1 AUSTRALIA F B RICE & CO Patent and Trade Mark Attorneys Patents Act 1990 JUROX PTY LTD COMPLETE SPECIFICATION INNOVATION PATENT Invention Title: Veterinary composition The following statement is a full description of this invention including the best method of performing it known to us:- 2 Veterinary composition Cross-Reference to Related Applications The present application claims priority from Australian Provisional Application 5 No. 2009902058 filed 8 May 2009, the content of which is incorporated herein by reference. Technical Field The present invention relates to compositions for external use in the prevention 10 and control of insect infestations of animals, the compositions comprising a specific crystal form of dicyclanil (4,6-diamino-2-cyclopropylaminopyrimidine-5-carbonitrile). Background Art The morphology and polymorphology of organo-chemical active substances is 15 of great importance to the chemical and pharmaceutical development thereof. Substances are known which only appear in a single crystal form; in addition, however, there are also substances which can form two, three or even more polymorphous crystal modifications. It is just as difficult to calculate or predict this possible morphological and 20 structural variety and the respective physico-chemical, especially thermodynamic stability respect thereof on a scientific-mathematical basis, as it is to calculate or predict their different behaviour when they are administered to an animal. The relevant polymorphism of an organo-chemical substance is always unpredictable in respect of the number of crystal modifications, the stability thereof and their therapeutic 25 efficacy in an animal. If two, three or more crystal modifications of a substance are known, then in general their absolute and relative physico-chemical stabilities may be determined. The different crystal modifications of one and the same substance may differ considerably from one another in many respects. These differences in morphology and polymorphism may have drastic effects on the development, storage 30 stability and bio-availability of individual dosage forms. The same also applies in respect of the physical and chemical properties of dicyclanil, a compound of formula 4,6-diamino-2-cyclopropylaminopyrimidine-5 carbonitrile with a published melting point of 249-251 C, which is disclosed in European Patent Specification EP-0 244360 BI both as a new compound and as an 35 agent for the control of insects pests and ectoparasites on warm-blooded animals. 1021139_.doc 3 Dicyclanil is an insect growth regulator belonging to the group of pyrimidinamines. Dicyclanil interferes with the chitin metabolism of the insect. Treated larvae will therefore be unable to moult to the next stage. Dicyclanil is therefore used as a veterinary drug for the control of ectoparasites on domestic and 5 farm animals. The molecule shows a high specificity for Dipteran fly larvae so may be used to provide long-term protection of sheep against the widespread myasis flies such as Lucilia Sericata, Lucilia cuprina and the like. Application is preferably effected by means of the "pour-on" process, whereby the formulation is finely dispersed to the back of the animal either directly or by a spray 10 appliance. This type of application has considerable advantages, since only the exposed places are sprayed and effects on the environment are thus minimised. It is precisely with formulations having suspended active substance, such as in the "pour-on" processes, that the different properties of the crystal modifications play a decisive role. Several crystal modifications of dicyclanil are known. One crystal modification 15 of dicyclanil is described in EP-0 244360 Bl. Others are disclosed in W099/10333. Each of the forms are significantly distinct from one another in respect of their physio chemical properties, their stability and, in part, their biological behaviour. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a 20 context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application. 25 Disclosure of Invention The invention provides compositions, uses and methods as defined in the appended claims. In work leading to the present disclosure, the inventors have surprisingly found a previously unknown crystal modification of dicyclanil and established that it is stable 30 in a pharmaceutically acceptable formulation. Further, they have also surprisingly found that such a formulation is efficacious in the control of insect infestations, particularly in the control of ectoparasite infestation. Accordingly, disclosed herein is a composition comprising a specific crystal modification of dicyclanil which is efficacious in the control of insect infestations, 35 particularly ectoparasite infestation, and is stable in a pharmaceutically acceptable 1021139_1.doc 4 formulation and which has not been previously used for the control of insect infestation. Throughout this specification, and unless it is stated to the contrary, the word "comprise", or variations such as "comprises" or "comprising", will be understood to 5 imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. Disclosed herein is a composition comprising an effective amount of a crystal modification of dicyclanil, at least one surfactant, at least one viscosity modifier and a 10 therapeutically acceptable carrier, wherein in Differential Scanning Calorimetry said crystal modification of dicyclanil exhibits a transformation in the temperature range of between 175*C and 197 0 C and possesses the following characteristic interlattice plane distances in [A 0 ] from X-ray diffraction measurements: 11.26±0.2, 9.1±0.2, 8.9±0.2, 8.01±0.2, 7.7±0.2, 7.48±0.2, 5.95±0.05, 5.81±0.05, 15 5.73±0.05, 5.62±0.05, 5.13±0.05, 4.88±0.05, 4.74±0.05, 4.60±0.05, 4.45±0.05, 4.28±0.05, 4.14±0.05, 4.00±0.05, 3.72±0.05, 3.58±0.05, 3.43±0.05, 3.39±0.05, 3.33±0.05, 3.27±0.05; 3.19±0.05, 3.13+0.05, 3.06±0.05, 2.96±0.05, 2.90±0.05, 2.86±0.05, 2.83±0.05. The composition disclosed herein is effective when used to prevent or control 20 insect infestation of an animal. Accordingly, also disclosed herein is a composition comprising an effective amount of a crystal modification of dicyclanil, at least one surfactant, at least one viscosity modifier and a therapeutically acceptable carrier when used to prevent or control insect infestation of an animal, wherein in Differential Scanning Calorimetry 25 said crystal modification of dicyclanil exhibits a transformation in the temperature range of between 175'C and 197 0 C and possesses the following characteristic interlattice plane distances in [A 0 ] from X-ray diffraction measurements: 11.26±0.2, 9.1±0.2, 8.9±0.2, 8.01±0.2, 7.7±0.2, 7.48±0.2, 5.95±0.05, 5.81±0.05, 5.73±0.05, 5.62±0.05, 5.13±0.05, 4.88±0.05, 4.74±0.05, 4.60±0.05, 4.45±0.05, 30 4.28±0.05, 4.14±0.05, 4.00±0.05, 3.72±0.05, 3.58±0.05, 3.43±0.05, 3.39±0.05, 3.33±0.05, 3.27±0.05; 3.19±0.05, 3.13±0.05, 3.06±0.05, 2.96±0.05, 2.90±0.05, 2.86±0.05, 2.83±0.05. Also disclosed herein is use of a composition comprising an effective amount of a crystal modification of dicyclanil, at least one surfactant, at least one viscosity 35 modifier and a therapeutically acceptable carrier in preventing or controlling insect infestation of an animal, wherein in Differential Scanning Calorimetry said crystal 1021139_.doc 5 modification of dicyclanil exhibits a transformation in the temperature range of between 175*C and 197 0 C and possesses the following characteristic interlattice plane distances in [A'] from X-ray diffraction measurements: 11.26±0.2, 9.1±0.2, 8.9±0.2, 8.01±0.2, 7.7±0.2, 7.48±0.2, 5.95±0.05, 5.81±0.05, 5 5.73±0.05, 5.62±0.05, 5.13±0.05, 4.88±0.05, 4.74±0.05, 4.60±0.05, 4.45±0.05, 4.28±0.05, 4.14±0.05, 4.00±0.05, 3.72±0.05, 3.58±0.05, 3.43±0.05, 3.39±0.05, 3.33±0.05, 3.27±0.05; 3.19±0.05, 3.13±0.05, 3.06±0.05, 2.96±0.05, 2.90±0.05, 2.86±0.05, 2.83±0.05. Also disclosed herein is a method of preventing or controlling insect infestations 10 of an animal, the method comprising topically administering to the animal a composition comprising: an effective amount of a crystal modification of dicyclanil, at least one surfactant, at least one viscosity modifier and a therapeutically acceptable carrier, wherein in Differential Scanning Calorimetry said crystal modification of dicyclanil exhibits a transformation in the temperature range of between 175*C and 15 197 0 C and possesses the following characteristic interlattice plane distances in [A 0 ] from X-ray diffraction measurements: 11.26±0.2, 9.1±0.2, 8.9±0.2, 8.01±0.2, 7.7±0.2, 7.48±0.2, 5.95±0.05, 5.81±0.05, 5.73±0.05, 5.62±0.05, 5.13±0.05, 4.88±0.05, 4.74±0.05, 4.60±0.05, 4.45±0.05, 4.28±0.05, 4.14±0.05, 4.00±0.05, 3.72±0.05, 3.58±0.05, 3.43±0.05, 3.39±0.05, 20 3.33±0.05, 3.27±0.05; 3.19±0.05, 3.13+0.05, 3.06±0.05, 2.96±0.05, 2.90±0.05, 2.86±0.05, 2.83±0.05. An "effective amount of a crystal modification of dicyclanil" is present in the composition disclosed herein. By "effective amount" it is meant that the dicyclanil is present in a concentration that is capable of controlling insects, particularly 25 ectoparasites, on an animal. Dicyclanil is preferably present in an amount of from 1 to 20%w/v of the composition, preferably from 2 to 10 % w/v and more preferably from 4 to 6 %w/v. In one embodiment, the dicyclanil is present in an amount of about 5%w/v. One or more surfactants are included in the composition of the invention, 30 preferably in an amount of from about 1.0 to 10%w/v. More preferably, the amount is in the range of from about 1 to 8%w/v, most preferably from about 1.5 to 5 %w/v. The surfactant may be selected from nonionic, anionic, cationic or amphoteric surfactants or mixtures thereof. Preferably a nonionic surfactant is used. Nonionic surfactants may be selected from the group consisting of C 8 -Cio alkylphenol ethoxylates, C 9 -C17 alcohol 35 ethoxylates, C 8
-C
20 alkyl amine ethoxylates, castor oil ethoxylates, lanolin alcohol ethoxylates, lanolin alcohol acetylates, sorbitan fatty acid ester ethoxylates, sorbitan 1021139_.doc 6 fatty acid esters, ethoxylated sorbitan etsers and mixtures thereof. The C 8 -Ci 0 alkylphenol ethoxylates preferably contain from 2 to 100 moles of ethylene oxide and may be selected from the commercially available Teric series products. Teric N9 TM is an alkyl phenol ethoxylate with 9 moles of ethylene oxide condensed onto nonyl 5 phenol. In one preferred embodiment, the surfactant is Teric N9TM . The Teric N97T is preferably present in the composition in an amount of about 4.5%w/v. SolulanTM is a mixture of acetylated lanolin alcohol and an ethoxylated sorbitan ester. In another TM TM preferred embodiment the surfactant is SolulanTM. The Solulan is preferably present in the composition in an amount of about 2%w/v. The sorbitan fatty acid ester 10 ethoxylates preferably contain from 4 to 20 moles of ethylene oxide and may be selected from polysorbate 60 and polysorbate 80. One or more viscosity modifiers are included in the composition of the invention, preferably in an amount of from about 0.05 to 15%w/v. In one embodiment the viscosity modifier is present in an amount of 0.1 to 5 %w/v. Preferably, the amount 15 is in the range of from about 0.1 to 2%w/v, most preferably about 0.2%w/v. In another embodiment, the viscosity modifier is in an amount of from about 3 to 6%w/v, more preferably about 5.2% w/v. Examples of suitable viscosity modifiers include, for example, methyl cellulose, xanthum gum and colloidal silica and polymeric pyrrolidones such as povidone. In one preferred embodiment the viscosity modifier is 20 AerosilT . Aerosil
TM
is an example of a colloidal silica. In another preferred embodiment, the modifier is xanthum gum. In another preferred embodiment the composition of the invention includes the viscosity modifiers AerosilTM and xanthum gum. The viscosity of the composition shall be optimised to enable the composition to 25 provide good suspensibility of dicyclanil and ease of application of the product to the animals. Preferably the viscosity of the composition is in the range of about 100 - 1000 cps, more preferably, about 300 - 800 cps, most preferably, about 500 - 700 cps, as measured at 25C using a Brookfield viscometer. The compositions disclosed herein comprises a "therapeutically acceptable 30 carrier" which allows the dicylcanil to remain in crystal form in the composition. The "therapeutically acceptable carrier" may be selected from one or more of the group consisting of water and any other solvent in which the crystal modification of dicyclanil will not be dissolved or is sparingly soluble, such as, for example, propylene glycol, medium chain triglycerides and oil. In one embodiment the "therapeutically acceptable 35 carrier" may be water alone. In another embodiment the "therapeutically acceptable carrier" may be a mixture of water and one or more solvents in which the crystal 1021139_.doc 7 modification of dicyclanil will not be dissolved or is sparingly soluble, such as, for example, propylene glycol, medium chain triglycerides and oil. In yet another embodiment, the "therapeutically acceptable carrier" may be a mixture of one or more solvents in which the crystal modification of dicyclanil will not be dissolved or is 5 sparingly soluble, such as, for example, one or more of the solvents selected from the group consisting of propylene glycol, medium chain triglycerides and oil, wherein no water is present. It will be understood that the "therapeutically acceptable carrier" is pharmaceutically safe to administer to an animal and does not cause skin irritation. The compositions disclosed herein are made to volume with the "therapeutically acceptable 10 carrier". In a preferred embodiment, the composition disclosed herein is an aqueous suspension composition and is made up to volume with water. The composition optionally includes pharmaceutically acceptable excipients and adjuvants such as, for example, one or more dispersants, preservatives, buffers and 15 anti-skinning agents. Examples of suitable dispersing agents include, for example, colloidal silica polymeric pyrrolidones such as povidone, glycerine and polyethylene glycol. It is believed that the dispersants change the density of the medium and help the dispersion of the solid phase. 20 It will be appreciated that one or more viscosity modifiers used in the composition disclosed herein may also function as a dispersant. In a preferred embodiment, one or more dispersants may be included in the composition in an amount of from about 0.05 to 15 %w/v. More preferably, the amount of dispersant is in the range of from about 1 to 10 %w/v, most preferably about 25 5.2 %w/v. In a preferred embodiment the dispersant is colloidal silica. As noted above, colloidal silica may simultaneously perform the role of dispersant and viscosity modifier. One or more preservatives may be included in the composition, such as, for example, hydroxybenzoate, benzyl alcohol, sorbic acid, sorbate salts and mixtures 30 thereof. One or more buffers may be included in the composition disclosed herein. Preferably, the pH of the composition is in the range of about 5-9, more preferably close to neutral (about pH 7). Examples of suitable buffers include, for example, phosphate, citro-phosphate and citro- buffers. 35 One or more anti-skinning agent may be included in the composition disclosed herein. An anti-skinning agent is used to minimise prevent or reduce the formation of 1021139_1.doc 8 skin on the surface of the composition due to evaporation on the surface of the liquid. Examples of suitable anti-skinning agents include, for example, polyols and silicon oil. In Differential Scanning Calorimetry (DSC), the crystal modification of dicyclanil for use in the present invention shows a transformation in the temperature 5 range of between 175'C and 197*C. A suitable heating rate is 2*C/minute. The temperature range and the kinetics of this conversion is dependent both on external measurement conditions and on different properties of the respective sample of dicyclanil. The preferred characterisation of crystal modification of dicyclanil is effected by means of the interlattice plane distances d of an X-ray diffraction diagram: 10 d in [A']: 11.26±0.2, 9.1±0.2, 8.9±0.2, 8.01+0.2, 7.7±0.2, 7.48±0.2, 5.95+0.05, 5.81±0.05, 5.73±0.05, 5.62±0.05, 5.13±0.05, 4.88+0.05, 4.74+0.05, 4.60±0.05, 4.45±0.05, 4.28±0.05, 4.14±0.05, 4.00±0.05, 3.72±0.05, 3.58±0.05, 3.43+0.05, 3.39±0.05, 3.33±0.05, 3.27±0.05; 3.19±0.05, 3.13±0.05, 3.06±0.05, 2.96±0.05, 2.90±0.05, 2.86±0.05, 2.83±0.05. 15 The most intensive reflexes in the X-ray diffraction diagram thus give the following interlattice plane distances: d in [A']: 9.1+0.2, 8.9±0.2, 8.01±0.2, 7.7±0.2, 5.95±0.05, 5.81±0.05, 5.73±0.05, 4.45±0.05, 4.14±0.05, 4.00±0.05, 3.72±0.05, 3.43±0.05, 3.39±0.05. Crystal modifications, hydrates and solvates may be distinguished by their X-ray 20 powder diagrams. X-ray powder diagrams are preferably used to characterise solid forms of organic substances. In particular, X-ray diffraction (XRD) diagrams are used advantageously and with good powers of affirmation to determine the different crystal modifications of a substance. In the case of hydrates and solvates, additional methods have to be used such as thermogravimetry or thermogravimetry-Fourier-transform 25 infrared-spectroscopy (TGFTIR) and other substance-specific methods. To characterise the crystal modification of dicyclanil included in the composition of the invention, measurements were carried out using samples of substance which were kept at room temperature. The XRD analysis was carried out using a X'Pert MPD XRD with a X'Celerator detector and the interlattice plane 30 distances of the most important lines were calculated. Results are shown in Table 1. 1021139_1.doc 9 Table 1: X-ray diffraction diagram (interlattice plane distances and intensities of the most important lines) of the crystal modification of dicyclanil. d[A"1 Intensity d[A"] Intensity 11.26 Very weak 3.58 Very weak 9.19 Very strong 3.43 Medium 8.90 Very strong 3.39 Medium 8.01 Very strong 3.33 Weak 7.70 Medium 3.27 Very weak 7.48 weak 3.19 Very weak 5.95 Strong 3.13 Very weak 5.81 medium 3.06 Very weak 5.73 Strong 2.96 Weak 5.62 Weak 2.90 Very weak 5.13 Very weak 2.86 Very weak 4.88 Very weak 2.83 Very weak 4.74 Very weak 4.60 Weak 4.45 Very strong 4.28 Very weak 4.14 Medium 4.00 Medium 3.72 Medium 5 The compositions disclosed herein are effective in preventing or controlling a variety of insect infestations, particularly ectoparasites, on an animal. In a preferred embodiment the compositions disclosed herein are ectoparasiticide compositions. The phrase "preventing or controlling" will be understood to mean that the insect infestation 10 of the animal is stopped or reduced following application of the composition to the animal. The composition disclosed herein is applied topically to the animal. Without being bound by theory, the inventors believe the composition is effective in controlling insects by eradicating insect larvae, essentially by inhibiting their growth and by preventing them from maturing. The composition may be applied topically to the 1021139_.doc 10 animal in a number of ways including for example, by way of applicator, such as a gun applicator, wherein the composition is poured or sprayed onto the animal. The composition may be used as it is or further diluted with water for use in a dip or jetting race. In a preferred embodiment the composition is applied as it is onto the animal 5 without further dilution. . The compositions disclosed herein are effective when used on a variety of animals. Examples of animals include sheep, goat, ruminants (including cattle) and camelids. The compositions disclosed herein are effective against insects, more 10 particularly ectoparasites, including but not limited to flies such as Lucilia Seriata and Lucilia cuprina, fleas and lice. In a preferred embodiment, the composition is used to prevent or control sheep blowfly (Lucilia cuprina) infestation of a sheep. Methods of formulation 15 To produce the compositions disclosed herein an effective amount of the crystal modification of dicyclanil disclosed herein, is dispersed in a mixture of surfactant, viscosity modifier, therapeutically acceptable carrier and optionally pharmaceutically acceptable excipients and adjuvants, followed by high speed mixing until uniform. It will be appreciated that the dose of the composition applied to the animal will 20 be dependant upon a number of factors including, for example, if the composition is to be used for body strike, crutch strike, striking after mulesing and the weight of the animal. Modes for Carrying Out the Invention 25 In order to better understand the nature of this invention a number of examples will be described. Example 1 : A composition according to the invention is shown in Table 2. 30 1021139_1.doc l1 Table 2 Quantity Function Supplier Dicyclanil -crystal 50 g/L 5%w/v Active Unisource modification Teric N9Tm 45 g/L 4.5%w/v Surfactant Huntsman (Nonionic surfactant - alkyl phenol ethoxylate with 9 moles of ethylene oxide condensed onto nonyl phenol) AerosilTM 50 g/L 5%w/v Dispersant/ Pacific (Colloidal silica) Viscosity Resource modifier Propylene glycol 50 g/L 5%w/v anti-skinning Unisource agent Xanthum Gum 2 g/L 0.2%w/v viscosity APS modifier Water g.s. to 1 L carrier To produce the composition according to Example 1, dicyclanil is dispersed in a 5 mixture of Teric N9TM , Aerosil T M , propylene glycol, xanthan gum and water followed by high speed mixing until uniform. The final volume is made up with water. The composition according to Example 1 is readily redispersable (or has good dispersibility) and remains chemically stable after three months of storage at shown in Table 3. 10 Table 3 Dicyclanil Content Initial 51 g/L 3 months at 30 0 C 50 g/L 3 months at 40'C 50 g/L 1021139_1.doc 12 Example 2: A composition according to the invention is shown in Table 4. Table 4: 5 Quality Function Supplier Dicyclanil -crystal 50 g/L 5%w/v Active Unisource modification Solulan TM 20 g/L 2%w/v Surfactant Unisource (Mixture of acetylated lanolin alcohol and an ethoxylated sorbitan ester.) AerosilTM 50 g/L 5%w/v Dispersant/ Pacific (Colloidal silica) Viscosity Resource modifier Propylene glycol 25 g/L 2.5%w/v anti-skinning Unisource agent Xanthum Gum 2 g/L 0.2%w/v viscosity APS modifier Water q.s. to 1 L carrier To produce the composition according to Example 2, dicyclanil is dispersed in a TM mixture of Solulan , Aerosil T M , propylene glycol, xanthan gum and water followed by high speed mixing until uniform. The final volume is made up with water. 10 Example 3 - Efficacy trial The efficacy of the composition according to Example 1 in preventing and controlling blowfly strike in sheep caused by the Australian blowfly Lucilia cuprina was assessed. 15 Seventy three mixed breed sheep including 53 adults and 20 lambs, were treated at Day 0 with a composition of Example 1. The composition was applied to each sheep by means of a spray-on applicator gun situated 15 to 25 cm above the fleece to achieve a 15 cm wide band at each pass. . Multiple passes were made to give the desired dose as shown in Table 5. At Day 0, adult sheep had 9 weeks of wool growth and lambs had 20 16 weeks of wool growth. 1021139_1.doc 13 Blowfly pressure during the trial was confirmed by using a LuciTrap . The LuciTrapTM system consists of a specifically designed trap and a blend of chemicals developed to attract and capture the Australian sheep blowfly (Lucilia cuprina). 5 Table 5 Sheep Weight Total Volume/Sheep Volume Per Number of Bands (kg) (mL) treatment Band (mL) 10-20 21 7 3 21-30 24 8 3 31-50 30 10 3 >50 36 12 3 The results are shown in Table 6. 10 Table 6 Strike Lucilia cuprina caught with LuciTrap T Day 0 N/A N/A Week 6 No strike 100 Week 8 No strike 34 Week 9 No strike 23 Week 10 No strike 200 Week 11 No strike 250 The results demonstrate that the crystal modification form of dicyclanil of Example 1 is highly effective in protecting the sheep from blowfly strike even at high 15 blowfly pressure such as existed in week 10 and week 11. No adverse reactions were found during the trial indicating that the composition is non-irritant and safe for topical use. 1021139_1.doc 14 Example 4 - Efficacy Trial The efficacy of the composition according to Example 1 was compared with a marketed product in preventing and controlling blowfly strike in sheep caused by the 5 Australian blowfly Lucilia cuprina. In the test group, 101 Merino wethers, aged approximately one year, were treated with a composition of Example 1 at Day 0, while in the comparative group, 100 Merino wethers, aged approximately one year, were treated with a marketed product at Day 0. The compositions were applied to each sheep by means of a spray-on applicator gun situated 15 to 25 cm above the fleece to 10 achieve a 15 cm wide band at each pass. Multiple passes were made to give the desired dose as shown in Table 7. 29 Untreated sheep were used as a control. Table 7 15 Sheep Weight Total Volume/Sheep Volume Per Number of Bands (kg) (mL) treatment Band (mL) 10-20 21 7 3 21-30 24 8 3 31-50 30 10 3 >50 36 12 3 Results The 29 untreated sheep were struck while no strike was found or recorded for the sheep treated with the composition of Example 1 or the marketed product 13 weeks 20 post-treatment. The results confirm that crystal modification form of dicyclanil of Example 1 is highly effective and equivalent to the product in the market in protecting the sheep from blowfly strike. It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific 25 embodiments without departing from the scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. 1021139_1.doc