EP0000704A1 - Polyäther, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Lipidabsorptionshemmer - Google Patents

Polyäther, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Lipidabsorptionshemmer Download PDF

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Publication number
EP0000704A1
EP0000704A1 EP78100357A EP78100357A EP0000704A1 EP 0000704 A1 EP0000704 A1 EP 0000704A1 EP 78100357 A EP78100357 A EP 78100357A EP 78100357 A EP78100357 A EP 78100357A EP 0000704 A1 EP0000704 A1 EP 0000704A1
Authority
EP
European Patent Office
Prior art keywords
ethylene oxide
oxide content
polymeric
molecular weight
polyethers
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.)
Withdrawn
Application number
EP78100357A
Other languages
German (de)
English (en)
French (fr)
Inventor
Gerd Dr. Steinert
Harald Dr. Horstmann
Rüdiger Dr. Sitt
Hans Peter Dr. Krause
Walter Dr. Plus
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
Publication of EP0000704A1 publication Critical patent/EP0000704A1/de
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
    • C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
    • C08G65/26—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds
    • C08G65/2603—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing oxygen
    • C08G65/2606—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing oxygen containing hydroxyl groups
    • C08G65/2609—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing oxygen containing hydroxyl groups containing aliphatic hydroxyl groups
    • 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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A61K31/77—Polymers containing oxygen of oxiranes

Definitions

  • the present invention relates to new polyethers, several processes for their preparation and their use as medicaments which influence the metabolism, in particular as lipid absorption inhibitors.
  • polyethers consisting of ethylene oxide and propylene oxide groups (see US Pat. No. 2,674,619). It is also known that polyoxyalkylenes with molecular weights of approx. 1000 to approx. 11,000 have surface-active properties and can also be used in pharmaceutical preparations. US Pat. No. 3,641,240 claims and describes the use of polyoxyalkylenes with a molecular weight of approximately 2000 to 10,000 and an ethylene oxide content of 50 to 90% as antithrombotics. In this patent it is expressly pointed out that the applicable Polyoxyalkylene should contain at least 50% ethylene oxide.
  • U.S. Patent 3,202,578 describes polyoxyalkylenes which can be used as laxatives. In addition to the laxative effect, this patent also mentions an effect on lowering cholesterol in the blood. According to the statements in this patent specification, such polyoxyalkylenes are particularly suitable as cholesterol-lowering compounds which have a molecular weight of 7,500 and contain 80% ethylene oxide.
  • polyethers of general structure (I) with an average molecular weight of 4000, a propylene oxide content of 70% and an ethylene oxide content of 30%.
  • the polyethers of the general structure (I) according to the invention are prepared by Propylene glycol in the presence of alkali hydroxide by polyaddition first with propylene oxide and then with a corresponding amount of ethylene oxide, the alkali metal hydroxide is then neutralized with aqueous mineral acid and, after dehydration of the polyether, removed by salt filtration.
  • the polyethers according to the invention have a narrow molecular weight distribution.
  • the characterization and composition of the polymeric oxyalkylene compounds is carried out analytically by determining the molecular weight from the hydroxyl number.
  • the ethylene oxide content is determined from the H-NMR spectrum.
  • the polyethers according to the invention surprisingly show very strong effects in the treatment of fat and carbohydrate metabolism disorders. In particular, they lower the elevated cholesterol in serum and tissue and at the same time reduce hypertriglyceridaemia.
  • the compounds according to the invention are suitable for the treatment of hyperlipoproteinaemia, atherosclerosis, obesity and for the treatment of metabolic disorders triggered thereby.
  • polyethers according to the invention of the present application have such a pronounced hypolipidemic effect in this molecular weight range from 3 to 5000, in particular 4000, and the special propylene oxide / ethylene oxide ratio. Since the compounds according to the invention are at the same time very well tolerated in addition to this strong action, they represent an enrichment of the pharmaceutical industry.
  • the present invention includes pharmaceutical preparations which, in addition to non-toxic, inert pharmaceutically suitable excipients, contain one or more compounds of the above formula or which consist of one or more compounds of the above formula, and processes for the preparation of these preparations.
  • the invention also includes pharmaceutical preparations in dosage units.
  • the dosage units can e.g. 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose.
  • a single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose.
  • Non-toxic, inert pharmaceutically suitable excipients are to be understood as solid, semisolid or liquid diluents, fillers and formulation auxiliaries of all kinds.
  • Tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes may be mentioned as preferred pharmaceutical preparations.
  • Tablets, coated tablets, capsules, pills and granules can contain the active ingredient (s) in addition to the usual carriers, such as (a) fillers and extenders, for example starches, Milk sugar, cane sugar, glucose, mannitol and silica, (b) binders, e.g. carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, (c) humectants, e.g. glycerin, (d) disintegrants, e.g. agar-agar, calcium carbonate and sodium bicarbonate, (e) dissolving agents , e.g. paraffin and (f) absorption accelerators, e.g.
  • fillers and extenders for example starches, Milk sugar, cane sugar, glucose, mannitol and silica
  • binders e.g. carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone
  • humectants e.g
  • quaternary ammonium compounds (g) wetting agents, e.g. cetycohol, glycerol monostearate, (h) adsorbents, e.g. kaolin and bentonite and (i) lubricants, e.g. talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) - (i).
  • wetting agents e.g. cetycohol, glycerol monostearate
  • adsorbents e.g. kaolin and bentonite
  • lubricants e.g. talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) - (i).
  • the tablets, dragees, capsules, pills and granules can be provided with the usual coatings and casings, optionally containing opacifying agents, and can also be composed such that they release the active ingredient (s) only or preferably in a certain part of the intestinal tract, if necessary with a delay , where as embedding compounds, for example Polymer substances and waxes can be used.
  • the active ingredient (s) can optionally also be in microencapsulated form with one or more of the above-mentioned excipients.
  • suppositories can contain the usual water-soluble or water-insoluble carriers, for example polyethylene glycols, fats, for example cocoa fat, and higher esters (for example C 14 alcohol with C 16 fatty acid) or mixtures of these substances.
  • water-soluble or water-insoluble carriers for example polyethylene glycols, fats, for example cocoa fat, and higher esters (for example C 14 alcohol with C 16 fatty acid) or mixtures of these substances.
  • solutions and emulsions can contain the usual carriers, such as solvents, solubilizers and emulsifiers, e.g. Water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerin, glycerol formate, fatty alcohol ester fatty acid, tetrahydrofuran desorbate or mixtures of these substances.
  • solvents e.g. Water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, in particular cottonseed
  • solutions and emulsions can also be in sterile and blood isotonic form.
  • suspensions can contain the usual carriers, such as liquid diluents, e.g. Water, ethyl alcohol, propylene glycol, suspending agents e.g. contain ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide, bentonite, agar and tragacanth or mixtures of these substances.
  • liquid diluents e.g. Water, ethyl alcohol, propylene glycol
  • suspending agents e.g. contain ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide, bentonite, agar and tragacanth or mixtures of these substances.
  • the formulation forms mentioned can also contain colorants, preservatives and additives which improve the smell and taste, for example peppermint oil and eucalyptus oil, and sweeteners, for example saccharin.
  • the therapeutically active compounds should be present in the pharmaceutical preparations listed above in a concentration of about 0.1 to 99.5, preferably about 0.5 to 95 percent by weight of the total mixture.
  • the pharmaceutical preparations listed above can also contain other active pharmaceutical ingredients.
  • the pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. by mixing the active substance or substances with the carrier substance or substances.
  • the present invention also includes the use of the compounds of the above formula and the use of pharmaceutical preparations which contain one or more compounds of the above formula in human and veterinary medicine for preventing, ameliorating and / or curing the above-mentioned diseases.
  • the active substances or the pharmaceutical preparations can be administered orally, parenterally, intraperitoneally and / or rectally, preferably orally.
  • the active ingredient (s) in amounts of about 0.05 to about 500, preferably 0.5 to 200 mg / kg body weight per 24 hours. , to be applied over 1 to 6 administrations, namely before or / and during or / and after the meal.
  • a single dose ent holds the active ingredient (s) preferably in amounts of about 0.1 to about 100 mg / kg body weight.
  • ea may be sufficient to make do with less than the above-mentioned amount of active ingredient, while in other cases the amount of active ingredient mentioned above must be exceeded.
  • the optimum dosage and type of application of the active ingredients required in each case can easily be determined by any person skilled in the art on the basis of his specialist knowledge.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Polymers & Plastics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
  • Polyethers (AREA)
EP78100357A 1977-07-21 1978-07-11 Polyäther, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Lipidabsorptionshemmer Withdrawn EP0000704A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19772732929 DE2732929A1 (de) 1977-07-21 1977-07-21 Polyaether, verfahren zu ihrer herstellung sowie ihre verwendung als lipidabsorptionshemmer
DE2732929 1977-07-21

Publications (1)

Publication Number Publication Date
EP0000704A1 true EP0000704A1 (de) 1979-02-21

Family

ID=6014492

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78100357A Withdrawn EP0000704A1 (de) 1977-07-21 1978-07-11 Polyäther, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Lipidabsorptionshemmer

Country Status (13)

Country Link
EP (1) EP0000704A1 (da)
JP (1) JPS5422497A (da)
AU (1) AU3806878A (da)
CA (1) CA1111453A (da)
DE (1) DE2732929A1 (da)
DK (1) DK324678A (da)
ES (1) ES471900A1 (da)
FI (1) FI782284A7 (da)
IL (1) IL55160A0 (da)
IT (1) IT1097831B (da)
NO (1) NO782332L (da)
PT (1) PT68307A (da)
ZA (1) ZA784129B (da)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0011237A1 (de) * 1978-11-18 1980-05-28 Bayer Ag Polyäther-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
EP0018591A1 (de) * 1979-04-25 1980-11-12 BASF Aktiengesellschaft Formmassen, enthaltend Styrolacrylnitril-Copolymerisate und Äthylenoxid-/Propylenoxid-Dreiblockcopolymerisate, Verwendung derselben und Formteile aus diesen
EP0103290A3 (de) * 1982-09-14 1984-09-05 Intermedicat Gmbh Pharmazeutische Zubereitungen zur Behandlung von unerwünschten Verwachsungen sowie deren Verwendung
EP0166958A1 (de) * 1984-06-02 1986-01-08 Hoechst Aktiengesellschaft Modifizierte Polyethylenglykole
WO1988006038A1 (en) * 1987-02-20 1988-08-25 Emory University Antiinfective compounds and method of use
EP0576612A4 (en) * 1991-03-19 1994-11-09 Cytrx Corp POLYOXYPROPYLEN / POLYOXYETHYLEN COPOLYMERE WITH IMPROVED BIOLOGICAL ACTIVITY.
US5674911A (en) * 1987-02-20 1997-10-07 Cytrx Corporation Antiinfective polyoxypropylene/polyoxyethylene copolymers and methods of use
US5811088A (en) * 1987-02-20 1998-09-22 Emory University Antiinfective compounds and methods of use
USRE38558E1 (en) 1991-03-19 2004-07-20 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
US6933286B2 (en) 1991-03-19 2005-08-23 R. Martin Emanuele Therapeutic delivery compositions and methods of use thereof
US7202225B1 (en) 1993-10-15 2007-04-10 Emanuele R Martin Therapeutic delivery compositions and methods of use thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6030650B2 (ja) * 1979-10-26 1985-07-17 日本油脂株式会社 座薬基剤組成物
CA2258744A1 (en) 1996-06-27 1997-12-31 G.D. Searle And Co. Particles comprising amphiphilic copolymers, having a cross-linked shell domain and an interior core domain, useful for pharmaceutical and other applications

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB610505A (en) * 1944-02-08 1948-10-18 Carbide & Carbon Chem Corp A method for making polyoxyalkylene glycols
FR1116M (fr) * 1961-02-02 1962-02-12 Bernard Andre Francois Mirande Utilisation de substances tensio-actives provenant de la condensation de l'oxyde d'éthylene sur les propylenes-glycols dans la résorption des oedemes locaux ou tissulaires systématisés.
NL6618108A (da) * 1965-12-23 1967-06-26

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB610505A (en) * 1944-02-08 1948-10-18 Carbide & Carbon Chem Corp A method for making polyoxyalkylene glycols
FR1116M (fr) * 1961-02-02 1962-02-12 Bernard Andre Francois Mirande Utilisation de substances tensio-actives provenant de la condensation de l'oxyde d'éthylene sur les propylenes-glycols dans la résorption des oedemes locaux ou tissulaires systématisés.
NL6618108A (da) * 1965-12-23 1967-06-26

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0011237A1 (de) * 1978-11-18 1980-05-28 Bayer Ag Polyäther-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
EP0018591A1 (de) * 1979-04-25 1980-11-12 BASF Aktiengesellschaft Formmassen, enthaltend Styrolacrylnitril-Copolymerisate und Äthylenoxid-/Propylenoxid-Dreiblockcopolymerisate, Verwendung derselben und Formteile aus diesen
EP0103290A3 (de) * 1982-09-14 1984-09-05 Intermedicat Gmbh Pharmazeutische Zubereitungen zur Behandlung von unerwünschten Verwachsungen sowie deren Verwendung
EP0166958A1 (de) * 1984-06-02 1986-01-08 Hoechst Aktiengesellschaft Modifizierte Polyethylenglykole
US5811088A (en) * 1987-02-20 1998-09-22 Emory University Antiinfective compounds and methods of use
WO1988006038A1 (en) * 1987-02-20 1988-08-25 Emory University Antiinfective compounds and method of use
US5674911A (en) * 1987-02-20 1997-10-07 Cytrx Corporation Antiinfective polyoxypropylene/polyoxyethylene copolymers and methods of use
US5990241A (en) * 1991-03-19 1999-11-23 Cytrx, Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
EP0576612A4 (en) * 1991-03-19 1994-11-09 Cytrx Corp POLYOXYPROPYLEN / POLYOXYETHYLEN COPOLYMERE WITH IMPROVED BIOLOGICAL ACTIVITY.
USRE36665E (en) * 1991-03-19 2000-04-18 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
USRE37285E1 (en) 1991-03-19 2001-07-17 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolmers with improved biological activity
US6359014B1 (en) 1991-03-19 2002-03-19 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
US6747064B2 (en) 1991-03-19 2004-06-08 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
USRE38558E1 (en) 1991-03-19 2004-07-20 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
US6933286B2 (en) 1991-03-19 2005-08-23 R. Martin Emanuele Therapeutic delivery compositions and methods of use thereof
US7202225B1 (en) 1993-10-15 2007-04-10 Emanuele R Martin Therapeutic delivery compositions and methods of use thereof

Also Published As

Publication number Publication date
DE2732929A1 (de) 1979-02-01
PT68307A (de) 1978-08-01
IT7825897A0 (it) 1978-07-19
FI782284A7 (fi) 1979-01-22
ES471900A1 (es) 1979-02-01
AU3806878A (en) 1980-01-17
ZA784129B (en) 1979-07-25
NO782332L (no) 1979-01-23
IT1097831B (it) 1985-08-31
IL55160A0 (en) 1978-09-29
CA1111453A (en) 1981-10-27
JPS5422497A (en) 1979-02-20
DK324678A (da) 1979-01-22

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RIN1 Information on inventor provided before grant (corrected)

Inventor name: SITT, RUEDIGER, DR.

Inventor name: PLUS, WALTER, DR.

Inventor name: KRAUSE, HANS PETER, DR.

Inventor name: STEINERT, GERD, DR.

Inventor name: HORSTMANN, HARALD, DR.