US3265577A - Method of relieving spasmodic conditions and pharmaceutical composition useful therefor - Google Patents

Method of relieving spasmodic conditions and pharmaceutical composition useful therefor Download PDF

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Publication number
US3265577A
US3265577A US493568A US49356865A US3265577A US 3265577 A US3265577 A US 3265577A US 493568 A US493568 A US 493568A US 49356865 A US49356865 A US 49356865A US 3265577 A US3265577 A US 3265577A
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US
United States
Prior art keywords
mebeverine
human
relieving
pharmaceutical composition
colon
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.)
Expired - Lifetime
Application number
US493568A
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English (en)
Inventor
Kralt Teunis
Moed Hendrik Durk
Asma Willem Johannes
Lindner Adolf
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US Philips Corp
North American Philips Co Inc
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US Philips Corp
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Publication of US3265577A publication Critical patent/US3265577A/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • A61K31/33—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
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4

Definitions

  • the instant invention relates to a new and novel method of relieving spasmodic conditions in the human being and to a novel pharmaceutical composition useful there- 01.
  • a principal object therefore, is to provide a method of relieving spastic conditions of the colon in human beings while inducing little or no side-effects.
  • mebeverine is particularly useful for the treatment of primary (essential) irritable colon syndrome i.e. spastic colitis and secondary irritable colon syndrome.
  • primary (essential) irritable colon syndrome i.e. spastic colitis and secondary irritable colon syndrome.
  • secondary colon irritable syndromes that may be treated are those due to gall bladder affections such as lbilliary dyskinesia and gall stones, diverticulosis, diverticulotis coli enteritis regionalis, enteritis, dysentery, ulcus ventriculi, duodenal ulcer, and diseases of the urinary tract such as renal calculi.
  • an analgesic drug such as dipyrone Novalgin Patented August 9, 1966 (e) (sodium 1 pheny1-2,3-dimethyl-5-pyrazolone 4- methylaminomethaneculfionate), phenyl butazone or meperedine hydrochloride
  • dipyrone Novalgin Patented August 9, 1966 (e) sodium 1 pheny1-2,3-dimethyl-5-pyrazolone 4- methylaminomethaneculfionate
  • phenyl butazone or meperedine hydrochloride Demeral hydrochloride should be included withthe mebeverine.
  • a sedative such as phenobarbital or a tranquilizer such as fluphenazine hydrochloride Prolixin, lprochloroperazine Oompazine, maprobamate and IChlOIOdIQZGPOXidG hydrochloride Librium may also be included.
  • the daily dosage of mebeverine is for an adult 200-400 mg., for a child (1-12 years) 50-250 mg. and for an infant up to 12 months less than 50 mg. Equivalent amounts of its non-toxic acid addition salts may be used.
  • the mebeverine may be administered orally in tablet or liquid form, by suppositories or parenterally by intramuscular injection.
  • the tablets and suppositories each contain from 20 to mg. of mebeverine.
  • the ampules for injection contain from 10 to 50 mg. of mebeverine per
  • the syrup contains from 4 to 20 mg. of mebeverine per cc.
  • the mebeverine may be prepared according to the method disclosed in our pending United States patent application Serial No. 280,784, filed May 16, 1963, of which the instant case is a continuation-in-part.
  • Suitable pharmaceutical formulations of mebeverine are as follows.
  • the mebeverine HCl tert. calcium phosphate, sugar and starch are sieved (40 mesh), moistened with ethanol/water (SO/50).
  • the mass is granulated, dried 5 hours at 50 C. and mixed with the tale and magnesiumstearate. From this mixture tablets are fiormed and coated at 40 C. with the molten massupol.
  • Each ampule contains 100 mg. mebeverine hydrochlo- Mebeverme 50 n sodiumnovaminesufonate 250 5
  • Each p contains 3gof Powdered Sugar 50 mebeverine hydrochloride and 2.5 -g. of Novalgm. Starch (potato) 25
  • Example Gelatin 2 Formaldehyde-caseine 4 tablet (50 mg. of mebeverine hydrochloride in each Talc 33 10 tablet) were administered three times a day to 6 infants Magnesium stearate 33 Of 4-6 Weeks for a period ofthree weeks. All of these Distd. Water, :1 liter/ 100,000 tablets.
  • a method of treating spastic conditions of the colon "T in a human comprising administering to said human a ggg tetrachlonde 1/ IOOOOOO member selected from the group consisting of the base 4' [N ethyl 1" methyl 2" (4' methoxy phen- Dlstd' Water :10 1/ 100900 tablets yl) ethylamino] butyl 3,4 dimethoxy benzoate and 1 ⁇ N l di It of l-fen l-2,3-d'meth lrazo- 1One g a u z acid 1 y Dy istasltgion toxic pharmaceutlcally acceptable acid addit on Ampules 'i' 2.
  • a method of treating spastic conditions of the colon Meheverme 20 in a human comprising orally administering to said husqdlumnovammesufonate 500 man a member selected from the group consisting of the Dlstd- Water: ad 1 base 4' [N ethyl-l"-met-hyl-2"-(4'-methoxy-phenyl)- VL suppository mebeVerine+NOva1gine ethylamino]-butyl-3,4-dimethoxy benzoate and its non- Meb v rj l-lcl 100 toxic pharmaceutically acceptable acid addition salts.
  • a method of treating spastic conditions of the colon Vehicle x 2150 in a human comprising parenterally administering to said xv hi 1 ltml re area from Veretable oils human a member selected from the group consisting of e M eftin g iioint 36-7 0. 40 the base 4'-[N-ethyl-l"-methyl-2"-(4"-methoxy-phenyl)- g fi q g p h ethylamino]-butyl-3,4-dimethoxy benzoate and its non- 1.1;,Z ?f3 toxic pharmaceutically acceptable acid addition salts. Acid value: 0.5 4. .
  • the method of claim 1 wherein the hydrochloride VII. Coated tablets mebeverine+phenobarbitalsalt 18 p y K l; Mgjtabl t 5. The method of claim 1 wherein 200-400 mg. of
  • Mebeverine.HCl 50.0 t e ba e or an equivalent amount of the salt is admin- Phenobarbit-al 10,0 istered daily to a human adult.
  • Polyvinylpyrrolidone 0.5 6- The method of claim 1 wherein -250 mg. of the Formaldehyde-caseine 4,5 base or the equivalent amount of the salt is administered Carboxymethylcellulose MZ 851 4.0 50 daily to a human bemg- Magnesium stearate 1.0 7- The method of claim 1 wherein up to 50 mg. of the Etha l b (d :45 li /1 000,- base or an equivalent amount of the salt is administered 000 tablets. daily to a human infant.
  • a method of treating spastic conditions of the colon b Coatm S 1 1 in a human comprising administering to said human a as Xamp 6 member selected from the group consisting of the base
  • Illustrative examples employing mebeverine are shown 4' [N ethyl 1" methyl 2" (4' methoxy phenin the following table and examples: yl) ethylamino] butyl 3,4 dimethoxy benzoate and TABLE Age in Duration of Undeslrable Case No. years Sex Diagnosis Daily dose treatment Eficct side efiects in days 1R.E 68 m Spastic eolitis 6c0ated tablets- 36 Excellent None. 2B.G.B 13 m Gastric spasms 2coated tablets 11 d0 Do. 3F.A 55 m Gastroduolocated tablets- 26 Good Do.
  • a method of treating spastic conditions of the colon in a human Comprising administering to said human 21 member selected from the group consisting of the base 4 [N ethyl 1" methyl 2" (4" methoxy-phenyl) ethylarnino] butyl 3,4 dimethoxy benzoate and its non-toxic pharmaceutically acceptable acid addition salts together with dipyrone.
  • An antispasmodic composition particularly adapted for treating spastic conditions in colons in humans comprising in an antispasmodically efiected amount, a member selected from the group consisting of the base 4'-[N- ethyl 1" methyl 2" (4"' methoxy-phenyl) ethyl amino]-butyl-3,4-dimethoxy benzoate and the pharmaceuti-cally acceptable acid addition salts thereof and a major amount of a pharmaceutical carrier therefor.
  • An antispasmodic composition particularly adapted for treating spastic conditions of the colon in humans comprising in an antispasmodically elfective amount, 4-
  • An antispasmodic composition particularly adapted for treating spastic conditions of the colon in humans comprising in an antispasmodically effective amount, 4'- [N ethyl 1" methyl 2" (4"' methoxy-phenyhethylamino]-butyl-3,4-dimethoxy benzoate hydrochloride, dipyrone and a major amount of a pharmaceutical carrier therefor.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US493568A 1957-11-23 1965-10-06 Method of relieving spasmodic conditions and pharmaceutical composition useful therefor Expired - Lifetime US3265577A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
NL222701 1957-11-23

Publications (1)

Publication Number Publication Date
US3265577A true US3265577A (en) 1966-08-09

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ID=19751044

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US493568A Expired - Lifetime US3265577A (en) 1957-11-23 1965-10-06 Method of relieving spasmodic conditions and pharmaceutical composition useful therefor

Country Status (7)

Country Link
US (1) US3265577A (forum.php)
CH (3) CH386447A (forum.php)
DK (1) DK104630C (forum.php)
FR (1) FR1219254A (forum.php)
GB (1) GB914783A (forum.php)
NL (1) NL112650C (forum.php)
OA (1) OA00968A (forum.php)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Also Published As

Publication number Publication date
CH386447A (de) 1965-01-15
NL112650C (forum.php)
DK104630C (da) 1966-06-13
OA00968A (fr) 1968-08-07
GB914783A (en) 1963-01-02
FR1219254A (fr) 1960-05-17
CH398629A (de) 1966-03-15
CH415663A (de) 1966-06-30

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