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WO1998018827A1 - Complexes d'insertion de beta-2-adrenergiques absorbes par les muqueuses buccales - Google Patents

Complexes d'insertion de beta-2-adrenergiques absorbes par les muqueuses buccales Download PDF

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Publication number
WO1998018827A1
WO1998018827A1 PCT/GB1997/002947 GB9702947W WO9818827A1 WO 1998018827 A1 WO1998018827 A1 WO 1998018827A1 GB 9702947 W GB9702947 W GB 9702947W WO 9818827 A1 WO9818827 A1 WO 9818827A1
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WO
WIPO (PCT)
Prior art keywords
cyclodextrin
beta
salbutamol
pharmaceutical composition
gamma
Prior art date
Application number
PCT/GB1997/002947
Other languages
English (en)
Inventor
Lawrence John Penkler
Luéta-Ann DE KOCK
Original Assignee
Farmarc Nederland B.V.
Dyer, Alison, Margaret
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 Farmarc Nederland B.V., Dyer, Alison, Margaret filed Critical Farmarc Nederland B.V.
Priority to JP52018398A priority Critical patent/JP2001503406A/ja
Priority to AU47179/97A priority patent/AU4717997A/en
Priority to EP97909509A priority patent/EP0934341A1/fr
Publication of WO1998018827A1 publication Critical patent/WO1998018827A1/fr

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    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • 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
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4704—2-Quinolinones, e.g. carbostyril
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • 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
    • A61K47/50—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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

  • therapy is usually administered by inhalation to deliver the drugs to the desired site of action.
  • the doses are approximately 5% of the dose required with oral administration.
  • the oral route may also be necessary. Difficulties associated with the use of inhalers may be overcome by the use of spacing devices to act as reservoirs for the drug to make it easier for the patient (especially a child) to inhale each dose.
  • COPD chronic obstructive pulmonary disease
  • bronchitis a range of disorders of progressive airflow limitation
  • emphysema a range of disorders of progressive airflow limitation
  • Drug treatment includes symptomatic and palliative therapy using bronchodilating agents.
  • First-line drug therapy for the treatment of COPD consists of bronchodilating agents to alleviate bronchospasm and any reversible component of airway obstruction.
  • the drug of first choice is a ⁇ 2 -selective agonist such as salbutamol or terbutaline given by inhalation.
  • Salbutamol is rapidly absorbed from the gastro-intestinal tract. It is subject to first-pass metabolism in the liver and possibly the gut wall. The main metabolite is an inactive sulphate conjugate. It is rapidly excreted in the urine as metabolites and unchanged drug; there is some excretion in the faeces. It has been suggested that the majority of an inhaled dose is swallowed and absorbed from the gut (see Goodman & Gilman's The Pharmacological Basis of Therapeutics, Eighth Edition, Volume 1, Chap. 10 p204). The plasma half-life of salbutamol has been estimated to range from about 2 to as much as 7 hours.
  • Cyclodextrin inclusion complexes may be prepared on the basis of liquid state, solid state or semi-solid state reactions between the components (J. Szejtli, Cyclodextrin Technology, Kluwer Academic Press). The first is accomplished by dissolving the cyclodextrin and guest in a suitable solvent or mixture of solvents and subsequently isolating the solid state complex by crystallisation, evaporation, spray drying or freeze drying. In the solid state method, the two components may be screened to uniform particle size and thoroughly mixed whereafter they are ground in a high energy mill with optional heating, screened and homogenized.
  • the downfield shifts of the aromatic protons were greater than those of the aliphatic protons, suggesting that the aromatic ring of salbutamol interacts more strongly with the beta-cyclodextrin.
  • the interior protons of the cyclodextrin molecule were shielded as a result of the anisotropy of the guest aromatic moiety.
  • the highest shifts of beta-cyclodextrin protons occurred for a molar ratio of 1:1 (salbutamol: beta-cyclodextrin) indicating the probable stoichiometry of the complex.
  • the selective ⁇ 2 -adrenergic agonist is preferably selected from the group consisting of salbutamol, metaproterenol, terbutaline, pirbuterol, formoterol, salmeterol, fenbuterol, orciprenaline, isoprenaline, hexoprenaline, reproterol, rimiterol, fenoterol, procaterol, mabuterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, coterol, eformoterol, tretoquinol and tulobuterol and the pharmaceutically acceptable salts thereof, such as for example the sulphate, methanesulfonate, hydrochloride, dihydrochloride, acetate or monoacetate salts.
  • an inclusion complex of salbutamol base and 2-hydroxypropyl-beta-cyclodextrin which has substantially the X-ray powder diffraction pattern of Figure 5 of the accompanying drawings or the Fourier Transform Infra-red spectrum of Figure 6 of the accompanying drawings.
  • Figure 1 shows an X-ray powder diffraction pattern of a 1:1 kneaded complex of salbutamol base and randomly methylated- ⁇ - cyclodextrin obtained from Example 1 ;
  • the crux of the invention is a pharmaceutical composition for oral mucosal delivery which comprises as an active ingredient an inclusion complex of (a) a selective ⁇ 2 -adrenergic agonist or a pharmaceutically acceptable salt thereof and (b) an unsubstituted beta- or gamma-cyclodextrin, together with a pharmaceutically acceptable carrier for oral mucosal delivery.
  • cyclodextrins such as 2-hydroxypropylated or methylated or sulphoalkylated derivatives of beta-cyclodextrin are the preferred cyclodextrins of the invention.
  • Gamma-cyclodextrin or 2- hydroxypropylated or methylated or sulphoalkylated derivatives of gamma- cyclodextrin may also be used in the same manner as the corresponding preferred beta-cyclodextrin derivatives.
  • the degree of substitution of the cyclodextrin derivatives may vary between 1 to 20 substituents per cyclodextrin molecule but more preferably between 3 to 15 substituents per cyclodextrin molecule.
  • a selective ⁇ 2 -adrenergic agonist through the mucosal tissue of the mouth avoids the problems associated with administration of these drugs by inhalation (i.e. only approximately 10% of the drug entering the lungs, difficulty with inhalation techniques resulting in therapeutic blood levels not being attained) and by oral administration (i.e. slower onset of action and extensive metabolism in the gastrointestinal tract).
  • Penetration enhancers may be used to promote the passage of the drug active across the mucosal membranes.
  • Typical permeation enhancers include fatty acids and their salts such as sodium caprate, sodium caprylate and sodium oleate, and bile salts such as sodium glycodeoxycholate, sodium glycocholate, sodium cholate and sodium taurodeoxycholate.
  • Other penetration enhancers may include tensides or non-ionic surfactants such as polyethylene glycol 660 hydroxystearate or polyoxyethylene lauryl ethers, fusidates such as sodium taurodihydrofusidate, azone and chitosan.
  • Example 1 Salbutamol base (2,00g) and methyl-beta-cyclodextrin (l l,57g) are mixed together in a mortar. Purified, deionized water (6ml) is added in aliquots with mixing to form a homogenous paste. The paste is dried in an oven at 40°C and atmospheric pressure. The dried complex is crushed with a pestle and passed through a 250 ⁇ m mesh sieve. At all processing stages, the compound is protected from light. The complex contains 14,1% mass/mass salbutamol base as determined by HPLC.
  • Salbutamol base (2,00g) and 2-hydroxypropyl-beta-cyclodextrin (12,6g) are mixed together in a mortar.
  • Purified, deionized water (10ml) is added in aliquots with mixing to form a homogenous paste. Continue grinding for 0,5 hours.
  • the paste is dried in an oven at 40°C and 5 millibar.
  • the dried complex is crushed with a pestle and passed through a 250 ⁇ m mesh sieve. At all processing stages, the compound is protected from light.
  • the complex contains 13,24% mass/mass salbutamol base as determined by HPLC.

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  • Health & Medical Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
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  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Emergency Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
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  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Materials Engineering (AREA)
  • Polymers & Plastics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

L'invention concerne une composition pharmaceutique, qui est destinée à être absorbée par les muqueuses buccales et qui comprend les éléments suivants: un ingrédient actif; un complexe d'insertion constitué (a) d'un antagoniste β2-adrénergique sélectionné ou l'un de ses sels pharmaceutiquement acceptables, tels que le salbutamol, et (b) d'une bêta- ou gamma-cyclodextrine substituée ou non substituée; et un support pharmaceutiquement acceptable, qui est destiné à permettre l'absorption par les muqueuses buccales. Ladite composition pharmaceutiquement acceptable est utilisée dans le traitement de maladies obstructives réversibles des voies respiratoires, telles que l'asthme.
PCT/GB1997/002947 1996-10-28 1997-10-27 Complexes d'insertion de beta-2-adrenergiques absorbes par les muqueuses buccales WO1998018827A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP52018398A JP2001503406A (ja) 1996-10-28 1997-10-27 医薬組成物
AU47179/97A AU4717997A (en) 1996-10-28 1997-10-27 Inclusion complexes of beta-2-andrenergics for oral mucosal delivery
EP97909509A EP0934341A1 (fr) 1996-10-28 1997-10-27 Complexes d'insertion de beta-2-adrenergiques absorbes par les muqueuses buccales

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ZA969049 1996-10-28
ZA96/9049 1996-10-28

Publications (1)

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WO1998018827A1 true WO1998018827A1 (fr) 1998-05-07

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EP (1) EP0934341A1 (fr)
JP (1) JP2001503406A (fr)
AU (1) AU4717997A (fr)
WO (1) WO1998018827A1 (fr)

Cited By (15)

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JP2003503493A (ja) * 1999-07-01 2003-01-28 イタルファルマコ ソシエタ ペル アチオニ パロキセチンとシクロデキストリンまたはシクロデキストリン誘導体との錯体
GB2403655A (en) * 2003-07-11 2005-01-12 Cipla Ltd Combined pharmaceutical product comprising a beta-2 adrenoreceptor agonist & an antihistamine for treatment of respiratory diseases such as asthma
EP1729724A4 (fr) * 2003-12-31 2008-07-23 Cydex Inc Formulation inhalable contenant de l'ether sulfoalkyle g-cyclodextrine et un corticosteroide
WO2012176143A1 (fr) * 2011-06-22 2012-12-27 Glenmark Pharmaceuticals Sa Composition pharmaceutique comprenant un antagoniste de trpa1 et un agoniste de bêta-2
US8449909B2 (en) 2004-06-12 2013-05-28 Collegium Pharmaceutical, Inc. Abuse-deterrent drug formulations
US8557291B2 (en) 2002-07-05 2013-10-15 Collegium Pharmaceutical, Inc. Abuse-deterrent pharmaceutical compositions of opioids and other drugs
US8795634B2 (en) 2008-09-12 2014-08-05 Critical Pharmaceuticals Limited Absorption of therapeutic agents across mucosal membranes or the skin
US8840928B2 (en) 2002-07-05 2014-09-23 Collegium Pharmaceutical, Inc. Tamper-resistant pharmaceutical compositions of opioids and other drugs
US9044398B2 (en) 2002-07-05 2015-06-02 Collegium Pharmaceutical, Inc. Abuse-deterrent pharmaceutical compositions of opiods and other drugs
US9352035B2 (en) 2002-09-06 2016-05-31 Alexion Pharmaceuticals, Inc. High concentration antibody formulations
US9737530B1 (en) 2016-06-23 2017-08-22 Collegium Pharmaceutical, Inc. Process of making stable abuse-deterrent oral formulations
US9827324B2 (en) 2003-12-31 2017-11-28 Cydex Pharmaceuticals, Inc. Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid
US10004729B2 (en) 2002-07-05 2018-06-26 Collegium Pharmaceutical, Inc. Tamper-resistant pharmaceutical compositions of opioids and other drugs
US10125191B2 (en) 2005-05-11 2018-11-13 Alexion Pharmaceutiacls, Inc. Compositions comprising an anti-C5 antibody
US10668060B2 (en) 2009-12-10 2020-06-02 Collegium Pharmaceutical, Inc. Tamper-resistant pharmaceutical compositions of opioids and other drugs

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Publication number Priority date Publication date Assignee Title
WO2004022096A1 (fr) * 2002-09-06 2004-03-18 Alexion Pharmaceuticals, Inc. Procede de traitement de l'asthme mettant en oeuvre des anticorps en complement du constituant c5
EP1655034A1 (fr) * 2004-10-10 2006-05-10 Université de Liège Utilisation d'un composé de cyclodextrine pour le traitement et la prévention des maladies inflammatoires bronchiques.
JP2013245213A (ja) * 2012-05-29 2013-12-09 Jx Nippon Oil & Energy Corp ビワ葉培養エキス−シクロデキストリン包接物

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US5080903A (en) * 1987-09-02 1992-01-14 Societe Civile Dite: "Medibrevex" Galenical forms of beta-2-mimetics for administration perlingually and sublingually
WO1996001129A1 (fr) * 1994-07-06 1996-01-18 Farmarc Nederland B.V. Complexe d'inclusion de ranitidine

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LEMESLE-LAMACHE: "Study of beta-cyclodextrin and ethylated beta-cyclodextrin salbutamol complexes, in vitro evaluation of sustained release bahaviour of salbutamol", INT. J. PHARM., vol. 141, no. 1,2, 1996, pages 117 - 124, XP002054595 *
MARQUES ET AL.: "Studies of cyclodextrin inclusion complexes. I The salbutamol-cyclodextrin comple as studied by phase solubility and DSC", INT. J. PHARM., vol. 63, 1990, pages 259 - 266, XP002054596 *
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