., sodium tripolyphosphate and glass H, and the like;

protoplasm such as bacteriocins, antibodies, enzymes such as papain, and the like;

fragrances, for example peppermint and spearmint oil containing ingredients such as eucalyptol, thymol, methyl salicylate and menthol;

proteins, such as collagen and keratin;

a preservative;

an opacifying agent;

a colorant;

a pH adjusting agent;

a sweetener;

pharmaceutically acceptable carriers such as starch, sucrose, water or water/alcohol systems, and the like;

surfactants, such as anionic, nonionic, cationic and zwitterionic or amphoteric surfactants;

particulate abrasives such as alumina, dicalcium phosphate, calcium pyrophosphate, hydroxyapatite, trimetaphosphates, insoluble hexametaphosphates and the like, including agglomerated particulate abrasives, typically in amounts between 3-60% by weight of the oral care composition;

humectants such as glycerin, sorbitol, propylene glycol, xylitol, lactitol, etc.;

a binder and a thickening agent, wherein the binder is a mixture of a binder and a thickening agent,such as sodium carboxymethylcellulose, xanthan gum, gum arabic and the like, and synthetic polymers, such as polyacrylates and carboxyvinyl polymers, e.g. carbopol^®；

Polymers that improve the delivery of active ingredients, such as biocides, may also be included. Examples of such polymers are copolymers of polyvinyl methyl ether with maleic anhydride and other similar delivery-enhancing polymers, such as those described in DE-A-3,942,643 (Colgate);

buffers and salts to buffer the pH and ionic strength of the oral care composition; and

other optional ingredients that may be included, for example, bleaching agents such as peroxy compounds, e.g., potassium peroxydiphosphate, effervescent systems such as sodium bicarbonate/citric acid systems, color-changing systems, and the like.

Liposomes can also be used to improve delivery or stability of the active ingredient.

The oral composition may be in any form commonly used in the art, such as toothpaste, gel, mousse, aerosol, gel, lozenge, powder, paste, etc., and may also be formulated into a system for use in a dual chamber dispenser.

Embodiments of the oral compositions of the present invention will now be further described with reference to the following non-limiting examples.

Example 1

The following experiments illustrate how the use of FGNC instead of PCC in an oral care composition can improve the stability of sodium monofluorophosphate.

Six typical oral compositions, four of which contained FGNC and the remainder PCC as chalk abrasive, were stored at 40 ℃ for six months. Each sample also contained 1.1% SMFP.

FGNC type	Weight-based median particle diameter (μm)	BET surface area (m)2/g)
			A	14.8	0.66
B	7	2.16
			C	9.4	1.43
D	5.1	2.49
			E	12.3	0.78
F	12.5	0.76
			G	6.4	2.33
			PCC (comparison)	6.9	5.74

Four pastes were prepared using standard methods, three of which were different FGNC compositions according to the invention, a PCC control. Each formulation contained 1.1% sodium monofluorophosphate.

TABLE 1

Chalk used in formulations	Water-extractable F- (as SMF), ppm
						Fresh and fresh	2 months old	3 months old	6 months old
					A	1325	1339	1358	1134
B	1338	1354	1119	874
					C	1323	1349	1396	1158
					PCC	1221	916	907	751

As can be seen from table 1, those pastes containing low surface area FGNC were much larger than the PCC paste for the stability of sodium monofluorophosphate as measured by the free fluoride. This was the case throughout the experiment.

Example 2

The following experiments illustrate how the use of FGNC as a chalk abrasive instead of PCC in a paste can improve the effectiveness of triclosan.

It is primarily concerned with analysing the growth of pure biofilm of bacteria formed in 96-well microtiter plates. The bacteria were treated with a toothpaste slurry and the time required to reach the selected turbidity was recorded.

150ml of Brine Heart Infusion (BHI) medium (purchased from Oxoid) was incubated with 1ml of bacterial culture (Staphylococcus negative) and incubated overnight at 37 ℃. 80ml of this overnight culture was transferred to a 15ml centrifuge tube and centrifuged at 3,500rpm for 7 minutes and the supernatant settled. The particles were redispersed in 5ml of Phosphate Buffered Saline (PBS) and subjected to two more centrifugation and redispersion steps.

The final suspension was diluted in PBS to give an optical density of 1(+/-0.1), as determined using a colorimeter equipped with a 630nm filter.

190ml of bacterial suspension was pipetted into each well of a 96-well Pierce maleic anhydride microtiter plate, the plate sealed and centrifuged at 2000rpm for 2 minutes. The suspension was poured out of the wells and the dish was washed 3 times with water, patted dry on paper towels between each wash.

Sufficient toothpaste slurry was prepared by weighing out the paste and then diluting with fortified saliva in a ratio of 1: 3. The mixture was stirred well for 30 minutes and then centrifuged at 3,500rpm for 30 minutes. The supernatant was collected and retained.

200 μ l of the test slurry was transferred to a biofilm pan and exposed for 30 seconds before removal and then patted dry in the usual manner. Each well was washed with water and dried three times before dropping 200. mu.l BHI and 80. mu.l sterile mineral oil into each well.

The disc is then analyzed with a microtiter plate reader. The selected microtiter Plate reader, Dynatech Dial Microtitre Plate Spectrophotometer 2B1037, has a dynamic program for determining the mean time for the wells to reach a certain optical density, usually 0.5.

All toothpaste gel slurries (four of which contained FGNC and the last PCC as chalk abrasive) were analysed and contained 0.3% triclosan.

Eight parallel test samples of each paste sample + control paste were analyzed on eight parallel wells of a microtiter plate. The time to reach the selected haze (0D ═ 0.5), i.e., the time required for regrowth, was averaged for each of the eight parallel test samples and is shown in table 2.

TABLE 2

Chalk type	Time (hours) required for reaching 0.5 O.D. of
		A	12.38
D	13.00
		B	13.02
C	12.65
PCC	10.14

The data clearly show that the time required to reach an optical density of 0.5 is much higher for the samples containing low surface area FGNC compared to the samples containing PCC as chalk abrasive. It can thus be concluded that the efficacy of triclosan is higher in pastes containing FGNC instead of PCC.

Example 3

In a further experiment, it was shown that the delivery of triclosan increased as the pH of the composition decreased.

Standard toothpastes containing FGNC or PCC and triclosan were tested using a saliva deposition model similar to that described in r.l. wijeijweera and i.kleinberg in archs. oral biol., volume 34, phase 1, 1989, pages 43-53, using in vitro samples and measuring the amount of triclosan delivered to the salivary deposits.

The results are shown in Table 3.

TABLE 3

Chalk type	pH	Triclosan concentration (ppm) in sediment result 1	Triclosan concentration (ppm) in sediment results 2
				A	8.88	439.8	291.7
D	8.87	401.37	275.07
				B	8.87	432.2	286.6
C	8.90	417.7	316.0
PCC	10.01	204.7	137.6

As can be seen from table 3, the low surface area FGNC paste with lower pH is more capable of delivering triclosan than the paste containing PCC as a chalk abrasive.

Example 4

In another experiment, the surprising result, namely the release of volatile flavor molecules from a simulated chalk toothpaste, was greatly enhanced after substituting PCC with low surface area FGNC.

35g of chalk was placed in a sealable vial together with 31.5g of water, 30g of sorbitol, 1 g of peppermint flavor oil (certainly wintergreen or spearmint flavor oils could also be used) and 2.5% sodium lauryl sulfate. The vial was sealed and incubated overnight at 37 ℃. The vapor phase (headspace) samples were analyzed by GC in the morning to measure perfume counts.

Using perfume headspace-GC analysis, the low surface area FGNC paste mimics have a much greater perfume release count than the PCC paste. See table 4.

TABLE 4

Chalk for use in simulated systems	Total area of fragrance after GC analysis (count)
		A	2078914
C	1955331
		D	2078317
F	2044280
		G	2031931
		PCC	1622905

This indicates that perfume can be easily released from low surface area FGNC systems, but less so from typical PCC systems.

Claims (12)

1. Oral composition comprising from 1 to 70 wt% of fine ground natural chalk based on the total composition, characterized in that the fine ground natural chalk is of a median particle size on weight basis of from 1 to 15 μm and a BET surface area of from 0.5 to 3m²Particulate matter per gram.

2. An oral composition according to claim 1, wherein the fine ground natural chalk is a particulate material having a median weight-based particle diameter of from 1.5 to 7 μm.

3. An oral composition according to claim 1, wherein the composition comprises precipitated calcium carbonate.

4. An oral composition according to any one of claims 1 to 3, wherein the composition comprises xylitol.

5. An oral composition according to any one of claims 1 to 3, wherein the composition comprises a bicarbonate salt of an alkali metal.

6. An oral composition according to any one of claims 1 to 3, wherein the composition comprises an alkaline earth metal salt of a phosphoglyceride.

7. An oral composition according to any one of claims 1 to 3, wherein the composition further comprises a base-labile flavour.

8. An oral composition according to claim 7, wherein the base-labile flavorant is methyl salicylate.

9. An oral composition according to any one of claims 1 to 3, wherein the composition contains a fluoride source as the anti-caries active.

10. An oral composition according to claim 9, wherein the fluoride source is an alkali metal monofluorophosphate salt.

11. An oral composition according to any one of claims 1 to 3, wherein the composition comprises triclosan.

12. An oral composition according to claim 11, wherein the composition comprises a dental antiallergic agent.