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WO2016196989A1 - Composition topique - Google Patents

Composition topique Download PDF

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Publication number
WO2016196989A1
WO2016196989A1 PCT/US2016/035813 US2016035813W WO2016196989A1 WO 2016196989 A1 WO2016196989 A1 WO 2016196989A1 US 2016035813 W US2016035813 W US 2016035813W WO 2016196989 A1 WO2016196989 A1 WO 2016196989A1
Authority
WO
WIPO (PCT)
Prior art keywords
topical composition
composition according
vancomycin
salt
squalane
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2016/035813
Other languages
English (en)
Inventor
Jun Inoue
Takahiro Ogawa
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Senju USA Inc
Original Assignee
Senju USA Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Senju USA Inc filed Critical Senju USA Inc
Publication of WO2016196989A1 publication Critical patent/WO2016196989A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0046—Ear
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to a topical composition comprising Vancomycin or a salt thereof and squalane, a method of stabilizing Vancomycin or a salt thereof in a topical composition, and a method of treating an infection of the eye, nose, ear or skin by administration of the topical composition to a patient in need thereof.
  • Squalane (Formula 1) is a structurally unique triterpene compound that is derived by hydrogenation of squalene. Squalane was so named because it was first isolated from shark (Squalus spp.) liver oil, which contains large quantities of squalane and is considered its richest source. Squalane is one of the main components (about 13%) of skin surface lipids, and is transported in serum, generally in association with very low density lipoproteins and is distributed ubiquitously in human tissues, with the greatest concentration in the skin. (See Document 1)
  • Vancomycin is an antibiotic classified as a glycopeptide antibiotic, and is primarily used for the treatment of serious infections caused by Gram-positive bacteria, such as Methicillin- resistant Staphylococcus aureus (MRSA) or multi -resistant Staphylococcus epidermidis (MRSE). Vancomycin has a water solubility of more than 5 mg/mL.
  • MRSA Methicillin- resistant Staphylococcus aureus
  • MRSE multi -resistant Staphylococcus epidermidis
  • a Vancomycin topical solution is not commercially available because of its instability in aqueous solution.
  • a composition comprising Vancomycin or a salt thereof, in combination with squalane is not known.
  • a method of treating an infection of the eye, nose, ear or skin by the administration of a composition comprising Vancomycin or a salt thereof and squalane to a patient in need thereof is not known.
  • Document 3 discloses an ophthalmic ointment for treating infective eye diseases, containing as an active ingredient from 0.01% to 5.0% of Vancomycin hydrochloride.
  • the disclosure relates only to an ophthalmic ointment, with no teaching of a topical solution. Problems associated with ophthalmic ointments include difficulty in application to the eye by patients, and the lack of comfort for patients after dosing for several hours.
  • Ophthalmic ointments have limited use in the day-time treatment of keratoconjunctivitis sicca, since the diminished visual activity experienced after administration of an ointment limits its use to night-time administration.
  • the use of eye ointment is often accompanied by visual impairment for 10-15 minutes, and bulk application can cause lengthy blurred vision for up to several hours, resulting in decreased patient satisfaction and restriction of daily activities.
  • See Document 5 See Document 5.
  • Document 6 discloses Vancomycin hydrochloride as an active ingredient in peroral oil suspensions or in soft gelatin capsules. However, no disclosure is provided regarding a topical solution, a use thereof, or any specific composition comprising squalane and Vancomycin or a salt thereof.
  • Document 7 discloses a topical, bactericidal composition comprising Vancomycin or Vancomycin HC1, and a method of using the composition for the treatment of MRSA in wounds.
  • the composition comprises potassium sorbate at a concentration of about 0.2% wt/wt; dimethylol dimethylhydantoin (DMDM hydantoin) at a concentration of about 0.1% wt/wt; boric acid at a concentration of about 0.5% wt/wt; carboxymethylcellulose (CMC) at a concentration of about 0.1%) wt/wt; sodium/calcium alginate mixture at a concentration of about 0.5% wt/wt; a cross-linked polyacrylate polymer, such as Carbopol 940, at a concentration of about 0.5% wt/wt; propylene glycol at a concentration of about 10.0% wt/wt; triethanolamine at a concentration of about 0.5% wt/wt; a sufficient quantity of deionized water; and an antibiotic at an effective concentration to reduce the amount of microbial organisms which result in MRSA infection.
  • DMDM hydantoin dimethylol dimethylhydantoin
  • Document 8 describes anhydrous, stable pharmaceutical compositions of Vancomycin for topical use for the treatment of dermal infections.
  • the composition comprises Vancomycin, in the form of the free base or a pharmaceutically acceptable salt, together with one or more glycols and/or ethers, such as diethylene glycol monomethyl ether, one or more fatty acid triglycerides and/or the polyoxyethylene derivatives, such as propylene glycol, and a gelling agent, such as carbopol.
  • glycols and/or ethers such as diethylene glycol monomethyl ether
  • one or more fatty acid triglycerides and/or the polyoxyethylene derivatives such as propylene glycol
  • a gelling agent such as carbopol.
  • Document 9 describes a pharmaceutical anhydrous formulation for topical use comprising Vancomycin, Vancomycin Hydrochloride, or Teicoplanin, dimethyl sulfoxide, one or more glycols and/or ethers, such as propylene glycol, optionally one or more fatty acids triglycerides and/or the polyoxyethylene derivatives, such as diethylene glycol monoethyl ether.
  • a topical solution comprising squalane and Vancomycin or a salt thereof, or a use thereof.
  • Documents 10 and 11 disclose a topical ointment comprising Vancomycin for treating skin conditions caused by bacterial infections.
  • the ointments include traditionally known ointment bases, such as liquid paraffin and white petrolatum.
  • the disclosure relates only to an ointment, with no specific disclosure of a topical solution comprising Vancomycin or a salt thereof.
  • the documents recognize the lack of topical formulations of Vancomycin, due to the instability thereof.
  • no disclosure is provided regarding a topical solution comprising Vancomycin or a salt thereof and squalane, or a use thereof.
  • Document 12 describes a topical spray preparation for burn treatment and microbial infections on humans or animals.
  • the non-aerosol preparation contains an antimicrobial drug, i.e., silver sulfadiazine, dispersed or solubilized in a cream or lotion base matrix which can be sprayed directly from a common trigger spray device.
  • an antimicrobial drug i.e., silver sulfadiazine
  • dispersed or solubilized in a cream or lotion base matrix which can be sprayed directly from a common trigger spray device.
  • a composition comprising squalane and Vancomycin or a salt thereof.
  • Document 13 describes an ophthalmic solution comprising squalane, as a two-layer separation-type eye drop.
  • Vancomycin or a salt thereof or a specific composition comprising squalane and Vancomycin or a salt thereof.
  • compositions in the art comprise Vancomycin or a salt thereof in combination with squalane.
  • a composition comprising Vancomycin or a salt thereof, in combination with squalane as the only solvent, is not known.
  • a method of treating an ocular, nose, ear or skin infection by the administration of a topical composition comprising a therapeutically effective amount of Vancomycin or a salt thereof and squalane is not known.
  • An object of the invention is to provide a topical composition comprising Vancomycin or a salt thereof, and squalane, wherein the composition has improved stability of Vancomycin or a salt thereof.
  • Another object of the invention is to provide a topical composition comprising Vancomycin or a salt thereof, and squalane, wherein the composition has improved comfort for the patient.
  • Another object of the invention is to provide a method of using the topical composition described above for treatment of an infection of the eye, nose, ear or skin in a patient in need thereof.
  • the present inventors have studied topical compositions comprising Vancomycin or a salt thereof and squalane.
  • the present inventors have discovered that the stability of Vancomycin or a salt thereof is improved in a solution comprising squalane.
  • the present inventors have further discovered methods of using the topical compositions comprising Vancomycin or a salt thereof and squalane to treat an infection of the eye, nose, ear or skin, wherein the patient has improved comfort.
  • the present invention provides:
  • a topical composition comprising Vancomycin or a salt thereof and a solvent.
  • concentration of Vancomycin or a salt thereof may be about 0.01 to 10 (w/v) %, about 0.1 to 8 (w/v) %, about 0.5 to 5 (w/v) %, or about 1 to 3 (w/v) %, wherein (w/v) % represents the fraction of the weight of Vancomycin or a salt thereof (g) to the volume of the solvent (mL).
  • solvent is squalane.
  • the one or more additional antibiotic is at least one selected from beta-Lactams (penicillin, cefem, carbapenem, cephalosporin), aminoglycosides, tetracyclines, macrolides, ketolides, polyene macrolides, new quinolones, Oxazolidinone, and chloramphenicol.
  • the one or more additional antibiotics is at least one selected from gentamycin, tobramycin, gatifloxacin, moxifloxacin, levofloxacin ofloxacin, norfloxacin, lomefloxacin, ciprofloxacin, cinoxacin, sparfloxacin, tosufloxacin, nalidixic acid, fleroxacin, and salts thereof.
  • a method of treating an infection of the eye, nose, ear or skin comprising topically administering a therapeutically effective amount of the topical composition according to any of the above (1) to (18) to the eye, nose, ear or skin of a patient in need thereof.
  • a method of improving the stability of Vancomycin or a salt thereof in solution comprising adding squalane to Vancomycin or the salt thereof.
  • (21) A method of forming a stable solution of Vancomycin or a salt thereof, by combining Vancomycin or a salt thereof with squalane.
  • Figure 1 shows the stability of Vancomycin in squalane at room temperature.
  • Figure 2 shows the stability of Vancomycin in squalane at 60°C.
  • Figure 3 shows the in vivo efficacy of a formulation comprising Vancomycin in squalane.
  • Figure 4 shows the effect on the degree of corneal opacity by a formulation comprising Vancomycin in squalane.
  • Figure 5 shows the effect on the area of corneal opacity by a formulation comprising Vancomycin in squalane.
  • Figure 6 shows the effect on the chemosis by a formulation comprising Vancomycin in squalane.
  • Figure 7 shows the effect on the conjunctival injection by a formulation comprising Vancomycin in squalane.
  • Figure 8 shows the effect on discharge by a formulation comprising Vancomycin in squalane.
  • the topical compositions comprise Vancomycin or a salt thereof and a solvent, wherein the solvent may be squalane.
  • the compositions are topically administrable therapeutic compositions for treatment of infections of the eye, nose, ear or skin. Further, the compositions have improved stability and provide improved comfort.
  • Vancomycin or a salt thereof includes Vancomycin in free base form, or any pharmaceutically acceptable salt thereof.
  • the pharmaceutically acceptable salt include, but are not limited to, inorganic acid salts including hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, and borate; sulfonates including methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and camphorsulfonate; organic carboxylates including formate, acetate, propionate, oxalate, hydroxyacetate, citrate, tartrate, succinate, maleate, benzoate, salicylate, fumarate, and phthalate.
  • the pharmaceutically acceptable salt may be hydrochloride, hydrobromide, sulfate, phosphate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, oxalate, or tartrate.
  • the pharmaceutically acceptable salt may be hydrochloride, hydrobromide, sulfate, methanesulfonate, or p-toluenesulfonate.
  • the pharmaceutically acceptable salt may be hydrochloride.
  • the topical composition comprises Vancomycin or a salt thereof, and a solvent.
  • the Vancomycin or a salt thereof may be present in the topical composition in a concentration of about 0.01 to 10 (w/v) %.
  • the concentration of Vancomycin or a salt thereof may be about 0.1 to 8 (w/v) %, about 0.5 to 5 (w/v) %, or about 1 to 3 (w/v) %.
  • the concentration of Vancomycin or a salt thereof may be about 0.01, 0.05, 0.1, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 (w/v) %.
  • the concentration of Vancomycin or a salt thereof may be about 0.5 to 3 (w/v) %.
  • (W/v) % represents the fraction of the weight of Vancomycin or a salt thereof (g) to the volume of the solvent (mL).
  • the solvent comprises squalane, which may be present in a concentration of about 50 to 100 (v/v) %.
  • concentration of squalane may be about 60 to 90 (v/v) %, about 70 to 80 (v/v) %, or about 75 to 85 (v/v) %, of the solvent.
  • concentration of squalane may be about 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 (v/v) %, of the solvent.
  • the solvent optionally includes mineral oil, which may be present in a concentration of about 0 to about 50 (v/v) %.
  • concentration of mineral oil may be about 10 to 40 (v/v) %, about 20 to 30 (v/v) %, or about 15 to 25 (v/v) %, of the solvent.
  • concentration of mineral oil may be about 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, or 0 (v/v) %, of the solvent.
  • the topical composition may further comprise one or more known pharmaceutically acceptable additives, thickening agents including but not limited to carboxy vinyl polymer, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and salts thereof, carriers, excipients or diluents, unless the incorporation thereof would adversely affect the intended purpose of the present invention.
  • thickening agents including but not limited to carboxy vinyl polymer, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and salts thereof, carriers, excipients or diluents, unless the incorporation thereof would adversely affect the intended purpose of the present invention.
  • the topical composition may be free of water.
  • the topical composition may be free of preservatives, such as surfactants.
  • the topical composition may also be free of dimethylsulfoxide.
  • a non-limiting embodiment of the invention is a composition consisting of Vancomycin or a salt thereof, squalane, and optionally mineral oil.
  • the topical composition may be provided in any pharmaceutical dosage form that is conventionally used as a topical preparation, including but not limited to an ophthalmic solution, an ear drop solution, a collunarium, a nasal spray, and a solution for cutaneous application.
  • the topical composition may be formulated in accordance with methods known in the art, including, but not limited to, those described in the United States Pharmacopeia.
  • solution encompasses solutions, suspensions and emulsions.
  • the topical composition may comprise one or more additional antibiotics, in addition to Vancomycin or a salt thereof.
  • the one or more additional antibiotic is at least one selected from beta-Lactams, including penicillin, cefem, carbapenem, and cephalosporin, aminoglycosides, tetracyclines, macrolides, ketolides, polyene macrolides, new quinolones, and chloramphenicol, including gentamycin, tobramycin, gatifloxacin, moxifloxacin, levofloxacin ofloxacin, norfloxacin, lomefloxacin, ciprofloxacin, cinoxacin, sparfloxacin, tosufloxacin, nalidixic acid, fleroxacin, and salts thereof.
  • beta-Lactams including penicillin, cefem, carbapenem, and cephalosporin, aminoglycosides, tetracyclines, macrolides, ketol
  • the topical composition may contain or may be used together with other appropriate pharmacologically effective substances, for example, steroidal anti-inflammatory agents (dexamethasone, prednisolone and the like), non-steroidal anti-inflammatory agents (diclofenac sodium, pranoprofen and the like), antiallergic agents (tranilast, ketotifen fumarate, sodium cromoglicate and the like), antihistamic agents (diphenhydramine hydrochloride and the like), glaucoma-treating agents (pilocarpine hydrochloride, physostigmine salicylate, timolol, isopropylunoprostone and the like), antibiotics (gentamycin sulfate, fradiomycin sulfate, tobramycin, sulbenicillin, cefmenoxime, erythromycin, colistin, oxytetracycline, polymyxin B, chloramphenicol, micro
  • the present invention encompasses a method of treating an infection of the eye, nose, ear or skin, comprising topically administering a therapeutically effective amount of the topical composition of the present invention, to the eye, nose, ear or skin of a patient in need thereof.
  • the present invention also encompasses a method of improving the stability of Vancomycin or a salt thereof in solution, or of forming a stable solution of Vancomycin or a salt thereof, comprising adding squalane to the Vancomycin or the salt thereof.
  • the topical composition may be administered to a mammal, including a human, rabbit, dog, cat, cattle, horse or monkey, which is or may be suffering from an infectious disease.
  • infectious disease include but are not limited to ear infections including otitis externa and otitis media, eye infections including conjunctivitis, bacterial keratitis, corneal ulcers and blepharitis, nose infections, skin infections including impetigo, ecthyma, Staphyl involvcoccal scalded skin syndrome (SSSS), erysipelas, cellulitis, abscess, necrotizing fasciitis, folliculitis, furunculosis conform carbunculosis and secondary skin infections, sinusitis, as well as symptoms resulting from infection, including but not limited to phlegmon.
  • SSSS Staphyl involvcoccal scalded skin syndrome
  • the administration route and the dose may vary depending on a symptom, age and body weight of a subject.
  • the Vancomycin or a salt thereof, provided in a concentration as previously disclosed, is contained in a formulation for administration to the subject in need thereof.
  • the formulation may be topically administered to the eye, nose, ear or skin, 1, 2, 3, 4, 5, 6, 7 or 8 times per day, in a single dose which comprises 1 2, 3, 4 or 5 drops, or as necessary.
  • the present invention is further illustrated in detail by the following Experimental Examples.
  • the Experimental Examples are merely illustrative, and are not intended to limit the scope of the present invention.
  • Vancomycin hydrochloride in squalane Suspensions of Vancomycin hydrochloride in squalane were prepared in the following manner. 5 mg of Vancomycin hydrochloride was added to 5 mL of squalane (Vancomycin Ophthalmic Suspension 2% in Squalane) (SQ) or 5 mM KH 2 P0 4 buffer (pH 3.2) (Control), and stored at room temperature or 60°C.
  • Vancomycin hydrochloride The contents of Vancomycin hydrochloride were analyzed by UPLC (using: a gradient 5% acetonitrile in 5 mM KH 2 P0 4 (pH 3.2) to 20% acetonitrile in 5 mM KH 2 P0 4 (pH 3.2) for 6 min, performed at 35 °C, with the flow rate of 0.6 mL/min, at 230 nm wavelength and 5 ⁇ _, injection volume, on Supelco Titan CI 8 1.9 ⁇ , 2.1 X 10 cm column.)
  • Vancomycin hydrochloride was stable in squalane for 8 weeks at room temperature. The remaining % of Vancomycin hydrochloride in the pH 3.2 buffer was lower, at about 90%.
  • compositions comprising Vancomycin hydrochloride and squalane had unexpectedly superior stability at room temperature and at 60 °C, when compared to the control buffer solution.
  • the eyes of eighteen Japanese white rabbits were anesthetized by administration of Oxybuprocaine hydrochloride (0.4 w/v %, Nitto Medic Co., Ltd, Toyama, Japan) eye drops.
  • Each eye was held steady with clamping forceps, 30 ⁇ ⁇ of MRS A (5 X 10 7 CFU/mL) was instilled, and the cornea surface was punctured with the edge of 24G needle at 16 points along cornea limbus.
  • 30 ⁇ ⁇ of MRSA was instilled and the eyelid was forced closed two times.
  • the eyes of the test rabbits were examined by slit-lamp biomicroscopy at 0 hours (before infection) and 8, 24, 32, 48 hours post infection.
  • Five parameters which are symptoms of infection of the eye were assessed to determine the severity of infection.
  • Each parameter was scored from 0 (normal) to 4 (maximal severity) for each eye of the rabbit, based upon the scale provided below.
  • 0 Normal cornea. Cornea appears with a slit lamp as having a bright grey line on the epithelial surface and a bright grey line on the endothelial surface, with a marble-like grey appearance of the stroma.
  • 0 Normal. May appear blanched to reddish pink without perilimbal injection (except at 12 and 6 o'clock positions) with vessels of the palpebral and bulbar conjunctiva easily observed.
  • Figure 4 demonstrates the results of the degree of corneal opacity.
  • Figure 5 demonstrates the results of the area of corneal opacity.
  • Figure 6 demonstrates the results of the chemosis, which assesses the edema of the conjunctiva of the eye.
  • Figure 7 demonstrates the results of the conjunctival injection, which assesses the redness of the eyes due to dilation of the conjunctival vessels overlying the sclera.
  • Figure 8 demonstrates the results of the discharge.
  • Vancomycin suspension is as effective as the Vancomycin ointment. This is unexpected, and advantageous, in view of the problems associated with ophthalmic ointments, including difficulty in application, lack of comfort, limited day-time use, visual impairment, blurred vision, and decreased patient satisfaction.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dermatology (AREA)
  • Communicable Diseases (AREA)
  • Ophthalmology & Optometry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Otolaryngology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une composition topique comprenant de la vancomycine ou un sel de celle-ci, ainsi que du squalane, la composition permettant une stabilité améliorée de la vancomycine ou de son sel. L'invention porte également sur une méthode de traitement d'une infection de l'œil, du nez, de l'oreille ou de la peau, par l'administration d'une quantité thérapeutiquement efficace de la composition topique à un patient en ayant besoin, ladite administration conférant un meilleur confort au patient.
PCT/US2016/035813 2015-06-03 2016-06-03 Composition topique Ceased WO2016196989A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201562170389P 2015-06-03 2015-06-03
US62/170,389 2015-06-03
US201562192610P 2015-07-15 2015-07-15
US62/192,610 2015-07-15

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WO2016196989A1 true WO2016196989A1 (fr) 2016-12-08

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US10159637B2 (en) 2016-06-10 2018-12-25 Clarity Cosmetics Inc. Non-comedogenic and non-acnegenic hair and scalp care formulations and method for use
EP3362096A4 (fr) * 2015-10-14 2019-06-12 Paul Gavaris Composition de traitement ophtalmique et véhicule pour l'administration de substances pharmaceutiques ou d'agents thérapeutiques
US20210401877A1 (en) * 2020-01-10 2021-12-30 Azura Ophthalmics Ltd. Instructions for composition and sensitivity

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US20100267624A1 (en) * 2007-10-31 2010-10-21 Vincenzo De Tommaso Vancomycin and teicoplanin anhydrous formulations for topical use
US20120171249A1 (en) * 2003-06-04 2012-07-05 Nanobio Corporation Compositions for inactivating pathogenic microorganisms, methods of making the compositions, and methods of use thereof
US20130224268A1 (en) * 2012-02-27 2013-08-29 Newgen Biopharma Corp. Topical delivery of hormonal and non hormonal nano formulations, methods of making and using the same

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US20120171249A1 (en) * 2003-06-04 2012-07-05 Nanobio Corporation Compositions for inactivating pathogenic microorganisms, methods of making the compositions, and methods of use thereof
US20100267624A1 (en) * 2007-10-31 2010-10-21 Vincenzo De Tommaso Vancomycin and teicoplanin anhydrous formulations for topical use
US20130224268A1 (en) * 2012-02-27 2013-08-29 Newgen Biopharma Corp. Topical delivery of hormonal and non hormonal nano formulations, methods of making and using the same

Cited By (8)

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