[go: up one dir, main page]

WO2000001390A1 - Formulations topiques d'aciclovir - Google Patents

Formulations topiques d'aciclovir Download PDF

Info

Publication number
WO2000001390A1
WO2000001390A1 PCT/EP1999/004606 EP9904606W WO0001390A1 WO 2000001390 A1 WO2000001390 A1 WO 2000001390A1 EP 9904606 W EP9904606 W EP 9904606W WO 0001390 A1 WO0001390 A1 WO 0001390A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
aciclovir
accordance
fact
esters
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/EP1999/004606
Other languages
English (en)
Inventor
Giancarlo Santus
Luciano Marcelloni
Roberto Golzi
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.)
Recordati SA
Original Assignee
Recordati SA
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 Recordati SA filed Critical Recordati SA
Priority to AU49054/99A priority Critical patent/AU4905499A/en
Publication of WO2000001390A1 publication Critical patent/WO2000001390A1/fr
Anticipated expiration legal-status Critical
Ceased 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
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles

Definitions

  • Object of the present invention are topical formulations useful in the treatment of viral infections of the skin and mucous membranes, which contain the active ingredient 9-(2-hydroxymethoxymethyl)guanine, known as aciclovir, and are characterised by the inclusion of sucrose esters as absorption promoters.
  • the present invention relates to topical formulations for the administration of aciclovir, which contain a sucroester as an element promoting absorption of the active ingredient through the skin.
  • the sucroesters are sucrose esters obtained by reaction of sucrose with one or more fatty acids having a linear chain with an even number of carbon atoms ranging from 12 to 18, are widely used and have many applications in the pharmaceutical and food fields. These esters are commercially known by the name SUCROESTER ® (Gattefosse S.A. - Saint Priest - France) or CRODESTA ® (Croda Surfactants Ltd. - Goole - UK).
  • Sucroesters belong to the class of non-ionic surfactants, are endowed with good stability and do not undergo - after preparation of the finished products - any hydrolytic processes of a chemical or enzymatic nature. Being made up of a sugar with fatty acids, they are absolutely harmless compounds and not at all aggressive against the skin, thus being an excipient capable of meeting all of the cosmetic requirements of a topical preparation. Description of invention
  • sucrose ester when added to the ingredients of topical formulations for the administration of aciclovir via emulsified mixtures of lipids in water, these formulations become particularly effective in improving absorption and tolerance of aciclovir compared to both the commercial formulations and those described in the previous art.
  • the topical formulations which are an object of the invention comprise: from 0.1% to 10% w/w of aciclovir or any of its salts or any of its esters; from 0.1 % to 40% w/w of a sucrose ester; from 20% to 40% w/w of water, incorporated in a mixture with an oily phase.
  • the lipidic component of the emulsion is made up of known materials and is emulsified with the aqueous component in accordance with processes known in the art.
  • One or more emulsifying agents can be added to the ingredient of the lipidic phase, which can be a fat or an oil, to make the emulsion stable in time.
  • the ingredients of the oily phase are chosen predominantly on the basis of the cosmetic characteristics desired in the finished products since the solubility of aciclovir in oils and fats is confined to a limited range.
  • Example of the lipidic materials which can be used are linear or branched mono- or dialkylesters of esters of fatty acids such as, for example, isopropylmyristate and isopropylpalmitate, mixtures of cetyl and stearyl alcohol known by the commercial name Crodamol ® , high-molecular-weight lipids such as white paraffin or liquid paraffin and other mineral oils.
  • emulsifiers and emulsion stabilising agents include cetyl alcohol, sodium lauryl sulphate, stearyl alcohol, polyoxyethylene alkylesters such as Brij ® 72 and 721 and polyoxystearyl esters such as Steareth ® 2 and 21.
  • the aqueous phase of the emulsion can also contain other ingredients such as glycerine and glycol.
  • the amount of these ingredients is preferably lower than 30%.
  • an amount higher than 30% of polyalcohols such as glycerine and glycol is normally added to the aqueous phase to be used for the emulsion in order to increase aciclovir solubility in the phase.
  • esters of sucrose to the formulation ingredients allows these amounts of glycol in the formulation to be reduced far below 30%, at the same time increasing the therapeutic and cosmetic efficacy of the formulation thanks to the ability of sucroesters to act as promoters of the absorption of the active ingredient through the skin.
  • the sucroesters being substances which result from the combination of sucrose with normal food fats and, in particular, myristic acid, oleic acid, palmitic acid or stearic acid, they have a molecular structure with amphiphilic characteristics, both lipophilic and hydrophilic. These amphiphilic characteristics can be appropriately modulated using the sucroester most suitable for the various absorption requirements. In fact, the higher the number of sugar hydroxyls substituted by fatty acids, the more the lipophilic characteristics of sucroesters increase, and vice versa.
  • the sucroesters are thus capable of acting as absorption promoters, helping permeation of substances which would otherwise be poorly absorbed.
  • the monoesters are particularly useful in helping formation of oil-in-water emulsions.
  • the sucrose monoesters are scarcely soluble in cold water, while they are soluble in hot water, ethyl alcohol and acetone.
  • Their amphiphilic characteristics are represented by HLB (Hydrophilic Lypophilic Balance) values which can range from 7 to 14. For example: sucrose monopalmitate (HLB 14), sucrose mono/distearate (HLB 11 ), sucrose distearate (HLB 7).
  • sucrose monopalmitate is preferred among the monoesters for its high HLB value which, in addition to helping formation of an oil-in-water emulsion, contributes to stabilising it.
  • composition ratios (w/w) for a formulation suitable for the administration of aciclovir according to the present invention include: sucrose monopalmitate 15%, aciclovir 5%, cetostearyl alcohol 3-10%, propylene glycol 5- 30%, mineral oil 5-15%, Steareth ® 21 2-5%, sodium lauryl sulphate 0.1-1%, purified water as needed to reach 100%.
  • preservatives such as, for example, p- oxybenzoates, sodium benzoate, benzalkonium chloride and the like, can be added to these formulations as a precautionary complement in case of long-term storage.
  • a process to prepare the above topical formulations, too, is an integrant part of the invention. This process consists in stirring aciclovir or any of its salts or esters, a sucrose ester, the active ingredients, the excipients making up the oily phase and those making up the aqueous phase in a suitable emulsifier, up to formation of an oil/water emulsion.
  • the method of formulating the emulsion can vary depending on the amount and nature of the ingredients and follows the processes known in emulsion formation described, for example, in A. R. Gennaro: “Remington: The Science and Practice of Pharmacy", 19th Ed., Ch. 21 , 282-291 , Mack Publ. Co. (1995).
  • the preferred method is that of hot(70°C)-suspending aciclovir in the aqueous phase together with the sucrose esters, sodium lauryl sulphate, propylene glycol and to finally add this mixture to the ingredients of the fatty phase kept in a melted state at a temperature of about 60 to 70°C.
  • the emulsion forms after the addition of the aqueous phase to the vigorously-stirred oily phase.
  • the preferred apparatus for formation of the emulsion is a turboemulsifier, which allows vigorous stirring under vacuum, thus avoiding incorporation of air and the consequent formation of bubbles in the final cream.
  • the topical formulation prepared in accordance with the invention can be used for the treatment or prevention of viral infections caused by Herpes zoster, Herpes varicella and type-1 or 2 Herpes simplex. In particular, it was found to be useful in cases of Herpes labialis.
  • the formulation should be applied to the skin 1 to 6 times daily, preferably from 3 to 5 times.
  • formulations referred to in the present invention can easily adapt to the topical administration of other antiviral analogues of aciclovir such as, for example, famciclovir, penciclovir, valaciclovir and the like, or their synergetic combinations with other antiviral agents such as derivatives of guanine, vidarabine, citarabine and the like.
  • An oily phase was prepared by melting a mixture made up of stringy petrolatum, mineral oil and cetostearyl alcohol at 60°C.
  • An aqueous solution made up of sodium lauryl sulphate, Poloxamer ® 407, propylene glycol, sucrose monopalmitate and water in which micronised aciclovir had been hot(60°C)-dispersed was slowly added to the hot-stirred oily phase, and allowed to cool to ambient temperature.
  • the cream which formed was filled into 10-gram aluminium tubes internally coated with epoxy resin.
  • An oily phase was prepared by melting at 60°C made up of stringy petrolatum, mineral oil and cetostearyl alcohol.
  • An aqueous phase made up of sodium lauryl sulphate, Poloxamer ® 407, propylene glycol, sucrose distearate and water in which micronised aciclovir had been hot(70°C)-suspended, was added to the oily phase. Addition was slow with continuous hot-stirring, and cooling to ambient temperature was allowed. The cream which formed was filled into 5-gram aluminium tubes internally coated with epoxy resin.
  • An oily phase made up of stringy petrolatum, mineral oil, cetyl and stearyl alcohol was prepared by melting at 60°C.
  • a fatty phase made up of stringy petrolatum, mineral oil and cetostearyl alcohol
  • the temperature was brought to 60°C and the ingredients were allowed to melt for about 30 minutes.
  • Water, sodium lauryl sulphate, Poloxamer® 407 were separately added into a 5-L dissolution tank and the mixture was heated to 70°C. After complete dissolution of the mixture, propylene glycol and sucrose monopalmitate were added and stirred for about 30 minutes at a temperature of 70°C. After achieving again complete dissolution, micronised aciclovir was added and suspended with stirring using an UltraTurrax ® homogeniser, and a constant temperature was maintained.
  • Example 1 The cream described in Example 1 was compared with the above commercial cream Zovirax ® using a percutaneous absorption apparatus (Crown Glass Company, New Jersey, USA) which uses continuous-flow Bronaugh cells to measure permeation through the skin of Guinea pigs (R. Bronaugh et al., Journal Pharmaceutical Sciences, 74, 64-67 (1985)).
  • the skin of Guinea pigs was mounted on Bronaugh cells having a surface of 0.3 sq.cm. to which an amount of cream equal to 200-250 mg was applied.
  • a solution of phosphate buffer pH 7.4 was circulated for 48 hours and the various fractions were collected every 8 hours.
  • the collected fractions were analysed by a reverse- phase HPLC method using a Waters-625 apparatus with a C18 ⁇ Bondapack column, injecting 20 ⁇ l, eluting with the mobile phase water:methanol:acetic-acid (840/160/1 ) at a rate of 1 ml/minute, determining absorption with a UV detector at 254 nm.
  • Table 1 The results of the permeation test are shown in Table 1 below: TABLE 1
  • Example 1 could permeate through the skin layer in 48 hours an amount of aciclovir higher by at least 25% than the amount which was permeated by the commercial reference formulation Zovirax ® 5% Cream. Based on this, the formulation which is an object of the invention allows improved drug permeation through the skin and induces improved drug absorption and, as a result, improved therapeutic efficacy.

Landscapes

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

Abstract

Formulations topiques destinées à l'administration d'aciclovir. Ces formulations peuvent être utilisées dans le traitement préventif et thérapeutique des infections causées par Herpes virus et se caractérisent par la présence d'esters de sucrose qui agissent en tant qu'activateurs de l'absorption du ou des ingrédients actifs.
PCT/EP1999/004606 1998-07-03 1999-07-02 Formulations topiques d'aciclovir Ceased WO2000001390A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU49054/99A AU4905499A (en) 1998-07-03 1999-07-02 Topical aciclovir formulations

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI981528 ITMI981528A1 (it) 1998-07-03 1998-07-03 Formulazioni topiche di aciclovir
ITMI98A001528 1998-07-03

Publications (1)

Publication Number Publication Date
WO2000001390A1 true WO2000001390A1 (fr) 2000-01-13

Family

ID=11380373

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/004606 Ceased WO2000001390A1 (fr) 1998-07-03 1999-07-02 Formulations topiques d'aciclovir

Country Status (3)

Country Link
AU (1) AU4905499A (fr)
IT (1) ITMI981528A1 (fr)
WO (1) WO2000001390A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001095878A1 (fr) * 2000-06-14 2001-12-20 EGIS Gyógyszergyár Rt. Procede de preparation d'un onguent sterile contenant de l'aciclovir
EP1789075A4 (fr) * 2004-08-25 2009-07-01 Uab Research Foundation Substances ameliorant l'absorption destinees a l'administration de medicaments
US20110245278A1 (en) * 2010-03-31 2011-10-06 Mustafa Nevzat Ilac Sanayii A.S. Compositions of opioid antagonists and methods for treating conditions caused by the varicella-zoster virus therewith
US8236768B2 (en) 2008-10-03 2012-08-07 3B Pharmaceuticals, Inc. Topical antiviral formulations
WO2012107564A1 (fr) * 2011-02-10 2012-08-16 Moberg Derma Ab Nouvelles préparations pour utilisation cutanée, transcutanée et par voie muqueuse
US8268791B2 (en) 2004-08-25 2012-09-18 Aegis Therapeutics, Llc. Alkylglycoside compositions for drug administration
US8551468B2 (en) 2004-08-25 2013-10-08 Aegis Therapeutics Llc Absorption enhancers for intranasal interferon administration
US8642564B2 (en) 2004-08-25 2014-02-04 Aegis Therapeutics, Llc Compositions for drug administration
US20140100181A1 (en) * 2008-12-23 2014-04-10 Galderma S.A. Topical pharmaceutical composition containing a water-sensitive active principle
US8895546B2 (en) 2009-03-27 2014-11-25 Hale Biopharma Ventures, Llc Administration of benzodiazepine compositions
US9114069B2 (en) 2004-08-25 2015-08-25 Aegis Therapeutics, Llc Antibacterial compositions for drug administration
US9283280B2 (en) 2008-12-22 2016-03-15 Aegis Therapeutics, Llc Compositions for drug administration
US9895444B2 (en) 2004-08-25 2018-02-20 Aegis Therapeutics, Llc Compositions for drug administration
US10046025B2 (en) 2006-06-23 2018-08-14 Aegis Therapeutics, Llc Stabilizing alkylglycoside compositions and methods thereof
GB201819418D0 (en) 2018-11-29 2019-01-16 Daniel Calladine Ltd Anti-viral compositions
US10265402B2 (en) 2004-08-25 2019-04-23 Aegis Therapeutics, Llc Absorption enhancers for drug administration
US11241414B2 (en) 2008-03-28 2022-02-08 Neurelis, Inc. Administration of benzodiazepine compositions
AU2020286340B2 (en) * 2011-12-22 2022-12-08 Leica Biosystems Melbourne Pty Ltd Laboratory instrument control system

Citations (8)

* 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
WO1994020072A1 (fr) * 1993-03-05 1994-09-15 Pharmacia Ab Particules lipidiques solides, particules d'agents bioactifs et leurs procedes de production et d'utilisation
WO1995016434A1 (fr) * 1993-12-13 1995-06-22 Lidak Pharmaceuticals Formulations d'alcool c20 a c28 a base d'ester de sucrose
US5447729A (en) * 1994-04-07 1995-09-05 Pharmavene, Inc. Multilamellar drug delivery systems
WO1995026715A2 (fr) * 1994-03-30 1995-10-12 Dumex-Alpharma A/S Utilisation d'esters d'acides gras comme substances bioadherentes
WO1996040144A1 (fr) * 1995-06-07 1996-12-19 Pharmavene, Inc. Administration d'acyclovir par voie orale
WO1997009978A1 (fr) * 1995-09-13 1997-03-20 Morten Sloth Weidner Utilisation d'esters de polyols pour augmenter la biodisponibilite orale de substances medicamenteuses, nouveaux esters et compositions pharmaceutiques les contenant
WO1997034607A1 (fr) * 1996-03-20 1997-09-25 Glaxo Group Limited Formulations d'aciclovir a usage local

Patent Citations (8)

* 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
WO1994020072A1 (fr) * 1993-03-05 1994-09-15 Pharmacia Ab Particules lipidiques solides, particules d'agents bioactifs et leurs procedes de production et d'utilisation
WO1995016434A1 (fr) * 1993-12-13 1995-06-22 Lidak Pharmaceuticals Formulations d'alcool c20 a c28 a base d'ester de sucrose
WO1995026715A2 (fr) * 1994-03-30 1995-10-12 Dumex-Alpharma A/S Utilisation d'esters d'acides gras comme substances bioadherentes
US5447729A (en) * 1994-04-07 1995-09-05 Pharmavene, Inc. Multilamellar drug delivery systems
WO1996040144A1 (fr) * 1995-06-07 1996-12-19 Pharmavene, Inc. Administration d'acyclovir par voie orale
WO1997009978A1 (fr) * 1995-09-13 1997-03-20 Morten Sloth Weidner Utilisation d'esters de polyols pour augmenter la biodisponibilite orale de substances medicamenteuses, nouveaux esters et compositions pharmaceutiques les contenant
WO1997034607A1 (fr) * 1996-03-20 1997-09-25 Glaxo Group Limited Formulations d'aciclovir a usage local

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001095878A1 (fr) * 2000-06-14 2001-12-20 EGIS Gyógyszergyár Rt. Procede de preparation d'un onguent sterile contenant de l'aciclovir
US10512694B2 (en) 2004-08-25 2019-12-24 Aegis Therapeutics, Llc Compositions for oral drug administration
US9895444B2 (en) 2004-08-25 2018-02-20 Aegis Therapeutics, Llc Compositions for drug administration
US11173209B2 (en) 2004-08-25 2021-11-16 Aegis Therapeutics, Llc Compositions for drug administration
US9642913B2 (en) 2004-08-25 2017-05-09 Aegis Therapeutics, Llc. Pharmaceutical composition including alkyl glycoside and an anti-seizure agent
US8268791B2 (en) 2004-08-25 2012-09-18 Aegis Therapeutics, Llc. Alkylglycoside compositions for drug administration
US8551468B2 (en) 2004-08-25 2013-10-08 Aegis Therapeutics Llc Absorption enhancers for intranasal interferon administration
US8642564B2 (en) 2004-08-25 2014-02-04 Aegis Therapeutics, Llc Compositions for drug administration
US10576156B2 (en) 2004-08-25 2020-03-03 Aegis Therapeutics, Llc Compositions for drug administration
US10265402B2 (en) 2004-08-25 2019-04-23 Aegis Therapeutics, Llc Absorption enhancers for drug administration
US8927497B2 (en) 2004-08-25 2015-01-06 Aegis Therapeutics, Llc. Absorption enhancers for intranasal administration
US9114069B2 (en) 2004-08-25 2015-08-25 Aegis Therapeutics, Llc Antibacterial compositions for drug administration
EP1789075A4 (fr) * 2004-08-25 2009-07-01 Uab Research Foundation Substances ameliorant l'absorption destinees a l'administration de medicaments
US10046025B2 (en) 2006-06-23 2018-08-14 Aegis Therapeutics, Llc Stabilizing alkylglycoside compositions and methods thereof
US9763876B2 (en) 2008-03-28 2017-09-19 Hale Biopharma Ventures, Llc Administration of benzodiazepine compositions
US12268664B1 (en) 2008-03-28 2025-04-08 Neurelis, Inc. Administration of benzodiazepine compositions
US11793786B2 (en) 2008-03-28 2023-10-24 Neurelis, Inc. Administration of benzodiazepine compositions
US11241414B2 (en) 2008-03-28 2022-02-08 Neurelis, Inc. Administration of benzodiazepine compositions
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
US9283280B2 (en) 2008-12-22 2016-03-15 Aegis Therapeutics, Llc Compositions for drug administration
US20140100181A1 (en) * 2008-12-23 2014-04-10 Galderma S.A. Topical pharmaceutical composition containing a water-sensitive active principle
US8895546B2 (en) 2009-03-27 2014-11-25 Hale Biopharma Ventures, Llc Administration of benzodiazepine compositions
US20110245278A1 (en) * 2010-03-31 2011-10-06 Mustafa Nevzat Ilac Sanayii A.S. Compositions of opioid antagonists and methods for treating conditions caused by the varicella-zoster virus therewith
US9283220B2 (en) * 2010-03-31 2016-03-15 Imuneks Farma Ilac Sanayi Ve Ticaret Anonim Sirketi Pak Is Merkezi Compositions of opioid antagonists and methods for treating conditions caused by the varicella-zoster virus therewith
WO2012107564A1 (fr) * 2011-02-10 2012-08-16 Moberg Derma Ab Nouvelles préparations pour utilisation cutanée, transcutanée et par voie muqueuse
US12324852B2 (en) 2011-06-14 2025-06-10 Neurelis, Inc. Administration of benzodiazepine compositions
US12337061B2 (en) 2011-06-14 2025-06-24 Neurelis, Inc. Administration of benzodiazepine compositions
AU2020286340B2 (en) * 2011-12-22 2022-12-08 Leica Biosystems Melbourne Pty Ltd Laboratory instrument control system
GB201819418D0 (en) 2018-11-29 2019-01-16 Daniel Calladine Ltd Anti-viral compositions
WO2020109442A1 (fr) 2018-11-29 2020-06-04 Daniel Calladine Limited Compositions antivirales

Also Published As

Publication number Publication date
ITMI981528A1 (it) 2000-01-03
AU4905499A (en) 2000-01-24

Similar Documents

Publication Publication Date Title
WO2000001390A1 (fr) Formulations topiques d'aciclovir
NL8201413A (nl) Farmaceutische preparaten voor plaatselijke toepassing en werkwijzen voor het bereiden en toepassen van deze preparaten.
US4963555A (en) Formulations of heterocyclic compounds
US4719239A (en) Pharmaceutical multicomponent systems and method of preparing same
EP0044543B1 (fr) Formulations topiques à base de 9(2-hydroxyéthoxyméthyl) guanine
EP0132027B1 (fr) Une émulsion grasse contenant une prostaglandine
WO1994005258A1 (fr) Emulsion pharmaceutique d'huile dans l'eau a action antivirale contenant de la 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) ou un sel ou ester de ladite substance
JP4858664B2 (ja) Ｗ／ｏ／ｗ型複合エマルション
FI101600B (fi) Menetelmä farmaseuttisen formulaation valmistamiseksi
EP0593562B1 (fr) Composition topique contenant du penciclovir
CA2022632A1 (fr) Formule pharmaceutique
JP4521899B2 (ja) クロタミトン含有皮膚外用液剤
JP7646342B2 (ja) 外用医薬組成物
JP2700990B2 (ja) 経皮吸収促進物質及び皮膚外用剤組成物
PL179003B1 (pl) Preparat o stosowaniu miejscowym zawierajacy acyklowir i sposób wytwarzania preparatu o stosowaniu miejscowym zawierajacego acyklowir PL
US11007161B1 (en) Ibuprofen nanoparticle carriers encapsulated with hermatic surfactant films
JP4895458B2 (ja) 経皮吸収促進剤およびその使用
JPH0414645B2 (fr)
JPH0366281B2 (fr)
KR20230054682A (ko) Jak 저해제 및 라우레스-4를 함유하는 국소 제형
JP2022096992A (ja) 外用医薬組成物
WO2005067941A1 (fr) Formulation topique d’aciclovir
JPH0369882B2 (fr)
JPWO1999009992A1 (ja) 血管新生促進剤
HK1012242B (en) Topical composition containing penciclovir

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN 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 ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL 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

121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: CA

122 Ep: pct application non-entry in european phase