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WO1988008304A1 - Composition pharmaceutique - Google Patents

Composition pharmaceutique Download PDF

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Publication number
WO1988008304A1
WO1988008304A1 PCT/HU1988/000025 HU8800025W WO8808304A1 WO 1988008304 A1 WO1988008304 A1 WO 1988008304A1 HU 8800025 W HU8800025 W HU 8800025W WO 8808304 A1 WO8808304 A1 WO 8808304A1
Authority
WO
WIPO (PCT)
Prior art keywords
cyclodextrin
benzoic acid
complex
active ingredient
inclusion complex
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/HU1988/000025
Other languages
English (en)
Inventor
Lajos Szente
József SZEJTLI
Halina MAGISZTRÁK
Erich HORVÁTH
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.)
Chinoin Private Co Ltd
Original Assignee
Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
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 Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt filed Critical Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Publication of WO1988008304A1 publication Critical patent/WO1988008304A1/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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L9/00—Disinfection, sterilisation or deodorisation of air
    • A61L9/015—Disinfection, sterilisation or deodorisation of air using gaseous or vaporous substances, e.g. ozone
    • A61L9/04—Disinfection, sterilisation or deodorisation of air using gaseous or vaporous substances, e.g. ozone using substances evaporated in the air without heating
    • A61L9/042—Disinfection, sterilisation or deodorisation of air using gaseous or vaporous substances, e.g. ozone using substances evaporated in the air without heating with the help of a macromolecular compound as a carrier or diluent
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
    • C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes

Definitions

  • the present invention relates to a pharmaceutical inhalant composition and a process to release the volatile active ingredients included to cyclodextrin.
  • the inhalant composition is a pharmaceutical composition which contains the vapour of the active ingredients or liquid drops of various size dispersed in the air.
  • the inhalant composition can have various forms: a natural source such as dried plant drug can be boiled in hot water or it can be extracted and ampouled and it has to be put in hot water after opening the ampoule and in certain instances aerosol prepared by burning (fume) or aerosol spray compositions can be used.
  • a natural source such as dried plant drug can be boiled in hot water or it can be extracted and ampouled and it has to be put in hot water after opening the ampoule and in certain instances aerosol prepared by burning (fume) or aerosol spray compositions can be used.
  • the treatment by inhalation can be performed in three forms: the active ingredient to be inhaled, a solution thereof or a cyclodextrin inclusion complex thereof is put into hot water and by utilizing the principle of steam distillation it is transferred to aerosol layer, another possibility is the already mentioned spray where the active ingredient is vapourized with an inert carrier gas under pressure, and according to the third possibility liquid active ingredient is administered to the respiratory system by using the vapourizing principle under clinical conditions and using air of several atmosphere.
  • the hot water evaporation is the most suitable method to ensure the appropriate amount of water for the respiratory mucous membrane to dissolve the thickened mucous and to enhance the blood supply of the respiratory tract by means of thermal effect and thereby to promote the utilization of the biologically active ingredient.
  • the disadvantage of this process is that the extent of the release of the active ingredient is not sufficient at the water temperature which ensures the vapour space which can be endured by the human respiratory system.
  • the release of the active ingredient is too slow and a significant amount of it remains in the hot water.
  • the volatile substances are significant in another field apart from the inhalation. They are important during air condition when ensuring the suitable vapour content and volatile substance content of the air.
  • By spreading of modern heating method the air of the apartments and working places gets very dry. This is the source of several deseases of the respiratory tract (drying out of mucous, asthma, etc.).
  • the moisturizing of the air is practically unavoidable, and it would be advantageous to use natural substances of pleasant odour and partially disinfectant activity in the form of aerosol.
  • the whole room can be scented to the desired extent or corresponding to the quality of the used aroma CD inclusion complex.
  • the dosage, the transfer and the storage of the active ingredients can be easily solved.
  • the release of the active ingredient from the complex can be performed by the following three methods: a) Enzymatic decomposition of the cyclodextrin forming the inclusion complex. This procedure is too slow and the enzyme has to be added separately. b) Dissolution of the complex In boiling water (100 °C) and its constant boiling. This cannot be used in case of inhalation or air scenting as mentioned before. c) By increasing the pH of the aqeuous solution. The solubility of cyclodextrin increases somewhat. This accelerates the release of the active ingredient as well.
  • beta-cyclodextrin forms a colourless inclusion complex with phenolphthaleine in an alkaline medium the stability contant of which is known.
  • a potent host molecule is added to the CD-volatile oil composition which is able to form with this cyclodextrin an inclusion complex of considerably higher stability displacing thereby the included volatile active ingredients.
  • the speed and extent of the release of volatile active ingredients included into cyclodextrin in hot water can be accelerated or enhanced by adding a suitable competitor host molecule.
  • the invention was really to find a competitior molecule which could form a more stable inclusion complex with cyclodextrin than the volatile active ingredients included into cyclodextrin.
  • the choice of the compounds was rather great, but the compounds had to meet the following requirements: the competitor host molecule has to be intoxic, easily accessible, solid, non-volatile with water, odourless and it should not react with the components of the inhalant composition. 23 compounds were tested which are shown in Table 1.
  • Aromatic benzoic acid compounds 4-hydroxy-benzoic acid 3-hydroxy-benzoic acid 2-hydroxy-benzoic acid 2-Nipagin-M (4-hydroxy-benzoic acidmethyl ester L-tyrozine L-tryptophan L-phenylalanine
  • Tween 21 poly-oxy-ethyleneTween type Tween 40 sorbitane trioleates, compounds Tween 61 Merck, Darmstadt, Germany Tween 85
  • Aralkyl-polyglycol- Arkopal N-090 ethers Arkopal N-050 (Sigma, St. Arkopal N-230 Luis, USA) Triton-X-100 (Röhm et Haas, Philadelphia, USA)
  • camphor-beta-CD complex active ingredient content 10 %
  • Nitrogen gas is bubbled through the flask with constant speed for 30 minutes.
  • the gas stream is let to a gas washing bottle cooled with ice and containing 50 cm 3 50 % aqueous ethanol solution.
  • the amount of the volatie substance consumed in the trap is determined UV-photometrically. The obtained results are shown in Table II.
  • camphor ⁇ -CD complex 325.3 100 camphor ⁇ -CD complex + benzoic acid 469.0 144 camphor ⁇ -CD complex + 2-hydroxybenzoic acid (salicylic acid) 387.8 119 camphor ⁇ -CD complex + 4-hydroxybenzoic acid 385.7 119 camphor ⁇ -CD complex + 4-hydroxybenzoic acid + diammonium sulphate 393.4 121 camphor ⁇ -CD complex + 4-hydroxybenzoic acid-methyl ester 378.0 116 camphor ⁇ -CD complex + sodium hydroxide 363.2 112
  • Table V shows that the benzoate ion is considerably weaker complexing agent (weaker competitor) than the free acid.
  • x Values higher than 1 are measured extinctions multiplied by dilution.
  • the most suitable compounds for releasing volatile materials from CD complex are benzoic acid and hydroxy derivatives thereof, and the most preferred compound is the benzoic acid.
  • the precondition of the applicability of benzoic acid and derivatives for inhalation purposes is in case of the used volatile oil complexes that the competitor molecules do not appear in the vapour space at a significant concentration and that they do not get into the respiratory system of the patient at a detrimental amount.
  • the inhelent pharmaceutical composition on air scenting composition is charactorized by containing a volatile oil-CD inclusion complex and a competitor host molecule as well as conventionally used excipitents.
  • the competitor host molecule forms a complex with CD of higher stability than the volatile active ingredients to be set free.
  • the composition contains benzoic acid and/or its hydroxy derivatives such as 2-hydroxy-benzoic acid (salicylic acid) or 4-hydroxy-benzoic acid in 1 to 50 % by weight related to the weight of the volatile active ingredient - CD inclusion complex.
  • the volatile active ingredient - CD inclusion complex contained in our composition can be as follows: camphor CD and/or menthol CD and/or eucalyptus oil CD and/or chamomile oil CD and/or peppermint oil CD and/or pine oil CD and/or beta-ionon CD and/or citral CD and/or lemon oil CD inclusion complex.
  • the beta-CD-inclusion complexes are most preferred.
  • Our present invention further relates to a process to the preparation of an inhalant pharmaceutical composition or air scenting composition containing the active volatile ingredient in the form of CD-inclusion complex by admixing to the volatile active ingredient CD-inclusion complex the competitor host molecule by method known per se.
  • competitor host molecules benzoic acid and/or its hydroxy derivatives such as 2-hydroxy-benzoic acid (salicylic acid) or 4-hydroxy-benzoic acid can be used in 1 to 50 % by weight related to the volatile active ingredient-CD inclusion complex.
  • camphor-CD and/or menthol-CD and/or eucalyptus-CD- and/or chamomile oil-CD and/or peppermint oil-CD and/or pine oil CD and/or beta-ionon-CD and/or citral-CD and/or lemon oil-CD inclusion complex can be used.
  • the use of beta-CD-inclusion complexes is most preferred.
  • the volatile active ingredient CD-inclusion complex and the competitor host molecule are admixed with each other in solid state, whereafter the conventionally used filler, diluents and formulating excipients are used to prepare powder or tablet forms of the pharmaceutical and cosmetical compositions.
  • Example 1 Further details of the present invention are further illustrated by the following Examples without limiting the scope of the invention to the Examples.
  • Example 1
  • composition of the volatile active ingredient corresponds to the composition of Diapulmon oily injectable active ingredient.
  • the mixture is homogenized for 30 minutes in a ball mill.
  • the thus obtained blend is filled to 3 or 5 g satchets and an inhalant powder composition is obtained.
  • the blend is granulated with the conventionally used additives of an effervescent tablet (sodium hydrogen carbonate + citric acid or tartaric acid and a tablet is obtained of 3 or 6 gramm which can be made effervescent in cold or hot water.
  • an effervescent tablet sodium hydrogen carbonate + citric acid or tartaric acid
  • composition An inhalation powder form containing volatile oils acting on the respiratory system in a cyclodextrin complex.
  • Example 1 The above mixture can be filled to satchets as given in Example 1 or tablets can be prepared according to Example 1.
  • composition An inhalation powder form containing volatile oil acting on the respiratory system.
  • Composition eucalyptus oil- ⁇ -cyclodextrin complex (10-11 % volatile material) 89 kg peppermint oil- ⁇ -cyclodextrin complex (10-11 % ethereal oil content) 78.5 kg chamomile- ⁇ -cyclodextrin complex
  • the product After homogenizing the above powder mixture the product can be used in a powder form or tablet form as given in Example 1.
  • a betaionon-beta-cyclodextrin compolex containing 10-12 % active ingredient is homogenized with tablet additives as given in Example 1 and with 6 .6 % by weight of benzoic acid related to the weight of the inclusion complex.
  • the mixture is granulated and finished in the form of effervescent tablets of 6 gramm.
  • composition citral or lemon oil- ⁇ -CD-complex

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Nanotechnology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Pulmonology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Otolaryngology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Composition pharmaceutique à inhaler ou composition parfumant l'air, comprenant un complexe d'inclusion principes actifs volatils-cyclodextrine et une molécule hôte concurrente ainsi que des excipients utilisés habituellement.
PCT/HU1988/000025 1987-04-23 1988-04-22 Composition pharmaceutique Ceased WO1988008304A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU871747A HU201685B (en) 1987-04-23 1987-04-23 For producing pharmaceutical compositions for inhalation and compositions for scenting air containing volatile active component in cyclodextrine inclusion, and air-scenting composition
HU1747/87 1987-04-23

Publications (1)

Publication Number Publication Date
WO1988008304A1 true WO1988008304A1 (fr) 1988-11-03

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ID=10955988

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU1988/000025 Ceased WO1988008304A1 (fr) 1987-04-23 1988-04-22 Composition pharmaceutique

Country Status (2)

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HU (1) HU201685B (fr)
WO (1) WO1988008304A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0393973A1 (fr) * 1989-04-18 1990-10-24 Lemon Grass Food Co., Ltd. Agent antitumoral contre le cancer du poumon
EP0400637A3 (fr) * 1989-06-02 1991-07-03 Fujisawa Pharmaceutical Co., Ltd. Préparation contenant la substance FR115224 pour une administration parentérale
FR2666227A1 (fr) * 1990-09-05 1992-03-06 Darcy Laboratoires Composition therapeutique notamment pour le traitement des affections de la cavite buccale.
WO1993017663A1 (fr) * 1992-03-10 1993-09-16 Fisons Plc Compositions pharmaceutiques d'inhalation
US5653971A (en) * 1995-06-30 1997-08-05 The Gillette Company Shaving aid composite with an inclusion complex of a skin-soothing agent and a cyclodextrin
WO2003037307A1 (fr) * 2001-10-30 2003-05-08 Alexza Molecular Delivery Corporation Volatilisation d'un medicament a partir d'un compose d'inclusion
US7090830B2 (en) 2001-05-24 2006-08-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US7458374B2 (en) 2002-05-13 2008-12-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
US7537009B2 (en) 2001-06-05 2009-05-26 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
US7540286B2 (en) 2004-06-03 2009-06-02 Alexza Pharmaceuticals, Inc. Multiple dose condensation aerosol devices and methods of forming condensation aerosols
EP1330266B2 (fr) † 2000-10-19 2009-08-26 Separex Procede de fabrication de tres fines particules constituees d'un principe insere dans une molecule hote
US7581540B2 (en) 2004-08-12 2009-09-01 Alexza Pharmaceuticals, Inc. Aerosol drug delivery device incorporating percussively activated heat packages
US7585493B2 (en) 2001-05-24 2009-09-08 Alexza Pharmaceuticals, Inc. Thin-film drug delivery article and method of use
WO2014146069A1 (fr) * 2013-03-15 2014-09-18 Altria Client Services Inc. Inhibition d'effets sur le système nerveux central du tabagisme et d'effets sensoriels du tabagisme
US8991387B2 (en) 2003-05-21 2015-03-31 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US9211382B2 (en) 2001-05-24 2015-12-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US11642473B2 (en) 2007-03-09 2023-05-09 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US12214119B2 (en) 2018-02-02 2025-02-04 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB679573A (en) * 1950-01-11 1952-09-17 Mentholatum Company Ltd Improvements in or relating to medicative inhalants
GB1450809A (en) * 1972-11-11 1976-09-29 Teijin Ltd Stupe composition
GB1515630A (en) * 1975-11-24 1978-06-28 Johnson & Son Inc S C Air freshener gels based on amylose
EP0013688A1 (fr) * 1978-12-15 1980-08-06 Kyoshin Co., Ltd. Produit parfumant à base de résines synthétiques et procédé pour la production dudit produit
US4247535A (en) * 1979-11-05 1981-01-27 American Cyanamid Company Modified cyclodextrin sulfate salts as complement inhibitors
EP0056995A1 (fr) * 1981-01-23 1982-08-04 The Wellcome Foundation Limited Complexe chimique
GB2173400A (en) * 1985-04-01 1986-10-15 Chinoin Gyogyszer Es Vegyeszet Dusting powders
EP0233615A2 (fr) * 1986-02-17 1987-08-26 Senju Pharmaceutical Co., Ltd. Préparation aqueuse et son procédé de fabrication

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB679573A (en) * 1950-01-11 1952-09-17 Mentholatum Company Ltd Improvements in or relating to medicative inhalants
GB1450809A (en) * 1972-11-11 1976-09-29 Teijin Ltd Stupe composition
GB1515630A (en) * 1975-11-24 1978-06-28 Johnson & Son Inc S C Air freshener gels based on amylose
EP0013688A1 (fr) * 1978-12-15 1980-08-06 Kyoshin Co., Ltd. Produit parfumant à base de résines synthétiques et procédé pour la production dudit produit
US4247535A (en) * 1979-11-05 1981-01-27 American Cyanamid Company Modified cyclodextrin sulfate salts as complement inhibitors
EP0056995A1 (fr) * 1981-01-23 1982-08-04 The Wellcome Foundation Limited Complexe chimique
GB2173400A (en) * 1985-04-01 1986-10-15 Chinoin Gyogyszer Es Vegyeszet Dusting powders
EP0233615A2 (fr) * 1986-02-17 1987-08-26 Senju Pharmaceutical Co., Ltd. Préparation aqueuse et son procédé de fabrication

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF PHARMACEUTICAL SCIENCES, Vol. 52, published 1963, J. COHEN, J.L. LACH, "Interaction of Pharmaceuticals with Schardinger Dextrins I", see pages 132-136. *

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0393973A1 (fr) * 1989-04-18 1990-10-24 Lemon Grass Food Co., Ltd. Agent antitumoral contre le cancer du poumon
EP0400637A3 (fr) * 1989-06-02 1991-07-03 Fujisawa Pharmaceutical Co., Ltd. Préparation contenant la substance FR115224 pour une administration parentérale
US5093127A (en) * 1989-06-02 1992-03-03 Fujisawa Pharmaceutical Co., Ltd. Preparation of fr115224 substrate for parenteral administration
FR2666227A1 (fr) * 1990-09-05 1992-03-06 Darcy Laboratoires Composition therapeutique notamment pour le traitement des affections de la cavite buccale.
WO1993017663A1 (fr) * 1992-03-10 1993-09-16 Fisons Plc Compositions pharmaceutiques d'inhalation
US5607662A (en) * 1992-03-10 1997-03-04 Fisons, Plc Pharmaceutical inhalation compositions
US5653971A (en) * 1995-06-30 1997-08-05 The Gillette Company Shaving aid composite with an inclusion complex of a skin-soothing agent and a cyclodextrin
EP1330266B2 (fr) † 2000-10-19 2009-08-26 Separex Procede de fabrication de tres fines particules constituees d'un principe insere dans une molecule hote
US9440034B2 (en) 2001-05-24 2016-09-13 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US7585493B2 (en) 2001-05-24 2009-09-08 Alexza Pharmaceuticals, Inc. Thin-film drug delivery article and method of use
US10350157B2 (en) 2001-05-24 2019-07-16 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US9211382B2 (en) 2001-05-24 2015-12-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US7090830B2 (en) 2001-05-24 2006-08-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US9308208B2 (en) 2001-06-05 2016-04-12 Alexza Pharmaceuticals, Inc. Aerosol generating method and device
US11065400B2 (en) 2001-06-05 2021-07-20 Alexza Pharmaceuticals, Inc. Aerosol forming device for use in inhalation therapy
US7537009B2 (en) 2001-06-05 2009-05-26 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
US8955512B2 (en) 2001-06-05 2015-02-17 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
US9687487B2 (en) 2001-06-05 2017-06-27 Alexza Pharmaceuticals, Inc. Aerosol forming device for use in inhalation therapy
US9439907B2 (en) 2001-06-05 2016-09-13 Alexza Pharmaceutical, Inc. Method of forming an aerosol for inhalation delivery
WO2003037307A1 (fr) * 2001-10-30 2003-05-08 Alexza Molecular Delivery Corporation Volatilisation d'un medicament a partir d'un compose d'inclusion
US7458374B2 (en) 2002-05-13 2008-12-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
US9370629B2 (en) 2003-05-21 2016-06-21 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US8991387B2 (en) 2003-05-21 2015-03-31 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US7540286B2 (en) 2004-06-03 2009-06-02 Alexza Pharmaceuticals, Inc. Multiple dose condensation aerosol devices and methods of forming condensation aerosols
US7581540B2 (en) 2004-08-12 2009-09-01 Alexza Pharmaceuticals, Inc. Aerosol drug delivery device incorporating percussively activated heat packages
US11642473B2 (en) 2007-03-09 2023-05-09 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US12138383B2 (en) 2007-03-09 2024-11-12 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US10335378B2 (en) 2013-03-15 2019-07-02 Altria Client Services Llc Inhibition of central nervous system effects from smoking and sensory effects from smoking
WO2014146069A1 (fr) * 2013-03-15 2014-09-18 Altria Client Services Inc. Inhibition d'effets sur le système nerveux central du tabagisme et d'effets sensoriels du tabagisme
US12214119B2 (en) 2018-02-02 2025-02-04 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device
US12214118B2 (en) 2018-02-02 2025-02-04 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device

Also Published As

Publication number Publication date
HU201685B (en) 1990-12-28
HUT46343A (en) 1988-10-28

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