US3689674A - Antihyperglycaemic agent - Google Patents

Antihyperglycaemic agent Download PDF

Info

Publication number
US3689674A
US3689674A US118962A US3689674DA US3689674A US 3689674 A US3689674 A US 3689674A US 118962 A US118962 A US 118962A US 3689674D A US3689674D A US 3689674DA US 3689674 A US3689674 A US 3689674A
Authority
US
United States
Prior art keywords
biguanide
phenyl
isopropyl
antihyperglycaemic
tablets
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
US118962A
Other languages
English (en)
Inventor
Hans-Joachim Kabbe
Harald Horstmann
Hans Plumpe
Walter Puls
Siegfried Petersen
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.)
Bayer AG
Original Assignee
Bayer AG
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 Bayer AG filed Critical Bayer AG
Application granted granted Critical
Publication of US3689674A publication Critical patent/US3689674A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
    • C07C279/24—Y being a hetero atom
    • C07C279/26—X and Y being nitrogen atoms, i.e. biguanides

Definitions

  • the present invention relates to the pharmaceutical use of a known biguanide, N -phenyl-N -isopropylbiguanide, and its non-toxic salts, as antihyperglycaemic agents.
  • N-p-chlorophenyl-N -isopropyl-biquanide for example, there has been described a slight blood sugar depressing effect which occurs only with toxic doses [K.K. Chen and R. C. Anderson, J. Pharmacol. Exp. Therap. 91,157, (1947)].
  • the present invention provides an antihyperglycaemic pharmaceutical composition containing N-phenyl-N -isopropyl-biguanide as an active ingredient or a non-toxic salt thereof, in admixture with a pharmaceutically acceptable solid or liquid diluent or carrier as hereinafter defined.
  • the expression pharmaceutically acceptable diluent or carrier means a non-toxic substance that when mixed with the active ingredient or ingredients renders it suitable for administration.
  • the expression excludes water, methanol, ethanol, butanol, B-ethoxyethanol, and other lowmolecular weight organic solvents commonly used in chemical synthesis, except in the presence of other 'pharmaceutically necessary ingredients such as salts in correct quantities to render the composition isotonic, buffers, surfactants, coloring and flavoring agents, and preservatives.
  • suitable liquid diluents and carriers are vegetable oils, polyols, buffered aqueous solutions, isotonic saline aqueous solutions, syrups and lotion bases.
  • suitable solid diluents and carriers are starches, cellulose and its derivatives, sugars, stearates and stearic acid, talc, and ointment bases.
  • Preferred pharmaceutical compositions of the invention are those adapted for oral administration.
  • the diluents and carriers used are preferably therefore those that adapt the active ingredient or ingredients for oral administration.
  • examples of such diluents and carriers are solid vehicles, excipients and lubricants such as glucose, lactose and sucrose, corn and potato starch, sodium carboxymethyl-cellulose, ethyl cellulose and cellulose acetate, powdered gum tragacanth, gelatin, alginic acid, agar, stearic acid and sodium, calcium and magnesium stearates.
  • compositions of the invention may also contain other nontoxic adjuvants and modifiers such as dyes, surfactants, perfumes, flavoring agents, preservatives and biocides.
  • the pharmaceutical composition of the invention preferably contains 10 to wt. percent of N -phenyl- N -isopropyl biguanide or salt thereof.
  • the preferred forms for oral administration preferably contain 20 to 80 wt. percent.
  • a preferred formulation for an orally administrable pharmaceutical composition according to the invention is the following
  • the lubricant reduces the friction between the particles of the powder and the granulate
  • the lubricant reduces the friction between the instruments (punches, dies, etc.) used to form the composition into tablets and the like, and the composition.
  • the lubricant also prevents the composition sticking to the instruments).
  • composition may for example be made up as plain or delayed-release tablets or dragees or filled into capsules.
  • the present invention also provides antihyperglycaemic medicaments in dosage unit form as hereinafter defined comprising N -phenyl-N -isopropyl biguanide or a non-toxic salt thereof either alone or in admixture with a pharmaceutically acceptable solid or liquid diluent or carrier.
  • a pharmaceutically acceptable solid or liquid diluent or carrier is preferably as defined above but can also be water or another common solvent.
  • the expression medicament in dosage unit form as used in the present specification means a medicament in the form of discrete portions each containing a unit dose or a multiple or sub-multiple of a unit dose of the active ingredient(s); for example, one, two, three, or four unit doses or a half, a third or a quarter of a unit dose.
  • a unit dose is the amount of the active ingredient(s) to be administered on one occasion and will usually be a daily dose, or for example a half, a third, or a quarter of a daily dose depending on whether the medicament is to be administered once or, for example, twice, three times, or four times a day.
  • the discrete portions constituting the medicament in dosage unit form can include a protective envelope.
  • the active ingredient can be undiluted and contained in such an envelope, or can be mixed with a pharmaceutically acceptable solid or liquid diluent or carrier as defined above.
  • Such portions can for example be 7 in monolithic coherent form, such as tablets, pills, suppositories, or dragees; in wrapped or concealed form, the active ingredients being within a protective envelope, such as wrapped powders, cachets, sachets,
  • a sterile solution suitable for parenteral injection such as ampoules of buffered, isotonic, sterile, pyrogen-free aqueous solution; or in any other form known in the art.
  • Preferred medicaments in dosage unit form according tothe invention are therefore those adapted for oral administration, .such as tablets, pills, dragees, capsules, and cachets, as well as wrapped powders containing the active ingredient in powdered form with a powdered diluent or carrier for suspension in water before being taken.
  • the preferred unit dose for administration of the medicaments of the invention is 5-100 mg. of N -phenyl-N -isopropyl-biguanide or salt thereof. This will normally be administered one to five times daily.
  • the preferred unit dose is also 5-100 mg.
  • One discrete portion of the medicament preferably contains about 30 mg. of N -phenyl-N -isopropyl-biguanide or salt thereof.
  • the invention further provides a method of depressing the blood sugar level in an animal which comprises administering to the animal (preferably perorally') a pharmaceutical composition according to the invention or a medicament in dosage unit form according to' the invention.
  • the biguanide, the lactose and half the quantity of maize starch are mixed, kneaded together with a paste of one quarter of the quantity of maize starch, pressed through a sieve with 3-5 mm. mesh size, and dried in a suitable drier at 6080C.
  • Thedry granulate is forced through a sieve with 0.8 -mm. mesh size, and the remaining quarter of the maize starch as well as the talcum and magnesium stearate are mixed in.
  • the resultant composition is pressed into round tablets of 8 mm. diameter and a total weight of 200 mg. with the help of an ordinary tablet press.
  • the biguanide and sec. calcium phosphate are mixed, kneaded with an aqueous solution of gelatin, sieved (3-5 mm) and dried (6080C). The dry granulate is sieved (0.8 mm). Finally the wheat starch and magnesium stearate are mixed in and the resultant.
  • composition formed into tablets in known manner round tablets, diameter 7 mm., gross tablet weight
  • Example 2 Delayed release tablets a) Two-layer dragee.
  • N -phenyl-N -isopropyl biguanide 15 mg. Sec. calcium phosphate 82 mg. Gelatin 2 mg.
  • Example 1(b) These ingredients are compounded as in Example 1(b) into round, suitably curved tablets 6.5 mm. in
  • Lacquering The nuclei are lacquered with a 10 percent solution of cellulose acetate phthalate (with some castor oil or diethylphthalate as plasticizer) in known manner until the nuclei satisfy the specifications of the pharmacopeia for resistance to gastic guice.
  • Sugar coating The lacquered nuclei'are next coated in known manner with the following suspension until the applied layer contains 15 mg. biguanide per dragee:
  • Wax-matrix tablets Per tablet N-phenyl-N -isopropyl biguanide 30 mg.
  • Hydrogenated castor oil 60 mg.
  • Example 3 Capsules a) Per capsule: N-phenyl-N-isopropyl biguanide 30 mg. Sec. calcium phosphate 1 l6 mg. Magnesium stearate 3 mg. Colloidal silicic acid 1 mg.
  • the ingredients are mixed and filled into hard gelatin capsules with a suitable capsule filling and closing machine.
  • the biguanide and lactose are mixed, kneaded with a solution of polyvinylpyrrolidone and stearic acid in methylene chloride, sieved (3-5 mm) and dried (506 0C).
  • the dry granulate is forced through a sieve with mesh width of 0.50.6 mm.
  • the colloidal silicic acid and talcum are mixed in, and the resultant composition is filled with a suitable apparatus into hard gelatin capsules.
  • the wax granulate described under 2(b) can, instead of being tabletted, also be filled into hard gelatin capsules. Capsules with delayed release of active ingredient are then obtained.
  • a method of depressing the blood sugar level of a hyperglycaemic animal comprising administering to the animal an antihyperglycaemic amount of N -phenyl- N -isopropyl-biguanide or a nontoxic salt thereof.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
US118962A 1970-03-03 1971-02-25 Antihyperglycaemic agent Expired - Lifetime US3689674A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19702009737 DE2009737A1 (de) 1970-03-03 1970-03-03 N tief 1 Phenyl N tief 5 iso propylbiguanid als Verbindung mit anti hypergIykamischer Wirkung

Publications (1)

Publication Number Publication Date
US3689674A true US3689674A (en) 1972-09-05

Family

ID=5763812

Family Applications (1)

Application Number Title Priority Date Filing Date
US118962A Expired - Lifetime US3689674A (en) 1970-03-03 1971-02-25 Antihyperglycaemic agent

Country Status (6)

Country Link
US (1) US3689674A (cs)
BE (1) BE763721A (cs)
DE (1) DE2009737A1 (cs)
FR (1) FR2085663B1 (cs)
NL (1) NL7102706A (cs)
ZA (1) ZA711191B (cs)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3879541A (en) * 1970-03-03 1975-04-22 Bayer Ag Antihyperglycemic methods and compositions
US4608248A (en) * 1985-11-08 1986-08-26 Warner-Lambert Company Process for time-controlled release of active ingredients
US5084449A (en) * 1984-05-22 1992-01-28 Dr. Karl Thomae Gmbh Anti-bacterial compositions comprising a substituted bis-(4-aminophenyl)-sulfone and a dihydro-folic acid reductase

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR934376A (fr) * 1945-10-08 1948-05-20 Ici Ltd Fabrication de dérivés de la biguanide

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
R. Chew et al., J. Pharmacal. Exp. Therap., 91, pp. 157 160, 1947. *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3879541A (en) * 1970-03-03 1975-04-22 Bayer Ag Antihyperglycemic methods and compositions
US5084449A (en) * 1984-05-22 1992-01-28 Dr. Karl Thomae Gmbh Anti-bacterial compositions comprising a substituted bis-(4-aminophenyl)-sulfone and a dihydro-folic acid reductase
US4608248A (en) * 1985-11-08 1986-08-26 Warner-Lambert Company Process for time-controlled release of active ingredients

Also Published As

Publication number Publication date
NL7102706A (cs) 1971-09-07
FR2085663A1 (cs) 1971-12-31
ZA711191B (en) 1971-11-24
FR2085663B1 (cs) 1974-08-30
DE2009737A1 (de) 1971-09-16
BE763721A (fr) 1971-09-03

Similar Documents

Publication Publication Date Title
US5529783A (en) Rotor granulation and coating of acetaminophen, pseudoephedrine, chlorpheniramine, and, optionally dextromethorphan
US5075114A (en) Taste masking and sustained release coatings for pharmaceuticals
US5292772A (en) Method for the prevention and control of epileptic seizure associated with Lennox-Gastaut syndrome
DE3853566T2 (de) Formulierungen von Tetrazyklinverbindungen mit kontrollierter Freisetzung.
US4273774A (en) Central nervous system compositions and method
CA2447926A1 (fr) Forme pharmaceutique orale antidiabetique "une prise par jour" comprenant une biguanide et au moins un autre principe actif
JPH07509456A (ja) ２型糖尿病および肥満の治療および予防のための１，３−ジシクロプロピメチル−８−アミノ−キサンチンの使用
DE69733752T2 (de) Arzneimittel enthaltend oxaprozin-natriumsalz,-kaliumsalz, oder-tris(hydroxymethyl)aminomethansalz
US3689674A (en) Antihyperglycaemic agent
WO1999000122A1 (de) Verfahren zur reduktion des körpergewichtes
DE60219940T2 (de) Verwendung von irbesartan zur vorbeugung oder behandlung pulmonaler hypertonie
US3144387A (en) Anti-inflammatory compositions
DE3877621T2 (de) Trockene orale theophyllinzubereitung mit verzoegerter freisetzung.
US3729563A (en) Method of treating movement disorders
US3360434A (en) Method for reducing blood pressure with phenylalanine derivatives
US3462534A (en) Production of an antidepressant effect with esters of gallic acid
US4049791A (en) Prolonged acting appetite suppressant and anti-obesity compositions containing amphetamine adipate, dextroamphetamine adipate, amphetamine sulfate and dextroamphetamine sulfate as the active agents
US3520975A (en) Anorexigenic compositions comprising fenfluramine and scopolamine
US3495005A (en) Compositions and methods for suppressing appetite with combinations of amphetamine and thioridazine
JPS62215526A (ja) 降圧剤
DE2951669C2 (de) Arzneimittel
JPH06506706A (ja) ベンゾフルメトールを含有する抗マラリア性の相乗作用組成物
DE3535950A1 (de) Kombinationspraeparat
DE69103294T2 (de) Verwendung der 3-Oxygermylpropionsäure zur Behandlung und Prävention von Diabetes verursacht durch Autoimmunkrankheiten.
DE3232830A1 (de) Arzneimittel