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WO2019057899A1 - Composition aqueuse comprenant au moins un phosholipide et aussi au moins un terpène à activité acaricide contre demodex - Google Patents

Composition aqueuse comprenant au moins un phosholipide et aussi au moins un terpène à activité acaricide contre demodex Download PDF

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Publication number
WO2019057899A1
WO2019057899A1 PCT/EP2018/075613 EP2018075613W WO2019057899A1 WO 2019057899 A1 WO2019057899 A1 WO 2019057899A1 EP 2018075613 W EP2018075613 W EP 2018075613W WO 2019057899 A1 WO2019057899 A1 WO 2019057899A1
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WIPO (PCT)
Prior art keywords
demodex
aqueous composition
phospholipid
terpene
skin
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Ceased
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PCT/EP2018/075613
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English (en)
Inventor
Tomasz Borowik
Marek Langner
Magdalena Przybylo
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Lipid Systems Sp ZOO
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Lipid Systems Sp ZOO
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Publication of WO2019057899A1 publication Critical patent/WO2019057899A1/fr
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/04—Oxygen or sulfur attached to an aliphatic side-chain of a carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/30—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests characterised by the surfactants
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N27/00—Biocides, pest repellants or attractants, or plant growth regulators containing hydrocarbons
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
    • A01N35/06—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing keto or thioketo groups as part of a ring, e.g. cyclohexanone, quinone; Derivatives thereof, e.g. ketals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N49/00—Biocides, pest repellants or attractants, or plant growth regulators, containing compounds containing the group, wherein m+n>=1, both X together may also mean —Y— or a direct carbon-to-carbon bond, and the carbon atoms marked with an asterisk are not part of any ring system other than that which may be formed by the atoms X, the carbon atoms in square brackets being part of any acyclic or cyclic structure, or the group, wherein A means a carbon atom or Y, n>=0, and not more than one of these carbon atoms being a member of the same ring system, e.g. juvenile insect hormones or mimics thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates

Definitions

  • the present invention relates to an aqueous composition comprising at least one phospholipid and further at least one terpene with acaricidal activity against Demodex.
  • the present invention further relates to the aqueous composition for use as a medicament.
  • the present invention also relates to the aqueous composition for use in the treatment of Demodex- induced inflammations in a human or a non-human mammal.
  • Demodex mites (of the class Arachnid and order Acarina) are microscopic ectoparasites that commonly infest the pilosebaceous unit of the skin of humans.
  • two ⁇ Demodex folliculorum, Demodex brevis are typically found on the human body surface. Demodex prevalence increases with age and is observed in 84% of the population at age 60 and 100% of the population over the age of 70.
  • Demodex species preferentially gather at the same skin area of the face, cheeks, forehead, nose, and external ear tract.
  • Active sebum excretion favours habitat and breeding in the sebaceous glands and hair follicles. This involves the Meibomian glands, which are sebaceous glands at the rim of the upper and lower eyelids, and the hair follicles of the eyelashes. Debris and waste generated by mites accumulate at the root of lashes forming cylindrical dandruff. Mites also mechanically block sebaceous ducts.
  • Uncontrolled skin Demodex infestation is usually related to a suppressed or compromised immune system. Demodicosis is most often seen in folliculitis, an inflammation of the hair follicles, which starts with the introduction of a skin pathogen (e.g. Demodex) to the hair follicle. Depending on the location, an uncontrolled skin Demodex infestation may be the cause of blepharitis, chalazia, rosacea, or acne in humans.
  • Blepharitis is a common eye condition characterized by inflammation of the eyelid, resulting in inflamed, irritated, itchy, and redden eyelid. Depending on the anatomic location, blepharitis is classified in anterior blepharitis, an infestation of the lid margin, and posterior blepharitis, an infestation of the Meibomian glands, also known as Meibomian gland disease. Chalazia are non-painful cysts on the eyelid resulting from chronic inflammation of a Meibomian gland. The inflammation may be caused by the blockage in one of the Meibomian glands of the upper and lower eyelids following a Demodex entry.
  • Rosacea typically affects the face and results in redness, pimples, swelling and small and superficial dilated blood vessels.
  • Acne is a long-term skin disease that occurs when hair follicles are clogged with dead skin cells and oil from the skin. It is characterized by blackheads or whiteheads, pimples, oily skin, and possible scarring. It primarily affects areas of the skin with a relatively high number of oil glands, including the face, upper part of the chest, and back.
  • a Demodex infestation as the cause for blepharitis or chalazia in humans may be diagnosed by slit-lamp examination to detect cylindrical dandruff at the root of lashes. Lash sampling and microscopic examination provide a diagnosis by identifying the Demodex mites in lashes with cylindrical dandruff. In vivo confocal microscopy (IVCM) has been used as a noninvasive method to diagnose Demodex infestation and allows a complete examination of the follicle with detecting mites burrowed deep into sebaceous glands.
  • IVCM In vivo confocal microscopy
  • a Demodex infestation as the cause of rosacea or acne in humans may be e.g. diagnosed by skin surface biopsies using quick hardening polymers such as cyano aery late or by skin scrapings.
  • Demodex mites also infest mammalian quadrupeds, in particular mammalian domestic animals such as cattle (Demodex bovis), goats (Demodex caprae), guinea pigs (Demodex caviae), horses (Demodex equi), sheep (Demodeex ovis), pigs (Demodex phyloides), dogs (Demodex canis, Demodex cornei, Demodex injai) and cats (Demodex cati, Demodex catoi). Under normal conditions, the infestation does not produce any clinical signs or disease.
  • mammalian domestic animals such as cattle (Demodex bovis), goats (Demodex caprae), guinea pigs (Demodex caviae), horses (Demodex equi), sheep (Demodeex ovis), pigs (Demodex phyloides), dogs (Demodex canis, Demodex cornei, Demodex injai) and cats (Demodex cati, Demodex
  • Demodicosis or demodectic mange may cause pustules, redness, scaling, hair loss, and severe infections of the skin.
  • the demodectic mange presents a difficult clinical problem for veterinarians, as it can involve the face and the entire body of the animal in some cases.
  • a diagnosis of a Demodex infestation in mammalian quadrupeds may be obtained by the inspection of skin biopsies or skin scrapings. Inflammations caused by Demodex may be treated systemically or topically.
  • Topical administration comprises the application of the active agent to body surfaces such as the skin or mucous membranes to treat conditions via a large range of base formulations such as creams, foams, gels, lotions, and ointments.
  • Terpenes are a class of organic compounds produced by a variety plants and some insects. Terpenes are the primary constituents of essential oils of many types of plants. The basic molecular formula of terpenes are multiples of isoprene units. Hemiterpenes consist of a single isoprene unit, monoterpenes consist of two isoprene units, sesquiterpenes consist of three isoprene units, diterpenes consist of four isoprene units, and so on.
  • Monoterpenes classify in acyclic, monocyclic, and bicyclic monoterpenes.
  • Sesquiterpenes classify in acyclic, monocyclic, bicyclic, and tricyclic sesquiterpenes.
  • a broad range of the biological properties of terpenes has been described, including cancer chemopreventive effects, antihyperglycemic and anti- inflammatory activities, antiviral, antimicrobial, antifungal, and acaricidal activities.
  • Acaricides are active agents that kill members of the arachnid subclass Acari, which includes ticks and mites.
  • Essential oils for topical administration have been disclosed in combination with Vaseline (WO 2009/032773), ethanol, mineral oil, baby shampoo (WO 2006/119174), triglycerides, vegetable oils, or mineral oils (WO 2014/167552, US 2012/0121694).
  • Components of essential oils such as terpinen-4-ol for topical administration have been disclosed in combination with mineral oil (Tighe S et al.,Tansl Vis Sci Technol, 2013, 3(7), Art. 2).
  • water-based compositions may be considered as preferred formulations when easily prepared and low priced, while ensuring an efficient delivery of the active agent at the treated skin areas.
  • the problems solved by the present invention may be described as the: (i) provision of an improved composition of an acaricidal terpene, (ii) an improved composition of an acaricidal terpene for use as a medicament, or (iii) an improved composition of an acaricidal terpene for use in the treatment of Demodex-mduced inflammations.
  • the present invention provides an aqueous composition comprising at least one phospholipid and further at least one terpene with acaricidal activity against Demodex.
  • the aqueous compositions of the present invention comprise high concentrations of terpenes and display a good skin adhesion.
  • the good skin adhesion ensures an efficient delivery of the terpenes into the skin areas affected by Demodex.
  • the aqueous compositions of the present inventions are administered on the skin areas of the eye, the good adhesion prevents their flow into the eye chamber.
  • lipids in the composition will integrate with the stratum corneum supporting the reconstruction of the skin damaged by Demodex.
  • the acaricidal activity of the compositions of the present invention may be measured by determining the reduced Demodex survival time in the respective composition relative to a control.
  • the control may be e.g. terpene alone or water. All lipids that contain phosphorus are called phospholipids.
  • Phospholipids are known for their use in pharmaceutical formulation. Natural or synthetic phospholipids are used in oral, dermal, and parenteral products. Phospholipids are surface-active, amphiphilic molecules, which comprise a polar head group and a lipophilic tail. Because of this amphiphilic character, they are used as emulsifier, wetting agent, solubilizer, and liposome former. Liposomes itself are used as drug delivery systems, solvents and permeability enhancers.
  • the phospholipids of the present composition essentially form liposomes.
  • Hydrophobic active agents may be inserted into the bilayer membrane and hydrophilic molecules may be entrapped in the aqueous centre.
  • the phospholipids are present as liposomes.
  • the present aqueous composition comprises at least one natural phospholipid.
  • the present aqueous composition comprises at least one natural zwitterionic phospholipid.
  • the present aqueous composition comprises at least one natural zwitterionic phospholipid and at least one natural anionic phospholipid.
  • the natural zwitterionic phospholipid is selected from the group consisting of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), sphingomyelin (SM), cholesterol (CH), and combinations thereof. Even more preferably, the natural zwitterionic phospholipid is PC.
  • the natural anionic phospholipid selected form the group consisting of phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatic acid (PA), cardiolipin, and combinations thereof. More preferably, the natural anionic phospholipid is selected from the group consisting of PS, PG, and combinations thereof. Even more preferably, the natural anionic phospholipid is PS.
  • the present aqueous composition comprises natural PC and at least one natural anionic phospholipid selected from the group of phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phopshatic acid (PA), cardiolipin, and combinations thereof.
  • PS phosphatidylserine
  • PI phosphatidylinositol
  • PG phosphatidylglycerol
  • PA phopshatic acid
  • cardiolipin cardiolipin
  • the present aqueous composition comprises natural PC and natural PS.
  • the present invention comprises at least one synthetic phospholipid.
  • the present aqueous composition comprises at least one synthetic zwitterionic phospholipid.
  • the present aqueous composition comprises at least one synthetic zwitterionic phospholipid and optionally at least one synthetic anionic phospholipid and optionally at least one synthetic cationic phospholipid.
  • the synthetic zwitterionic phospholipid is selected from the group consisting of saturated or unsaturated synthetic PC or PE.
  • the synthetic zwitterionic phospholipid is selected from the group consisting of 12:0, 13:0, 14:0, 15:0, 16:0, 17:0, 18:0, 19:0, 20:0, 14: 1, 16: 1, 18: 1, 18:2, 20:1 PC or PE, and combinations thereof.
  • the synthetic zwitterionic phospholipid is selected from 1,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, 16:0 PC), l,2-distearoyl-sn-glycero-3- phosphocholine (DSPC, 18:0 PC), l,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC, 18: 1 PC), and combinations thereof.
  • DPPC 1,2- dipalmitoyl-sn-glycero-3-phosphocholine
  • DSPC l,2-distearoyl-sn-glycero-3- phosphocholine
  • DOPC l,2-dioleoyl-sn-glycero-3-phosphocholine
  • the synthetic anionic phospholipid is selected from the group consisting of saturated or unsaturated synthetic PS or PG.
  • the synthetic phospholipid is selected from the group consisting of 12:0, 14:0, 16:0, 18:0, 18: 1 PS or PG, and combinations thereof.
  • the synthetic anionic phospholipid is selected from l,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS, 16:0 PS), 1 ,2-distearoyl- sn-glycero-3-phospho-L-serine (DSPS, 18:0 PS), l ,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS, 18: 1 PS), and combinations thereof.
  • DPPS dipalmitoyl-sn-glycero-3-phospho-L-serine
  • DSPS 1 ,2-distearoyl- sn-glycero-3-phospho-L-serine
  • DOPS 18: 1 PS
  • the synthetic cationic phospholipid selected from the group consisting of dimethyldioctadecylammonium (DDAB) and l,2-stearoyl-3- trimethylammonium-propane (TAP).
  • DDAB dimethyldioctadecylammonium
  • TAP l,2-stearoyl-3- trimethylammonium-propane
  • the synthetic cationic phospholipid is selected from 18:0 DDAB, l,2-dioleoyl-3-trimethylammonium-propane (DOTAP, 18: 1 TAP), and combinations thereof.
  • the aqueous composition of the present invention comprises at least one synthetic zwitterionic phospholipid and at least one synthetic anionic phospholipid.
  • the present aqueous composition comprises DOPC and DOPS.
  • the aqueous composition of the present invention comprises a mixture of at least one natural phospholipid and at least one synthetic phospholipid.
  • the natural and phospholipids and synthetic phospholipids are as mentioned above.
  • the present aqueous composition comprises at least one synthetic zwitterionic phospolipid and at least one natural anionic phospholipid.
  • the present aqueous composition comprises at least one natural zwitterionic phospholipid and at least one synthetic anionic phospholipid.
  • the present aqueous composition comprises natural zwitterionic PC and/or PE, preferably PC, and synthetic anionic DOPS and/or DSPS, preferably DOPS.
  • the weight ratio of the at least one zwitterionic phospholipid to the at least one anionic lipid is in the range of 5:0.1 to 5: 1, preferably 3: 1 to 5 : 1.
  • the at least one terpene is selected from the group consisting of monocyclic monoterpenes, bicyclic monoterpenes, and combinations thereof.
  • the monocyclic monoterpenes are selected from the group consisting of terpinen-4-ol, a-terpinene, ⁇ -terpinene, limonene, carvone, and combinations thereof. It is even more preferred that the monocyclic monoterpenes are selected from the group consisting of terpinen-4-ol, limonene, and combinations thereof. It is particularly preferred that the monocyclic monoterpene is terpinen-4-ol.
  • the bicyclic monoterpenes are selected from the group consisting of a-pinene, sabinene, 1,4-cineole, 1,8-cineole, and combinations thereof. It is more preferred that the bicyclic monoterpenes are selected from the group consisting of sabinene, 1,8-cineole, and combinations thereof. In case not otherwise stated, the compounds comprise all possible constitutional and spatial isomers. It is further preferred that the aqueous composition comprises at least one fatty acid. Preferably, the fatty acid is selected from the group consisting of saturated fatty acids, unsaturated fatty acids, and combinations thereof.
  • the fatty acid is selected from the group of long-chain fatty acids with an aliphatic chain length in the range of C13-C20.
  • the fatty acid is selected from the group consisting of oleic acid, linoleic acid, and combinations thereof.
  • the aqueous composition of the present invention comprises an alcohol selected from the group consisting of ethanol, propylene glycol, and combinations thereof.
  • the alcohol is propylene glycol.
  • the weight ratio of terpene to phospholipid in the aqueous composition of the present invention is in the range of 1 :0.5 to 1 :50, preferably 1 : 1 to 1 :20, preferably 1 :2 to 1 : 10, preferably 1 :2 to 1 :5, preferably 1 :2.5 to 1 :3.5.
  • aqueous composition of the present invention comprises:
  • the aqueous composition of the present invention comprises 5 to 15 wt.-%, more preferably 5 to 12 wt.-% terpene relative to the total weight of the composition.
  • aqueous composition of the present invention comprises: 5 to 15 wt.-% terpene,
  • aqueous composition of the present invention comprises: 5 to 12 wt.-% terpene,
  • the phospholipid is preferably comprised by a zwitterionic phospholipid and optionally an anionic phospholipid,
  • aqueous composition of the present invention comprises: 5 to 12 wt.-% terpene,
  • the phospholipid is preferably comprised by a zwitterionic phospholipid and optionally an anionic phospholipid,
  • the zwitterionic phospholipids and anionic phospholipids are present in a weight ratio in the range of 5:0.1 to 5: 1, preferably 3 : 1 to 5: 1.
  • the present aqueous compositions are prepared by mixing the phospholipid and terpene at temperatures in the range of 30 to 50 °C, preferably 35 to 45 °C, and preferably for 1 to 10 h, preferably 2 to 8 h, preferably 2 to 4 h.
  • the phospholipid/terpene mixture is further mixed with water and optionally an alcohol at temperatures in the range of 30 to 50 °C, preferably 35 to 45 °C, and preferably for 1 to 10 h, preferably 2 to 8 h, preferably 2 to 4 h, so that the aqueous compositions of the present invention are provided.
  • the present invention provides aqueous compositions comprising at least one phospholipid and further at least one terpene with acaricidal activity against Demodex for use as medicament.
  • the aqueous compositions comprising at least one phospholipid and further at least one terpene with acaricidal activity against Demodex are provided for use as medicament in a human or non-human mammal.
  • compositions of the present inventions may be administered in the form a topical solution, lotion, cream, ointment, gel, foam, paste, or tincture.
  • the compositions of the present invention may be provided in a tube, a jar, a bottle, a bottle squeezer, a dropper, a spray bottle, or as wet wipes impregnated therewith.
  • Suitable excipients which may be further added to the compositions of the present invention are fillers, humectants, emulsifiers, solubilizers, buffers, thickeners, binders, antioxidants, preservatives, absorption enhancers, and combinations thereof.
  • the present invention provides an aqueous composition comprising at least one phospholipid and further at least one terpene with acaricidal activity for use in the treatment and prophylaxis of Demodex- induced inflammations in a human.
  • the inflammations are selected from the group consisting of Demodex- induced blepharitis, Demodex- induced rosacea, Demodex- induced acne and Demodex- induced Meibomian gland dysfunction.
  • the present invention provides an aqueous composition comprising at least one phospholipid and further at least one terpene with acaricidal activity for use in the treatment and prophylaxis of Demodex-mduced inflammations in a non-human mammal.
  • the inflammations are selected from the group consisting of demodectic mange.
  • the non-human mammal is a domestic animal, preferably selected from the group consisting of cattle, goats, guinea pigs, horses, sheep, pigs, dogs, and cats, more preferably selected from the group consisting of dogs and cats.
  • Adhesive force values between skin and terpene compositions of the present inventions were determined with a torsion balance (WTW, Techniprot, Tru) relative to water. For each composition a fresh skin sample was used. Every composition was measured in triplicate with standard deviation value smaller than 5% and each skin sample was used for one composition measurement only. For each individual skin sample the adhesive force value between water and skin was determined first, followed by the determination of the adhesive force between composition and skin. Skin was obtained from Polish Landrace pigs that were sacrificed for non-scientific purposes before the skin was harvested. Samples of whole skin were excised from the shank area. Strips of skin samples were cut at a thickness of approximately 1 mm using a scalpel.
  • the skin samples of 15 x 15 mm were prepared for the adhesive force value measurements.
  • the weight of skin samples was determined. A single 15 x 15 mm piece of skin was stapled, with stratum corneum side facing out to give the area of contact with the surface of the examined medium (water) equal to 4 x 15mm (60 mm 2 ).
  • the piece of skin was connected to the torsion balance arm with a 50 mm long silk tread.
  • Demodex mites were collected from eyelashes of diagnosed patients. Three eyelashes were collected from each eye, by means of tweezers. Immediately after collection, the eyelashes were placed on a slide and examined for Demodex presence and their motility under 200x magnification. Vital mites were placed in a drop of tested substance and the motility of mites was observed continuously from 0-30 min, then every 10 minutes up to the end of the experiment after 180 min. Demodex survival time was measured starting from the substance application on mites ending with the lack of mite signs of vitality. Movements of legs were used as the survival indicator. As a control, Demodex survival time in saline (140 mM NaCl) was used.
  • Terpinen-4-ol was mixed with phospholipids and optionally propylene glycol at 40 °C, 200 rpm and 0.4 bar for 3 h in a thermostated mixing device (UMC5 electronic, Stephan Machinery GmbH, Germany) to obtain an amphiphilic phase.
  • the amphiphilic phase was hydrated by the addition of water or water + propylene glycol at 40 °C, 200 rpm and 0.4 bar for 12 h (UMC5 electronic, Stephan Machinery GmbH, Germany) to give a high viscosity composition (Ex. 1 to Ex. 5).
  • a sample prepared as described was further mixed with a thickener at 25 °C, 200 rpm and 0.4 bar for 180 min (Ex. 6).
  • compositions according to the present invention are superior to the use of terpinen-4-ol alone.
  • the addition of alcohol or alcohol and negatively charged phospholipid (DOPS Avanti, USA) further increase the adhesion force.

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Abstract

La présente invention concerne une composition aqueuse comprenant au moins un phospholipide et aussi au moins un terpène ayant une activité acaricide contre Demodex. La présente invention concerne en outre la composition aqueuse destinée à être utilisés en tant que médicament. La présente invention concerne également la composition aqueuse destinée à être utilisée dans le traitement d'inflammations induites par Demodex chez un être humain ou un mammifère non humain.
PCT/EP2018/075613 2017-09-22 2018-09-21 Composition aqueuse comprenant au moins un phosholipide et aussi au moins un terpène à activité acaricide contre demodex Ceased WO2019057899A1 (fr)

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EP17461609 2017-09-22
EP17461609.4 2017-09-22

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WO2019057899A1 true WO2019057899A1 (fr) 2019-03-28

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006119174A1 (fr) 2005-04-30 2006-11-09 Ocular Surface Center, P.A. Methode de traitement oculaire de demodex
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