DESC:3. PREAMBLE TO THE DESCRIPTION
COMPLETE
The following specification particularly describes the invention and the manner in which it is to be performed.
FIELD OF THE INVENTION
The present invention relates to compositions and methods for killing ectoparasites and/or preventing or inhibiting the adhesion of ectoparasites to a Subject. The compositions are useful against a variety of ectoparasites that afflict subject. Preferably the subject is a mammals, more preferably subject is human. Yet another aspect of the invention relate to method of prevention and/or treatment of ectoparasites infestation. Another aspect of the invention relate to a stable formulation comprising of fatty acid esters or siloxanes or mixture thereof, for prevention and/or treatment of ectoparasites infestation and also manufacturing processes thereof.

BACKGROUND
An ectoparasitic infestation is a parasitic disease caused by organisms that live primarily on the surface of the subject.
Head lice are small wingless biting insects or parasites which live and breed in human hair and feed by sucking blood from the scalp. An infestation of head lice, called Pediculus humanus capitis, most often affects children and usually results from the direct transfer of lice from the hair of one person to the hair of another. They infest people of all socio-economic positions and age groups.
Adult lice are about the size of sesame seeds. The eggs, called nits, are even smaller - about the size of a dandruff flake. Lice and nits are found on or near the scalp, most often at the neckline and behind the ears. They can be found on the head, eyebrows, eyelashes and pubic hairs of people and each type of lice is different.
Head lice move by crawling; they cannot hop or fly. Head lice are spread by direct contact with the hair of an infested person. Anyone who comes in head-to-head contact with someone who already has head lice is at greatest risk. Spread by contact with clothing (such as hats, scarves, coats) or other personal items (such as combs, brushes, or towels) used by an infested person is uncommon. Teale A et al teaches that it is estimated that it takes at least 30 seconds for lice to move from one head to another, therefore fleeting contact will be insufficient for transferring lice between heads (Head lice: evidence-based guidelines based on the Stafford Report, 2008 Update. Public Health Medicine Environmental Group2008)
Head lice have three forms: the egg (also called a nit), the nymph, and the adult.
• Egg/Nit: Nits are lice eggs laid by the adult female louse at the base of the hair shaft nearest the scalp. Nits are firmly attached to the hair shaft and are oval-shaped and very small (about the size of a knot in thread) and hard to see. Nits often appear yellow or white although live nits sometimes appear to be the same colour as the hair of the infested person. Nits are often confused with dandruff, scabs, or hair spray droplets and dirt particles. Head lice nits usually take about 8–9 days to hatch. Eggs that are likely to hatch are usually located no more than ¼ inch from the base of the hair shaft. Nits located further than ¼ inch from the base of hair shaft may very well be already hatched or dead, non-viable nits, or empty nits or casings. This is difficult to distinguish with naked eye.
• Nymph: A nymph is an immature louse that hatches from the nit. A nymph looks like an adult head louse, but is smaller. To live, a nymph must feed on blood. Nymphs mature into adults about 9–12 days after hatching from the nit.
• Adult: The fully grown and developed adult louse is about the size of a sesame seed, has a six legs, and is tan to greyish white in colour. Adult head lice may look darker in persons with dark hair than in persons with light hair. To survive, adult head lice must feed on blood. An adult head louse can live about 30 days on a person’s head but will die within one or two days if it falls off a person. Adult female head lice are usually larger than males and can lay about six eggs each day. Head lice are wingless, 2 mm to 4 mm long (as adults), six-legged, bloodsucking insects that live on the human scalp.
Infested children usually carry less than 20 mature head lice (and often<10) at a time, which live 3 to 4 weeks if left untreated. Head lice live close to the scalp surface, which provides food, warmth, shelter and moisture. The head louse feeds every 3 to 6 hours by sucking blood, injecting saliva simultaneously. After mating, the adult female louse can produce five or six eggs (nits) per day for 30 days, each ‘glued’ to a hair shaft near the scalp. The eggs hatch 9 to 10 days later into nymphs that molt several times over the next 9 to 15 days to become adult head lice. The hatched empty eggshells remain on the hair but are not a source of infestation. Nymphs and adult head lice can survive for only 1 to 2 days away from the human subject. While eggs can survive away from the subject for up to 3 days, they require the higher temperatures found near the scalp to hatch.
An infestation with lice is called pediculosis and usually involves less than 10 live lice. Itching occurs if the individual with lice becomes sensitized to antigenic components in the saliva injected as the louse feeds. On the first infestation, sensitization commonly takes 4 to 6 weeks. However, some individuals remain asymptomatic and never itch. In cases with heavy infestations, secondary bacterial infection of the excoriated scalp may occur. (Head lice infestations: A clinical update. Cummings, C et al, Paediatrics & Child Health, 23; (1) e18–e24, Feb 15, 2018).
The common characteristics of head lice are,
• Itching: Itching on the scalp, neck and ears is the most common symptom. This is an allergic reaction to louse saliva. When a person has an infestation for the first time, itching may occur after two to six weeks after infestation.
• Lice on scalp: Lice may be visible but are difficult to spot because they're small, avoid light and move quickly.
• Lice eggs (nits) on hair shafts: Nits stick to hair shafts. Incubating nits may be difficult to see because they're very tiny. They're easiest to spot around the ears and the hairline of the neck. Empty nits may be easier to spot because they're lighter in colour and further from the scalp. However, the presence of nits doesn't necessarily indicate an active infestation.

The diagnosis of a head lice infestation is best made by finding a live nymph or adult louse on the scalp or hair of a person. Use of a magnifying lens and a fine-toothed comb may be helpful to find live lice. If crawling lice are not seen, finding nits firmly attached within a ¼ inch of base of the hair shafts strongly suggests, but does not confirm, that a person is infested and should be treated.
Topical treatments commonly used for head lice infestation include Pyrethrins, that are derived from chrysanthemums and are stabilized by addition of piperonyl butoxide (e.g., RID®, Pronto®, and ClearLice®), other topical treatments available are Permethrin Cream 1% (Nix®), Malathion Lotion 0.5% (Ovide® and Prioderm®), Ivermectin 0.5% (Sklice®), Spinosad 0.9% Suspension (Natroba®), Benzyl alcohol 5% (Ulesfia ®) and Dimethicones, synthetic silicone oils.
The treatment of human head lice infestation, healthcare providers are increasingly concerned about lice becoming resistant to existing pesticide treatments. Traditional pesticides, used to control these pests, have a neurological mechanism of action. This invention describes a topical composition with a non-traditional mechanism of action, based on physical disruption of the wax layer that covers the cuticle of the louse exoskeleton. All insects, including human head lice, have a wax-covered exoskeleton. This wax, composed of hydrocarbons, provides the insect with protection against water loss and is therefore critical to its survival. When the protective wax is disrupted, water loss becomes uncontrollable and irreversible, leading to dehydration and death. A specific pattern of hydrocarbons has been found in all of the head louse cuticular wax studied. Iso-octane effectively removes these hydrocarbons from human head lice’s cuticular wax.
Oral Agents used Off-Label for Lice includes trimethoprim-sulfamethoxazole but is potential for severe allergic reactions and promoting bacterial resistance limit its use in this setting. Off label use of Oral ivermectin (Stromectal®). Use of oral ivermectin should be considered in individuals with head lice infestation who have failed topical pediculicide treatment. (Common Child and Adolescent Cutaneous Infestations and Fungal Infections. Alter, S et al, Curr Probl Pediatr Adolesc Health Care, 48:3-25, 2018).
Other treatment includes,
• Wet-combing: Combing wet hair with a fine-toothed nit comb may remove lice and some nits.
• Essential oils like tea tree oil, Anise oil, Nerolidol, a chemical compound found in many plant oils can also be used but because of the variability of their constitution, the effects may not be reproducible.
• Smothering agents: A number of household products can be used to treat head lice infestations. The reasoning is that these products deprive the lice and incubating eggs of air. The product is applied to the hair, covered with a shower cap and left on overnight. Products used for this purpose include, Mayonnaise, Olive oil, Butter, Petroleum jelly.
• Dehydration: This method involves a specialized machine that uses a hot air at a higher flow rate in an attempt to kill head lice and their eggs through dehydration.
• Manual Removal
US Publication No. 2007/0098750 discloses Pesticidal compositions containing synergistic combination of plant essential oils as active along with isopropyl myristate or analogues as synergist.
Burgess (PJ online The Pharmaceutical Journal (Vol-280) Page No. 371-375, Mar 29, 2018) et al discloses a review on Randomised, controlled, parallel group clinical trials to evaluate the efficacy of isopropyl myristate/Cyclomethicone solution against head lice. Results shows that using two applications of IPM/C one week apart cured head louse infestation significantly more effectively than Permithrin 1%.
Nalini Kaul (Journal of Cutaneous Medicine and Surgery, Vol 11, Issue 5, Sep 01, 2007) et al North American Efficacy and Safety of a Novel Pediculicide Rinse, Isopropyl Myristate 50% (Resultz). Study discloses the IPM was found to be effective in the proof of concept study and comparator trial using a positive control. IPM was also well tolerated, with minimal adverse events. All adverse events were mild, resolving. Also data suggest that IPM is a safe and effective therapy for the treatment of head lice in children and adults. IPM's mechanical mechanism of action makes development of lice resistance unlikely.
Carl Cummings (Head lice infestations: A clinical update, Paediatrics & Child Health, 23; (1) e18–e24, Feb 15, 2018) et al discloses that household products, such as mayonnaise, petroleum jelly, olive oil, tub margarine and thick hair gel, have been suggested as treatments for head lice.
US Patent No. 8,815,270 discloses head lice topical composition comprising combination of about 50% fatty acid ester (IPM) and about 50% siloxane (w/w) and composition is free of any other agent in an amount effective for killing said ectoparasites. The requires that composition essentially consist of combination of at least 25 % w/w Isopropyl Myristate and at least 25 % w/w of cyclomethicone. The US patent 8,815,270 do not provide any teaching for using either of Isopropyl Myristate or cyclomethicone for prevention or treatment of ectoparasite.
EP Patent No. 2470006 discloses medication for topical application in preventing and/or combatting head lice and/or nits without any active principle or chemical insecticide molecule; wherein composition comprises at least one surfactant, oily phase & hydrophilic phase; wherein oily phase includes at least one fat and an oily component other than the fat. The application further discloses composition comprising between 20 – 30 wt % surfactant; between 10 – 35 wt % surface active co-agent or co-surfactant, between 5 wt. % and 40 wt. % of a fat and between 5 wt. % and 10 wt. % of at least one oily component other than the fat, between 20 – 40 wt % hydrophilic phase comprising water, or a mixture of water and alcohol, or glycerol, or polyethylene glycol.
All the treatments mentioned above in the art have some or the other disadvantage like most of topical medicines approved by regulatory authority uses pesticides in nature while oral treatments apart from being off-label do not provide any significant relief from lice. Other treatments like wet-combing, essential oils, smothering agents, dehydration and manual removal are tedious and many times not much effective. Thus, there is a need to develop new and improved pharmaceutical composition for prevention and/or treatment of ectoparasite infestation which is free of insecticide and provides quick and complete relief from ectoparasites.

SUMMARY OF THE INVENTION
The present invention provides novel compositions for use against ectoparasite infestation. In particular, the present invention provides topical compositions, and methods for using same to control ectoparasite infestation. The present invention also provides safe and effective means of prevention and/or treatment, while also providing compositions which are non-toxic to humans and animals.
One aspect of the present invention, there is provided pharmaceutical composition comprising Fatty acid esters or siloxanes or mixtures thereof.
Another aspect of this invention, there is provided pharmaceutical composition comprising Isopropyl myristate or Cyclomethicone or mixtures thereof.
Another aspect of this invention is a pharmaceutical composition that comprises fatty acid esters or siloxanes or mixtures thereof and pharmaceutically acceptable vehicle. The composition may also contain at least one additional pharmaceutical agent.
Another aspect of present invention provides compositions for prevention of ectoparasites on a subject.
Another aspect of present invention provides compositions for treatment of ectoparasites on a Subject.
Another aspect of present invention provides methods for prevention of ectoparasites on a Subject.
Another aspect of present invention provides methods for treatment of ectoparasites on a Subject.
Another aspect of the present invention is to provide a therapeutically effective amount of composition for topical administration to a Subject in need of such prevention.
Yet another aspect of the present invention is to provide a therapeutically effective amount of composition for topical administration to a human in need of such treatment.
Another aspect of this invention provides methods of manufacturing a medicament for preventing ectoparasites infestation.
Another aspect of this invention provides methods of manufacturing a medicament for treating ectoparasites infestation
Another aspect of this invention provides methods of application of a medicament for preventing ectoparasites infestation.
Another aspect of this invention provides methods of application of a medicament for treating ectoparasites infestation.
The present invention also provides methods of treating and/or preventing head lice infestation on a mammal by topically administering a composition of present invention to affected area of mammal. Composition of this invention may be administered in combination with fatty acid/ ester compounds and siloxanes. The combination therapy may be administered as (a) a single composition which comprises a compound of this invention, at least one additional pharmaceutical agent described herein and a pharmaceutically acceptable excipient, diluent, or carrier; or (b) two separate pharmaceutical compositions comprising (i) a first composition comprising a compound of this invention and a pharmaceutically acceptable excipient, diluent, or carrier, and (ii) a second composition comprising at least one additional pharmaceutical agent described herein and a pharmaceutically acceptable excipient, diluent, or carrier administered simultaneously or immediately after one another. The pharmaceutical compositions may be administered simultaneously or sequentially and in any order.

OBJECTIVE OF THE INVENTION:
An object of the present invention is to provide the composition for prevention of ectoparasites.
An object of the present invention is to provide the composition for treatment of ectoparasites.
An object of the present invention is to provide the composition for prevention of lice.
An object of the present invention is to provide the composition for treatment of lice.
Another object of the present invention is to provide the composition for prevention of head lice.
Another object of the present invention is to provide the composition for treatment of head lice.
Yet another object of the present invention is to provide the topical composition for prevention of ectoparasites.
Yet another object of the present invention is to provide the topical composition for treatment of ectoparasites.
Yet another object of the present invention is to provide the topical composition for prevention of head lice.
Yet another object of the present invention is to provide the topical composition for treatment of head lice.
It is another object of the present invention to provide methods for the prevention of ectoparasites.
It is another object of the present invention to provide methods for the treatment of ectoparasites.
Another object of the present invention is providing the method for preparation of topical composition.
Another object of the present invention is providing the method for preparation of topical composition comprising fatty acid ester or siloxane or combination thereof.
Yet another object of the present invention is providing the method for preparation of topical composition comprising fatty acid ester or siloxane or combination thereof for the prevention of ectoparasites.
Yet another object of the present invention is providing the method for preparation of topical composition comprising fatty acid ester or siloxane or combination thereof for the prevention of head lice.
Yet another object of the present invention is providing the method for preparation of topical composition comprising fatty acid ester or siloxane or combination thereof for the treatment of ectoparasites.
Yet another object of the present invention is providing the method for preparation of topical composition comprising fatty acid ester or siloxane or combination thereof for the treatment of head lice.
Another object of the present invention is to provide the topical composition of fatty acid ester or siloxane or combination thereof.
Another object of the present invention is to provide the topical composition of fatty acid ester.
Another object of the present invention is to provide the topical composition of Isopropyl myristate.
Yet another object of the present invention is to provide the topical composition of siloxane.
Yet another object of the present invention is to provide the topical composition of Cyclomethicone.
Another object of the present invention is to provide the method for preparation of topical composition of fatty acid ester.
Another object of the present invention is to provide the method for preparation of topical composition of siloxane.
Yet another object of the present invention is to provide the composition for topical application of fatty acid ester with pharmaceutically acceptable vehicle.
Yet another object of the present invention is to provide the composition for topical application of Siloxane with pharmaceutically acceptable vehicle.
Yet another object of the present invention is to provide the composition for topical application of fatty acid ester and/or siloxanes with pharmaceutically acceptable vehicle.
Another object of the invention is to provide methods of application of fatty acid ester or siloxane or combination thereof.
Another aspect of this invention provides methods of application of fatty acid ester or siloxane or combination thereof for the prevention of ectoparasites.
Another aspect of this invention provides methods of application of fatty acid ester or siloxane or combination thereof for the prevention of head lice.
Another aspect of this invention provides methods of application of fatty acid ester or siloxane or combination thereof for the treatment of ectoparasites.
Another aspect of this invention provides methods of application of fatty acid ester or siloxane or combination thereof for the treatment of head lice.
It is another object of the invention is to provide a safe and effective means for the topical administration of fatty acid ester or siloxane or combination thereof.

DETAILED DESCRIPTION OF THE INVENTION
Before describing the present invention in detail, it is to be understood that this invention is not limited to specific pharmacologically active carriers, formulation types, treatments, so forth, and as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.
The present invention is of topical pharmaceutical composition comprising fatty acid ester or siloxanes or mixture thereof for the prevention and/or treatment of ectoparasites infestation. It also relates to the topical pharmaceutical composition comprising Isopropyl myristate or Cyclomethicone or mixture thereof for the prevention and/or treatment of head lice infestation.
The present invention relates to a topical pharmaceutical composition comprising fatty acid ester or siloxanes or mixture thereof with the pharmaceutically acceptable vehicle for the prevention and/or treatment of ectoparasites infestation. The present invention also relates to a topical pharmaceutical composition comprising Isopropyl myristate or Cyclomethicone or mixture thereof with the vegetable oil for the prevention and/or treatment of head lice infestation.
The treatment of human head lice infestation, healthcare providers are increasingly concerned about lice becoming resistant to existing pesticide treatments. Traditional pesticides, used to control these pests, have a neurological mechanism of action. This invention describes a topical composition with a non-traditional mechanism of action, based on physical disruption of the wax layer that covers the cuticle of the louse exoskeleton. All insects, including human head lice, have a wax-covered exoskeleton. This wax, composed of hydrocarbons, provides the insect with protection against water loss and is therefore critical to its survival. When the protective wax is disrupted, water loss becomes uncontrollable and irreversible, leading to dehydration and death. A specific pattern of hydrocarbons has been found in all of the head louse cuticular wax studied. Iso-octane effectively removes these hydrocarbons from human head lice’s cuticular wax. Present invention uses the same mechanism by using siloxanes and fatty acid esters which acts on lice by same mechanism.

DEFINITIONS:
The term “prevention” as disclosed in this specification meaning action taken to decrease the chance of ectoparasite infestation.
The term “treatment” as disclosed in this specification meaning the management and care of a subject to remove ectoparasite.
The term “ectoparasite” as discloses in this specification meaning a parasite that lives on or in the skin but not within the body. Ectoparasites infest the skin and its appendages, such as the hair and sebaceous glands, and most external orifices, especially the ears, nares, and orbits. Ectoparasites programmed to feed on human hosts to complete their life cycles. The ectoparasites of this invention are selected from but not limited to scabies (Sarcoptes scabiei), the common bed bug (Cimex lectularius), fleas, ticks and lice, including the body louse (Pediculus humanis), pubic louse (Phthirius pubis), and head louse (Pediculus humanus capitis).
The term “Head louse” or its plural “Head lice” are same and can be used interchangeably as disclosed in this specification meaning these are tiny insects that feed on blood from the human scalp.
The term “Subject” as disclosed in this specification meaning a mammal as commonly understood to one of ordinary skill in the art to which the present subject matter pertains, more specifically human.
It is noted that, as used in the present application including this specification and the claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise.
Unless defined otherwise, all other technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the present subject matter pertains.
Compositions of the present invention the preferable ratio of fatty acid ester and pharmaceutically acceptable vehicle is 1:1. But the amounts of the ingredients may can also vary substantially. For example, the composition can also be in the ratio of 1:9, about 1:4, about 3:7, about 2:3, about 3:2, about 7:3, about 4:1, or about 9:1 of fatty acid ester and the pharmaceutically acceptable vehicle. It is preferred that the ratio of fatty acid ester be less than 6.5:3.5 or 7:3 and at more than 2:8, 2.5:7.5, or 3.5:6.5 with pharmaceutically acceptable vehicle, and most preferably at about 5.5:4.5 or 1:1.
Another embodiment the composition contains fatty acid ester is in range of about 10 to about 90 %; about 20 and about 80 %; about 10 to about 70 %; about 25% to about 50 %.
One embodiment the composition contains fatty acid ester and vehicle in the ratio of 1:1 and does not contain any other ingredients.
In another embodiment the composition may contain combination of two or more fatty acid/esters and/or siloxanes. These may be included in desired proportions with vehicle accordingly. Example of Fatty acids/esters includes which can be used in accordance to but not limited to Isopropyl Adipate, Isopropyl Palmitate, Isopropyl linoleate, Isopropyl Lanolate, Isopropyl oleate, Transcutol P, Methyl palmitate, Methyl myristate, Isopropyl myristate, Dimethyl Adipate, Ethyl methyl Adipate, Methyl lineolate, Methyl oleate, Ethyl palmitate, Ethyl myristate, Diethyl Adipate, Ethyl lineolate, Propylene Glycol, Dimethyl sulfoxide, Ethyl oleate, Laurocapram, Pyrrolidones, Oxazolidinones or other structurally similar moieties can be methyl, ethyl derivatives of above acids/esters or mixtures thereof.
Another embodiment of current invention contains compositions of siloxane and pharmaceutically acceptable vehicle is in preferable ratio of 1:1. But the actual amounts of the ingredients may vary substantially. For example, the composition can also be in the ratio of 1:9, about 1:4, about 3:7, about 2:3, about 3:2, about 7:3, about 4:1, or about 9:1 of Siloxane and the pharmaceutically acceptable vehicle. It is preferred that the ratio of siloxane be less than 6.5:3.5 or 7:3 and at more than 2:8, 2.5:7.5 or 3.5:6.5 with pharmaceutically acceptable vehicle, and most preferably at about 5.5:4.5 or 1:1.
Another embodiment the composition contains siloxane is in range of about 10 to about 90 %; about 20 and about 80 %; about 10 to about 70 %; about 25% to about 50 %.
One embodiment of the composition contains siloxane and vehicle in the ratio of 1:1 and does not contain any other ingredients. In another embodiment the composition may contain combination of two or more siloxanes and/or fatty acid/esters. These may be included in desired proportions with the vehicle accordingly. Preferred agent includes cyclic siloxanes. Example of siloxanes includes which can be used in accordance to but not limited to cyclic siloxanes such as hexamethylcyclotrisiloxane, cyclomethicone, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane or other structurally similar moieties or derivatives of above siloxane or mixtures thereof.
In another embodiment the composition may contain vehicle selected from vegetable oil such as (but not limited to) soybean oil, peanut oil, castor oil, corn oil, fractionated coconut oil, cottonseed oil, olive oil, grape seed oil, sunflower oil, etc .; mineral oils such as (but Not limited to) paraffin oil, paraffin, polysiloxane, etc .; aliphatic or cyclic hydrocarbons (including limonene) or, for example, medium chain (such as C 8 to C 12 ) triglycerides or mixtures thereof. In one embodiment, a solvent and / or additive that controls the penetration rate of the active agent may be added to a composition comprising one of the formulation carriers described herein, which formulations include Carriers of alkyl esters such as diethyl sebacate or the like.
In another embodiment, a solvent and / or additive that controls the penetration rate of the active agent may be added to a vehicle containing other solvents described herein or may be used alone in the composition
Another embodiment the composition contains vehicle is in range of about 10 to about 90 %; about 20 and about 80 %; about 10 to about 70 %; about 25% to about 50 %.
Another embodiment of present invention can be used along with device for removing ectoparasite infestation.
The composition of current invention can be prepared using techniques known in art.
The composition of present invention are prepared by mixing fatty acid ester or siloxane or mixture thereof with suitable vehicle in appropriate ratio in homogenizer or appropriate mixing vessel and stirred until uniform solution is formed.
In another embodiment the topical dosage forms according to the invention can be in any form like Cream, gel, lotion, solution, emulsion and suspension or can be develop in any suitable form used for application to hairs.
While this provisional application contains the principal inventive concepts, the complete patent application pursuant hereto, will fully and particularly describe the preferred embodiments of the present invention.
It is to be understood that the invention described in specification, it is not limited to specific pharmacologically active carriers, formulation types, treatments, preventions, so forth, and as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

EXAMPLES
Example 1: In vitro study to investigate Pediculicidal activity or Anti-lice Assay
The Pediculicidal Activity or Anti-lice Assay was performed by filter paper diffusion method. Stock solution of the test products at desired volume were prepared. A Total of 4 petri dishes was taken for each formulation i.e. Test drug (1 original (T1) + 1 duplicate (T2)) + 1 placebo (P) + 1 negative control (NC). Whatman filter No.1 paper was placed at the bottom of each petri dishes. Test organism – The head lice, the adults and nymphs after careful selection under dissecting microscope was identified and separated. The test organisms in a ratio of 7/3 (adult/nymph) was divided in to 4 groups (preferably 10 lice each) consisting of 2 plates with a test drug (1 original + 1 duplicate), 1 plate with the negative control and 1 plate with the placebo and was placed on filter paper at the bottom of petri dish with lid kept open. The Lice were confined on Whatman Filter No1 paper using metal rings. 1ml each of the Test sample was poured on the test organisms by using 1ml Micropipette, placed on filter paper in the original and the duplicate plate and allowed to spread as a thin layer of 4 cm2. The lids were closed immediately. 1 ml of blinded oil and distilled water was added to the placebo and the negative control plates respectively. All the petri dishes were covered with the lid and set aside for 1 hour in a dark chamber at 30-32° C and 70 ± 1 % humidity. After 1 hour, the dishes were taken out and lice to be carefully transferred to another Whatman filter paper placed petri dish. About 0.5 to 1ml of distilled water was added to allow rinsing/ washing out. Post wash-out, lice was transferred to another clean Whatman filter paper placed petri dish (experimental units) and a water-soaked cotton plug was placed in each petri dish to maintain the moisture content. The experiment units (dishes with lice) were observed under a dissecting microscope for any possible movement of lice. The criterion for mortality is inability of lice to walk over the filter paper. This procedure was repeated every one hour for 8 hours. The results were recorded at every time point as per protocol. Then the experiment units were placed back in to the dark chamber under the same conditions mentioned above for 18 hours. After 18 hours, the experiment units (dishes with lice) were observed under a dissecting microscope for any possible movement of lice and the results were recorded. Again, at 24 hours, the experiment units (dishes with lice) was observed under a dissecting microscope for any possible movement of lice and the results were recorded.
Percentage mortalities corrected by Abbott's formula.
% Test mortality - % Control mortality X 100
100% - % Control mortality
Observations: After the drug was added; at the end of every one hour the experiment units (dishes with lice) was observed under a dissecting microscope for any possible movement of lice and the criterion for mortality is the inability of lice to walk over the filter paper. Determining the mortality was performed for every hour for 8 hours. Finally, these units were again observed after 18 and 24 hours for lice movement.
Table 1: Lice Mortality Study
Sr. No. Groups No of lice After 1 hour After 18 hour After 24 hour
No of live lice No of dead lice % Mortality No of live lice No of dead lice % Mortality No of live lice No of dead lice % Mortality
1
T1
10
0
10
100
0
10
100
0
10
100

2
T2
10
0
10
100
0
10
100
0
10
100

3
P
10
10
0
0
9
1
10
0
10
100

4
NC
10
10
0
0
10
0
0
0
10
100

Result: The Table 1 indicated that Test product tested in duplicate exhibited pediculicidal activity at the end of one hour only as compared to Placebo and negative control.

Example 2: A double-blind randomized study to compare the efficacy, safety and local tolerability of composition of present invention compared to a topical vehicle control in subjects with head lice (Pediculus humanus capitis) infestation
The composition of present invention would be evaluated for efficacy, safety & tolerability using double blind randomized study against placebo. Patient would be provided with instruction for use of product at the time of enrolment. The amount of Investigational product to be applied depends on the length of the scalp hair, but no more would be used than necessary to properly cover the scalp and hair. The exposure time of the Investigational Product would be10 ±5 minutes or 2 hours ±5 minutes or overnight. Following application, the product would be directly washed out (one rinse). No commercial shampoo would be applied to exclude any potential effect on head lice. The study subjects would be 5 year and older age Healthy male and non-pregnant women.
The primary end point for study would be percentage of participants who were lice-free (i.e. no live lice or adults or nymphs or nits) after the last treatment with either test or placebo and secondary end points would be i) number of participants reporting treatment-emergent adverse events post-treatment with either test group or placebo group; ii) incidence of Skin/Scalp Irritation Before Treatment and Post-treatment With Either in test group or placebo group.
The efficacy would be evaluated as cure rate of the test product for all baseline infestations at either day 7 or day 14 or day 21 or at all 3 intervals. The cure rate is the proportion of patients without any living lice, corrected for re-infestation. Whereas safety would be evaluated based on any adverse event reported either in by patient or observed & determined by investigator.
The statistical evaluation such as would be made at the end of study for both test and placebo & result would be determined for safety, efficacy and local tolerability of test over placebo.

Example 3: Topical dosage form of Fatty acid ester
Table 2: Composition of Fatty acid ester
Ingredient Concentration
(a) (b) (c) (d) (e)
Fatty acid ester 10% 30% 50% 70% 90%
Vegetable oil 90% 70% 50% 30% 10%

Manufacturing Process:
Step 1: The required quantity of Fatty acid ester was weighed in suitable SS vessel.
Step 2: The required quantity of vegetable oil was weighed in main mixing vessel.
Step 3: The weighed quantity of Fatty acid ester was added to main mixing vessel under stirring at 1000 ± 200 rpm.
Step 4: The contents were stirred for 60 minutes at 1000 ± 200 rpm.
Step 5: The final yield of batch was recorded after completion of stirring of step 4.
Step 6: The batch was then filed into appropriate container & labelled.

Example 4: Topical dosage form of Siloxane
Table 3: Composition of Siloxane
Ingredient Concentration
(a) (b) (c) (d) (e)
Siloxane 20% 40% 60% 80% 90%
Vegetable oil 80% 60% 40% 20% 10%

Manufacturing Process:
Step 1: The required quantity of siloxane was weighed in suitable SS vessel.
Step 2: The required quantity of vegetable oil was weighed in main mixing vessel.
Step 3: The weighed quantity of siloxane was added to main mixing vessel under stirring at 1000 ± 200 rpm.
Step 4: The contents were stirred for 60 minutes at 1000 ± 200 rpm.
Step 5: The final yield of batch was recorded after completion of stirring of step 4.
Step 6: The batch was then filed into appropriate container & labelled.

Example 5: Topical dosage form of Isopropyl myristate
Table 4: Composition of Isopropyl myristate
Ingredient Concentration
(a) (b) (c) (d) (e)
Isopropyl myristate 10% 25% 50% 65% 80%
Vegetable oil 90% 75% 50% 35% 20%

Composition of Example 5 was manufactured by using manufacturing process as described herein Example 3.

Example 6: Topical dosage form of Isopropyl myristate
Table 5: Composition of Isopropyl myristate
Ingredient Concentration
(a) (b) (c) (d) (e)
Isopropyl myristate 15% 30% 50% 75% 85%
Olive oil 85% 70% 50% 25% 15%

Composition of Example 6 is manufactured by using manufacturing process as described herein Example 3.

Example 7: Topical dosage form of Methyl lineolate
Table 6: Composition of Methyl lineolate
Ingredient Concentration
(a) (b) (c) (d) (e)
Methyl lineolate 10% 30% 50% 70% 90%
Olive oil 90% 70% 50% 30% 10%

Composition of Example 7 was manufactured by using manufacturing process as described herein Example 3.

Example 8: Topical dosage form of Ethyl methyl Adipate
Table 7: Composition of Ethyl methyl Adipate
Ingredient Concentration
(a) (b) (c) (d) (e)
Ethyl methyl Adipate 25% 35% 45% 50% 70%
Coconut oil 75% 65% 55% 50% 30%

Composition of Example 8 was manufactured by using manufacturing process as described herein Example 3.

Example 9: Topical dosage form of Isopropyl myristate
Table 8: Composition of Isopropyl myristate
Ingredient Concentration
(a) (b) (c) (d) (e)
Isopropyl myristate 20% 35% 50% 70% 85%
Coconut oil 80% 55% 50% 30% 15%

Composition of Example 9 was manufactured by using manufacturing process as described herein Example 3.

Example 10: Topical dosage form of Cyclomethicone
Table 9: Composition of Cyclomethicone
Ingredient Concentration
(a) (b) (c) (d) (e)
Cyclomethicone 15% 30% 50% 75% 85%
Vegetable oil 85% 70% 50% 25% 15%

Composition of Example 10 was manufactured by using manufacturing process as described herein Example 4.

Example 11: Topical dosage form of Cyclomethicone
Table 10: Composition of Cyclomethicone
Ingredient Concentration
(a) (b) (c) (d) (e)
Cyclomethicone 25% 35% 45% 50% 70%
Coconut oil 75% 65% 55% 50% 30%

Composition of Example 11 was manufactured by using manufacturing process as described herein Example 4.

Example 12: Topical dosage form of Dodecamethylcyclohexasiloxane
Table 11: Composition of Dodecamethylcyclohexasiloxane
Ingredient Concentration
(a) (b) (c) (d) (e)
Dodecamethylcyclo-
hexasiloxane 20% 35% 50% 70% 85%
Coconut oil 80% 55% 50% 30% 15%

Composition of Example 12 was manufactured by using manufacturing process as described herein Example 4.
Example 13: Topical dosage form of Cyclomethicone
Table 12: Composition of of Cyclomethicone
Ingredient Concentration
(a) (b) (c) (d) (e)
Cyclomethicone 10% 30% 45% 50% 85%
Olive oil 90% 70% 55% 50% 15%

Composition of Example 13 was manufactured by using manufacturing process as described herein Example 4.

Example 14: Topical dosage form of hexamethylcyclotrisiloxane
Table 13: Composition of Hexamethylcyclo-trisiloxane
Ingredient Concentration
(a) (b) (c) (d) (e)
Hexamethylcyclo-trisiloxane 10% 30% 50% 70% 90%
Olive oil 90% 70% 50% 30% 10%

Composition of Example 14 was manufactured by using manufacturing process as described herein Example 4.

Example 15: Topical dosage form of Fatty acid ester and siloxane
Table 14: Composition of Fatty acid ester and Siloxane
Ingredient Concentration
(a) (b) (c) (d) (e)
Fatty acid ester 20% 10% 50% 25% 35%
Siloxane 30% 40% 10% 25% 15%
Vegetable oil 50% 50% 40% 50% 50%

Manufacturing Process:
Step 1: The required quantity of Fatty acid ester and siloxane were weighed in suitable SS vessel.
Step 2: The required quantity of vegetable oil was weighed in main mixing vessel.
Step 3: The weighed quantities of Fatty acid ester and siloxane were added to main mixing vessel under stirring at 1000 ± 200 rpm.
Step 4: The contents were stirred for 60 minutes at 1000 ± 200 rpm.
Step 5: The final yield of batch was recorded after completion of stirring of step 4.
Step 6: The batch was then filed into appropriate container & labelled.

Example 16: Topical dosage form of Isopropyl myristate and Cyclomethicone
Table 15: Composition of Isopropyl myristate and Cyclomethicone
Ingredient Concentration
(a) (b) (c) (d) (e)
Isopropyl myristate 20% 40% 40% 25% 30%
Cyclomethicone 30% 40% 10% 25% 30%
Olive oil 50% 20% 50% 50% 40%

Composition of Example 16 was manufactured by using manufacturing process as described herein Example 15.

Example 17 (A): Topical dosage form of Isopropyl myristate
Table 16: Composition of Isopropyl myristate
Ingredient Concentration
Isopropyl myristate 100 gm
Fractionated coconut oil 100 gm

Composition of Example 17 (A) was manufactured by using manufacturing process as described herein Example 3. The composition was further evaluated for physiochemical properties like appearance, viscosity, surface tension, specific gravity.
Observation: The evaluation of physiochemical properties are listed in Table 17.
Table 17: Physiochemical Properties
Test Observation
Appearance Clear Transparent solution
Viscosity (cP) 8.4
Surface tension (mN/m) 29.11
Specific gravity 0.896

The composition of example 17 (A) was also evaluated for stability at accelerated condition (40°C/75%RH) and at 30°C/65%RH. The stability data is provided in table 18.
Table 18: Stability Data
Initial 1 Month 3 Month 6 Month 9 Month 12 Month
30°C/ 65% RH 40°C/ 75% RH 30°C/ 65% RH 40°C/ 75% RH 25°C/ 60% RH 30°C/ 65% RH 25°C/ 60% RH 30°C/ 65% RH 25°C/ 60% RH 30°C/ 65% RH
Viscosity (cP) 10.6 10.67 10.66 10.77 10.92 10.74 10.64 11.28 11.15 14.40 13.84
Description Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid Clear colour-less oily liquid
Assay 99.7 99.7 99.9 99.1 100.9 101.5 99.9 98.2 98.6 99.90 99.50

Result: The stability data indicates that composition is stable & does not degrade even at accelerated condition at end of 6 months.

Example 17 (B): Topical dosage form of Isopropyl myristate
Table 19: Composition of Isopropyl myristate
Ingredient Concentration
Isopropyl myristate 100 gm
Olive oil 100 gm

Composition of Example 17 (B) is manufactured by using manufacturing process as described herein Example 3. The composition was further evaluated for physiochemical properties like appearance, viscosity, surface tension, specific gravity.

Observation: The evaluation of physiochemical properties are listed in Table 20.
Table 20: Physiochemical Properties
Test Observation
Appearance Clear Yellowish solution
Viscosity (cP) 13.6
Surface tension (mN/m) 29.91
Specific gravity 0.885

The composition of example 17 (B) was also evaluated for stability at accelerated condition (40°C/75%RH) and at 30°C/65%RH. The stability data is provided in table 21.

Table 21: Stability Data
Initial 1 Month 3 Month 6 Month
30°C/ 65%RH 40°C/ 75%RH 30°C/ 65%RH 40°C/ 75%RH 30°C/ 65%RH 40°C/ 75%RH
Viscosity (cP) 17.19 17.2 17.28 17.27 17.15 17.28 17.32
Description Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid
Assay 100.6 100.6 100.6 101.5 102.3 101.5 100.9

Result: The stability data indicates that composition is stable & does not degrade even at accelerated condition at end of 6 months.

Example 18 (A): Topical dosage form of Cyclomethicone
Table 22: Composition of Cyclomethicone
Ingredient Concentration
Cyclomethicone 100 gm
Fractionated coconut oil 100 gm

Composition of Example 18 (A) was manufactured by using manufacturing process as described herein Example 4. The composition was further evaluated for physiochemical properties like appearance, viscosity, specific gravity.
Observation: The evaluation of physiochemical properties are listed in Table 23.
Table 23: Physiochemical Properties
Test Observation
Appearance Clear Transparent solution
Viscosity (cP) 7.79
Specific gravity 0.955

The composition of example 18 (A) was also evaluated for stability at accelerated condition (40°C/75%RH) and at 30°C/65%RH. The stability data is provided in table 24.

Table 24: Stability Data
Initial 1 Month 3 Month 6 Month
30°C/ 65%RH 40°C/ 75%RH 30°C/ 65%RH 40°C/ 75%RH 30°C/ 65%RH 40°C/ 75%RH
Viscosity (cP) 9.82 10.47 10.43 10.5 10.49 10.58 10.52
Description Clear colourless oily liquid Clear colourless oily liquid Clear colourless oily liquid Clear colourless oily liquid Clear colourless oily liquid Clear colourless oily liquid Clear colourless oily liquid

Result: The stability data indicates that composition is stable & does not degrade even at accelerated condition at end of 6 months.

Example 18 (B): Topical dosage form of Cyclomethicone
Table 25: Composition of Cyclomethicone
Ingredient Concentration
Cyclomethicone 100 gm
Olive oil 100 gm

Composition of Example 18 (B) is manufactured by using manufacturing process as described herein Example 4. The composition was further evaluated for physiochemical properties like appearance, viscosity, specific gravity.
Observation: The evaluation of physiochemical properties are listed in Table 26.
Table 26: Physiochemical Properties
Test Observation
Appearance Clear Yellowish solution
Viscosity (Initial) (cP) 13.2
Specific gravity 0.876

The composition of example 18 (B) was also evaluated for stability at accelerated condition (40°C/75%RH) and at 30°C/65%RH. The stability data is provided in table 27.

Table 27: Stability Data
Initial 1 Month 3 Month 6 Month
30°C/ 65%RH 40°C/ 75%RH 30°C/ 65%RH 40°C/ 75%RH 30°C/ 65%RH 40°C/ 75%RH
Viscosity (cP) 19.13
19.49
19.66
19.23
19.54
19.1
19.51

Description Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid Clear yellowish oily liquid

Result: The stability data indicates that composition is stable & does not degrade even at accelerated condition at end of 6 months.
,CLAIMS:WE CLAIM:
1. A composition for topical application comprising fatty acid ester and/or siloxanes with pharmaceutically acceptable vehicle for the treatment or prevention of ectoparasites.
2. The fatty acid ester according to claim 1 are selected from the group of Isopropyl Adipate, Isopropyl Palmitate, Isopropyl linoleate, Isopropyl Lanolate, Isopropyl oleate, Transcutol P, Methyl palmitate, Methyl myristate, Isopropyl myristate, Dimethyl Adipate, Ethyl methyl Adipate, Methyl lineolate, Methyl oleate, Ethyl palmitate, Ethyl myristate, Diethyl Adipate, Ethyl lineolate, Propylene Glycol, Dimethyl sulfoxide, Ethyl oleate, Laurocapram, Pyrrolidones, Oxazolidinones or methyl, ethyl derivatives of acids/esters or mixtures thereof.
3. The siloxanes according to claim 1 are selected from the group of hexamethylcyclotrisiloxane, cyclomethicone, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane or derivatives or mixtures thereof.
4. The pharmaceutically acceptable vehicle according to claim 1 is Vegetable oil.
5. The Vegetable oil according to claim 4 is selected from Fractionated coconut oil, Coconut oil or Olive oil.
6. The ectoparasites according to claim 1 are lice.
7. The ectoparasites according to claim 1 are head lice.
8. A method for preparation of topical composition comprising fatty acid ester or siloxane or combination thereof with pharmaceutically acceptable vehicle for the treatment or prevention of ectoparasites includes following steps:
a) The required quantity of Fatty acid ester and/or siloxane were weighed in suitable SS vessel.
b) The required quantity of vegetable oil was weighed in main mixing vessel.
c) The weighed quantities of Fatty acid ester and/or siloxane were added to main mixing vessel under stirring at 1000 ± 200 rpm.
d) The contents were stirred for 60 minutes at 1000 ± 200 rpm.
e) The final yield of batch was recorded after completion of stirring of step d.
f) The batch was then filed into appropriate container & labelled.
9. A method of application of topical composition comprising fatty acid ester or siloxane or combination thereof with pharmaceutically acceptable vehicle for the treatment or prevention of ectoparasites.

Dated this 13th day of May, 2020

Mehul Shah
Applicant, Encube Ethicals Private Limited