EP2780004A1 - Filmbildende formulierung - Google Patents

Filmbildende formulierung

Info

Publication number
EP2780004A1
EP2780004A1 EP12787066.5A EP12787066A EP2780004A1 EP 2780004 A1 EP2780004 A1 EP 2780004A1 EP 12787066 A EP12787066 A EP 12787066A EP 2780004 A1 EP2780004 A1 EP 2780004A1
Authority
EP
European Patent Office
Prior art keywords
formulation
formulation according
film
solvent
propellant
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.)
Withdrawn
Application number
EP12787066.5A
Other languages
English (en)
French (fr)
Inventor
Nicola Cardy
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.)
LRC Products Ltd
Original Assignee
LRC Products Ltd
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 LRC Products Ltd filed Critical LRC Products Ltd
Publication of EP2780004A1 publication Critical patent/EP2780004A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/12—Keratolytics, e.g. wart or anti-corn preparations

Definitions

  • the present invention relates to a formulation capable of forming a film on topical administration, which formulation may be used in the treatment of warts.
  • Warts are generally small, rough growths of skin that are caused by the human papilloma virus (HPV). They typically grow on a person's hands or feet forming an unsightly blemish. Although mostly harmless, some warts can be irritating and/or painful. Warts are sometimes referred to as verrucas.
  • HPV human papilloma virus
  • Prior art methods of treating warts include cryosurgery, which typically involves using liquid nitrogen to freeze the wart so that it falls off, and keratolysis, which typically involves using salicylic acid to remove dead skin cells and filing of the area with a pumice stone or emery board.
  • Cryosurgery needs to be performed by a medical technician and often requires repeat visits until a wart is successfully treated.
  • Keratolytic treatments can be purchased as over-the-counter remedies and can be applied by a person with a wart to the affected area.
  • removing a wart by keratolysis requires repeated cleaning of the affected area, applying the keratolytic treatment and filing of the area with a pumice stone or emery board. It can take quite a long time to remove a wart by keratolysis, making keratolysis time consuming and labour intensive.
  • the present invention seeks to provide an improved over-the-counter remedy for the treatment for warts.
  • a formulation capable of forming a film on topical administration, said formulation comprising: at least one active ingredient effective in the treatment of warts;
  • an aerosol dispenser comprising the formulation of the present invention.
  • an aerosol dispenser may comprise a reservoir of the formulation of the present invention.
  • the at least one active ingredient effective in the treatment of warts may comprise an ingredient that disrupts the activity of the cells of the wart through its osmotic effect resulting in cell dehydration.
  • Cell dehydration stimulates a cell mediated immune response which results in the elimination of the wart.
  • an active ingredient is saline (i.e. sodium chloride solution), however, solutions of other alkali metal salts and alkaline earth metal salts (e.g. potassium chloride or magnesium sulphate) may also be effective.
  • any concentrated salt solution that does not irritate a person's skin may be used.
  • the at least one active ingredient effective in the treatment of warts is present in a saturating amount in the formulation.
  • saturated we also include substantially saturated, wherein at least 80% of that amount of the active ingredient needed to achieve saturation is present. This amount is preferably at least 90%, and more preferably 95%.
  • the formulation be as close to saturated as possible.
  • Supersaturated solutions are also included, but these are generally less preferred, as they are not generally stable, and have short shelf- lives. It is preferred that the amount of active ingredient present be as close to full saturation as possible, but many solutions are not stable at such high concentrations. In such cases, the addition of antinucleating agents, may be advantageous, as may a slight drop in saturation, down as far as 80%>, which is considered to be a saturating amount for the purposes of the present invention.
  • One advantage of the present invention lies in the combined high saturation levels and the use of propellant. Evaporation is almost instantaneous on application and the boiling during transfer from the dispenser to the site of administration has the effect of causing the evaporation of a substantial amount of the solvent. The almost explosive decompression of the propellant causes the disruption and loss of solvent by evaporation. This loss can be up to 50% and even higher.
  • the formulation may comprise from 5 wt% to 65 wt% of saline, preferably from 25 wt% to 65 wt%, more preferably from 35 wt% to 55 wt% of saline and most preferably from 35 wt% to 40wt%.
  • the at least one active ingredient effective in the treatment of warts may comprise a kerato lytic ingredient.
  • One example of such an active ingredient is urea.
  • the formulation may comprise up to 10 wt% of urea, from 2 wt% to 5 wt% of urea, preferably from 3 wt% to 4 wt% of urea.
  • the formulation of the present invention may comprise a combination of active ingredients effective in the treatment of warts.
  • active ingredients effective in the treatment of warts.
  • the inventors have found that a combination of saline and urea is particularly effective in the treatment of warts.
  • the solvent may be any suitable solvent, but is preferably selected from the group consisting of water, cyclomethicone, benzyl alcohol, propylene glycol, polyethylene glycol, propylene carbonate, ethanol, dimethyl sulphoxide, glycerin, isopropyl alcohol, isopropyl myristate, oleic acid and combinations thereof.
  • the formulation may further comprise a co-solvent.
  • the quantity of solvent and optional co-solvent present in the formulation may be varied depending on the nature and concentration of the at least one active ingredient and the other excipients.
  • the formulation may comprise from 15 wt% to 45 wt% of solvent, preferably from 25 wt% to 35 wt% of solvent.
  • the formulation may comprise from 5 wt% to 25 wt% of co-solvent.
  • the solvent and optional co-solvent of the present invention act as a vehicle for the at least one active ingredient to ensure the at least one active ingredient can be applied to the affected area. Once applied, at least part of the solvent and co-solvent may evaporate to produce a more concentrated solution of the at least one active ingredient in contact with the wart.
  • the film- forming agent may be any suitable film- forming agent, but is preferably selected from the group consisting of polyethylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol, acrylic polymers, acrylic copolymers, methacrylate polymers, methacrylate copolymers, poly (vinyl acetate), cellulose based polymers, cellulose based co-polymers and combinations thereof.
  • Examples of specific film-forming agents suitable for use in the formulation of the present invention include Eudragit (a cationic copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate).
  • the quantity of film- forming agent present in the formulation may be varied depending on the nature of the film- forming agent and the other excipients.
  • the formulation may comprise up to 10 wt% of film- forming agent, from 0.25 wt% to 6.00 wt% of film-forming agent, 0.25 wt% to 2.50 wt% of film- forming agent, preferably from 1 wt% to 2 wt% of film- forming agent.
  • the formulation may optionally contain a solubilising agent.
  • the formulation may comprise up to 15 wt% of solubiliser, from 0.25 wt% to 6.00 wt% of solubiliser, 0.25 wt% to 2.50 wt% of solubiliser, preferably from 0.50 wt% to 1 wt% of solubiliser, Any suitable solubilising agent can be used.
  • the solubiliser is typically a hydrophilic glycol ether, for example an alkyl ether, such as ethylene, polyethylene, propylene or butylene glycol ether, as the solubiliser.
  • ethylene glycol ethers include, but are not limited to, ethylene glycol monoalkyl ethers, such as ethylene glycol mo no methyl ether, ethylene glycol dialkyl ethers, such as ethylene glycol dimethyl ether, and ethylene glycol monoalkyl ether esters, such as ethylene glycol monoethyl ether acetate.
  • polyethylene glycol ethers include, but are not limited to, diethylene glycol monoalkyl ethers, such as diethylene glycol monobutyl ether, diethylene glycol dialkyl ethers; and diethylene glycol monoalkyl ether esters, such as diethylene glycol monoethyl ether acetate, and diethylene glycol monoethyl ether.
  • Suitable solubilising agents also include those products sold under the Dowanol name.
  • a preferred solubilising agent is 2-(2-ethoxy- ethoxy) ethanol, also known under the tradename Transcutol (diethylene glycol monoethyl ether).
  • the film- forming agent forms a film over the wart thereby holding the at least one active ingredient in contact with the wart and forming a barrier.
  • the barrier may help prevent the spread of HPV.
  • the propellant may be any suitable propellant, but is preferably selected from the group consisting of dimethyl ether, HFA 134a, HFA 152 and HFA 227 and combinations thereof.
  • the propellant dissipates before touching the affected area to produce a more concentrated solution of the at least one active ingredient in contact with the wart.
  • the quantity of propellant present in the formulation may be varied depending on the nature of the propellant.
  • the formulation may comprise from 10 wt% to 70 wt% of propellant, preferably from 10 wt% to 45 wt% of propellant, more preferably from 20 wt% to 35 wt% of propellant.
  • the formulations of the invention are suitable for administration as aerosols or as solutions.
  • the propellant is typically highly volatile requiring that the formulation be kept pressure-sealed.
  • the formulation may be sprayed from an aerosol dispenser onto an affected area.
  • the formulation was prepared in a 6 gram batch by accurately weighing all the excipients except the DME directly into a clear glass canister, and then crimping the canister with a 50 ⁇ valve. The canister was then placed onto an orbital shaker and shaken at 400 rpm until the polymer had solvated and the powdered excipients were fully dissolved. The DME was then added in the canister using a Pamasol filling machine. The canister was then placed onto an orbital shaker and further shaken at 400 rpm until a clear solution had formed.
  • Epidermal membrane mounted on filter paper was prepared from human skin (taken during an abdominoplasty). A phosphate buffered saline (PBS) solution was also prepared. The integrity of human epidermal membrane was tested by placing the epidermal membrane between two halves of a Franz diffusion cell. The integrity of human epidermal membrane was tested before and after application of formulations according to the present invention and placebo formulations, as follows: The top and bottom of the Franz cell were filled with PBS solution using a syringe. The Franz cell was stirred continuously using PTFE-coated magnetic stirrer bar and maintained at 37 °C in a pre-calibrated water bath. Once the Franz cell had been stirred for approximately 30 minutes, the resistance of the membrane was measured using an LCR DATABRIDGE (Model 6401). The PBS solution was then removed from the top of the cell and the skin dried using tissue.
  • LCR DATABRIDGE Model 6401
  • the formulation on the surface of the skin was then removed by gently washing the surface of the skin with ethanol three times. This was carried out by gently transferring 1 ml of ethanol onto the surface of the skin using a pipette and then removing and re-applying fresh ethanol three times. No abrasive or rubbing technique was employed to avoid any potential damage to the skin surface. The membranes were all visually checked to ensure complete removal of the films.
  • the top of the Franz cell were then filled with PBS solution.
  • the bottom of the Franz cell was then continuously stirred. After approximately 30 minutes, the resistance of the membrane was measured again using the LCR DATABRIDGE (Model 6401).
  • epidermal membrane mounted on filter paper was prepared from human skin and a PBS solution was also prepared.
  • the integrity of human epidermal membrane was tested by placing the epidermal membrane between two halves of a Franz diffusion cell, and the integrity of human epidermal membrane was tested before and after application of formulations according to the present invention and placebo formulations.
  • the Franz cells Following completer removal of the films from the epidermal membrane samples, the Franz cells. PBS solution was placed in the bottom of the Franz cell, which was continuously stirred. After approximately 2 hours and 24 hours fluid was removed from the bottom of the cells and an equal volume of PBS solution was replaced. The data was presented as the total amount ⁇ g) of methylparaben permeating over 2 hours and 24 hours, following treatment of epidermal membrane with perturbation formulations - see Figure 4. The results indicate that there is a decrease in resistance across the skin following exposure to the saline formulation. The placebo formulation confirms that the decrease in the resistance across the skin was due to the active components and not due to the formulation or cleaning procedure employed.
  • the formulations were actuated once onto a silicone membrane from distances of 5, 7 and 10 cm.
  • the film formed was left to dry for a minimum of 30 minutes at ambient temperature ( ⁇ 25 °C).
  • the silicone membrane was then folded to determine the flexibility of the film.
  • the odour of the formulation was determined during the water resistance testing prior to adding the water to the Petri dish and the odour was assessed from the film from a distance of approximately 5 cm. None of the formulations had an odour.
  • the formulations were actuated once onto a silicone membrane from a distance of 7 cm.
  • the film formed was left to dry for a minimum of 30 minutes at ambient temperature ( ⁇ 25°C).
  • ambient temperature ⁇ 25°C.
  • the film present on the membrane was rubbed for 10 seconds and visually checked for its presence on the glove. If the film was present on the membrane after 10 s rubbing, the rubbing was repeated.
  • the formulations were actuated once onto a skin sample.
  • the film formed was left to dry for a minimum of 30 minutes at ambient temperature ( ⁇ 25°C).
  • the presence of the film on the skin was visually checked after 1, 2, 4, 8 and 24 hours.
  • the formulations were actuated once onto a weight boat from a distance of 7 cm, and after the formulations had dried, the weight boat was placed onto a balance and the balance was tared.
  • the experiment was performed in triplicate. All of the formulations investigated demonstrated no tackiness, as shown by a weight gain of 0.000 ⁇ 0.000 grams.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP12787066.5A 2011-11-18 2012-11-13 Filmbildende formulierung Withdrawn EP2780004A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1119923.9A GB2496656B (en) 2011-11-18 2011-11-18 Film-Forming Formulation
PCT/GB2012/052816 WO2013072676A1 (en) 2011-11-18 2012-11-13 Film-forming formulation

Publications (1)

Publication Number Publication Date
EP2780004A1 true EP2780004A1 (de) 2014-09-24

Family

ID=45475364

Family Applications (1)

Application Number Title Priority Date Filing Date
EP12787066.5A Withdrawn EP2780004A1 (de) 2011-11-18 2012-11-13 Filmbildende formulierung

Country Status (3)

Country Link
EP (1) EP2780004A1 (de)
GB (1) GB2496656B (de)
WO (1) WO2013072676A1 (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9770609B2 (en) 2015-04-01 2017-09-26 Neat Feat Products Limited Urea based skin treatment

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060193789A1 (en) * 2002-10-25 2006-08-31 Foamix Ltd. Film forming foamable composition
US20050271596A1 (en) * 2002-10-25 2005-12-08 Foamix Ltd. Vasoactive kit and composition and uses thereof
WO2004091577A1 (en) * 2003-04-17 2004-10-28 Porten Pharmaceutical Ab Composition, method and pharmaceutical preparation for pharmaceutical spray suspensions
US20070189977A1 (en) * 2004-06-07 2007-08-16 Jie Zhang Spray-on formulations and methods for dermal delivery of drugs
FR2892023B1 (fr) * 2005-10-14 2009-09-25 Galderma Sa Composition pharmaceutique a base d'amorolfine et d'agent filmogene hydrosoluble pour application ungueale et peri-ungueale
AU2006339350A1 (en) * 2005-12-14 2007-09-07 Zars Pharma, Inc. Compositions and methods for dermal delivery of drugs
CA2633466A1 (en) * 2005-12-14 2007-06-21 Zars Pharma, Inc. Spray-on formulations and methods for dermal delivery of drugs
AU2006326034A1 (en) * 2005-12-14 2007-06-21 Zars Pharma, Inc. Flux-enabling compositions and methods for dermal delivery of drugs
WO2008075207A2 (en) * 2006-04-04 2008-06-26 Foamix Ltd. Anti-infection augmentation foamable compositions and kit and uses thereof
WO2010114973A1 (en) * 2009-04-01 2010-10-07 Jie Zhang Methods for treating myofascial, muscle, and/or back pain

Also Published As

Publication number Publication date
GB201119923D0 (en) 2012-01-04
WO2013072676A1 (en) 2013-05-23
GB2496656B (en) 2015-12-09
GB2496656A (en) 2013-05-22

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