DENTIFRICE COMPOSITION

The present invention relates to dentifrices, particularly to toothpastes and more particularly to toothpastes that contain zinc salts, while exhibiting lower astringency.

Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of the common general knowledge in the field.

The incorporation of zinc salts into dentifrice compositions to beneficially reduce oral malodour is well known in the art. However, the astringency of zinc salts is a major drawback in its use in dentifrice compositions creating an unpleasant astringent taste in the mouth. In addition, the efficacy against plaque, calculus and odour development is short-lived. Usually, complex formation of zinc with anionic counter ions, such as citrate, reduces its astringency but also reduces its solubility and/or biological availability.

Various attempts have been made in the past to overcome and/or reduce the astringency of dentifrices containing zinc salts .

EP0162574 (1985, Johnson & Johnson) describes the reduction of astringency by the use of pluronic type of polymers, i.e. polyethylene oxide - polypropylene oxide block copolymers as surfactants. The present inventors have found that while this provides for reduction of astringency, it remains a costly option.

Similarly, EP0251542 (1988, Lion Corporation) describes reduction of astringency of zinc salts by the use of polyoxyethylene-hydrogenated castor oil.

There is a need for newer and better ways of reducing the astringent effect of dentifrice compositions containing zinc salts .

It is an object of the present invention to provide for a dentifrice composition that includes zinc salts, while having relatively lower astringency.

It is an object of the present invention to provide a dentifrice composition that offers enhanced level of breath freshness .

The present inventors have found that the astringent aftereffect associated with dentifrice compositions containing zinc salts can be reduced to a significant extent by the use of a polyethylene oxide and a humectant.

The present inventors have surprisingly observed that while the compositions exhibited significant reduction in astringency, the compositions also offered protection against oral malodour for a significantly longer period of time upon continued usage.

According to an aspect of the present invention, there is provided a dentifrice composition that includes: (i) 0.1 to 5 % by weight zinc salt;

(ii) 0.01 to 1.0 % by weight polyethylene oxide having molecular weight of from 100,000 to 8,000,000 g/mol; and

(iii) 10 to 70 % by weight of a humectant.

Preferably, it includes 0.1 to 2 % by weight zinc salt.

Preferably the composition includes 0.1 to 0.5 % by weight polyethylene oxide of molecular weight from 100,000 to 8,000,000 g/mol.

Throughout this specification, reference to "the high molecular weight polyethylene oxide for use according to the invention" should be understood to mean polyethylene oxide of molecular weight from 100,000 to 8,000,000 g/mol.

Preferably the zinc salt is selected from zinc chloride, zinc sulphate or zinc citrate, more preferably it is zinc sulphate .

According to another aspect of the present invention, there is provided a process for making a dentifrice composition that includes mixing 0.1 to 5 parts by weight zinc salt with 0.01 to 1 parts by weight polyethylene oxide having molecular weight of from 100,000 to 8,000,000 g/mol and 10 to 70 parts by weight humectant, with a suitable vehicle.

According to another aspect of the present invention there is provided use of a dentifrice composition according to the invention.

The term "dentifrice", as used herein, means a substance for cleaning the teeth which is suitable for application with a toothbrush and is rinsed off after use. It can be a paste, gel, or liquid formulation. Dentifrice compositions herein can be single, dual or multi phase preparations such as deep striped, surface striped, multilayered, core in sheath, for example having gel surrounding paste, or any combination thereof .

A single phase may include a liquid carrier with one or more insoluble particles, such as of a dental abrasive, homogeneously dispersed within it.

When the dentifrice composition comprises more than one phase, said phases may be contained in physically separated compartments of a dispenser and dispensed side-by-side or they may contained in packaging in which they are in direct contact .

An essential component of the dentifrice compositions according to the invention is a zinc salt. Zinc salts are effective as antimicrobial agents.

The zinc salt preferably has a solubility of at least 0. Ig per lOOg water but insoluble materials such as zinc oxide can provide soluble zinc salts if used in conjunction with other solubilizing materials, such sodium citrate.

Zinc salts useful in the present invention include zinc chloride, zinc sulphate, zinc nitrate, zinc citrate, zinc gluconate, zinc acetate, zinc lactate and zinc salicylate.

Mixed salts such as sodium zinc citrate can also be used. Preferred zinc salts are zinc salts of organic acids such as zinc citrate, zinc lactate, zinc maleate, zinc salicylate, zinc gluconate and zinc ascorbate. However, the most preferred salt is Zinc sulphate. Mixtures of different zinc salts can be used. The zinc salt is preferably incorporated in the oral care composition of the present invention at a concentration of about 0.1 to 5 % by weight and preferably about 0.1 to about 2% by weight and most preferably, the zinc salt level is from 0.1 to 0.5% by weight. Excess amounts of zinc will lead to unacceptable taste and higher level of astringency and may cause problems of compatibility with other ingredients such as e.g., precipitation of anionic polymers.

While not wishing to be bound by any theory, it is believed that the polyethylene oxide having molecular weight of from 100,000 to 8,000,000 g/mol used in the present invention affords a slippery feel to the oral cavity and thereby re- lubricates the mouth. Preferably, the molecular weight is from 600,000 to 2,000,000 g/mol, and more preferably from 800,000 to 1,000,000 g/mol. "POLYOX ^® " is the trade name for a high molecular weight polyethylene oxide produced by Dow Chemicals. A particularly preferred material is available from Dow Chemicals as POLYOX ^® WSR 301-NF. Useful levels of the high molecular weight polyethylene oxide for use according to the invention are from about 0.01% to about 1%, preferably from about 0.1% to about 0.5 % and most preferably 0.1 % to 0.2 % by weight of the composition. Additional level of such polyethylene oxide was observed to present problems with its dispersion in the medium.

The dentifrice composition according to the invention includes a humectant which enhances flavour, prevents harsh taste and provides a fresh and pleasant sensation in the mouth. It also prevents caking of the dentifrice. The humectant serves to keep the dentifrice compositions from hardening upon exposure to air and may also impart a desirable sweetness to the formulations to further minimize the astringency ascribed to the zinc salt. Humectant is preferably present in a total amount of about 10-70%, more preferably about 25-60% by weight. Typical humectants include sorbitol (typically added as 70% aqueous solution) , glycerine, maltitol and xylitol. Most preferably the dentifrice contains about 16-30% glycerine in an opaque cream base, while a combination of 10 to 30 wt% glycerine and 30 to 50 wt% sorbitol (as 70% aqueous solution) is used for clear gel compositions. For the avoidance of doubt, a gel composition comprising 20 wt% glycerine and 40 wt% sorbitol (as 70% aqueous solution) would comprise humectant in a total amount of 48 wt% (20+ [40x0.70 ] ) , assuming no other humectants present.

Sorbitol solution supplies sweetness and body to the composition and gives a desirable mouth feel. It is preferred that a mixture of glycerine and sorbitol is used for a lubricated mouth feel.

In general, an effective amount of sweetener is utilized to provide the level of sweetness desired. This amount will vary with the sweetener selected and the composition.

The amount of sweetener normally present is from about 0.0025 % by weight to about 60 % by weight of the dentifrice composition .

When a substantially visually clear gel is desired, water is generally not present at more than 10%, typically about 2-5% by weight. When the dentifrice is opaque, greater amounts of water may be present. Water employed in the preparation of commercially suitable dentifrices should preferably be deionised and free of impurities. Water comprises from about 0.05 to 70.0%, preferably from about 15.0 to 50.0% by weight of the formulations. These amounts of water include the free water which is added and also that which is introduced with other materials, such as 70% aqueous sorbitol solution.

For a transparent dentifrice, the liquid phase of the composition of the present invention is preferably formulated such that its refractive index closely matches the refractive index of the silicas which are also present in the composition. The liquid phase usually comprises water and a humectant, the latter usually being sorbitol or glycerol. Water has an RI (refractive index) of 1.333; sorbitol (70% aqueous solution) has an RI of 1.457 and glycerine has an RI of 1.473. The refractive index of the liquid phase can be calculated from the respective refractive indices of the constituting ingredients.

The compositions of the invention may contain further optional ingredients, as long as the clarity of the dentifrices, when in gel form, is thereby not impaired and

the RI of the liquid phase is about the RI of the low refractive index abrasive silica.

Another preferred ingredient is a water-soluble fluoride compound, used in an amount sufficient to give a fluoride concentration in the composition of from about 0.0025% to about 0.5% by weight, to provide anti-caries effectiveness. A wide variety of fluoride ion-yielding materials can be employed as sources of soluble fluoride in the present compositions. Representative fluoride ion sources include stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate and many others. Stannous fluoride and sodium fluoride are particularly preferred, as well as mixtures thereof.

If, however, sodium fluoride is used in combination with the long chain polyphosphates then it is preferably kept in a separate phase.

The dentifrices of the invention may also contain coloured particles suspended therein, e.g. coloured silica agglomerates or other coloured particles to impart a "speckled" appearance to the dentifrices. The colouring agent may be in the form of an aqueous solution, preferably 1% colouring agent in a solution of water. Colour solutions generally comprise from 0.01% to 5% by weight of the composition .

Titanium dioxide may also be added to the present composition. Titanium dioxide is a white powder which adds

opacity to the compositions. Titanium dioxide may comprise from 0.25% to 5%, by weight of the composition.

In addition to the high molecular weight polyethylene oxide for use according to the invention, further gelling or binding agent such as organic thickeners of natural and synthetic gums may be incorporated in the compositions of the present invention. Examples of such thickeners are carrageenan (Irish moss), xanthan gum, sodium carboxymethyl cellulose, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, and hydroxyethyl cellulose.

Compositions according to the invention may also include polyethylene oxide of molecular weight less than 100,000. Such materials, for example polyethylene glycol 1500, are often included to improve the cohesion of the composition.

The organic thickener may be incorporated in the compositions of the present invention at a concentration of 10 about 0.25 to about 2% by weight and preferably about 0.5 to about 1% by weight of the composition. Synthetic finely divided pyrogenic silica such as those sold under the trademarks CAB-O-SIL ^® M-5, SYLOID ^® 244, SYLOID ^® 266 and AEROSIL ^® D-200 may also be employed in amounts of about 1-5% by weight to promote thickening or gelling of the dentifrice .

Antibacterial agents commonly known in the art may also be employed in the dentifrice compositions of the instant

invention to provide a total content of such agents of up to about 5% by weight.

The taste of the composition may be modified by employing suitable flavouring or sweetening materials. Examples of suitable flavouring constituents include the flavouring oils, e.g. oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon and orange as well as methylsalicylate, oil of wintergreen, oil of peppermint, oil of spearmint, clove bud oil, menthol, anethole, methyl salicylate, eucalyptol, cassia, 1-menthyl acetate, sage, eugenol, parsley oil, oxanone, alpha-irisone, marjoram, lemon, orange, propenyl guaethol, cinnamon, vanillin, ethyl vanillin, heliotropine, 4-cis-heptenal, diacetyl, methyl-para-tert-butyl phenyl acetate, and mixtures thereof.

A flavour system is generally used in the compositions at levels of from 0.001% to 5%, by weight of the composition. Addition of the flavour takes care of the metallic aftertaste of Zinc salts.

The composition further preferably includes a coolant. Preferred coolants in the present compositions are the paramenthane carboxyamide agents such as N-ethyl-p-menthan- 3-carboxamide, (known commercially as "WS-3") and mixtures thereof and menthone glycerine acetal (known commercially as "MGA") .

Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, sodium cyclamate, perillartine, and

saccharine. The present invention may also include xylitol. Xylitol is a sugar alcohol that is used as a sweetener and humectant. Xylitol may provide a therapeutic effect, such as an antibacterial or anticaries effect.

The present compositions typically comprise xylitol at a level from 0.01% to 25%, preferably from 3% to 15%, more preferably from 5% to 12%, and most preferably from 9% to 11% by weight of the total composition. Alternatively, if xylitol is used as a sweetener, it may be present at a lower level, such as from 0.005% to 5%, by weight of the dentifrice composition.

Surfactant levels cited herein are on a 100% active basis, even though common raw materials such as sodium lauryl sulphate may be supplied as aqueous solutions of lower activity. The surfactant is important for oral cleaning, both thorough removal of dirt from surfaces and in foam generation to suspend removed dirt. Suitable surfactant levels are from about 2% to about 15%, preferably from about 2.2% to about 10%, more preferably from about 2.5 to about 5% by weight of the total composition. Suitable surfactants for use herein include anionic, amphoteric, non-ionic, zwitterionic and cationic surfactants, though anionic, amphoteric, non-ionic and zwitterionic surfactants (and mixtures thereof) are preferred.

An abrasive is normally included in the composition. Abrasives may be selected from water-insoluble alkali or alkaline earth metal salts of metaphosphate, calcium carbonate, aluminate and silicate. Especially preferred are

silica, dicalcium phosphate and calcium carbonate. Amount of the abrasive range from about 5 to about 80% by weight of the composition. Also suitable are chalk-type abrasives such as calcium and magnesium carbonates, silicas including xerogels, hydrogels, aerogels and precipitates, alumina and hydrates thereof.

Abrasives include alpha alumina trihydrate, aluminosilicates such as calcined aluminium silicate and aluminium silicate, magnesium and zirconium silicates such as magnesium trisilicate and thermosetting polymerised resins such as particulate condensation products of urea and formaldehyde, polymethylmethacrylate, powdered polyethylene. Mixtures of abrasives can also be used.

The abrasive polishing materials generally have an average particle size of from about 0.1 to about 30 microns, preferably from about 5 to 15 microns.

Silica dental abrasives of various types offer exceptional dental cleaning and polishing performance without unduly abrading tooth enamel or dentin. The silica abrasive can be precipitated silica or silica gels for example silica xerogels marketed under the trade name SYLOID ^® by W. R. Grace & Company, Davison Chemical Division. Suitable precipitated silica materials include those marketed by the J. M. Huber Corporation under the trade name, ZEODENT ^® 119 or ZEODENT ^® 118. Suitable abrasive levels are from about 1% to about 40%, preferably at least about 2%, such as from about 2% to about 20%, more preferably at least about 5%, such as from about 5% to about 15% by weight of the composition.

Tartar control agents may be incorporated into compositions of this invention, especially effective are agents containing phosphorous. Inorganic phosphorous tartar control agents may include any of the water-soluble pyrophosphates such as disodium pyrophosphate, dipotassium pyrophosphate and mixtures of these with tetrapotassium pyrophosphates or tetrasodium pyrophosphates.

Organic phosphorous compounds that may serve as tartar control agents include polyphosphonates such as disodium ethane-l-hydroxy-1, 1-diphosphonate (EHDP) and methanediphosphonic acid.

Typically compositions according to the invention have a pH in the range of 5 to 8, preferably 6.5 to 7.5, e.g. 7.

The present invention also relates to a process for making a dentifrice composition that includes mixing 0.1 to 5 parts by weight zinc salt with 0.01 to 1 parts by weight polyethylene oxide having molecular weight of from 100,000 to 8,000,000 g/mol and 10 to 70 parts by weight humectant, with a suitable vehicle.

To prepare a dentifrice composition of the present invention, one may add the humectants, such as glycerine and sorbitol, the high molecular polyethylene oxide for use according to the invention, and the zinc salt to water and mix for 10 to 15 minutes in a conventional mixer. Thereafter, optional ingredients, e.g. silica and carboxymethylcellulose, may be added and mixing continued

for a further 10 to 15 minutes, followed by addition of surfactants. The mix may then be de-aerated under vacuum. Flavour and colour ingredients may then be added and mixing continued for a further 10-15 minutes and further de- aeratation under vacuum. The resultant product is typically a stable dentifrice of texture like that of normal gels and of satisfactory flavour.

The invention will now be explained in greater details with the help of the following non-limiting examples.

Example 1

A core and sheath type of toothpaste was made with the core and the sheath being a gel. The ingredients of the composition (Composition -1) have been listed in table-1.

Similarly, placebo toothpaste (gel) was made, which had all ingredients except for zinc sulphate. The balance was made up by adding little extra water.

Table- 1

Performance of Composition-1 and the placebo toothpaste was compared.

Organoleptic studies

190 volunteers in the age group of 18-45 (both male and female) in good health participated in the organoleptic odour study. All volunteers were stratified by age, gender and baseline scores. The volunteers had at least 24 teeth, of which at least 20 teeth had no disease of teeth or gums. They were asked to avoid antibiotics for 3 weeks before test

and were asked to refrain from oral activities ( brushing, gargling, rinsing, eating , drinking , chewing gum, smoking) at least two hours before testing. Volunteers abstained from eating spicy food for 24 hours prior to each visit and refrained from consuming alcohol for 24 hours before each visit .

Four trained organoleptic judges participated in scoring the volunteers. These judges were also asked to refrain from drinking hot beverages, smoking, consuming alcohol or using cosmetics during the study. Each volunteer was asked to close the mouth for 60 seconds and not swallow during this period. After one minute the volunteer breathed out the mouth air gently through a diameter of 24mm / length 5 cm tube at a distance of approximately 10 cm from the nose of the odour judge who were hidden behind the screen and would immediately record the odour on a 0-5 organoleptic scale.

The organoleptic scale of 0 to 5 was as follows: 0 No odour present

1 Barely noticeable odour. Odour is of low intensity and within organoleptically acceptable limits.

2 Slight to moderate odour. Odour is clearly noticeable and slightly unpleasant. 3 Moderate to high malodour. Clearly noticeable, unpleasant malodour of moderate intensity

4 Strong malodour of high intensity

5 Extremely foul odour

All volunteers were asked to refrain from brushing 12 hours prior to the baseline reading. Only those volunteers with

breath score of 3 or > 3 were selected for the study. After the baseline score, they were made to brush their teeth with one full brush length of toothpaste for 3 minutes, followed by rinsing with 25 ml of water. Each volunteer was asked to refrain from drinking and eating till the end of evaluation. The volunteers were scored by at least two judges at all the time points: before brushing (12 hrs post brushing), 10 minutes after brushing and 2 hours after brushing. All analysis was carried out with the student's t-test to derive the significance at 95% confidence level.

The results are summarised in table-2 below.

Table-2

''Comp-l is Composition-1 ,

Thus it will be seen that Composition-1 offers a significant reduction in oral malodour level on day-1 itself, even after two hours of brushing.

Further, the Composition-1 offers significant reduction in malodour level even before brushing (i.e. after 12 hours from the last brushing, overnight) on 4 weeks of continued use (twice daily) and the difference between the placebo score and that of composition-1 after 2 hours of brushing in this case is very significant. This therefore, goes to

- I i

indicate that the composition is capable of offering protection against oral malodour for a significantly longer period of time upon continued usage.

Halimeter Studies

Further, the above results were also verified by analysing the Volatile Sulphur Content (VSC) in the breath of the volunteers, as this is a direct and more reliable method of analysis. The breath of the volunteers were analysed by using an instrument called a halimeter, which detects and shows the VSC levels in ppb (parts per billion) .

In this case, the tests were also done after 2 and 4 weeks of continued use for which 188 volunteers in the age group of 18-45 (both male and female) participated.

All volunteers were stratified on the basis of age, gender and baseline score being a controlled parallel group design study. All volunteers with a VSC score >120 ppb and < 250 ppb were included in the study.

They were asked to avoid antibiotics for 3 weeks before test and were asked to refrain from oral activities ( brushing, gargling, rinsing, eating , drinking , chewing gum, smoking) at least two hours before testing. Volunteers abstained from eating spicy foods for 24 hours prior to each visit.

They also refrained from consuming alcohol for 24 hours before each visit. Oral malodour measurements (an average of 3 readings) were made on each volunteer using the Halimeter. On the morning of each test, the volunteers did not consume any food/confectionery or use any mouthwash prior to their baseline assessment. Volunteers abstained from eating and

drinking for the duration of each visit. After the baseline assessment, volunteers were made to brush one full brush length with the appropriate dentifrice for 2 minutes. Oral malodour measurements were made using the InterScan Halimeter Model RH-17K (standard Operating Procedure) at 12 hours before brushing, 10 minutes after brushing and 2 hours post brushing.

The baseline reading for both the product groups were matched. The analysis was carried out with the "student's t- test" to obtain the significance at 95% confidence level. The above protocol of short term design was followed after 4 weeks of product use, and measurements on the halimeter were taken at 12 hours before brushing, 10 minutes after brushing and 2 hours post brushing for both the control toothpaste and Composition-1.

The results of before brushing and 2 hours post-brushing are summarised in table-3 below.

Table-3

cComp-l is Composition-1

Thus it can be seen that the composition-1 according to the invention, reduces VSC levels significantly, and more so, after continued use for 2 and 4 weeks.

In addition to the above experiments, the volunteers who had used the individual compositions for a period of 4 weeks, self-assessed the composition-1 and placebo for their comparative Freshness values after use and rated the same on a scale of 0 to 5, 0 being the lowest and 5 being the best after the end of the period. The results are summarised in table-4 below.

Table-4

*Comp-l is Composition-1.

The results indicate that the freshness score for the composition-1 was higher as compared to that for the placebo, especially after brushing, and after 2 hours of brushing .

Example 2

In another set of experiments, compositions containing 0.2, 0.4 and 0.7% zinc sulphate were made in which the formulations were identical to that in Table-1, except for the increased/decreased levels of zinc Sulphate, with a corresponding increase/decrease in the content of water in the corresponding formulations.

Efficacy of the dentifrices was evaluated by studying BDCOH (4 , 4 ' -bis (dimethylamino) diphenylcarbinol) levels in saliva, pre and post brushing. This is also an indicator of the level of malodour.

Study of BDCOH levels in breath

In-vivo protocol Approximately 2 ml saliva samples were collected in an autoclaved plastic vial from 50 volunteers (each) before brushing and before eating anything in the morning. The samples were diluted to different level of dilutions and BDCOH solution was added in the vial. A micro titre plate was read at 620 nm in SpectraMax plate reader and the concentration of salivary thiols was calculated. This is inversely proportional to concentration of salivary thiols.

Ex-vivo protocol 35 volunteers produced un-stimulated saliva samples after brushing with placebo and Composition-1 at zero-time, 30 minutes post-brush and 2 hrs post-brush. The samples were assayed for concentration of salivary thiols after 24 hours of incubation using BDCOH. The micro titre plate was read at 620 nm in SpectraMax Plate reader and the concentration of salivary thiols was calculated.

Higher the concentration of BDCOH, lower the concentration of salivary thiols in the incubated saliva samples.

Results (BDCOH values) are compiled in table-5 below.

Table-5

Values in the above table indicate that the BDCOH levels showed an increase after brushing, to a significant extent, especially for compositions containing 0.2 to 0.7% Zinc Sulphate. This indicates that the inventive compositions are able to prevent the formation of malodour causing salivary thiols to a significant extent, even after 2 hours of brushing .

In addition to providing benefits against malodour, the compositions according to the invention also provide other desirable consumer benefits.

The following composition, Comparative Example 1, was prepared and was used by 200 volunteers for a period of 1 week, twice daily. Thereafter, they rated the composition for various consumer desirable benefits, as being on parity or better than the composition according to the invention as in table-1.

The composition of Comparative Example-1 was prepared was as per the formulation in table-6 below.

Table- 6

Comparative ratings given by the volunteers for the compositions have been summarised in the table-7 below.

Table- 7

The data in table-7 indicates that the volunteers preferred Composition 1 over Comparative Example 1 for most of the important attributes.

The above table indicates that Composition 1 (in accordance with the invention) is able to meet most of the desirable consumer attributes, when compared to a formulation devoid of high molecular weight polyethylene oxide in accordance.

In addition, Composition-1 and Comparative Example-1 were also compared by 15 expert panel members. The aim of this study was to evaluate and compare the mouth feel, foam levels, flavour intensity and flavour related attributes.

Panellists brushed their teeth with one full brush length for 60 seconds. They assessed the various attributes using the line scale from 0 to 10, zero being the lowest and 10 being the highest score. Average results of their comparative assessment have been compiled in the following table-8.

Table-8

From the scores in table-8 (in particular the relative astringency scores) as well as from the data in table-7 above, it is clear that Composition-1, in accordance with the invention has much lower astringency score when compared to the astringency of Comparative Example-1.

It will be appreciated that the illustrated examples, provides for a dentifrice composition including zinc salts, while having relatively lower astringency.

It will also be appreciated that the illustrated examples, provides for a dentifrice composition which gives enhanced level of breath freshness, particularly overnight breath freshness .

Although the invention has been described with reference to specific embodiments, it will be appreciated by those

skilled in the art that the invention may be embodied in many other forms .