WO1999012545A2 - Medicaments contenant acyclovir - Google Patents

Medicaments contenant acyclovir Download PDF

Info

Publication number
WO1999012545A2
WO1999012545A2 PCT/EP1998/005560 EP9805560W WO9912545A2 WO 1999012545 A2 WO1999012545 A2 WO 1999012545A2 EP 9805560 W EP9805560 W EP 9805560W WO 9912545 A2 WO9912545 A2 WO 9912545A2
Authority
WO
WIPO (PCT)
Prior art keywords
aciclovir
formulation according
aqueous gel
herpes
gel formulation
Prior art date
Application number
PCT/EP1998/005560
Other languages
English (en)
Other versions
WO1999012545A3 (fr
Inventor
Robin Currie
Mickey Lee Wells
Sandra Kay Olive Williams
Original Assignee
Glaxo Group Limited
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 Glaxo Group Limited filed Critical Glaxo Group Limited
Priority to AU97408/98A priority Critical patent/AU9740898A/en
Publication of WO1999012545A2 publication Critical patent/WO1999012545A2/fr
Publication of WO1999012545A3 publication Critical patent/WO1999012545A3/fr

Links

Classifications

    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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

Definitions

  • This invention relates to a topical pharmaceutical formulation suitable for use in treating virus infections of the skin and mucosa, and in particular it relates to topical formulations containing 9-(2-hydroxyethoxymethyl)guanine, otherwise known as aciclovir, and hereinafter referred to as such.
  • Aciclovir and pharmaceutically acceptable salts and esters thereof are known to have antiviral activity against various classes of DNA and RNA viruses both in vitro and in vivo, see UK patent No. 1 523 865.
  • the compound is active against herpes simplex virus which causes herpetic keratitis in rabbits, herpetic encephalitis in mice, and cutaneous herpes in guinea pigs.
  • Aciclovir has been found to be effective in the treatment of herpes simplex virus and herpes zoster virus in humans.
  • references to aciclovir should be understood to include also its pharmaceutically acceptable salts and esters unless the context clearly indicates otherwise.
  • Aciclovir suffers from the disadvantage that it has a low solubility in water and is almost totally insoluble in hydrophobic solvent systems. It is accordingly difficult to produce a topical formulation containing a sufficient dissolved concentration of active ingredient for it to exert its full effect and also to optimise the flux of the compound into the skin. In addition to ease of release, it is also important that any formulation of a pharmaceutically active compound should be stable for long periods of time, should not lose its potency, should not discolour or form insoluble substances or complexes, and also should not be unduly irritating to the skin or mucosa.
  • European Patent No. 0 044 543 describes oil-in-water topical pharmaceutical formulations of aciclovir wherein the aqueous phase contains at least 30% of a water miscible polyhydric alcohol,
  • Co-pending International patent application No. PCT/GB97/00779 relates to oil- in-water topical pharmaceutical formulations of aciclovir comprising at least 10% by weight of diethylene glycol monoethyl ether. Surprisingly, it has now been found that, despite its poor solubility in water, it is possible to formulate aciclovir into a topical aqueous gel formulation that exhibits the required stability and allows flux of the compound into the skin.
  • the present invention provides an aqueous gel formulation for the topical delivery of aciclovir, the formulation comprising
  • Such a topical formulation may contain from 0.075% to 10% w/w aciclovir or a pharmaceutically acceptable salt or ester thereof, relative to the total weight of the formulation, from 0.5% to 80% w/w of pharmaceutically acceptable co- solvent, from 15% to 80% w/w water and a pharmaceutically acceptable gel forming agent or thickener.
  • Compositions according to the invention may also include one or more buffering agents and optionally a surfactant. All ingredients will be "pharmaceutically acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.
  • Such formulations have particularly advantageous properties, in particular, enhanced efficacy together with low irritancy and good physical stability.
  • compositions contain 1-10% by wt of aciclovir, 1-65% by wt of co- solvent, 0.01-5% of a buffering agent, 0.001-8% of a surfactant and up to 15% of an organic or inorganic polymeric or colloidal gel thickener, with purified water to 100%.
  • formulations according to the invention contain at least 15% water.
  • Suitable thickening or gel forming agents include colloidal silicon dioxide, HPMC (hydroxypropylmethylcellulose) and carbomer 943P.
  • Suitable co-solvents include glycerol formal, propylene glycol, dimethyl isosorbide (DMI), NDMS (n-decylmethylsulphoxide), isopropyl alcohol and diethylene glycol monoethyl ether.
  • Diethylene glycol monoethyl ether is manufactured by Gatttefosse S.A., 36 Chemin de Genas, b.p. 603, 69804 Saint-Priest Cedex, France, under the tradename TRANSCUTOLTM.
  • Suitable buffering agents include triethanolamine (TEA), sodium hydroxide, potassium citrate, sodium citrate, sodium phosphate and EDTA (ethylenediaminetetra-acetic acid).
  • TAA triethanolamine
  • sodium hydroxide sodium hydroxide
  • potassium citrate sodium citrate
  • sodium phosphate sodium phosphate
  • EDTA ethylenediaminetetra-acetic acid
  • Suitable surfactants include anionic surfactants such as sodium lauryl sulphate, cationic surfactants such as benzalkonium chloride and, preferably, non-ionic surfactants such as polyvinyl alcohol and polyoxyethylene sorbitan fatty acid esters (polysorbates). Particularly preferred is Tween 20 ® (polysorbate 20).
  • the composition comprises from 2 to 6% w/w aciclovir, e.g. 5%, from 20 to 50% w/w co-solvent, e.g. 40%, together with water, a pharmaceutically acceptable thickener and a buffering agent.
  • the present invention provides the use of an aqueous gel formulation of the invention in the treatment or prevention of viral infections caused by a virus of the Herpes family, for example by Herpes zoster, Herpes varicella or Herpes simplex type I or 2. Also provided is the use of aciclovir in the preparation of an aqueous gel formulation for the treatment or prophylaxis of infectious disease caused by a member of the Herpes family of viruses, particularly Herpes simplex, Herpes varicella or Herpes zoster.
  • Aciclovir may be prepared by methods known in the art, for example, as disclosed in British patent No. GB1523865, the content of which is hereby incorporated herein by reference. It will be appreciated that salts of aciclovir can be prepared and, accordingly, the present invention extends to formulations comprising physiologically acceptable salts of aciclovir.
  • the particle size of the crystalline material may be reduced by conventional methods, for example, by micronisation.
  • Gel formulations according to the invention in which the thickener is Carbomer 943P may have the following composition:
  • Gel formulations according to the invention in which the thickener is colloidal silicon dioxide may have the following composition:
  • Formulations according to the invention may be buffered to improve stability.
  • compositions may be buffered to have a pH of from about 4 to about 13.
  • Suitable buffers are those discussed above which are physiologically acceptable upon topical administration.
  • Preferred high pH formulations have a pH above 9, suitably in the range 9 to 11.
  • the preferred buffer for high pH formulations is sodium hydroxide.
  • Low pH formulations may be buffered to have a pH of from about 4 to about 9.
  • Preferred low pH formulations have a pH of between 4 and 8, suitably below 7, desirably in the range 4 to 6.
  • the preferred buffer for low pH formulations is triethanolamine (TEA) or a mixture thereof with EDTA.
  • High pH gel formulations according to the invention may have the following composition:
  • the formulations of the invention may, if desired, include one or more pharmaceutically acceptable preservatives or other excipients well known in the field of topical pharmaceuticals e.g. humectants, emollients, antioxidants, chelating agents etc.
  • the formulations may include ingredients well known from the cosmetics field such as colourants or fragrances.
  • Preservatives which may optionally be employed in formulations according to the present invention include thiomerosal, benzalkonium chloride, methyl paraben.
  • Humectants which may optionally be employed in formulations according to the present invention include propylene glycol, glycerol, sorbitol.
  • Emollients which may optionally be employed in formulations according to the present invention include cetostearyl alcohol, glycerin, glyceryl monostearate.
  • Antioxidants which may optionally be employed in formulations according to the present invention include butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), ascorbic acid.
  • Chelating agents which may optionally be employed in formulations according to the present invention include citric acid monohydrate, EDTA.
  • the formulations according to the invention may, if desired, contain a combination of two or more active ingredients. Accordingly, the present invention further provides topical formulations in accordance with the invention which contain aciclovir and at least one other active ingredient.
  • Suitable active ingredients for use in such combination formulations include acemannan, pain relief or anaesthetic agents such as lidocaine or bupivocaine and antipruritic agents such as menthol.
  • the present invention also provides a method for the preparation of a topical pharmaceutical formulation, as hereinbefore defined, which comprises mixing the aciclovir, co-solvent and pharmaceutically acceptable thickener with water.
  • the aciclovir may initially be mixed with water to form a "drug phase" in which the drug may be in solution or a mixed solution/suspension, and this may then be incorporated into a "gel phase".
  • the gel phase may be formed by slow addition of the thickener, with propeller agitation, to a mixture of water, co-solvent and any necessary buffering agent.
  • the aciclovir may be mixed with the co-solvent, buffering agent (if used) and water and then the thickener or gelling agent added slowly, with propeller agitation.
  • a topical formulation of the present invention may be used in the treatment or prevention of viral infections caused for example by Herpes zoster, Herpes varicella and Herpes simplex types I and 2, which cause diseases such as shingles, chicken pox, cold sores and genital herpes.
  • Administration of medicament may be indicated for the treatment of mild, moderate or severe symptoms or for prophylactic treatment. It will be appreciated that the precise dose administered and the frequency of administration will depend on many factors and may ultimately be at the discretion of an attendant physician.
  • a further aspect of the present invention therefore provides a method of treating a herpes viral infection in a mammal, particularly a human, by topical administration of a formulation according to the invention.
  • the chemical and physical stability of the formulations according to the invention may be determined by techniques well known to those skilled in the art.
  • the chemical stability of the components may be determined by HPLC assay after prolonged storage of the product.
  • Physical stability may be determined after storage or stress e.g. centrifugation by microscopic examination or by visual appearance (e.g. looking for separation, settling or other physical changes).
  • examples 3-5 below were made according to the procedure set out in example 2 above.
  • the formulation of example 6 was made according to the procedure set out in example 1 above.
  • the formulation of example 7 was made by mixing water and aciclovir by stirring with propeller agitation to form the "drug phase".
  • Sodium hydroxide was dissolved in water, ethanol, propylene glycol and Transcutol and HPMC was slowly sprinkled in, while mixing with propeller agitation. Mixing continued until the HPMC was completely dispersed, then the "drug phase" was added and mixed well using sweep agitation.
  • HPMC 1.66 sodium hydroxide 0.80 ethanol 2.00 water (USP) to: to: to: to: to:
  • mice were anaesthetised the skin of the snout region was lightly abraded with a roto-tool. Groups of ten mice were then innoculated on the skin of the snout from an SC-16
  • HSV stock solution diluted to a final concentration of 1.1 E8 PFU/ml.
  • the abrasion area was then swabbed for ten seconds with a sterile cotton swab soaked with the viral stock.
  • TREATMENT Mice were treated for four days starting three days post- innoculation (PI) and continuing through day seven. Mice in four groups of 10 were treated topically twice daily with one of the formulations from Examples 3-6. A further group of 10 mice received no treatment (negative control) and one group of 10 were treated with aciclovir oil-in-water cream (positive control) as disclosed in EP-B-0044543.
  • ASSESSMENT Lesions were scored at the same time each day. The scoring system is outlined below:
  • mice After infection, the animals were randomly divided into groups of 2, to include untreated virus control and 6 treatment groups.
  • test formulations Treatment of infected animals with test formulations commenced 18 hours post infection and continued twice daily (8.30 a.m. and 4.30 p.m.) for 3 days. Therapy consisted of 1 ml of test cream being applied directly to the infected flank from previously loaded 5ml syringes. Four groups of animals were treated topically twice daily with one of the formulations from Examples 3-7. A further group of 2 guinea pigs received no treatment (negative control) and one group was treated with aciclovir oil-in-water cream (positive control) as disclosed in EP-B-0044543.
  • the formulations of the present invention are shown to be comparable to aciclovir cream in the levels of reduction in lesion scores, and % survival of the animals.
  • all the tested formulations of the invention showed an antiviral effect during the three days of treatment (lesion scores compared to untreated control) and Examples 4 and 7 were comparable to aciclovir cream during treatment, although the Example 4 formulation exhibited a "bounce back" effect on cessation of treatment.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Inorganic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une formulation pharmaceutique topique servant à traiter des infections virales de la peau et des muqueuses et, en particulier, des formulations topiques de gel aqueux contenant 9-(2-hydroxyéthoxyméthyl)guanine, connue sous le non d'aciclovir, présentant la stabilité requise et permettant au composé de s'écouler vers l'intérieur de la peau.
PCT/EP1998/005560 1997-09-05 1998-09-03 Medicaments contenant acyclovir WO1999012545A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU97408/98A AU9740898A (en) 1997-09-05 1998-09-03 Medicaments containing acyclovir

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9718791.8A GB9718791D0 (en) 1997-09-05 1997-09-05 Medicaments
GB9718791.8 1997-09-05

Publications (2)

Publication Number Publication Date
WO1999012545A2 true WO1999012545A2 (fr) 1999-03-18
WO1999012545A3 WO1999012545A3 (fr) 1999-06-10

Family

ID=10818545

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/005560 WO1999012545A2 (fr) 1997-09-05 1998-09-03 Medicaments contenant acyclovir

Country Status (3)

Country Link
AU (1) AU9740898A (fr)
GB (1) GB9718791D0 (fr)
WO (1) WO1999012545A2 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2837102A1 (fr) * 2002-03-18 2003-09-19 Palbian Snc Composition a l'etat de gel aqueux, procede de fabrication et utilisation pour la fabrication d'un medicament, notamment antiherpetique
GB2370774B (en) * 1999-09-22 2004-12-08 B Ron Johnson Anti-infective compositions for treating disordered tissue such as cold sores
AU2004202929B2 (en) * 1999-09-22 2006-11-23 B. Ron Johnson Systems for agitated delivery of anti-infective compositions to treat disordered tissue such as cold sores
EP1758532A2 (fr) * 2004-06-03 2007-03-07 David M. Richliln Preparation topique ainsi que procede d'administration transdermique et de localisation d'agents therapeutiques
EP1765293A2 (fr) * 2004-06-24 2007-03-28 Idexx Laboratories, Inc. Compositions pharmaceutiques destinees a l'administration medicamenteuse et methodes de traitement ou de prevention d'etats au moyen de celles-ci
FR2924024A1 (fr) * 2007-11-27 2009-05-29 Centre Nat Rech Scient Nanoparticules d'actifs therapeutiques de faible solubilite aqueuse
US20090270429A1 (en) * 2008-03-17 2009-10-29 Medivir Ab Antiviral formulation
US8236768B2 (en) 2008-10-03 2012-08-07 3B Pharmaceuticals, Inc. Topical antiviral formulations
US8771712B2 (en) * 2006-05-09 2014-07-08 Emisphere Technologies, Inc. Topical administration of acyclovir
US8846725B2 (en) 2011-01-24 2014-09-30 Quadex Pharmaceuticals, Llc Highly penetrating compositions and methods for treating pathogen-induced disordered tissues
US9125911B2 (en) 2013-03-14 2015-09-08 Quadex Pharmaceuticals, Llc Combined systemic and topical treatment of disordered tissues

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9463180B2 (en) 2013-03-14 2016-10-11 Quadex Pharmaceuticals, Llc Treatment of molluscum contagiosum
US9549930B2 (en) 2013-03-14 2017-01-24 Quadex Pharmaceuticals, Llc Combined systemic and topical treatment of disordered and/or prodromal stage tissue

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0044543A1 (fr) * 1980-07-18 1982-01-27 The Wellcome Foundation Limited Formulations topiques à base de 9(2-hydroxyéthoxyméthyl) guanine
EP0551626A1 (fr) * 1991-12-19 1993-07-21 LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d. Gel thermoréversible utile comme excipient pharmaceutique pour une formation galénique
EP0614659A2 (fr) * 1993-03-11 1994-09-14 Taro Pharmaceutical Industries Limited Compositions pharmaceutiques semi-solides et un dispositif pour l'administration de ces compositions
EP0679390A2 (fr) * 1994-04-29 1995-11-02 Zyma SA Préparations pharmaceutiques vaporisables pour l'application topique
DE4425322A1 (de) * 1994-07-18 1996-01-25 Merck Patent Gmbh Virostatika in hydrophober Gelgrundlage
EP0733357A1 (fr) * 1995-03-22 1996-09-25 Dompé S.P.A. Compositions pharmaceutiques sous forme de gel thixotropique
WO1997034607A1 (fr) * 1996-03-20 1997-09-25 Glaxo Group Limited Formulations d'aciclovir a usage local

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0044543A1 (fr) * 1980-07-18 1982-01-27 The Wellcome Foundation Limited Formulations topiques à base de 9(2-hydroxyéthoxyméthyl) guanine
EP0551626A1 (fr) * 1991-12-19 1993-07-21 LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d. Gel thermoréversible utile comme excipient pharmaceutique pour une formation galénique
EP0614659A2 (fr) * 1993-03-11 1994-09-14 Taro Pharmaceutical Industries Limited Compositions pharmaceutiques semi-solides et un dispositif pour l'administration de ces compositions
EP0679390A2 (fr) * 1994-04-29 1995-11-02 Zyma SA Préparations pharmaceutiques vaporisables pour l'application topique
DE4425322A1 (de) * 1994-07-18 1996-01-25 Merck Patent Gmbh Virostatika in hydrophober Gelgrundlage
EP0733357A1 (fr) * 1995-03-22 1996-09-25 Dompé S.P.A. Compositions pharmaceutiques sous forme de gel thixotropique
WO1997034607A1 (fr) * 1996-03-20 1997-09-25 Glaxo Group Limited Formulations d'aciclovir a usage local

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2370774B (en) * 1999-09-22 2004-12-08 B Ron Johnson Anti-infective compositions for treating disordered tissue such as cold sores
AU2004202929B2 (en) * 1999-09-22 2006-11-23 B. Ron Johnson Systems for agitated delivery of anti-infective compositions to treat disordered tissue such as cold sores
WO2003077922A1 (fr) * 2002-03-18 2003-09-25 Palbian Societe En Nom Collectif Composition a l'etat de gel aqueux, procede de fabrication et utilisation pour la fabrication d'un medicament, notament antiherpetique
FR2837102A1 (fr) * 2002-03-18 2003-09-19 Palbian Snc Composition a l'etat de gel aqueux, procede de fabrication et utilisation pour la fabrication d'un medicament, notamment antiherpetique
EP1758532A2 (fr) * 2004-06-03 2007-03-07 David M. Richliln Preparation topique ainsi que procede d'administration transdermique et de localisation d'agents therapeutiques
EP1758532A4 (fr) * 2004-06-03 2012-08-08 David M Richliln Preparation topique ainsi que procede d'administration transdermique et de localisation d'agents therapeutiques
EP1765293A4 (fr) * 2004-06-24 2012-05-30 Idexx Lab Inc Compositions pharmaceutiques destinees a l'administration medicamenteuse et methodes de traitement ou de prevention d'etats au moyen de celles-ci
EP1765293A2 (fr) * 2004-06-24 2007-03-28 Idexx Laboratories, Inc. Compositions pharmaceutiques destinees a l'administration medicamenteuse et methodes de traitement ou de prevention d'etats au moyen de celles-ci
US8771712B2 (en) * 2006-05-09 2014-07-08 Emisphere Technologies, Inc. Topical administration of acyclovir
WO2009071850A3 (fr) * 2007-11-27 2009-11-26 Centre National De La Recherche Scientifique Nanoparticules d'actifs therapeutiques de faible solubilite aqueuse
JP2011506276A (ja) * 2007-11-27 2011-03-03 セントレ・ナショナル・デ・ラ・レシェルシェ・サイエンティフィーク 水溶解度の低い治療剤のナノ粒子
WO2009071850A2 (fr) * 2007-11-27 2009-06-11 Centre National De La Recherche Scientifique Nanoparticules d'actifs therapeutiques de faible solubilite aqueuse
CN101925365B (zh) * 2007-11-27 2013-03-06 国家科研中心 具有低水溶解度的治疗性活性物质的纳米颗粒
FR2924024A1 (fr) * 2007-11-27 2009-05-29 Centre Nat Rech Scient Nanoparticules d'actifs therapeutiques de faible solubilite aqueuse
US8962552B2 (en) 2007-11-27 2015-02-24 Centre Nationale De Recherche Scientifique Nanoparticles of therapeutic agents having low water solubility
US20090270429A1 (en) * 2008-03-17 2009-10-29 Medivir Ab Antiviral formulation
US8236768B2 (en) 2008-10-03 2012-08-07 3B Pharmaceuticals, Inc. Topical antiviral formulations
US9144576B2 (en) 2008-10-03 2015-09-29 3B Pharmaceuticals, Inc. Topical antiviral formulations
US8846725B2 (en) 2011-01-24 2014-09-30 Quadex Pharmaceuticals, Llc Highly penetrating compositions and methods for treating pathogen-induced disordered tissues
US9314526B2 (en) 2011-01-24 2016-04-19 Quadex Pharmaceuticals, Llc Highly penetrating compositions with benzocaine for treating disordered tissues
US9125911B2 (en) 2013-03-14 2015-09-08 Quadex Pharmaceuticals, Llc Combined systemic and topical treatment of disordered tissues

Also Published As

Publication number Publication date
AU9740898A (en) 1999-03-29
WO1999012545A3 (fr) 1999-06-10
GB9718791D0 (en) 1997-11-12

Similar Documents

Publication Publication Date Title
CA2646667C (fr) Methode de traitement des bouffees de chaleur par des preparations transdermiquea ou transmucosiques
US9770406B2 (en) Medicament for the treatment of viral skin and tumour diseases
JP6438466B2 (ja) イベルメクチンによる丘疹膿疱性の酒さの治療
CN106604717B (zh) 局部用双氯芬酸钠组合物
WO1996002244A1 (fr) Preparation pour usage local employee dans la prevention et le traitement de lesions et plaies associees a un herpesvirus
WO1999012545A2 (fr) Medicaments contenant acyclovir
WO1997034607A1 (fr) Formulations d'aciclovir a usage local
KR20080053319A (ko) 브리부딘을 함유하는 헤르페스 각막염 치료용 광안정 약학조성물
JP2010511723A (ja) 局所医薬組成物
WO2017029298A1 (fr) Composition antivirale topique
US20130197089A1 (en) Compositions for the treatment of actinic keratosis
EP1140117B1 (fr) Compositions d'acyclovir contenant du dimethicone
EP1242062B1 (fr) Compositions pharmaceutiques pour l'administration topique dans la cavite buccale de produits anti-inflammatoires non steroides
US20090068125A1 (en) Treatment for mucositis
WO1997045123A1 (fr) Formulations pharmaceutiques topiques comprenant de l'aciclovir
JP2002529520A (ja) プロピレングリコールおよびアルカン酸イソプロピルエステルを含む抗ウイルス製剤
JPH09143096A (ja) ウィルス疾患用医薬組成物
US20220040138A1 (en) Teriflunomide topical pharmaceutical compositions
JPWO2004069261A1 (ja) 抗ヘルペスウイルス外用製剤の製造方法
JPH0959149A (ja) 消炎鎮痛組成物
EP0787490A1 (fr) Préparation topique pour la prevention et le traitement des lesions et des escarres associées avec le virus d'herpes
EP0723448A1 (fr) Utilisation de penciclorine dans le traitement des algies post-therapeutiques
MXPA01006490A (en) Aciclovir compositions containing dimethicone
MX2008013207A (es) Metodos para tratamiento de bochornos con formulaciones para aplicacion transdermica o transmucosa.

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM HR HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM HR HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

NENP Non-entry into the national phase in:

Ref country code: KR

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase in:

Ref country code: CA