WO1995011006A1 - Highly active sulphonyl urea preparations exhibiting rapid or controlled release of the active substance, and method of producing them - Google Patents
Highly active sulphonyl urea preparations exhibiting rapid or controlled release of the active substance, and method of producing them Download PDFInfo
- Publication number
- WO1995011006A1 WO1995011006A1 PCT/EP1994/003368 EP9403368W WO9511006A1 WO 1995011006 A1 WO1995011006 A1 WO 1995011006A1 EP 9403368 W EP9403368 W EP 9403368W WO 9511006 A1 WO9511006 A1 WO 9511006A1
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- WO
- WIPO (PCT)
- Prior art keywords
- preparation
- water
- alcohol
- active ingredient
- sulfonylurea
- Prior art date
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Classifications
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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
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- the invention relates to highly effective preparation forms of sulfonylurea derivatives which are sparingly water-soluble or which release the active ingredient, and to processes for solubilizing sulfonylurea derivatives which are sparingly water-soluble.
- the effectiveness of a pharmaceutical substance depends to a large extent on its form of application. In general, for a systemic effect, the drug must either be injected directly into the bloodstream or applied in a resorbable form.
- Absorption of a substance is understood to mean its absorption into the bloodstream or the lymphatic system, from where it is distributed into the whole organism. The rate of absorption and the rate of absorption (ratio of the resorbable portion to the applied amount) depend on numerous factors. Decisive for the effectiveness and bioavailability of many orally or parenterally administered drugs is their solubility in an aqueous medium.
- a group of drugs, their bioavailability and thus effectiveness strongly depend on their solubility in an aqueous environment are the sulfonylurea derivatives. These substances are currently used to lower blood sugar (diabetes mellitus).
- glibenclamide Using the example of the best-known representative, glibenclamide (INN), the aim is to show what influence the solubility has on the onset of action, the effectiveness and the dose required for this.
- Glibenclamide also known as glyburide in American parlance, is a sulfonylurea derivative with the chemical IUPAC name: N-4-2- (5-chloro-2-methoxybenzamido) -ethyl-phenylsulfonyl-N'-cyclohexylurea.
- the molecular weight is 494.02, the melting point is 172 to 174 ° C (see R. Gröning: drug profiles and bioavailability data of finished drugs, drug monograph Glibenclamid, Deutscher maschinerverlag, Stuttgart, pages 1 to 7, 1987) .
- Glibenclamide is an odorless, crystalline, white substance which is practically insoluble in water and ether and only moderately soluble in alcohol and chloroform. With alkalis it forms salts which, however, have a very limited solubility in water in comparison to tolbutamide, a substance which also lowers blood sugar.
- the other therapeutically used sulfonylurea derivatives e.g. Glipizid, Glibornurid, Gliquidon, Glisoxepid and Glimeprid, all similar solubility properties.
- sulfonylurea derivatives are used worldwide in daily doses of 1-250 mg for the treatment of sugar disease (diabetes mellitus).
- Two mechanisms can be distinguished in the event of a lowering of blood sugar, namely a pancreatic and an extra pancreatic. effect (see product information from Boehringer Mannheim GmbH and Hoechst AG, Frankfurt / Main, 1984, on Euglucon R N, Semi-Euglucon R N).
- pancreatic effect leads to an increase in insulin secretion through an increased responsiveness of the beta cells of the pancreas to glucose.
- glibenclamide is one of the biopharmaceutical problematic medicinal substances.
- the water solubility is also pH-dependent, in the acidic range glibenclamide is practically insoluble in water.
- DE-OS 23 48 334 describes a rapidly absorbable form of preparation of glibenclamide and a process for its preparation.
- Glibenclamide was processed by fine grinding on a large, defined surface or by the finest precipitation from organic solvents in dispersing agents to form easily and quickly absorbable preparations.
- very fine crystals with a surface area of 3 to 10 m 2 were obtained. Studies have shown that increasing the surface area increases the solubility and dissolution rate, which also improves the bioavailability.
- DE-OS 23 55 743 lists examples which show that the processing of glibenclamide at elevated temperatures, for example by incorporation into melts of higher molecular weight polyethylene glycols, is detrimental to stability.
- the active substance is available in vivo, precisely coordinated, as and when required, which can prevent the occurrence of increased or strongly fluctuating blood sugar values.
- Hyperglycaemia caused by food intake or other influences, can be prevented or quickly normalized.
- compositions which do not meet these requirements for a rapid release of active substance harbor the risk of hyperglycaemia if an insufficient amount of active substance is available for absorption due to insufficient solubility or release.
- a prerequisite for rapid absorption is, however, that the active ingredient from the pharmaceutical form is available for release in a dissolved or colloidally dissolved or molecularly dispersed form, if possible. Only if these conditions are met can the active ingredient be rapidly absorbed and thus become effective.
- the present invention is therefore based on the object of providing a method for improving the solubility of poorly soluble sulfonylurea derivatives. Furthermore, effective, fast or controlled release and thus easily absorbable formulations of poorly soluble sulfonylurea derivatives, such as e.g. Glibenclamid, Glipizid, etc., are provided.
- the sparingly soluble active ingredients should be brought into solution in a molecularly disperse manner using a simple process and pharmacologically and toxicologically acceptable auxiliaries.
- the active ingredient should be divided and have good solubility due to the large surface area.
- the molecularly dispersed active ingredient is to be applied to customary pharmaceutical carrier materials or also embedded therein in order to increase the surface area, so that an active ingredient-auxiliary alloy is obtained.
- the process for producing the preparation forms according to the invention should be technically simple to carry out, require no complex apparatus and should not have any complicated process steps.
- the production should be possible with commercially available auxiliaries and simple means.
- the chemical or physical properties of the active substances or auxiliaries should not be adversely affected by the production process.
- the required amount of polyethylene glycol can be reduced up to 10 times with reference to Examples 1 and 2 in DE-OS 23 55 743 if the sulfonylurea derivatives are used in an alcohol, one or more polyol (s) and / or in sugar alcohols which have previously been dissolved in water or alcohol-water mixtures, and the mixture is subsequently mixed with 0.5 to 2 mol, preferably 1 mol, of alkali metal hydroxide or ammonia.
- the manufacturing method according to the invention therefore not only enables a reduction of the required auxiliary substances quantity, but at the same time represents an easy and gentle method for dissolving the poorly soluble sulfonylurea derivatives.
- the invention relates to highly effective preparation forms of sulfonylurea derivatives which release the active ingredient quickly or in a controlled manner, which are characterized in that they contain one or more sulfonylurea derivative (s) as active ingredient (s), one or more polyol (s) with the exception of polyethylene glycol and / or one or several sugar alcohols, previously dissolved in water or alcohol-water mixtures, contain an alkaline substance and, if appropriate, suitable pharmaceutically acceptable auxiliaries or flavorings and, if appropriate, further pharmaceutically active substances.
- the invention further relates to a method for producing a highly effective preparation of sulfonylurea derivatives which releases the active ingredient quickly or in a controlled manner, which is characterized in that one or more sulfonylurea derivative (s) are used as active ingredient (s), if appropriate after the previous one Wetting with an alcohol, in an alcohol or one or more polyol (s) except polyethylene glycol and / or one or more sugar alcohol (s), dissolved in water or an alcohol / water mixture, suspended, with an alkali mixed reacting substance and optionally adding other suitable pharmaceutically acceptable auxiliary and flavoring agents and optionally other pharmaceutically active substances until a solid or liquid preparation form is obtained.
- the preparation forms preferably contain 1 to 1000 parts of propylene glycol, glycerol, hexylene glycol or mixtures thereof and / or 1 to 500 parts of sugar alcohols, dissolved in 2 to 2000 parts of water, in relation to one part of active ingredient. water or alcohol-water mixtures and 0.5 to 3 moles, preferably 1 mole, of an alkaline substance and, if appropriate, 0.01 to 1000 parts of pharmaceutically compatible auxiliaries and flavorings.
- 1 part of sparingly soluble sulfonylurea derivative is preferably suspended in 3 to 1000 parts of ethanol or polyols such as propylene glycol etc. or sugar alcohols which have previously been dissolved in water or water / ethanol mixtures, with 0.5 to 2 mol, preferably about 1 mole, an alkaline substance and optionally other pharmaceutically acceptable auxiliaries and flavorings are mixed so that a liquid or solid preparation is obtained.
- the sulfonylurea derivatives can be any sulfonylurea derivatives. They are preferably glibenclamide (glyburide), glipizide, glimeprid, gliquidon, glisoxepid, glibornuride, glicalzide, glisentide, glisolamide, glybuzole, glyclopyramide and glyclamide.
- glibenclamide glyburide
- glipizide glimeprid
- gliquidon glisoxepid
- glibornuride glicalzide
- glisentide glisolamide
- glybuzole glyclopyramide
- Non-toxic products such as e.g. Glycerin, propylene glycol, hexylene glycol or mixtures thereof, and sugar alcohols, such as e.g. Sorbitol, mannitol, xylitol, isomalt or mixtures thereof in solution in water or alcohol-water mixtures are used.
- sugar alcohols are preferably dissolved in a concentration of 10% to 70% in water or ethanol-water mixtures.
- the alkaline substance can be any pharmaceutically acceptable and toxicologically acceptable alkaline substance, such as alkali or alkaline earth metal hydroxides or ammonia, which can form salts with sulfonylureas. It is preferred in a - in ⁇
- the preparations can furthermore contain pharmaceutically compatible and toxicologically acceptable auxiliaries and flavorings, as are usually used in solid or liquid dosage forms.
- auxiliaries and flavorings include customary excipients, such as lactose, starch, microcrystalline cellulose, croscarmelose, calcium carbonate, calcium diphosphate, Pluronic polyols, cellulose ethers, alginic acid derivatives, Eudragit, magnesium stearate, silicon dioxide, colorants, sugar substitutes, preservatives, isotropic substances, buffering agents, surface-buffering substances, surface-active substances ⁇ active compounds, flavorings, suppositories, etc., alone or in a mixture, to mention.
- customary excipients such as lactose, starch, microcrystalline cellulose, croscarmelose, calcium carbonate, calcium diphosphate, Pluronic polyols, cellulose ethers, alginic acid derivatives, Eudragit, magnesium stearate, silicon dioxide, colorants
- the preparation can also be used as flavoring substances, sugar substitutes, such as fructose, saccharin, aspartame, etc., as well as preservatives, such as e.g. Para-hydroxybenzoic acid esters, benzyl alcohols, sorbic acid or salts thereof in a concentration of 0.1 to 2 wt .-% of the formulation.
- other pharmaceutically active substances can be added to the preparation form. These are preferably other blood sugar lowering drugs, such as ⁇ -glucosidase inhibitors, such as e.g. Acarbose, miglitol or aldose reductase inhibitors, such as e.g. Alrestatin sodium or Voglibase.
- These other active ingredients can be formulated either separately from or together with the sulfonylureas.
- the preparation forms can be in liquid, solid or semi-solid form.
- Liquid dosage forms are, for example, solutions for oral (juices, drops), nasal (nasal drops, nasal sprays) or parenteral (injection or infusion) application.
- Solid and semi-solid dosage forms can be, for example, granules (dry juice, sachets), tablets, capsules, pellets, film-coated tablets. be dragées and suppositories.
- the dosage forms can be formulated in such a way that the entire active ingredient is released either within a very short time or in a time-controlled manner.
- Liquid dosage forms e.g. Drip solutions have so far not been available for therapy as commercial products.
- the drip solution allows an individual dosage adapted to the disease state and the food supply. Due to the fact that the active ingredient is present in a molecularly dispersed form in the preparation according to the invention, it is directly available for absorption and thus allows rapid absorption and optimal bioavailability.
- the alcohol used in each case is preferably ethanol in 94 to 96% pharmaceutical quality and purity according to the requirements of the pharmacopoeia. If necessary, 90% or 70% ethanol can also be used, eg mixtures of 90 parts of ethanol and 10 parts of water. Depending on the solubility of the sulfonylurea derivative used, it may be expedient to first disperse the active ingredient in an alcohol, preferably ethanol, for better wetting, and then with the sugar alcohol, previously in water or an alcohol-water mixture , preferably an ethanol-water mixture, has been suspended. Alcohols other than ethanol can also be used, for example methanol or isopropanol, optionally in dilution with water.
- a 100 was obtained from glibenclamide tablets which were produced in accordance with the method according to the invention in an in vitro dissolution test (paddle apparatus according to USP XXII, 75 revolutions per minute, buffer pH 7.4, UV measurement at 227 nm) % release of the active ingredient within 5 to 15 minutes, as can be seen in the attached figures.
- a c m ⁇ C of 189 ng / ml, t max of 1.7 h and an AUC of 635 ng xh / ml were obtained.
- the reduction in blood glucose determined at the same time proves that very good bioavailability and effectiveness can be achieved with the method according to the invention.
- FIG. 2 the glibenclamide formulation according to the invention in comparison to Euglucon N.
- the process for producing liquid dosage forms is simple.
- the sparingly soluble sulfonylurea derivative, e.g. Glibenclamide is suspended in a stirred kettle in 4 to 1000 parts of propylene glycol, hexylene glycol or sugar alcohols, previously dissolved in water or an ethanol-water mixture with stirring, and as long as with an alkali-reacting substance, e.g. 0.1 molar ammonia solution or sodium hydroxide solution are added until a homogeneous solution is obtained.
- This solution can then, if necessary, with other suitable auxiliaries, such as Water, sweeteners, flavorings and preservatives are mixed and then used therapeutically to lower blood sugar as a liquid pharmaceutical dosage form (e.g. as a drip solution or juice).
- an undiluted active ingredient solution is used on tableting aids, e.g. Starch, lactose, mannitol, microcrystalline cellulose or disintegrant, grown in a commercial mixing kettle or fluidized bed granulator. Excess alcohol, ammonia or water can then be removed in the drying cabinet.
- tableting aids e.g. Starch, lactose, mannitol, microcrystalline cellulose or disintegrant
- the solution in a very finely divided form on adjuvants customary in pharmacy, such as mannitol, lactose, starch, microcrystalline cellulose or disintegrants persistence agents or mixtures thereof.
- adjuvants customary in pharmacy such as mannitol, lactose, starch, microcrystalline cellulose or disintegrants persistence agents or mixtures thereof.
- the molecularly dispersed glibenclamide distributed as a solid solution according to the invention is so finely dispersed and so wettable that a further increase in the rate of solution should theoretically no longer be possible.
- the active ingredient immediately dissolves with the disintegration of the molecules in a molecularly disperse manner, as has been shown by in-vitro release studies with tablets containing glibenclamide. According to the Noyes-Whitney law, the larger the wettable surface of the particles to be dissolved, the faster the dissolution rate.
- the sulfonylurea derivatives used according to the invention are usually administered in daily doses of 1 to 250 mg, depending on the sulfonylurea derivative used.
- This dose can be formulated into single or multiple doses, starting from the sulfonylurea derivatives dissolved according to the invention, according to a method known to the person skilled in the art.
- the exact dose to be administered can be adjusted by the treating doctor depending on the severity of the condition to be treated and the patient.
- Example 2 3.5 g of glibenclamide are suspended in 700 g of propylene glycol with stirring and mixed with 7.1 g of 0.1N sodium hydroxide solution.
- Example 2 3.5 g of glibenclamide are suspended in 700 g of propylene glycol with stirring and mixed with 7.1 g of 0.1N sodium hydroxide solution.
- glipizide 4.5 g are mixed with stirring in 80 g of hexylene glycol and 20 g of 70% aqueous sorbitol solution and 2% (w / v) ammonia solution is added until a solution is obtained.
- glimeprid 1 g is stirred in 200 g of propylene glycol and 50 g of 20% aqueous xylitol solution, and 0.1N potassium hydroxide solution is added until a solution is obtained.
- glisoxepid 8 g are mixed in 1000 g of propylene glycol and 0.5N sodium hydroxide solution is added until a solution is obtained.
- glipizide 10 g are suspended in 80 g of ethanol and 35 g of 70% sorbent solution and 5% (w / v) ammonia solution is added until a solution is obtained. This is grown on 360 g lactose. After drying and sieving, granules are obtained. This can then be mixed with 100 g of a tabletting auxiliary mixture and pressed into tablets.
- glibenclamide 5 g are suspended in 50 g of ethanol and 50 g of Karion F (70% sorbitol solution) and 0.5N sodium hydroxide solution is added until a solution is obtained. This is grown on a mixture of 315 g lactose and 50 g corn starch, 20 g microcrystalline cellulose and 72 g acarbose, sieved and granulated. After mixing with 0.5% silicon dioxide and magnesium stearate in each case, 350 mg of powder mixture are filled into hard gelatin capsules.
- Karion F 50% sorbitol solution
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP7511289A JPH09504015A (en) | 1993-10-22 | 1994-10-12 | Highly effective sulfonylurea formulations that release active substances in a rapid or controlled manner and methods for their preparation |
EP94929538A EP0724427A1 (en) | 1993-10-22 | 1994-10-12 | Highly active sulphonyl urea preparations exhibiting rapid or controlled release of the active substance, and method of producing them |
AU78555/94A AU7855594A (en) | 1993-10-22 | 1994-10-12 | Highly active sulphonyl urea preparations exhibiting rapid or controlled release of the active substance, and method of producing them |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4336159A DE4336159A1 (en) | 1993-10-22 | 1993-10-22 | Highly effective forms of preparation of sulfonylureas that release the active ingredient quickly or in a controlled manner and processes for their preparation |
DEP4336159.5 | 1993-10-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1995011006A1 true WO1995011006A1 (en) | 1995-04-27 |
Family
ID=6500829
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1994/003368 WO1995011006A1 (en) | 1993-10-22 | 1994-10-12 | Highly active sulphonyl urea preparations exhibiting rapid or controlled release of the active substance, and method of producing them |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0724427A1 (en) |
JP (1) | JPH09504015A (en) |
AU (1) | AU7855594A (en) |
CA (1) | CA2173366A1 (en) |
DE (1) | DE4336159A1 (en) |
HU (1) | HUT74684A (en) |
NZ (1) | NZ274501A (en) |
WO (1) | WO1995011006A1 (en) |
Cited By (17)
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WO2000018373A1 (en) * | 1999-02-01 | 2000-04-06 | Adir Et Compagnie | Core tablet for controlled release of gliclazide after oral administration |
EP1693415A2 (en) | 2005-02-19 | 2006-08-23 | Degussa GmbH | Polymer powder with blockpolyetheramide, and the use in a process and moulding produced from this polymer powder |
EP1743759A1 (en) | 2005-07-16 | 2007-01-17 | Degussa GmbH | Use of cyclic oligomers in a forming process and object produced by this process |
EP1982816A1 (en) | 2007-04-20 | 2008-10-22 | Evonik Degussa GmbH | Composite powder, its use in a moulding method and moulds made of this composite powder |
EP2103643A1 (en) | 2008-03-19 | 2009-09-23 | Evonik Degussa GmbH | Copolyamide powder and its production, its use in a moulding method and object made of this copolyamide powder |
US7611693B2 (en) | 2003-09-17 | 2009-11-03 | Board Of Regents, The Univerisity Of Texas System | Mechanism-based targeted pancreatic beta cell imaging and therapy |
EP2543700A1 (en) | 2011-07-06 | 2013-01-09 | Evonik Degussa GmbH | Powder containing particles coated with polymer |
EP2543457A1 (en) | 2011-07-06 | 2013-01-09 | Evonik Degussa GmbH | Powder containing core particles coated with polymer containing metals, metal oxides, metal nitrides or half metal nitrides |
EP2543696A1 (en) | 2011-07-06 | 2013-01-09 | Evonik Degussa GmbH | Powder containing core particles coated with polymer |
EP2543701A1 (en) | 2011-07-06 | 2013-01-09 | Evonik Degussa GmbH | Powder containing inorganic particles coated with polymer |
EP2650106A1 (en) | 2012-04-11 | 2013-10-16 | Evonik Industries AG | Polymer powder with adapted melt behaviour |
US8865053B2 (en) | 2004-05-14 | 2014-10-21 | Evonik Degussa Gmbh | Process for the production of moldings |
EP1840155B1 (en) | 2006-04-01 | 2016-12-28 | Evonik Degussa GmbH | Polymer powder, method for manufacturing and utilising such a powder and moulded parts made thereof |
US10710301B2 (en) | 2016-05-13 | 2020-07-14 | Hewlett-Packard Development Company, L.P. | Material sets |
US10717232B2 (en) | 2016-05-13 | 2020-07-21 | Hewlett-Packard Development Company, L.P. | Material sets |
DE202022000644U1 (en) | 2022-03-15 | 2022-04-21 | Evonik Operations Gmbh | Powder for processing in a layer-by-layer process with visible and near-infrared lasers |
EP4245506A1 (en) | 2022-03-15 | 2023-09-20 | Evonik Operations GmbH | Powder for processing in a layer-by-layer method with lasers in the visible and near infrared range |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4064574B2 (en) * | 1998-07-29 | 2008-03-19 | 株式会社資生堂 | Anti-diabetic topical skin preparation |
EP2181705A1 (en) | 2008-10-31 | 2010-05-05 | Disphar International B.V. | Sustained-release formulation of gliclazide |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0086468A2 (en) * | 1982-02-15 | 1983-08-24 | Hoechst Uk Limited | Oral anti-diabetic preparation |
EP0418553A1 (en) * | 1989-08-23 | 1991-03-27 | Kurt H. Prof. Dr. Bauer | High potency, rapidly resorbable glibenclamide preparations, process for their preparation and their use |
-
1993
- 1993-10-22 DE DE4336159A patent/DE4336159A1/en not_active Withdrawn
-
1994
- 1994-10-12 EP EP94929538A patent/EP0724427A1/en not_active Withdrawn
- 1994-10-12 CA CA002173366A patent/CA2173366A1/en not_active Abandoned
- 1994-10-12 HU HU9600956A patent/HUT74684A/en unknown
- 1994-10-12 AU AU78555/94A patent/AU7855594A/en not_active Abandoned
- 1994-10-12 NZ NZ274501A patent/NZ274501A/en unknown
- 1994-10-12 JP JP7511289A patent/JPH09504015A/en active Pending
- 1994-10-12 WO PCT/EP1994/003368 patent/WO1995011006A1/en not_active Application Discontinuation
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EP0086468A2 (en) * | 1982-02-15 | 1983-08-24 | Hoechst Uk Limited | Oral anti-diabetic preparation |
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Also Published As
Publication number | Publication date |
---|---|
CA2173366A1 (en) | 1995-04-27 |
NZ274501A (en) | 1997-03-24 |
HU9600956D0 (en) | 1996-06-28 |
HUT74684A (en) | 1997-01-28 |
DE4336159A1 (en) | 1995-04-27 |
EP0724427A1 (en) | 1996-08-07 |
JPH09504015A (en) | 1997-04-22 |
AU7855594A (en) | 1995-05-08 |
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