Title of Invention

"HYDRO-DISPERSIBLE VETERINARY COMPOSITION"

Abstract

The present invention relates to a stable, safe and a dispersible synergistic veterinary composition containing Deltamethrin, Oil of Melaleuca in combination with a solvent, stabilizer and emulsifiers having cent percent tick-kill rate (acaricidal activity), fly repellant activity with an enhanced protection time for re-infestation by parasites and the invention also relates to a process for the preparation of the said composition. 17

Full Text

HYDRO-DISPERSIBLE VETERINARY COMPOSITION Field of the invention The present invention relates to a stable, safe and an efficient hydro-dispersible synergistic composition containing Deltamethrin (d-cis isomer), Oil of Melaleuca in combination with a solvent, stabilizer and emulsifiers having cent percent tick-kill rate (acaricidal activity) and fly repellent activity. The said composition also provides an enhanced protection time for re-infestation by parasites. The invention also relates to a process for the preparation of the composition. Background and Prior art of the invention Dairy animals suffer from heavy infestation of external parasites like ticks, mites, lice and flies. The infestation is particularly severe in tropical countries in Asia and Africa and more so in summers. Cattle can be infested with several types of ticks like Boophilus spcs, Hyalomma species, Amblyomma species, Rhipicephalus species, Haemaphysalis species, Dermacentor species, Ixodes species, Otobius species, Ornithodorus spcs, etc. External parasites bring about itching and skin irritations causing animals to scratch, rub, and bite infested areas. Severe case with mange infestation results in thickened skin, hair loss, and lesions. Losses occur from these parasites due to irritation, blood loss, depressed appetite, and decreased milk production. Ectoparasites act as vectors for various haemo-protozoan and tick-borne infections like babesiosis, trypanosomiasis, theileriosis, tick-fever etc. Infested cows produce less milk, affecting herd's profits. Blood loss caused by sucking parasites can become so severe it causes anemia and may lead to abortion in young heifers. Extreme infestations can result in death. Currently available products for the control of external parasites include synthetic pyrethroids (Deltamethrin (d-cis isomer), Cypermethrin, Fenvalerate etc.) Amitraz and, organophosphorus preparations such as Malathion, DDT etc. Deltamethrin (d-cis isomer), fourth generation synthetic dibromo-pyrethroid, consists of one exclusive therapeutic pure isomer of a composite ester. Of the eight possible stereoisomers, it contains only the (d-cis isomer) or [1R, c/'s; alpha S] which acts as an axonic poison by acting on axons in peripheral and central nervous system by interacting with sodium channels in mammals and/or insects giving a knockdown effect. They stimulate nerve cells to produce repetitive discharge and eventually cause paralysis, convulsions and death. Prior art formulations of deltamethrin are prepared in non-aqueous solvents such as CIX, which have high to moderate acute oral toxicity (LD50 Value Deltamethrin (d-cis isomer) as a sole active ingredient of the composition is marketed by few companies like Intervet India Private Limited (Butox), Cadila Pharmaceuticals Limited (Deltarin) and Jubilant Organosys Limited (Anytix). These products are used to control only the infection caused by parasites in animals. Existing prior art preparations do not provide complete and long-lasting freedom from ectoparasites. Drug-resistance has developed with Deltamethrin (d-cis isomer) and other existing products due to prolonged use. Reinfestation or reoccurrence takes place within 4-8 days after applying these products on skin of the animals. Other disadvantages of using existing Deltamethrin (d-cis isomer) formulation are low tick-kill rate (upto 70-80%), lack of fly-repellant action, higher volatility, low biodegradability and adverse side-effects. Side effects associated with its use are tremors, convulsions, salivation and frothy discharge from mouth etc. Poor biodegradability of existing products is a key issue with environmentalists. Melaleuca alternifolia, or Australian tea tree oil as it is more commonly known, is 100% natural oil which is an antiseptic, acaricide, and a fungicide. It is made entirely from a renewable natural resource and is completely eco friendly. Its major active component is terpinen-4-ol. Australian Tea Tree Oil (Melaleuca Oil) has shown its antimicrobial activity against a variety of micro organisms. The composition of the present invention contains active ingredients Deltamethrin (d-cis isomer) and Oil of Melaleuca in combination with a solvent, stabilizer and emulsifiers having cent percent tick-kill rate (acaricidal activity) and fly repellant activity. The said composition also provides an enhanced protection time by two folds for reinfestation by parasites. This dual effect is not achieved from any of the existing prior art composition containing Deltamethrin (d-cis isomer). In addition, composition of the present invention overcomes the limitations associated with the compositions of the prior art containing ectoparasiticidal agents, providing an eco friendly, efficient and safe product. The dual effect and an enhanced protection time for reinfestation by parasites has never been achieved by any of the prior art compositions. An optimum level of acaricidal activity coupled with fly repellant activity of a stable and safe composition of the present invention is achieved by human intervention in the present work and is not to be considered as a mere coincidence. Objects of the invention: An object of the present invention is to develop an effective, safe and stable synergistic composition to act against ecto-parasites in animals Another object of the present invention is to provide a composition having cent percent tick-kill rate and fly repellant activity. Yet another object of the present invention is to provide a composition which can have long duration of action to delay the re-infestation period by ecto-parasites. Still another object of the present invention is to provide a composition containing Deltamethrin(d-cis isomer) in combination with a product of herbal origin, solvent, stabilizer and emulsifiers. Yet another object of the present invention is to use a herbal oil which also provides an effect of an adjuvant. Still another object of the present invention is to provide composition having minimum toxicity Still yet another object of the present invention is to provide a biodegradable and eco friendly composition. Still another object of the present invention is to provide a composition having low volatility. Still yet another object of the present invention is to provide a hydro dispersible veterinary composition. Summary of the invention The present invention relates to a stable, safe and an efficient emulsifiable synergistic composition containing Deltamethrin (d-cis isomer), Oil of Melaleuca in combination with a solvent, stabilizer and emulsifiers having cent percent tick-kill rate (acaricidal activity) and fly repellant activity. The said composition also provides an enhanced protection time for re-infestation by parasites. The invention also relates to a process for the preparation of the composition. Detailed description of the invention Accordingly, the present invention relates to a stable, safe and an efficient hydro-dispersible synergistic composition for veterinary use, the said composition comprising of: Ingredients W/W (%) a) Deltamethrin 1.0 to 5.0 b) A herbal Oil 5.0 to 10.0 c) A stablizer 2.0 to 4.0 d) A solvent q.s e) At least an Emulsifier 2.0 to 18.0 In an embodiment of the invention provides a composition wherein herbal oil used is oil of Melaleuca alternifolia and the Deltamethrin used is d-cis isomer. Another embodiment of the invention, wherein the solvent used is selected from a petroleum based solvent or CIX solvent. CIX (or C-nine) solvent is a non-aqueous solvent popularly used in the chemical industry. Yet another embodiment of the invention, wherein the preferable solvent is petroleum based solvent. Still another embodiment of the invention, wherein the stabilizer used belongs to Oxo alcohols of linear alkyl olefins. Yet another embodiment of the invention, wherein the stabilizer used is epoxidised soya bean oil. Still yet another embodiment of the invention provide the use of an herbal oil selected from oil of Melaleuca alternifolia or Melaleuca aetheroleum. Still another embodiment of the invention the herbal oil also acts as an adjuvant. Yet another embodiment of the invention, wherein the emulsifiers used are Polyoxyl-m glyceryl triricinoleate (castor oil polyglycol ether 36-40), dodecyl benzene sulfonic acid calcium salt linear (CABS) and/or Monoxynol-n (nonyl phenol polyglycol ether 9-10). Still another embodiment of the invention provides acaricidal activity by exhibiting cent percent tick-kill rate against various parasites. One more embodiment of the invention provides a composition, which also exhibits fly repellant activity. Still another embodiment of the invention provides the composition which is having low volatility and also having biodegradable nature. Yet another embodiment of the invention provides an enhanced protection time by two folds for re infestation by ecto-parasites. Still yet another embodiment of the invention is to provide an effective composition to act against infestation caused by ticks in animals (buffaloes, cattle, pigs, camels and dogs). Still another embodiment of the invention, the infection caused by ticks belonging to genus Boophilus, Hyalomma, Amblyomma, Rhipicephalus, Haemapysalais, Dermacentor, Otobius, Ornithodorus and / or loxodes. Yet another embodiment of the invention provides a stable hydro dispersible composition at 53-55°C for a period of at least 14 days. Different concentrations of Melaleuca alternifolia and Deltamethrin (d-cis isomer) were evaluated for stability and efficacy. Upto 50% cone, of Oil of Melaleuca and upto 5% of Deltamethrin (d-cis isomer). The formulation of 5-10% Oil of Melaleuca and 1-5% of Deltamethrin (d-cis isomer) was found to be most stable and efficient. Different solvents, stabilizer and emulsifiers have been used and studied for obtaining composition containing Deltamethrin (d-cis isomer) to overcome the limitations of the existing prior art products. Few of them evaluated are Citronella Lemon grass oil, neem oil and oil of melaleuca. The formulations of Deltamethrin with Neem Oil and Citronella Lemon Grass Oil were not stable and in both instances deltamethrin was degraded i.e., ester-cleavage products were formed. The composition of the present invention was arrived at after selection of suitable herbal oil which can also act as an adjuvant to obtain synergistic therapeutic effect as a stronger acaricidal agent associated with a fly repellant activity. Preparation of Oil of Melaleuca: Oil of Melaleuca is prepared by steam distillation from the leaves of the Melaleuca alternifolia tree. The pharmaceutical grade oil (Terpinen-4-ol Type) was chosen as an adjuvant for Deltamethrin (d-cis isomer), with Terpinen-4-ol content not less than 36.6% and 1,8-Cineole content in the preparation not more than 2.8%. Various concentrations of Oil of melaleuca were evaluated with different concentrations of Deltamethrin (d-cis isomer), measuring the distinct features (1) tick-kill rate (2) volatility (3) biodegradability (4) side-effects (5) fly-repellant action. Tick-Kill rates of the present invention and existing product have also been compared. The stability studies, accelerated storage test have also been conducted for the composition of present invention. (Table Removed)The invention is illustrated by the following examples and should not be construed to limit the scope of the present invention. EXAMPLES Example 1 Preparation of Oil of Melaleuca The leaves of the Melaleuca species is subjected to steam distillation to obtain the required oil containing Terpinent-4-ol content not less than 36.6% and 1,8-Cineole content not more than 2.8% constituting pharmaceutical grade oil. Example 2 General procedure for the preparation of synergistic Hydro-dispersible concentrates composition containing Deltamethrin (d-cis isomer) Blend a mixture of emulsifiers and establish the stability of the mixture for a period of at least 5 days. Blend separately deltamethrin (d- cis isomer) and oil of Melalueca in a required quantity in a solvent. Add mixture of emulsifiers to this and stir it for 30 minutes, followed by addition of a stabilizer. Stir the mixture thus obtained for another 60 minutes to yield the required composition. Example 3 As per example 2, composition containing Deltamethrin (d-cis isomer, 0.75%) and oil of Melaleuca alternifolia (30%) is prepared. The composition obtained exhibited adverse skin reaction due to the presence of high concentration of oil. Example 4 Composition containing Deltamethrin (d-cis isomer, 1.25%) and oil of Melaleuca alternifolia (10%) as per example 2 is prepared. The composition obtained exhibited 100% acaricidal activity and 100% fly repellant activity. Example 5 As per example 2, composition containing Deltamethrin (d-cis isomer, 1.75%) and oil of Melaleuca alternifolia (8%) is prepared. The composition obtained exhibited 100% acaricidal activity and 100% fly repellant activity. Example 6 As per the procedure mentioned in example 2, composition containing Deltamethrin (d-cis isomer, 2.50%) and oil of Melaleuca alternifolia (8%) is prepared. The composition obtained exhibited 70% acarcidal activity and 100% fly repellant activity. Example 7 As per the procedure mentioned in example 2 composition containing Deltamethrin (d-cis isomer, 4.0%) and oil of Melaleuca alternifolia (3%) is prepared. The composition obtained exhibited 70% acarcidal activity without significant fly repellant activity. Example 8 As per the procedure mentioned in example 2 composition containing Deltamethrin (d-cis isomer, 1.25%) and oil of Melaleuca alternifolia (2%) is pre4pared and evaluated for acacridal activity. The composition obtained exhibited 70% acacridal activity without fly repellant activity. Example 9 Prepared composition containing Deltamethrin (d-cis isomer,7.50%) and oil of Melaleuca alternifolia (2%) as per example 2. The composition obtained was found to be unstable due to the presence of high concentration of deltamethrin(d-cis isomer). Example 10 Test for acaricidal activity and fly repellant activity: Prepare a spray solution containing approximately 2 to 4 ml concentrate of the composition per liter of water. Use around 3 to 5 liters of this spray solution per adult animal for proper wetting of parasite infested areas. Allow the solution to dry on the skin of the animal. Collect the parasites fallen off on the ground & after wiping off skin surface of the animal, count and check individually for any sign of motility / life. New product mixed with required quantity of water is used as spray/dip treatment (Table Removed) Main advantages of the invention • The product of the present invention is highly biodegradable, as it uses a natural product • External parasites resistant to existing ectoparasiticides are susceptible to the product of the present invention (100% Tick-kill rate against 70-80% tick- kill rate achieved from existing Deltamethrin (d-cis isomer) product). • Reinfestation with ectoparasites is delayed by more than 10 days by using the product of the present invention due to its lower volatility, has longer residual action (minimum 3-weeks) as compared to 7-10 days residual action of existing product. • Present invention also exhibits fly repellent action, which is not noticed with Deltamethrin (d-cis isomer) preparation using C IX solvent. • Lack of side effects like convulsions, tremors and salivation associated with the composition of the present invention. I / We claim: 1) A hydro-dispersible synergistic composition for veterinary use, said composition comprising of: Ingredients WAV (%age) a) Deltamethrin (d-cis isomer) 1.0 to 5.0 b) Oil of Melaleuca alternifolia or oil of Melaleuca aetheroleum 5.0 to 10.0 c) Stablizer 2.0 to 4.0 d) At least an Emulsifier 2.0 to 18.0 e) Solvent q.s to l00 2) The composition as claimed in claim 1, wherein the solvent used is preferably a petroleum-based solvent. 3) The composition as claimed in claim 2, wherein the solvent used is CIX solvent. 4) The composition as claimed in claim 1, wherein the stabilizer is an Oxo alcohol of linear alkyl olefin. 5) The composition as claimed in claim 1, wherein the stabilizer is epoxidised soya bean oil. 6) The composition as claimed in claim 1, wherein the emulsifier is selected from a group consisting of polyoxyl-m glycery triricinoleate, castor oil polyglycol ether 36-40, dodecyl benzene sulfonic acid calcium salt linear, monoxynol-n and nonyl phenol polygiycol ether 9-10. 7) The composition as claimed in claim 1, wherein the veterinary use is for acaricidal activity or for fly repellant activity. 8) The composition as claimed in claim 1, wherein the said hydro-dispersible emulsion composition is stable at 53-55°C for a period of upto 21 days.

Documents:

164-del-2004-abstract.pdf

164-DEL-2004-Claims-(21-07-2008).pdf

164-DEL-2004-Claims-(29-08-2008).pdf

164-del-2004-claims.pdf

164-DEL-2004-Correspondence-Others-(01-11-2010).pdf

164-DEL-2004-Correspondence-Others-(20-08-2008).pdf

164-DEL-2004-Correspondence-Others-(21-07-2008).pdf

164-DEL-2004-Correspondence-Others-(29-08-2008).pdf

164-del-2004-correspondence-others.pdf

164-del-2004-correspondence-po.pdf

164-DEL-2004-Description (Complete)-(29-08-2008).pdf

164-del-2004-description (complete)-21-07-2008.pdf

164-del-2004-description (complete).pdf

164-del-2004-drawings.pdf

164-del-2004-form-1.pdf

164-DEL-2004-Form-15-(01-11-2010).pdf

164-del-2004-form-18.pdf

164-DEL-2004-Form-2-(21-07-2008).pdf

164-del-2004-form-2.pdf

164-del-2004-form-26.pdf

164-del-2004-form-3.pdf

164-del-2004-form-5.pdf

164-DEL-2004-Other Document-(21-07-2008).pdf