US3472861A - N-substitution products of norscopolamine and quaternary salts thereof - Google Patents

N-substitution products of norscopolamine and quaternary salts thereof Download PDF

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Publication number
US3472861A
US3472861A US611262A US3472861DA US3472861A US 3472861 A US3472861 A US 3472861A US 611262 A US611262 A US 611262A US 3472861D A US3472861D A US 3472861DA US 3472861 A US3472861 A US 3472861A
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norscopolamine
theory
prepared
yield
white crystals
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Karl Zeile
Rolf Banholzer
Gerhard Walther
Werner Schulz
Helmut Wick
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CH Boehringer Sohn AG and Co KG
Boehringer Ingelheim GmbH
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CH Boehringer Sohn AG and Co KG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
    • C07D451/06—Oxygen atoms
    • C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine

Definitions

  • This invention relates to novel N-substituted derivatives of norscopolamine and quaternary ammonium salts thereof, as well as to a process of preparing these compounds.
  • the present invention relates to (1) Novel racemic or optically active norscopolamine derivatives of the formula wherein R is straight or branched acyclic hydrocarbyl of 2 to 16 carbon atoms, monocyclic or bicyclic aryl, halo-substituted monocyclic or bicyclic aryl, alkoxy, alkoxycarbonyl, aliphatic or aromatic acyl of 1 to 10 carbon atoms, aliphatic or aromatic acyloxy of 1 to 10 carbon atoms, monoalkylamino of 1 to carbon atoms, dialkylamino of 2 to 20 carbon atoms, aralkylamino, hydroxy-substituted straight or branched alkyl of 1 to 16 carbon atoms, amino-substituted straight or branched alkyl of 1 to 16 carbon atoms, theophyllinyl-substituted straight or branched alkyl of 1 to 16 carbon atoms, cyano-substituted
  • R is hydrogen or aliphatic, aromatic or araliphatic acyl of 2 to 16 carbon atoms
  • X is the anion of an acid, such as a hydrohalic acid or an aliphatic or aromatic sulfonic acid, and
  • R is acyclic hydrocarbyl of 1 to 16 carbon atoms.
  • the norscopolamine derivatives of the Formula I above may be prepared by reacting norscopolamine or an O- acyl derivative thereof, that is, a compound of the formula wherein R has the same meanings as in Formula I, with a molar equivalent of a compound of the formula RX (III) 'ice wherein R has the same meanings as in Formula I, and X has the same meanings as in Formula la.
  • the reaction between compounds 11 and III is carried out under conditions which are customarily employed for reactions of this kind, that is, in the presence of an inert organic solvent and of an acid-acceptor, and at a temperature between the solidification point and boiling point of the reaction mixture.
  • suitable inert organic solvents are ether, lower alkanols, benzene, toluene, carbon tetrachloride and preferably acetonitrile.
  • Suitable acid-acceptors are inorganic bases and tertiary organic bases, such as sodium carbonate and trimethylarnine.
  • a separate acid-acceptor is not obligatory; instead, a portion of the norscopolamine base, i.e. compound II, may simultaneously serve as the acid-acceptor.
  • a reaction temperature of 160 C. is advantageously used.
  • this reaction product may subsequently be transformed into the corresponding compound of the Formula I wherein R is aliphatic, aromatic or araliphatic acyl by reacting said reaction product with a customary acylating agent.
  • This acylation reaction may also be carried out in the presence of an inert organic solvent of the type referred to above.
  • optically active compound of the Formula I is generally prepared from the corresponding optically active starting compound of the Formula II; however, it may also be obtained by customary separation of the racemate into its optically active components with the aid of optically active auxiliary acids, such as dibenzoyl- D-tartaric acid or d-3-bromocamphor 8-sulfonic acid.
  • optically active auxiliary acids such as dibenzoyl- D-tartaric acid or d-3-bromocamphor 8-sulfonic acid.
  • a tertiary norscopolamine derivative of the Formula I which may, if desired, be transformed pursuant to customary methods into a nontoxic, pharmacologically acceptable acid addition salt thereof; this transformation may, for example, be effected by acidifying a solution of the free tertiary base with the desired acid, or by double decomposition.
  • acids which will form nontoxic, pharmacologically acceptable acid addition salts with a norscopolamine compound of the Formula I include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, lactic acid, tartaric acid, succinic acid, maleic acid, 8- chlorotheophylline and the like.
  • the double decomposition method it is advantageous to select as a reaction partner for the norscopolamine derivative addition salt a salt which forms with the anion to be replaced a difficultly soluble and therefore easily separable salt.
  • a hydrochloride addition salt is to be transformed into another acid addition salt, it is advantageous to use as a double decomposition reaction partner for the hydrochloride the silver salt of the anion to be introduced.
  • a tertiary norscopolamine derivative of the Formula I may be transformed into a corresponding quaternary N-substituted norscopolammonium salt of the Formula Ia above by reacting the tertiary compound with an alkylating agent of the formula R2X V) wherein R and X have the same meanings as in Formula Ia.
  • the quaternization reaction is carried out under the same conditions as the reaction between compounds 11 and III, except that it is advantageous to use room temperature or an only slightly elevated reaction temperature, such as from 30 to 40 C.
  • the corresponding optically active tertiary compound of the Formula I must be used as the starting material; similarly, a racemic quaternary salt is prepared from the corresponding racemic tertiary compound.
  • this hydrogen atom may subsequently be replaced by an aliphatic, aromatic or araliphatic acyl radical of 2 to 16 carbon atoms in the same manner as described above in connection with the subsequent acylation of a tertiary compound of the Formula I wherein R is hydrogen.
  • the anion X- in a quaternary compound of the Formula Ia obtained by any of the above methods may, if desired, be exchanged for another anion by customary procedures, such as by double decomposition; the double decomposition reaction is carried out in the same manner and under the same conditions as the double decomposition reaction described above in connection with the conversion of an acid addition salt of a teritary compound I into another acid addition salt.
  • EXAMPLE 1 Preparation of -N-ethyl-norscopolamine and its hydrochloride 14.5 gm. (0.05 mol) of ()-norscopolamine and 5.4 gm. (0.05 mol) of ethyl bromide were dissolved in 30 cc. of acetonitrile, 5.3 gm. (0.05 mol) of anhydrous sodium carbonate were suspended in the solution, and the suspension was heated at the boiling point for ten hours. After a boiling time of 2.5 and 5 hours, respectively, the supply of ethyl bromide and sodium carbonate in the reaction mixture was replenished by adding each time 5.4 gm. (0.05 mol) of ethyl bromide and 5.3 gm.
  • EXAMPLE 14 Using a procedure analogous to that described in Example 11, )-N-n-heptyl-norscopolamine methobromide, white crystals (from methanol/ether), M.P. 179- 180 C. (decomposition), was prepared from n-heptylnorscopolamine and methyl bromide. The yield was 7.9 gm. (87.7% of theory).
  • EXAMPLE 18 Using a procedure analogous to that described in Example 11, ()-N-n-undecyl-norscopolamine methobromide, white crystals (from methanol/ether), M.P. 176-177 C. (decomposition), was prepared from N-n-undecyl-norscopolamine and methyl bromide. The yield was 6.8 gm. (93.4% of theory).
  • EXAMPLE 29 Using a procedure analogous to that described in Example l, (-)-N-n-hexadecyl-norscopolamine hydrochloride, white crystals (from acetonitrile), M.P. 151-152 C. was prepared from ()-norscopolamine and nhexadecyl bromide. The total reaction time was 41 hours, and the supply of hexadecyl bromide and sodium carbonate was replenished after 5, 8 and 31 hours. The yield was 15.7 gm. (57.1% of theory).
  • EXAMPLE 32 Using a procedure analogous to that described in Example 31, ()-N-p-chlorobenzyl-norscopolamine, white crystals (from cyclohexane), M.P. 75-76 C., was prepared from ()-norsc0polamine and p-chlorobenzyl chloride. The total reaction time was 12 hours, and 0.025 mol of p-chlorobenzyl chloride and 0.025 mol of sodium carbonate were added after 2.5 hours to replenish the supply. The yield was 18.0 gm. (86.9% of theory).
  • EXAMPLE 34 Using a procedure analogous to that described in Example 1, ()-N-(N',N'-dibenzyl-aminoethyl)-norscopolamine dihydrochloride, white crystals (from ethanol/ ether), M.P. 193-194 C. (decomp.), was prepared from (-)-norscopolamine, N,N-dibenzyl-aminoethyl bromide and sodium carbonate. The total reaction time was four days. The yield was 19.8 gm. (67.6% of theory).
  • EXAMPLE 35 Using a procedure analogous to that described in Example 1, -N- 7-ethyl-theophyllinyl) -norscopolamine hydrochloride, white crystals (from methanol/ether), M.P. l66-167 C. (decomp.), was prepared from norscopolamine, 7-ethyl-theophylline bromide and sodium carbonate. The total reaction time was seven days. The yield was 15.5 gm. (58.3% of theory).
  • EXAMPLE 40* Using a procedure analogous to that described in EX- -N-[i-cyanoethyl-norscopolamine, white crystals (firom water), M.P. 106 C., was prepared from ()-norscopolamine, B-bromo-propionitrile and sodium carbonate. The total reaction time was 90 hours, and 0.025 mol of fi-bromopropionitrile and 0.025 mol of so dium carbonate were added after 7, 14, 28, 54 and 61 hours. The yield was 10.1 gm. (59.0% of theory).
  • EXAMPLE 41 2.0 was prepared from N isopropyl-norscpolamine and methyl bromide. The yield was 44.3% of theory.
  • EXAMPLE 46 Using a procedure analogous to that described in Example 11, (-)-N-n-nonyl-norscopolamine methobromide, white crystals (from methanol/ether), M.P. 171 C. (decomp.), was prepared from ()-N-n-nonylnorscopolamine and methyl bromide. The yield was 85.0% of theory.
  • EXAMPLE 47 Using a procedure analogous to that described in EX- ample 11, ()-N-n-hexadecyl-norscopolamine methobromide, white crystals (from acetone), M.P. 174-175 C. (decomp.), was prepared from ()-N-n-hexadecylnorscopolamine and methyl bromide. The yield was 75.8% of theory.
  • EXAMPLE 55 Preparation of -N-n-heptyl-norscopolamine methomethanesulfonate 13.5 gm. (0.035 mol) of (--)-N-n-heptyl-norscopolamine were dissolved in 20 cc. of acetonitrile, 4.4 gm. (0.04 mol) of methyl methanesulfonate were added to the solution, and the mixture was allowed to stand for six days at 60 C. The precipitate formed thereby was collected and recrystallized from a mixture of acetone and ether. 10.2 gm.
  • EXAMPLE 60 In the quaternary salts of the Formula Ia the spasmolytic activity predominates; especially active in this respect are the levorotatory quaternary salts of the Formula Ia wherein R is an acyclic, saturated or unsaturated hydrocarbon, such as ()-N-ethyl-norscopolamine methobromide or (-)-N-allyl-norscopolamine methobromide.
  • compositions in dosage unit form consisting essentially of an inert pharmaceutical carrier and one dosage unit of the active ingredient, such as tablets, coated pills, solutions, suspensions, emulsions, wettable powders, syrups, capsules, wafers suppositories and the like.
  • One dosage unit of the compound according to the present invention is from 0.08 to 5.0 mgm./kg. body weight, preferably from 0.16 to 3.3 mgm./kg. body weight.
  • a dosage unit composition according to the present invention may also comprise one or more other active ingredients, such as analgesics, antiphlogistics, psychotherapeutics, sedatives and tranquilizers.
  • compositions comprising a compound of the invention as an active ingredient.
  • the parts are parts by weight unless otherwise specified.
  • the suppository composition is compounded from the following ingredients:
  • the norscopolamine compound is admixed with the lactose, and the mixture is homogeneously distributed in the molten cocoa butter.
  • the composition is then poured into cooled suppository molds, each holding 1740 mgm. of the composition.
  • Each finished suppository contains 10 mgm. of the active ingredient.
  • n-orscopolamine compound is intimately admixed with about one-half the indicated amount of each of the other ingredients except the soluble starch, and the mixture is moistened with an aqueous solution of the soluble starch.
  • the moist mass is granulated by forcing it through a fine-mesh screen, the granulate is dried and then admixed with the remaining half of the ingredients, and the composition is pressed into 80 mgm.-pill cores, which are subsequently coated with a thin shell of a customary pill-coating composition consisting essentially of titanium dioxide, sugar, gum arabic, polyvinylpyrrolidone and talcum.
  • a customary pill-coating composition consisting essentially of titanium dioxide, sugar, gum arabic, polyvinylpyrrolidone and talcum.
  • Each finished coated pill contain mgm. of the norscopolamine compound.
  • EXAMPLE 64 Enteric-coated pills
  • the pill core composition is compounded from the Compounding procedure.-The pill cores are prepared in a manner analogous to that described in Example 63, except that the composition is pressed into 365 mgm.-pill cores. The latter are then coated with a thin enteric shell with the aid of a solution of 43.0 parts of cellulose acetate phthalate in an organic solvent. The enteric-coated pills are thereafter provided with an additional coating as in Example 63. Each coated pill contains 100 mgm. of the norscopolam'me compound.
  • EXAMPLE 65 Suppositories with additional active ingredient
  • the suppository composition is compounded from the following ingredients:
  • each suppository mold holds 221 mgm. of the composition.
  • Each suppository contains 30 mgm. of
  • EXAMPLE 66 Compounding procedure.-The quaternary norscopol amine compound is dissolved in the demineralized water, and the solution is admixed with a solution of the p-hydroxybenzoic acid esters in the ethanol. 1 cc. of the finished solution (20 drops) contains 0.03 mgm. of the norscopolamine compound.
  • Example 63 The compounding procedure is analogous to that of Example 63, except that mgm.-pill cores are formed.
  • Each coated pill contains 10 mgm. of the quaternary norscopolamine compound and 10 mgm. of the benzo diazepinone compound.
  • any other compounds embraced by Formula I or a nontoxic, pharmacologically acceptable acid addition salt thereof, or any other quaternary salt embraced by Formula Ia may be substituted for the particular norscopolamine compound illustrated in Examples 61 through 67.
  • the amount of active ingredient in these examples may be varied to achieve the dosage unit range set forth above, and the amounts and nature of the inert pharmaceutical carrier ingredients may be varied to meet particular requirements.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
US611262A 1966-01-26 1967-01-24 N-substitution products of norscopolamine and quaternary salts thereof Expired - Lifetime US3472861A (en)

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DE1670048A DE1670048C3 (de) 1966-01-26 1966-01-26 Neue Norscopolaminderivate

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US611262A Expired - Lifetime US3472861A (en) 1966-01-26 1967-01-24 N-substitution products of norscopolamine and quaternary salts thereof
US852877A Expired - Lifetime US3557125A (en) 1966-01-26 1969-08-25 (-)-n-ethyl-o-(benzoyl or p-nitrobenzoyl)-norscopolamine and salts thereof

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US852877A Expired - Lifetime US3557125A (en) 1966-01-26 1969-08-25 (-)-n-ethyl-o-(benzoyl or p-nitrobenzoyl)-norscopolamine and salts thereof

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US (2) US3472861A (fr)
CH (1) CH481922A (fr)
DE (1) DE1670048C3 (fr)
DK (1) DK120756B (fr)
FI (1) FI48189C (fr)
FR (2) FR1558279A (fr)
GB (1) GB1178305A (fr)
IL (1) IL27311A (fr)
IT (1) IT1117193B (fr)
YU (1) YU32683B (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3538102A (en) * 1968-03-12 1970-11-03 Boehringer Sohn Ingelheim Process for the preparation of (-)-norscopolamine
US4016279A (en) * 1971-07-13 1977-04-05 Boehringer Ingelheim Gmbh Spray compositions for inhalation therapy of bronchial disorders
US4060618A (en) * 1975-02-21 1977-11-29 Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler Quaternary xanthinylalkyl nortropine
US4385048A (en) * 1979-02-02 1983-05-24 Boehringer Ingelheim Gmbh Methods for the treatment of nasal hypersecretion
US4558054A (en) * 1983-07-26 1985-12-10 Valeas S.P.A. Spasmolytic endo-8,8-dialkyl-8-azoniabicyclo (3.2.1) octane-6,7-exo-epoxy-3-alkyl-carboxylate salts
US20040244794A1 (en) * 2001-08-09 2004-12-09 Richards David Hugh Inhalation device with a pharmaceutical composition
US20070167468A1 (en) * 2004-08-06 2007-07-19 Sanofi-Aventis Deutschland Gmbh Substituted bicyclic 8-pyrr0lidinoxanthines, methods for their production, pharmaceutical formulations and their use
US20070197563A1 (en) * 2004-08-06 2007-08-23 Sanofi-Aventis Deutschland Gmbh Substituted, bicyclic 8-pyrrolidinoxanthines, and methods for their use as inhibitors of dipeptidyl peptidase
WO2010106988A1 (fr) 2009-03-17 2010-09-23 第一三共株式会社 Dérivé d'amide
EP2682103A2 (fr) 2012-07-05 2014-01-08 Sanovel Ilac Sanayi ve Ticaret A.S. Compositions comprenant un antagoniste du récepteur muscarinique et du sorbitol
EP2682129A2 (fr) 2012-07-05 2014-01-08 Sanovel Ilac Sanayi ve Ticaret A.S. Compositions comprenant un antagoniste du récepteur muscarinique et du glucose anhydre
EP2682100A2 (fr) 2012-07-05 2014-01-08 Sanovel Ilac Sanayi ve Ticaret A.S. Compositions d'inhalation comprenant un antagoniste du récepteur muscarinique
US10111957B2 (en) 2012-07-05 2018-10-30 Arven Ilac Snayi ve Ticaret A.S. Inhalation compositions comprising glucose anhydrous

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5258388A (en) * 1986-03-17 1993-11-02 University Of Florida Anticholinergic compounds, compositions and methods of treatment
IE60645B1 (en) * 1986-03-17 1994-08-10 Univ Florida Anticholinergic compounds, pharmaceutical compositions and method of treatment
US5223528A (en) * 1986-03-17 1993-06-29 University Of Florida Anticholinergic compounds, composititons and methods of treatment
ES2107973B1 (es) * 1996-05-17 1998-07-01 Salvador Rafael Aguilar Procedimiento para la decoracion de productos alimenticios.
ES2671874T3 (es) 2007-10-18 2018-06-11 Rose U, Llc Formulaciones tópicas de glicopirrolato

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2814623A (en) * 1955-12-05 1957-11-26 Upjohn Co Certain esters of n-methyl scopolamine quaternary ammonium salts

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2814623A (en) * 1955-12-05 1957-11-26 Upjohn Co Certain esters of n-methyl scopolamine quaternary ammonium salts

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3538102A (en) * 1968-03-12 1970-11-03 Boehringer Sohn Ingelheim Process for the preparation of (-)-norscopolamine
US4016279A (en) * 1971-07-13 1977-04-05 Boehringer Ingelheim Gmbh Spray compositions for inhalation therapy of bronchial disorders
US4060618A (en) * 1975-02-21 1977-11-29 Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler Quaternary xanthinylalkyl nortropine
US4385048A (en) * 1979-02-02 1983-05-24 Boehringer Ingelheim Gmbh Methods for the treatment of nasal hypersecretion
US4558054A (en) * 1983-07-26 1985-12-10 Valeas S.P.A. Spasmolytic endo-8,8-dialkyl-8-azoniabicyclo (3.2.1) octane-6,7-exo-epoxy-3-alkyl-carboxylate salts
US20040244794A1 (en) * 2001-08-09 2004-12-09 Richards David Hugh Inhalation device with a pharmaceutical composition
US7888343B2 (en) * 2004-08-06 2011-02-15 Sanofi-A Ventis Deutschland GmbH Substituted, bicyclic 8-pyrrolidinoxanthines, and methods for their use as inhibitors of dipeptidyl peptidase
US20070167468A1 (en) * 2004-08-06 2007-07-19 Sanofi-Aventis Deutschland Gmbh Substituted bicyclic 8-pyrr0lidinoxanthines, methods for their production, pharmaceutical formulations and their use
US20070197563A1 (en) * 2004-08-06 2007-08-23 Sanofi-Aventis Deutschland Gmbh Substituted, bicyclic 8-pyrrolidinoxanthines, and methods for their use as inhibitors of dipeptidyl peptidase
US7838528B2 (en) * 2004-08-06 2010-11-23 Sanofi-Aventis Deutschland Gmbh Substituted bicyclic 8-pyrrolidinoxanthines, methods for their production, pharmaceutical formulations and their use
WO2010106988A1 (fr) 2009-03-17 2010-09-23 第一三共株式会社 Dérivé d'amide
US8476253B2 (en) 2009-03-17 2013-07-02 Daiichi Sankyo Company, Limited Amide derivative
EP2682103A2 (fr) 2012-07-05 2014-01-08 Sanovel Ilac Sanayi ve Ticaret A.S. Compositions comprenant un antagoniste du récepteur muscarinique et du sorbitol
EP2682129A2 (fr) 2012-07-05 2014-01-08 Sanovel Ilac Sanayi ve Ticaret A.S. Compositions comprenant un antagoniste du récepteur muscarinique et du glucose anhydre
EP2682100A2 (fr) 2012-07-05 2014-01-08 Sanovel Ilac Sanayi ve Ticaret A.S. Compositions d'inhalation comprenant un antagoniste du récepteur muscarinique
WO2014007769A1 (fr) 2012-07-05 2014-01-09 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Compositions comprenant un antagoniste du récepteur muscarinique et du glucose anhydre
US10105316B2 (en) 2012-07-05 2018-10-23 Arven llac Sanayi Ve Ticaret A.S. Inhalation compositions comprising muscarinic receptor antagonist
US10111957B2 (en) 2012-07-05 2018-10-30 Arven Ilac Snayi ve Ticaret A.S. Inhalation compositions comprising glucose anhydrous

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Publication number Publication date
DE1670048C3 (de) 1980-09-04
YU32683B (en) 1975-04-30
US3557125A (en) 1971-01-19
IT7949430A0 (it) 1979-06-15
FR6937M (fr) 1969-05-12
CH481922A (de) 1969-11-30
IL27311A (en) 1971-02-25
DE1670048A1 (de) 1970-08-13
FI48189C (fi) 1974-07-10
IT1117193B (it) 1986-02-17
FR1558279A (fr) 1969-02-28
YU10467A (en) 1974-10-31
DE1670048B2 (de) 1980-01-10
DK120756B (da) 1971-07-12
GB1178305A (en) 1970-01-21
FI48189B (fr) 1974-04-01

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