Antiparasitic composition

Abstract

The present invention relates to an antiparasitic composition comprising an antiparasitic agent and a semifluorinated alkane.

Description

[0001] This application is a divisional application of Chinese patent application No. 202180012215.3, entitled "Antiparasitic Composition", filed on February 6, 2021. Technical Field

[0002] This invention relates to compositions and methods for treating parasitic infections of the skin, particularly ectoparasitic infections. Background Technology

[0003] The term ectoparasitic infection refers to a parasitic disease caused by animals such as arthropods (i.e., mites, ticks, and lice) and worms. Ectopic infections are parasitic diseases caused by organisms that primarily live on the surface of a host. Examples of ectoparasitic infections are scabies, body lice, head lice, ticks, and fleas.

[0004] Mites are among the smallest arthropods. Most mite species are harmless to humans or domestic animals, but a few can colonize mammals and cause allergic diseases. Many types of itchy rashes are caused by mites. Among them, scabies is caused by the parasitic mite Sarcoptes scabiei. Scabies is a contagious infection that spreads through skin-to-skin contact and sometimes through contact with contaminated materials. Scabies is transmitted by female Sarcoptes scabiei mites, which burrow into the stratum corneum to lay eggs and then die after 30 to 60 days. If infection occurs, the first papules appear within 2 to 5 weeks. The main symptom of scabies is intense itching, which becomes particularly severe at night. Preferred areas of infection are areas with thin skin (Deutsches Ärzteblatt International 2016;113:757-62 / Supplementary material).

[0005] Since mites reside in the stratum corneum, topical treatment with anti-scabies medications is usually sufficient to kill the mites, larvae, and eggs. One of the first-line treatments for scabies is permethrin, as it is effective against different types of scabies regardless of the patient's age. A 5% permethrin cream is commercially available. Each tube of 5% permethrin cream contains 0.45 g of benzyl alcohol, which may cause allergic reactions such as allergic contact dermatitis. Permethrin is also commercially available as a solution, InfectoPedicul® 430 mg / 100 ml, for one-time treatment of hair in cases of head lice. This solution specifically contains 96% ethanol, 2-propanol, and water.

[0006] Clomidon is an anti-scabies and antipruritic agent available as a cream or lotion for external use only. It is a colorless to slightly yellow oil with a faint amine odor. It is miscible with alcohol and methanol. Clomidon is toxic to scabies mites. Clomidon is available as a 10% lotion, cream, ointment, and a 5% gel. Treatment takes 3 to 5 days to be effective.

[0007] Benzyl benzoate is another option for treating scabies. This substance exhibits good acaricide and ovicidal activity. Commercial products containing benzyl benzoate contain propylene glycol and cetylstearyl, potential contact allergens. Benzyl benzoate emulsions (Antiscabiosum®) are available in 25% and 10% concentrations. Apply the emulsion to the skin for three consecutive days and remove it only on the fourth day via shower.

[0008] Demodex is a genus of tiny mites that live in or near the hair follicles of mammals. Two species live on humans: *Demodex folliculorum* and *Demodex brevis*, both often referred to as eyelash mites. These two species are primarily found on the face, around the nose, eyelashes, and eyebrows, but can also appear elsewhere on the body. The mites can be eradicated with topical insecticides such as clomiphene cream, permethrin cream, ivermectin cream, and topical or systemic metronidazole.

[0009] Lice are nearly invisible wingless insects that infest the head, body, or genital area and feed on blood. They are easily spread from person to person through close contact and sharing clothing and other personal items. Head lice and pubic lice live directly on the body, while body lice live on clothing and bedding.

[0010] To treat head lice, apply an over-the-counter shampoo or cream containing pyrethroid + piperonyl butyl ether for 10 minutes and then rinse. Prescription permethrin (the synthetic form of pyrethroid) is also effective, either as a liquid or as a cream. Lindane, a prescription medication, can be applied as a wash or shampoo. It can also cure lice infestations, but is not as effective as other formulations.

[0011] All these lice treatments are repeated for 7 to 10 days to kill newly hatched lice. Lice may begin to develop resistance to the drug and become difficult to kill. If lice resist standard treatment, a single dose of ivermectin is usually administered orally. Lice affecting eyelashes can be treated with: application of petroleum jelly for 8 to 10 days, fluorescein eye drops, oral ivermectin, petroleum jelly ointment, physostigmine ointment, or careful removal of each louse with instruments.

[0012] One of the drawbacks of commercial antiparasitic compositions is that they contain alcohol, which causes additional irritation and pain to the skin, especially in the presence of lesions.

[0013] Most commercial antiparasitic compositions are semi-solid formulations in the form of gels, ointments, or creams, which are difficult to distribute evenly over large areas of skin or body surface and do not spread on their own to hard-to-reach areas of the body, such as the back and skin folds. For example, scabies patients require hospitalization because existing products cannot treat large areas of skin, such as the entire body surface, on their own.

[0014] EP2286663B1 describes an alcohol-free composition containing isopropyl myristate, and a method for killing ectoparasites on a subject. Summary of the Invention

[0015] The object of the present invention is to provide an antiparasitic composition for external application to the skin of a subject and for the treatment of parasitic infections such as scabies, lice and ticks.

[0016] The object of this invention is achieved according to the claims. This invention provides an antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane.

[0017] In a second aspect, the present invention provides an antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane, said antiparasitic composition being used as a pharmaceutical agent, particularly for a method of treating parasitic infection.

[0018] In a third aspect, a method for applying an antiparasitic composition topically is also provided, the method comprising applying the antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane using a swab, a roller dispenser, or a spray dispenser.

[0019] In a fourth aspect, a method for treating parasitic infection is provided, the method comprising applying topically an antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane to the skin of a subject in need.

[0020] In a fifth aspect, the present invention provides a kit comprising a) an antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane, and b) a dispenser selected from roller dispensers, spray dispensers, and wipe dispensers.

[0021] The inventors of this invention have discovered that an antiparasitic composition can be obtained by mixing an antiparasitic agent with a semi-fluorinated alkane. This composition has the advantages of being alcohol-free and easy to spread on the skin, for example, through non-contact application using a roller dispenser, a wet wipe, or a spray dispenser, thus simplifying the application process to the subject's skin. The composition of this invention has the further advantage of leaving no greasy residue on the skin.

[0022] The compositions of the present invention have the following further advantages: when applied by a roller dispenser, spray dispenser, or wet wipe, they allow for easy and rapid coverage of large or small areas of skin. The compositions of the present invention are characterized by self-spreading, allowing for easy and rapid coverage of hard-to-reach areas, such as the back or skin folds, when applied non-contactly using a spray dispenser, roller dispenser, or wet wipe.

[0023] The compositions of the present invention are anhydrous and do not require preservatives, surfactants, or additional penetration enhancers, all of which can cause pain and local tolerance problems in inflamed skin during short-term and long-term use.

[0024] The composition of this invention differs from any cream, ointment, or foam in its ease of application and improved skin safety, especially when applied to sensitive or difficult-to-treat areas such as the scalp, face, intertrigo, genitals, nails, hands, and feet. It will be delivered in liquid form using a special container designed for non-contact application. There is no need to rub or massage the composition into the skin, and it will be possible to put on clothing shortly after application without a long wait for absorption. Fabrics such as clothing or sheets / pillows will not be soiled. Detailed Implementation

[0025] The present invention provides an antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane.

[0026] An antiparasitic agent is a drug used to treat parasitic diseases, such as those caused by ectoparasites and parasitic fungi. In a preferred embodiment of the invention, the antiparasitic agent is an ectoparasitic agent. An ectoparasitic agent is an antiparasitic drug used to treat ectoparasitic infections, i.e., a drug used to kill parasites living on the surface of the body. Preferably, the antiparasitic agent is an ectoparasitic agent selected from pyrethroids, pyrethroids, aniline, benzoate esters, more preferably pyrethroids, benzoate esters, or aniline benzoate, and most preferably pyrethroids or aniline esters.

[0027] Aniline (or phenylamide) is a class of compounds that are acyl derivatives of aniline. Pyrethroids are synthetic chemical insecticides whose chemical structures are adapted from those of pyrethrin, a plant-based insecticide derived from chrysanthemum.

[0028] In a preferred embodiment, the antiparasitic agent is selected from permethrin, benzyl benzoate, and clomiphene. More preferably, the antiparasitic agent is selected from permethrin and clomiphene, with permethrin being the most preferred.

[0029] In another preferred embodiment, the antiparasitic agent is selected from permethrin, benzyl benzoate, cromamide, ivermectin and lindane.

[0030] The antiparasitic agent may be present at a concentration of up to 10% w / v, preferably up to 5% w / v, relative to the total volume of the composition. In a preferred embodiment, the antiparasitic agent is present at a concentration of from 0.5% w / v to 10% w / v, preferably from 0.5% w / v to 5% w / v, relative to the total volume of the composition. In another preferred embodiment, the antiparasitic agent is present at a concentration of from 0.5% w / v to 1.5% w / v, preferably from about 1% w / v, relative to the total volume of the composition.

[0031] Unless otherwise stated, the term “% w / v” as used throughout this document in conjunction with the compositions of the present invention expresses the amount of a component of the composition (e.g., an antiparasitic agent) as a weight percentage relative to the total volume of the composition (where “w” represents weight and “v” represents volume). For example, 0.05% (w / v) can be understood to relate to 0.5 mg of the component in 1 mL of the composition, and 0.1% (w / v) would correspond to 1.0 mg of the component in 1 mL of the composition.

[0032] As used herein, the term "semi-fluorinated alkane" (also referred to as "SFA" throughout this document) means a linear or branched compound consisting of at least one perfluorinated segment (F-segment) and at least one nonfluorinated segment (H-segment). Preferably, the semi-fluorinated alkane is a linear or branched compound consisting of one perfluorinated segment (F-segment) and one nonfluorinated segment (H-segment). Preferably, the semi-fluorinated alkane is a compound existing in a liquid state in the temperature range of 4ºC to 40ºC.

[0033] Preferably, the F-segment and H-segment of the linear or branched semi-fluorinated alkane independently comprise 2 to 10 carbon atoms. According to a preferred embodiment of the invention, the semi-fluorinated alkane is a straight-chain compound of the formula (F(CF2)n(CH2)mH), wherein n and m are integers independently selected from the range of 2 to 10.

[0034] According to another nomenclature, straight-chain semi-fluorinated alkanes can be designated FnHm, where F indicates a perfluorinated hydrocarbon segment, H indicates a non-fluorinated hydrocarbon segment, and n and m are the number of carbon atoms in the corresponding segment. For example, F4H5 is used for 1-perfluorobutylpentane. In a preferred embodiment of the invention, the semi-fluorinated alkane is a semi-fluorinated alkane of the formula F(CF2)n(CH2)mH, wherein n is selected from 4 to 6 and m is selected from 5 to 10. More preferably, semi-fluorinated alkanes are selected from F4H5, F4H6, F4H8, F4H10, F6H6, F6H8, F8H8, and F6H10. Most preferably, semi-fluorinated alkanes are selected from F4H8, F4H5, F6H6, and F6H8, or the semi-fluorinated alkane is F6H8. Preferred are semi-fluorinated alkanes selected from F4H4, F4H5, F4H6, F4H8, F4H10, F6H2, F6H4, F6H6, F6H8, F8H8, and F6H10.

[0035] In this invention, the composition may comprise a semi-fluorinated alkane in an amount from about 75% (w / w) to about 99% (w / w), more preferably from about 90% (w / w) to about 99% (w / w), relative to the total weight of the composition. In a most preferred embodiment of the invention, the composition comprises a semi-fluorinated alkane in an amount of at least 75% w / w, preferably at least 85% w / w, more preferably at least 90% w / w, relative to the total weight of the composition.

[0036] As used herein, the term "spreadability" or "spreadability" refers to the characteristic of a composition that allows it to be distributed on the skin. Spreadability relates to the contact angle of droplets of a liquid or semi-solid composition on a standardized substrate and is a measure of lubricity, which is directly related to the coefficient of friction. The efficacy of topical therapies depends on spreading the pharmaceutical composition into a uniform layer for administration of a standard dose to the patient. Therefore, spreadability is an important characteristic of these compositions and is responsible for the correct transfer of dosage to the target site, ease of application on a substrate, and, most importantly, consumer preference. The antiparasitic compositions of the present invention exhibit excellent spreadability and are therefore particularly suitable for application to sensitive or hard-to-reach areas of the body or skin and / or non-contact application to the skin.

[0037] In this invention, the composition may contain more than one type of semi-fluorinated alkane; preferably, the composition may contain a mixture of at least two semi-fluorinated alkanes; more preferably, the composition may contain a mixture of at least two semi-fluorinated alkanes, wherein at least one is characterized by a vapor pressure of at least 2, more preferably at least 4, and even more preferably at least 10 mmHg at 25ºC; thus allowing the semi-fluorinated alkane to evaporate rapidly upon application to the skin. Preferably, the antiparasitic composition may contain a mixture of at least two semi-fluorinated alkanes, wherein the semi-fluorinated alkane that allows rapid evaporation upon application to the skin is selected from F6H2, F4H4, or F4H5; preferably, the semi-fluorinated alkane is F6H2.

[0038] In a preferred embodiment, the composition of the present invention is a liquid or semi-solid composition, that is, an antiparasitic agent dissolved or suspended in a semi-fluorinated alkane. In a most preferred embodiment, the composition of the present invention is a solution, such as a liquid solution or a semi-solid solution.

[0039] In one embodiment, the present invention relates to an antiparasitic composition comprising an antiparasitic agent dissolved in a medium containing a semi-fluorinated alkane. Preferably, the antiparasitic composition comprises an antiparasitic agent dissolved in a medium containing a semi-fluorinated alkane and optionally one or more excipients. More preferably, the antiparasitic composition comprises an antiparasitic agent dissolved in a medium containing a semi-fluorinated alkane and optionally one or more excipients selected from oily excipients and cosolvents.

[0040] The antiparasitic composition of the present invention is preferably formulated as a solution, thus allowing the composition to be applied to the skin using, for example, a wet wipe, a roller dispenser, or a spray dispenser. The wet wipe may comprise a substrate such as a nonwoven material impregnated with the antiparasitic composition. The wet wipe is particularly useful when the area to be treated is small (such as the face, scalp, and areas around the eyes, eyebrows, and eyelashes).

[0041] Alternatively, the antiparasitic composition of the present invention can be placed in a dispenser such as a roller dispenser, spray dispenser, or dropper. Applying the antiparasitic composition of the present invention via a roller dispenser or spray dispenser can be used for situations where the entire body or a large body area must be treated, as well as for situations where local application to a small area of ​​skin is required, for example. A dropper can be used for local application to a small area of ​​skin.

[0042] Preferably, the compositions of the present invention are in the form of a wet wipe, a roller coat, or a spray composition. Hereinafter, compositions in the form of a wet wipe, a roller coat, or a spray composition refer to compositions formulated in a manner suitable for use in or incorporated into devices such as wet wipes, roller coat dispensers, or spray dispensers. More preferably, the compositions of the present invention are in the form of a roller coat or a spray composition. Even more preferably, the compositions of the present invention are in the form of a spray composition.

[0043] Preferably, the compositions of the present invention are provided in a form that allows for non-contact application, i.e., application to and administration to the skin is performed without contact with the target skin area. Therefore, the compositions of the present invention are provided in a form that allows for non-contact application, i.e., as a spray, roller, dropper, or wet wipe. In this document, compositions in the form of a spray, roller, dropper, or wet wipe refer to compositions formulated in a manner suitable for non-contact application for use or inclusion in devices such as spray dispensers, roller dispensers, droppers, or wet wipes packaged in bags. More preferably, the antiparasitic compositions of the present invention for non-contact application are in the form of a spray composition or a roller. Even more preferably, the antiparasitic compositions of the present invention for non-contact application are in the form of a spray composition.

[0044] The antiparasitic composition of the present invention is anhydrous and does not require pharmaceutical ingredients selected from preservatives, surfactants, or penetration enhancers. Therefore, the antiparasitic composition of the present invention is anhydrous and preferably free of preservatives, surfactants, and / or penetration enhancers.

[0045] In a preferred embodiment, the antiparasitic composition is a topical liquid composition preferably applied non-contactly to a large area of ​​skin, uniformly distributing the antiparasitic agent onto the target site or area using only a small volume of composition. Herein, the invention utilizes the excellent spreading ability of semi-fluorinated alkanes, when applied as microdroplets, to allow uniform coverage of a target skin area exceeding 0.5 cm² per microliter of composition. Using a roller or spray dispenser, thereby applying the composition to the target skin area non-contactly, the antiparasitic composition of the present invention allows uniform coverage of even larger target skin areas per microliter of composition, for example, uniform coverage of target skin areas exceeding 0.5, 1, 2, 3, 4, 5, 10, or 15 cm².

[0046] The antiparasitic composition of the present invention is preferably alcohol-free. The absence of alcohol constitutes another advantage of the composition of the present invention, as alcohol can cause further skin irritation or allergic reactions. In a preferred embodiment, the composition of the present invention is free of alcohol and / or preservatives and / or water. In a preferred embodiment, the antiparasitic composition of the present invention is free of water, alcohol, and preservatives.

[0047] The compositions of the present invention may also contain one or more other excipients as additional components. As used herein, the term "excipient" refers to any pharmaceutically acceptable natural or synthetic substance that can be added to the compositions of the present invention. The compositions of the present invention may contain one or more excipients, such as antioxidants, preservatives, lipid or oily excipients, cosolvents, waxes, surfactants, or lubricants, or combinations thereof.

[0048] Suitable antioxidants that can be used include, for example, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), vitamin E, vitamin E derivatives (i.e., α-tocopherol acetate), and / or ascorbic acid or its derivatives.

[0049] Suitable oily excipients that can be added to the compositions of the present invention include, for example, vegetable oils (i.e., soybean oil, olive oil, sesame oil, cottonseed oil, castor oil, sweet almond oil), mineral oils (i.e., petrolatum and liquid paraffin), medium-chain triglycerides (MCTs), oily fatty acids, squalane, squalene, essential oils, silicone oils, isopropyl myristate, oily fatty alcohols, sorbitol and esters of fatty acids, oily sucrose esters, or any other oily substance that the skin is physiologically tolerable. In a preferred embodiment, the compositions of the present invention comprise an oily excipient selected from squalane, silicone oil, mineral oil, essential oils, liquid triglycerides, medium-chain triglycerides, vegetable oils, preferably squalane, paraffin oil, and medium-chain triglycerides.

[0050] Examples of co-solvents that may be included in the antiparasitic composition are isopropanol, ethanol, liquid medium-chain triglycerides, N-methyl-2-pyrrolidone, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, ethyl acetate, ethyl oleate, octyldodecyl alcohol, and diethyl sebacate. Preferably, the co-solvent is selected from isopropanol, ethanol, liquid medium-chain triglycerides, diethylene glycol monoethyl ether, and diethyl sebacate.

[0051] Examples of waxes that can be included in antiparasitic compositions are plant waxes, animal waxes, or petroleum-derived waxes.

[0052] In a preferred embodiment, the composition of the present invention further comprises an oily excipient, preferably selected from squalane, mineral oil, and medium-chain triglycerides. The oily excipient may be present in an amount from 0 to 25% w / w, preferably from 0 to 10% w / w, and more preferably from 0 to 5% w / w, relative to the total weight of the composition. Preferably, the composition according to the present invention further comprises an oily excipient selected from squalane, paraffin oil, and medium-chain triglycerides, at a concentration from 0 to 25% w / w, more preferably from 0 to 10% w / w, and most preferably from 0 to 5% w / w, relative to the total weight of the composition.

[0053] In another preferred embodiment, the antiparasitic composition comprises ivermectin, a semi-fluorinated alkane, and a co-solvent; more preferably, the composition comprises ivermectin, a semi-fluorinated alkane, and an alcohol (such as ethanol or isopropanol).

[0054] In a preferred embodiment, the antiparasitic composition of the present invention

[0055] - Contains 0.1% w / v to 5% w / v permethrin dissolved in a medium containing F6H8, and optionally one or more excipients selected from co-solvents and / or oily excipients, or constitutes thereof, or

[0056] - Contains 0.5% w / v permethrin dissolved in a medium containing F6H8 and optionally one or more excipients selected from co-solvents and / or oily excipients, or constitutes thereof, or

[0057] - Contains 0.1% w / v to 5% w / v clomiton dissolved in a medium containing F6H8, and optionally one or more excipients selected from co-solvents and / or oily excipients, or constitutes thereof, or

[0058] - Contains 1% w / v clomiton dissolved in a medium containing F6H8 and optionally one or more excipients selected from co-solvents and / or oily excipients, or constitutes thereof, or

[0059] - Contains 0.1% w / v to 5% w / v ivermectin dissolved in a medium containing F6H8, and optionally one or more excipients selected from co-solvents and / or oily excipients, or

[0060] - Contains 1% w / v ivermectin dissolved in a medium containing F6H8 and optionally one or more excipients selected from co-solvents and / or oily excipients, or constitutes thereof.

[0061] In another preferred embodiment, the antiparasitic composition of the present invention is a liquid composition that can be applied topically, said liquid composition

[0062] - Containing, or consisting of, 0.1% w / v to 5% w / v permethrin dissolved in a medium containing F6H8, and optionally one or more excipients selected from co-solvents and / or oily excipients, or the liquid composition thereof, or the liquid composition thereof.

[0063] - Contains 0.5% w / v permethrin dissolved in a medium containing F6H8 and optionally one or more excipients selected from co-solvents and / or oily excipients, or constitutes thereof, or the liquid composition thereof.

[0064] - Containing 0.1% w / v to 5% w / v clomiton dissolved in a medium containing F6H8, and optionally one or more excipients selected from co-solvents and / or oily excipients, or consisting thereof, or the liquid composition thereof.

[0065] - Contains 1% w / v clomiton dissolved in a medium containing F6H8 and optionally one or more excipients selected from co-solvents and / or oily excipients, or constitutes thereof, or the liquid composition thereof.

[0066] - Containing 0.1% w / v to 5% w / v ivermectin dissolved in a medium containing F6H8, and optionally one or more excipients selected from co-solvents and / or oily excipients, or the liquid composition thereof.

[0067] - Contains 1% w / v ivermectin dissolved in a medium containing F6H8 and optionally one or more excipients selected from co-solvents and / or oily excipients, or constitutes thereof.

[0068] And when applied via non-contact application, the composition is configured to (or effectively) cover at least 0.5 cm² of skin area per microliter.

[0069] In a second aspect, the present invention provides an antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane, said antiparasitic composition being used as a pharmaceutical agent, particularly for a method of treating parasitic infections. Preferably, the parasitic infection is an ectoparasitic infection, more preferably a mite infection or a lice infection, most preferably selected from scabies, head lice infection, body lice infection, eyelash and eyebrow mite infection (such as Demodex flea infection), and eyelash and eyebrow lice infection. Even more preferably, the parasitic infection is selected from scabies, head lice infection, body lice infection, eyelash and eyebrow lice infection, eyelash and eyebrow mite infection, tick infection, and flea infection.

[0070] In another preferred embodiment, the parasite infection is associated with, or caused by, scabies, head lice, body lice, eyelash lice, eyebrow lice, eyelash mites (Demodex mites), eyebrow mites, ticks, or fleas.

[0071] All embodiments described above in conjunction with the first aspect of the present invention are applicable to antiparasitic compositions used as pharmaceuticals and as methods for treating parasitic infections.

[0072] In a third aspect, a method for topical application of an antiparasitic composition is also provided, the method comprising applying the antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane using a swab, a roller dispenser, or a spray dispenser. Preferably, the method is applied to the skin of a subject in need.

[0073] Unless otherwise stated, as used herein, a roller applicator or roller dispenser means a dispensing device comprising a container on which a movable applicator ball is mounted for storing and applying the composition contained in the container to a subject's body or to any other surface. As used herein, a spray dispenser means a dispensing device that turns a liquid into a fine mist, such as a spray bottle with a pump. As used herein, a wipe or wet wipe means a damp cloth.

[0074] All embodiments described above in conjunction with the first aspect of the present invention are applicable to the method of applying the antiparasitic composition for external use in accordance with the third aspect of the present invention.

[0075] In a fourth aspect, a method for treating parasitic infections is provided, the method comprising applying topically an antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane to the skin of a subject in need. In a preferred embodiment, the method of treating parasitic infections comprises applying the antiparasitic composition of the present invention to the skin of a subject in need using a roller applicator, a spray applicator, or a wiping agent. In a more preferred embodiment, the method of treating parasitic infections comprises applying the antiparasitic composition of the present invention to the skin of a subject in need using a roller applicator, a spray applicator with a pump, or a wiping agent.

[0076] Preferably, the parasitic infection is an ectoparasitic infection, more preferably a mite infection or a lice infection, and most preferably an infection of scabies, head lice, body lice, eyelash and eyebrow mites (such as Demodex mite infection), and eyelash and eyebrow lice infection.

[0077] All embodiments described above in conjunction with the first aspect of the present invention are applicable to the method for treating parasitic infection according to the fourth aspect of the present invention.

[0078] In a fifth aspect, the present invention provides a kit comprising a) an antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane and b) a dispenser selected from roller dispensers, spray dispensers and wipes.

[0079] All embodiments described above in conjunction with the first aspect of the present invention are applicable to the reagent kit of the fifth aspect of the present invention.

[0080] The following are the numbered items included in this invention:

[0081] 1. An antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane.

[0082] 2. The antiparasitic composition according to Project 1, wherein the antiparasitic composition is in the form of a liquid or semi-solid composition, preferably a liquid solution.

[0083] 3. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is an ectoparasitic agent.

[0084] 4. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is selected from pyrethroids, pyrethroids, aniline, and benzoate.

[0085] 5. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is selected from pyrethroids, benzoates, or aniline.

[0086] 6. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is selected from pyrethroids or aniline.

[0087] 7. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is selected from permethrin, cromamide, and benzyl benzoate, or wherein the antiparasitic agent is selected from permethrin, cromamide, benzyl benzoate, ivermectin, and lindane.

[0088] 8. The antiparasitic composition according to any one of the preceding items, wherein the semi-fluorinated alkane has the general formula F(CF2)n(CH2)mH, wherein n and m are integers selected independently from the range of 2 to 10.

[0089] 9. The antiparasitic composition according to any one of the preceding items, wherein the semi-fluorinated alkane has the formula F(CF2)n(CH2)mH, wherein n is selected from 4 to 6 and m is selected from 5 to 10.

[0090] 10. The antiparasitic composition according to any one of the preceding items, wherein the semi-fluorinated alkane is selected from F4H5, F4H6, F4H8, F4H10, F6H6, F6H8, F8H8, F6H10 or selected from F4H4, F4H5, F4H6, F4H8, F4H10, F6H2, F6H4, F6H6, F6H8, F8H8, F6H10.

[0091] 11. The antiparasitic composition according to any one of the preceding items, wherein the semifluorinated alkane is selected from F4H8, F4H5, F6H6 and F6H8.

[0092] 12. The antiparasitic composition according to any one of the preceding items, wherein the semifluorinated alkane is selected from F4H8, F6H6 and F6H8.

[0093] 13. The antiparasitic composition according to any one of the preceding items, wherein the semi-fluorinated alkane is F6H8.

[0094] 14. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is present at a concentration of from 0.5% w / v to 10% w / v relative to the total volume of the composition.

[0095] 15. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is present at a concentration of from 0.5% w / v to 5% w / v relative to the total volume of the composition.

[0096] 16. The antiparasitic composition according to any one of the preceding items, wherein the composition further comprises an oily excipient.

[0097] 17. The antiparasitic composition according to any one of the preceding items, wherein the composition further comprises an oily excipient selected from squalane, silicone oil, mineral oil, essential oil, liquid triglycerides, medium-chain triglycerides, and vegetable oils.

[0098] 18. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition further comprises an oily excipient selected from squalane, paraffin oil, and medium-chain triglycerides.

[0099] 19. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition further comprises squalane.

[0100] 20. The antiparasitic composition according to any one of items 16 to 19, wherein the oily excipient is present at a concentration of 0 to 25% w / w relative to the total weight of the composition.

[0101] 21. The antiparasitic composition according to item 20, wherein the oily excipient is present at a concentration of 0 to 10% w / w relative to the total weight of the composition.

[0102] 22. The antiparasitic composition according to any one of items 1 to 15, wherein the composition comprises an antiparasitic agent and a semi-fluorinated alkane.

[0103] 23. The antiparasitic composition according to any one of items 1 to 21, wherein the composition comprises an antiparasitic agent, a semi-fluorinated alkane and an oily excipient, or wherein the composition comprises an antiparasitic agent, a semi-fluorinated alkane and a cosolvent.

[0104] 24. The antiparasitic composition according to any one of the preceding items, wherein the composition is alcohol-free.

[0105] 25. The antiparasitic composition according to any one of the preceding items, wherein the composition is water-free.

[0106] 26. The antiparasitic composition according to any one of the preceding items, wherein the composition is free of preservatives.

[0107] 27. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition is in the form of a wet wipe, a roller or a spray composition, or wherein the composition is provided in a dropper.

[0108] 28. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition is used as a pharmaceutical agent.

[0109] 29. The antiparasitic composition according to any one of the preceding items, and a method of using the antiparasitic composition to treat parasitic infection.

[0110] 30. The antiparasitic composition for the said use according to item 29, wherein the parasitic infection is selected from mite infection and lice infection, or wherein the parasitic infection is related to or caused by scabies, head lice, body lice, eyelash lice, eyebrow lice, eyelash mites (Demodex genus), eyebrow mites, ticks or fleas.

[0111] 31. The antiparasitic composition for the said use according to item 30, wherein the parasitic infection is selected from scabies, head lice, body lice, eyelash and eyebrow lice, eyelash and eyebrow mite, tick, and flea.

[0112] 32. The antiparasitic composition for the stated purpose according to item 31, wherein the parasitic infection is scabies.

[0113] 33. An antiparasitic composition for the said use according to any one of items 29 to 32, wherein the antiparasitic agent is permethrin.

[0114] 34. A method of applying an antiparasitic composition topically, the method comprising applying the antiparasitic composition according to any one of items 1 to 27 using a swab, a roller dispenser, or a spray dispenser.

[0115] 35. A method for treating parasitic infection, the method comprising applying topically an antiparasitic composition according to any one of items 1 to 27 to the skin or a surface contaminated with parasites of a subject in need.

[0116] 36. The method according to item 35, wherein the antiparasitic composition is applied using a roller dispenser, spray dispenser, or wiping agent.

[0117] 37. A kit comprising a) an antiparasitic composition according to any one of items 1-27, and b) a swab, spray dispenser, or roller dispenser.

[0118] 38. The kit according to item 37, the kit further comprising instructions for use.

[0119] 39. The antiparasitic composition according to any one of items 1-27, wherein the antiparasitic composition comprises or consists of 0.1% w / v to 5% w / v permethrin, F6H8, and one or more excipients optionally selected from cosolvents and / or oily excipients.

[0120] 40. The antiparasitic composition according to any one of items 1-27, wherein the antiparasitic composition comprises or consists of 0.1% w / v to 5% w / v of clomiphene, F6H8 and one or more excipients optionally selected from cosolvents and / or oily excipients.

[0121] 41. The antiparasitic composition according to any one of items 1-27, wherein the antiparasitic composition comprises 0.1% w / v to 5% w / v ivermectin, F6H8 and one or more excipients selected from cosolvents and / or oily excipients, or is composed thereof.

[0122] 42. A method for applying an antiparasitic composition over a large area of ​​skin, the method comprising applying the antiparasitic composition according to any one of items 1 to 27 or 39 to 42 topically to a target skin area by non-contact application.

[0123] 43. The method according to item 42, wherein the composition effectively covers at least 0.5 cm² / µL of target skin area applied by non-contact application.

[0124] The following examples are used to illustrate the present invention; however, these examples should not be construed as limiting the scope of the invention.

[0125] Example

[0126] Example 1

[0127] Preparation of a 5% w / v permethrin solution in F4H8.

[0128] Weigh 250 mg of permethrin (Dr. Reddy's, Ph.Eur. grade, cis:trans 25:75) into a 5 ml volumetric flask; then fill the flask to 5 ml with F4H8 (Novaliq, purity > 99%), seal, and shake at 280 rpm at room temperature for 16 h. The resulting 50 mg / ml solution appears clear.

[0129] Example 2

[0130] Preparation of a 10% w / v cromite solution in F6H8

[0131] Weigh 500 mg of cromatathan (SynTech, Ph.Eur. grade) into a 5 ml volumetric flask; then fill the flask to 5 ml with F6H8 (Novaliq, purity > 99%), seal, and shake at 280 rpm at room temperature for 5 min. The resulting 100 mg / ml solution appears clear.

[0132] Example 3

[0133] Preparation of benzyl benzoate solution in F4H5

[0134] Weigh 500 mg of benzyl benzoate (Symrise, purity > 99%) into a 5 ml volumetric flask, then fill the flask to 5 ml with F4H5 (Novaliq, purity > 99%), seal, and shake at 280 rpm at room temperature for 5 min. The resulting 100 mg / ml solution appears clear.

[0135] Example 4

[0136] The following solubility tests were performed according to the procedures described in Examples 1 to 3, as shown in Tables 1, 2 and 3.

[0137] Table 1: Solubility test of permethrin

[0138]

[0139] Table 2: Cromitone Solubility Test

[0140]

[0141] Table 3: Solubility test of benzyl benzoate

[0142]

[0143] This disclosure relates to the following implementation plan:

[0144] 1. An antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane.

[0145] 2. The antiparasitic composition according to claim 1, wherein the antiparasitic composition is a liquid or semi-solid composition, preferably a solution.

[0146] 3. The antiparasitic composition according to any one of the preceding claims, wherein the antiparasitic agent is selected from pyrethroids, pyrethroids, aniline, and benzoate.

[0147] 4. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is selected from permethrin, cromamide, ivermectin, lindane and benzyl benzoate.

[0148] 5. The antiparasitic composition according to any one of the preceding claims, wherein the semi-fluorinated alkane has the general formula F(CF2)n(CH2)mH, wherein n and m are integers selected independently from the range of 2 to 10.

[0149] 6. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition is in the form of a swab, dropper, roller or spray composition.

[0150] 7. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition further comprises an oily excipient and / or a cosolvent.

[0151] 8. The antiparasitic composition according to any one of the preceding items, wherein the composition does not contain alcohol.

[0152] 9. The antiparasitic composition according to any one of the preceding items, wherein the composition is free of water, preservatives, penetration enhancers and / or surfactants.

[0153] 10. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic agent is permethrin.

[0154] 11. The antiparasitic composition according to any one of the preceding items, wherein the semi-fluorinated alkane is F6H8.

[0155] 12. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition comprises or consists of 0.1% w / v to 5% w / v permethrin, F6H8, and one or more excipients optionally selected from cosolvents and / or oily excipients.

[0156] 13. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition comprises or consists of 0.1% w / v to 5% w / v of clomiphene, F6H8 and one or more excipients optionally selected from cosolvents and / or oily excipients.

[0157] 14. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition comprises 0.1% w / v to 5% w / v ivermectin, F6H8 and one or more excipients selected from cosolvents and / or oily excipients, or is composed thereof.

[0158] 15. The antiparasitic composition according to any one of the preceding claims, wherein when applied by non-contact application, the composition is configured to cover at least 0.5 cm² skin area per microliter.

[0159] 16. The antiparasitic composition according to any one of the preceding items, wherein the antiparasitic composition is used as a pharmaceutical agent.

[0160] 17. The antiparasitic composition according to any one of claims 1 to 15, wherein the antiparasitic composition is used for a method of applying the composition topically via non-contact application.

[0161] 18. The antiparasitic composition for the stated purpose according to items 16 to 17, wherein the composition is applied by a spray dispenser, a roller dispenser, or a dropper.

[0162] 19. An antiparasitic composition for the purpose according to any one of claims 16 to 18, wherein the antiparasitic composition is used in a method of treating parasitic infection.

[0163] 20. The antiparasitic composition for the purpose according to claim 19, wherein the parasitic infection is selected from mite infection, lice infection, flea infection and tick infection.

[0164] 21. The antiparasitic composition for the stated purpose according to claim 20, wherein the parasitic infection is selected from scabies, head lice, body lice, eyelash lice, eyebrow lice, eyelash mites, or eyebrow mites.

[0165] 22. The antiparasitic composition for the said purpose according to items 16 to 21, wherein when applied by non-contact application, the composition is configured to cover at least 0.5 cm² skin area / µL.

[0166] 23. A method of applying an antiparasitic composition topically, the method comprising applying the antiparasitic composition according to any one of claims 1 to 15 using a swab, a roller dispenser, a spray dispenser, or a dropper.

[0167] 24. The method according to item 23, wherein the composition is applied by non-contact application.

[0168] 25. The method according to claims 23 to 24, wherein the composition is applied over a large area of ​​the skin.

[0169] 26. The method according to item 23 or 25, wherein the composition is applied by a roller applicator or a spray applicator.

[0170] 27. A kit comprising a) an antiparasitic composition according to any one of claims 1 to 15, and b) a swab, spray dispenser, roller dispenser, or dropper.

[0171] 28. A method for applying an antiparasitic composition over a large area of ​​skin, the method comprising applying the antiparasitic composition according to any one of claims 1 to 15 topically to a target skin area by non-contact application.

[0172] 29. The method according to item 28, wherein the composition effectively covers at least 0.5 cm² of the target skin area / µL of the applied composition.

Claims

1. An antiparasitic composition comprising an antiparasitic agent and a semi-fluorinated alkane.

2. The antiparasitic composition according to claim 1, wherein the antiparasitic composition is a liquid or semi-solid composition, preferably a solution.

3. The antiparasitic composition according to any one of the preceding claims, wherein the antiparasitic agent is selected from pyrethroids, pyrethroids, aniline, and benzoate.

4. The antiparasitic composition according to any one of the preceding claims, wherein the antiparasitic agent is selected from permethrin, cromamide, ivermectin, lindane, and benzyl benzoate.

5. The antiparasitic composition according to any one of the preceding claims, wherein the semi-fluorinated alkane has the general formula F(CF2)n(CH2)mH, wherein n and m are integers selected independently from the range of 2 to 10.

6. The antiparasitic composition according to any one of the preceding claims, wherein the antiparasitic composition is in the form of a swab, dropper, roller, or spray composition.

7. The antiparasitic composition according to any one of the preceding claims, wherein the antiparasitic composition further comprises an oily excipient and / or a cosolvent.

8. The antiparasitic composition according to any one of the preceding claims, wherein the composition is alcohol-free.

9. The antiparasitic composition according to any one of the preceding claims, wherein the composition is free of water, preservatives, penetration enhancers and / or surfactants.

10. The antiparasitic composition according to any one of the preceding claims, wherein the antiparasitic agent is permethrin.

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