NO743394L - - Google Patents
Info
- Publication number
- NO743394L NO743394L NO743394A NO743394A NO743394L NO 743394 L NO743394 L NO 743394L NO 743394 A NO743394 A NO 743394A NO 743394 A NO743394 A NO 743394A NO 743394 L NO743394 L NO 743394L
- Authority
- NO
- Norway
- Prior art keywords
- glibenclamide
- phenformin
- salt
- preparation according
- hydrochloride
- Prior art date
Links
- 229960004580 glibenclamide Drugs 0.000 claims description 27
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 24
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical class NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 8
- QMNAQPMXDMLOLD-UHFFFAOYSA-N 6-methyl-4-oxo-5,6-dihydrothieno[2,3-b]thiopyran-2-sulfonamide Chemical compound S1C(C)CC(=O)C2=C1SC(S(N)(=O)=O)=C2 QMNAQPMXDMLOLD-UHFFFAOYSA-N 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 229960001753 phenformin hydrochloride Drugs 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 239000011248 coating agent Substances 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 239000011159 matrix material Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- YSUCWSWKRIOILX-UHFFFAOYSA-N 1-(diaminomethylidene)-2-(2-phenylethyl)guanidine;hydrochloride Chemical compound Cl.NC(N)=NC(N)=NCCC1=CC=CC=C1 YSUCWSWKRIOILX-UHFFFAOYSA-N 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims 2
- 239000008187 granular material Substances 0.000 description 15
- 229960003243 phenformin Drugs 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 239000001993 wax Substances 0.000 description 7
- 229920002261 Corn starch Polymers 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000008120 corn starch Substances 0.000 description 6
- 229940099112 cornstarch Drugs 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 229940123208 Biguanide Drugs 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 229940100389 Sulfonylurea Drugs 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000004898 kneading Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 229960004111 buformin Drugs 0.000 description 1
- XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Inorganic materials [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 239000001175 calcium sulphate Substances 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
Classifications
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Legemiddeltilberedninger tilMedicinal preparations for
oral diabetes-behandling.oral diabetes treatment.
Oppfinnelsens gjenstand er en l^gemiddeltilberedningThe object of the invention is a pharmaceutical preparation
til oral diabetes-behandling og en fremgangsmåte til dens; fremstilling. for oral diabetes treatment and a method thereof; manufacture.
Spesielt vedrører oppfinnelsen en terapeutisk tilbeæd-ning, bestående av en' fast kombinasjon av N-4.-V~~2-(5-klor-2-metoksy-benzamido)-etylZ-fenyl-sulfonyl-N'-cykloheksylurinstoff(kalt Glibenclamid) og l-(2-fenyletyl)-biguanid-hydroklorid (kalt fen-forminhydroklorid), eller et farmasøytisk anvendbart salt herav. In particular, the invention relates to a therapeutic dressing, consisting of a fixed combination of N-4.-V~2-(5-chloro-2-methoxy-benzamido)-ethylZ-phenyl-sulfonyl-N'-cyclohexylurea (called Glibenclamide) and 1-(2-phenylethyl)-biguanide hydrochloride (called phenformin hydrochloride), or a pharmaceutically usable salt thereof.
Diabetikeren som ikke behøver insulin og som reagerer utilstrekkelig på diett alene, behandles i tillegg med orale medi-kamenter. Hertil anvendes sulfonylurinstoffer, hvis hovedsakelige virkningsmekanisme består i frigjøring av endogen insulin eller biguanide preparater, som i det vesentlige ved en hemming av gluko- rieogenensen ved en økning av det anaerobe glukosestoffskifte i legemsperiferien og ved en-hemning av den intestinale :glukosere-sorpsjon senker sukkersykes blodsukkerspeil. Diabetics who do not need insulin and who respond insufficiently to diet alone are additionally treated with oral medications. For this, sulfonylureas are used, whose main mechanism of action consists in the release of endogenous insulin or biguanide preparations, which essentially by inhibiting glucoreogenesis by increasing anaerobic glucose metabolism in the body's periphery and by inhibiting intestinal glucose absorption lowers diabetic's blood sugar level.
Den fri kombinasjon, dvs. adskilt administrering av sulfonylurinstoff- og biguanidpreparater, har i lengere tid vist seg egnet i terapien av diabetikere, som ikke reagerer på en sulfo-nylurinstof f-monoterapi. Ved en stor prosentsats kan karbohydrat-stof f skifte rekompenseres ved en kombinas j onstérapi'. På grunn av deres, forskjellige virkningsmekanisme kompletterer de betazytotrope stoffer og biguanider seg méd hensyn til den antidiabetiske effekt. The free combination, i.e. separate administration of sulfonylurea and biguanide preparations, has for a long time proved suitable in the therapy of diabetics who do not respond to a sulfonylurea monotherapy. In the case of a large percentage, carbohydrate-substance replacement can be compensated by a combination therapy. Due to their different mechanism of action, the betazytotropic substances and biguanides complement each other with regard to the antidiabetic effect.
Ved en terapi.med begge stoffer i fri kombinasjon fremkommer en additiv effekt på blodsukkersenkningen. Det er omtalt fordelen av en slik kombinert terapi; deri viser seg spesielt egnet ved svikt i en sulf onylurinstof f-monoterapi'. Således omtales at den kombinerte behandling ved 50% av senmangler muliggjorde og ved mer enn to. år videreføringen av en tablettbehandling. In a therapy with both substances in free combination, an additive effect on the lowering of blood sugar appears. The advantage of such a combined therapy is discussed; therein proves to be particularly suitable in case of failure of a sulphonylurea monotherapy'. Thus, it is mentioned that the combined treatment enabled 50% of tendon defects and more than two. years the continuation of a tablet treatment.
Enskjønt det av en fast'kombinasjon i forhold til den fri var det ikke å vente noen prinsippielle fordeler, ble det overraskende funnet at den faste-kombinasjon ifølge oppfinnelsen av fenforminsalt.og glibenclamid. ikke bare har fordelene med den fri kombinasjon,, men at kombinasjonsapparatets .virkning overgår' virkningen av den adskilte, administrering av begge komponenter. Although no advantages in principle were to be expected from a fixed combination compared to the free one, it was surprisingly found that the fixed combination according to the invention of phenformin salt and glibenclamide. not only has the advantages of the free combination,, but that the effect of the combination apparatus exceeds that of the separate administration of both components.
Av et kombinasjonspreparat, som har en slik syner-gistisk virkning, må glibenclamidet.med .en gang i maven frigjøres og fenforminsaltet frigjøres protrahert. Dette oppnås ved at man sammenfatter de to virksomme stoffer i en do ser in gs enhet, hvori fenforminsaltet: foreligger i retardert, form og glibenclamid i mave-saftoppløselig form. Of a combination preparation, which has such a synergistic effect, the glibenclamide must be released immediately in the stomach and the phenformin salt released protractedly. This is achieved by combining the two active substances in one dosage unit, in which the phenformin salt: is available in a retarded form and glibenclamide in a gastric juice-soluble form.
Spesielt, foretrukket er tosjiktstabletter, drasjeer eller manteltabletter, idet begge sistrevnte kjerner består av fenforminsalt i retardert form, hvorpå glibenclamid pådrasjeres resp. som ommantles med glibenclamid. In particular, two-layer tablets, coated tablets or coated tablets are preferred, as both last-cracked cores consist of phenformin salt in retarded form, on which glibenclamide is applied respectively. which is coated with glibenclamide.
Fremstillingen av tilberedningene foregår etterThe preparation of the preparations takes place after
i og for seg kjente metoder.per se known methods.
Penforminsaltet innleires fortrinnsvis i en voks-matrdls med vanlige bærestoffer og frigjøringsregulerende stoffer, som eksempelvis natriumklorid, natriumcitrat, natrium- e'ller kaliumfosfat eller spesielt melkesukker. Som voks egner det seg naturlige, og syntetiske, som. f.eks .. bievoks eller montan-estervoks . Av de angjeldende bærestoffer skal det eksempelvis nevnes: Kalsiumfosfat.eller -sulfat og aluminiumoksyd samt spesielt aluminiumhydroksyd. The penformin salt is preferably embedded in a wax matrix with usual carriers and release-regulating substances, such as sodium chloride, sodium citrate, sodium or potassium phosphate or especially milk sugar. Natural and synthetic waxes are suitable, such as eg .. beeswax or montan ester wax . Of the carrier substances in question, examples should be mentioned: Calcium phosphate or sulphate and aluminum oxide and especially aluminum hydroxide.
Dosrelasjonen av enkeltkomponenter glibenclamid The dosage relationship of individual components glibenclamide
f enforminsaltet utgjør fortrinnsvis 1 : 10, Preparater, som inneholder 2,5 til 5S0 mg glibenclamid og 25 til 50 mg fenforminhydro-klorid er foretrukket. Ved den høyere virksomme, stoffdose har to-sjiktstablettene vist seg som spesielt fordelaktige. The phenformin salt is preferably 1:10. Preparations containing 2.5 to 550 mg glibenclamide and 25 to 50 mg phenformin hydrochloride are preferred. At the higher effective drug dose, the two-layer tablets have proven to be particularly advantageous.
Den synergistiske virkning.av de to virksomme stoffer i en tilberedning ifølge oppfinnelsen kunne vises ved hjelp av følgende undersøkelser: Det i undersøkelsen anvendte preparat inneholdt i form av en tosjiktstablett pr. enhet 2,5 mg glibenclamid til om-gående frigjøring og 25' mg fenformin-hydroklorid innleiret i et retardasjonssjikt til protrahert frigjøring, (ifølge eksempel 1). The synergistic effect of the two active substances in a preparation according to the invention could be demonstrated with the help of the following investigations: The preparation used in the investigation contained in the form of a two-layer tablet per unit 2.5 mg glibenclamide for immediate release and 25 mg phenformin hydrochloride embedded in a retardation layer for prolonged release, (according to example 1).
Det ble i første rekke beregnet hvilke dose glibenclamid og av et biguanid (100 mg buformin og 500 mg metformin ble satt likt med 50 mg.fenformin) tilsvarte en bestemt innstillings - kvalitet før omstilling på kombinasjonspreparatet.. Deretter ble alle pasienter oppdelt i samme innstillingskvalitet. etter deres dose, som beregnet samlet dose og dividert med det eventuelle tilfelleantall. It was primarily calculated which dose of glibenclamide and of a biguanide (100 mg buformin and 500 mg metformin were added equally to 50 mg phenformin) corresponded to a specific setting quality before switching to the combination preparation. Then all patients were divided into the same setting quality . according to their dose, as calculated total dose and divided by the possible number of cases.
Den kliniske undersøkelse av tilberedningen ifølge oppfinnelsen førte til det overraskende resultat at ved diabetikere, som under den forangående. frie kombinasjonsterapi har meget god resp. god innstillingskvalitet, kunne det oppnås en dosisinnsparing. The clinical examination of the preparation according to the invention led to the surprising result that in diabetics, as under the preceding. free combination therapy has very good resp. good setting quality, a dose saving could be achieved.
Med administrering av de to i en legemiddelform kombinerte virksomme stoffer fremkommer en farmakologisk synergisme. With the administration of the two active substances combined in a pharmaceutical form, a pharmacological synergism emerges.
Den spesielle fordel ved denne tilberedning ligger altså i at den ønskede terapeutiske virkning oppnås med doser som-ligger under de som er nødvendige' for behandling med de enkelte komponenter. The particular advantage of this preparation therefore lies in the fact that the desired therapeutic effect is achieved with doses which are below those necessary for treatment with the individual components.
Tabell 1 viser den tydelige redusering av begge kompp-nenter (ca. 1/3) ved de "meget godt" til "godt" innstilte pasienter. Table 1 shows the clear reduction of both components (approx. 1/3) in the "very good" to "good" adjusted patients.
Som ytterligere fordel ved kombinasjonstilberedningen i forhold til administrering av enkeltkomponentene:er det å fremheve at antallet av "måtelig" innstilte som også "sviktende" betegnede As a further advantage of the combination preparation in relation to the administration of the individual components: it is worth emphasizing that the number of "moderately" adjusted as well as "failingly" designated
diabetikere ble nedsatt.diabetics were reduced.
Også ved diabetikere som under overnevnte terapi viste en bedre enn "måtelig" innstilling, bedret stoffvekseltil-standen seg etter omstilling på tilberedningen ifølge oppfinnelsen. Noen insulinpasienter kunne likeledes omstilles til glibenclamid-fenformin-tilberedningen. Also in diabetics who during the above-mentioned therapy showed a better than "moderate" attitude, the metabolic state improved after switching to the preparation according to the invention. Some insulin patients could also be switched to the glibenclamide-phenformin preparation.
Preparatet har vist seg spesielt egnet ved eldre (ofte glemske) pasienter. Her kommer fastkombinasjonen spesielt til fordel, fordi den nedsetter faren for å glemme resp. feilinntak av to -adskilt anordnede komponenter, som det må regnes med ved enhver permanent medikasjon. Ulemper ved denne fastkombinasjon ble ikke iakttatt. ' The preparation has proven particularly suitable for elderly (often forgetful) patients. Here, the fixed combination is particularly beneficial, because it reduces the risk of forgetting or wrong intake of two separately arranged components, which must be taken into account with any permanent medication. Disadvantages of this fixed combination were not observed. '
Av fenformin er det kjent at det fra en bestemt individuell forskjellig dosis, overveiende kan frembringe gastrointestinale bivirkninger. En spesiell fordel ved den galeniske applikasjonsform ifølge oppfinnelsen er å se i at den i en voksmatriks innleirede fenformin-hydrokloriddel frigjøres protrahert og således reduseres de gastrointestinale ubehag til et minimum. I motsetning hertil er det ønskelig med en hurtig frigjøring av glibenclamid.. Begge krav oppfylles av tilberedningen ifølge oppfinnelsen. Of phenformin, it is known that from a certain individual different dose, it can predominantly produce gastrointestinal side effects. A particular advantage of the galenic application form according to the invention is that the phenformin hydrochloride part embedded in a wax matrix is released protractedly and thus the gastrointestinal discomfort is reduced to a minimum. In contrast, a rapid release of glibenclamide is desirable. Both requirements are met by the preparation according to the invention.
I det i$Lgende skal det ved utvalgte eksempler for-klares sammensetning og fremstilling av tilberedningen ifølge oppfinnelsen. In the following, the composition and preparation of the preparation according to the invention will be explained by means of selected examples.
Eksempel 1. (Tosjiktstabletter)Example 1. (Bilayer tablets)
Sammensetning:Composition:
Fremstilling av Glibenclamidsjiktet (10G.000 tabletter). Production of the Glibenclamide layer (10G,000 tablets).
Av bestanddelene 1 til 3 fremstilles en homogen blanding og denne knaes ved hjelp av maisstivelsesklister (= 0,5 kg maisstivelse som del av 3) og forarbeides på.vanlig måte til et granulat. From the components 1 to 3, a homogeneous mixture is prepared and this is kneaded with the help of corn starch paste (= 0.5 kg corn starch as part of 3) and processed in the usual way into a granule.
Til det tørre granulat tilblandes 0,275 kg maisstivelse (som del av 3) og bestanddelene 4, 5 og 6. 0.275 kg of corn starch (as part of 3) and components 4, 5 and 6 are mixed with the dry granules.
Fremstillingen av fenformin- retardsjiktet (100.000 tabletter). The production of the phenformin retard layer (100,000 tablets).
Bestanddelene 7, 8, 9 og 11 blandes homogent og impregneres med en oppløsning av voksen 10 i eri egnet blande- resp. kna-maskin. Components 7, 8, 9 and 11 are mixed homogeneously and impregnated with a solution of wax 10 in a suitable mixing or kneading machine.
Som oppløsningsmiddel for voksen egner det seg klorerte hydrokarboner. As a solvent for the wax, chlorinated hydrocarbons are suitable.
Den jevnt gjennomfuktede masse tørkes på vanlig måte, granuleres og blandes deretter med bestanddelene 12 og 13. The evenly moistened mass is dried in the usual way, granulated and then mixed with components 12 and 13.
Glibenclamidgranulatet og fenformin-retardgranulatet presses til tosjiktstabletter. The glibenclamide granulate and the phenformin retard granulate are pressed into bilayer tablets.
Eksempel 2 (manteltabletter).Example 2 (coated tablets).
Sammensetning:Composition:
Fremstilling av glibenclamidgranulatet Production of the glibenclamide granulate
som omtalt ved eksempel 1.as discussed in example 1.
Til knaing av blanding 1 - 3 anvendes maisstivelsesklister fremstilt av 1,7 kg maisstivelse (del av 3). Den til det tørre granulat tilblandede maisstivelsesdel utgjør 1 kg (del av 3). Fremstilling av fenformin- retardgranulat. For kneading mixture 1 - 3, cornstarch paste made from 1.7 kg of cornstarch (part of 3) is used. The cornstarch part mixed into the dry granules amounts to 1 kg (part of 3). Production of phenformin retard granules.
Blandingen av bestanddelene 7>8 og 9 impregneres som omtalt i eksempel 1 med oppløsningen av voksen og det herav frem-stilte tørre granulat blanées med bestanddelene 11 og 12. The mixture of components 7, 8 and 9 is impregnated as described in example 1 with the solution of wax and the resulting dry granules are mixed with components 11 and 12.
Glibenclamidgranulatet og fenformin-retardgranulatet presses på en presscoater til mant elt ab lett er.. Av fenformin-retardgranulatet presses i første rekke en kjerne og-denne kjerne ommantles med glibenclamidgranulatet. The glibenclamide granulate and the phenformin retard granulate are pressed on a press coater until the material is smooth. A core is first pressed from the phenformin retard granulate and this core is coated with the glibenclamide granulate.
Eksempel 3 (Tos jikts.tabletter)Example 3 (Two jikts.tablets)
Sammensetning:Composition:
Fremstilling av Glibenclamidsjikt (100.000 tabletter), ifølge eksempel 1. Det kan presses det i eksempel 1 omtalte granulat med dobbelt sluttvekt. Production of Glibenclamide layer (100,000 tablets), according to example 1. The granules mentioned in example 1 can be pressed with twice the final weight.
Fremstilling av fenformin- retardsjikt (100.000 tabletter) ifølge eksempel 1. Production of phenformin retard layer (100,000 tablets) according to example 1.
Glibenclamidgranulatet og fenformin-retardgranulatet presses til tosjiktstabletter.. The glibenclamide granules and the phenformin retard granules are pressed into two-layer tablets.
Eksempel 4 (drasjeer).Example 4 (draches).
Det presses, tilsvarende sammensetningen.ifølge eksempel 2, bikonvekse fenformin-retardkjerner (1 kjerne inneholder 25 mg fenformin-hydroklorid). Corresponding to the composition according to example 2, biconvex phenformin retard cores are pressed (1 core contains 25 mg of phenformin hydrochloride).
Fenformin-retardkjernen drasjeres på vanlig måte ogThe phenformin retard core is draped in the usual way and
i drasjeringsdekket innarbeides 2,5 mg glibenclamid. 2.5 mg glibenclamide is incorporated into the dressing.
Glibenclamidet dispergeres hertil i drasjeringssuspen^sjonen og fordeles ved forstøvning jevnt på kjernen. For this purpose, the glibenclamide is dispersed in the coating suspension and distributed by atomization evenly on the core.
En ytterligere fremgangsmåte består i at man fukter drasjekjernen jevnt med en klebeoppløsning av følgende sammensetning: A further method consists in moistening the cover core evenly with an adhesive solution of the following composition:
På é,en jevnt med klebeoppløsning fuktede kjerne på-pudres glibenclamid i blanding med hjelpestoffer og de således belagte kjerner tørkes med blåseluft. Denne prosess gjentas således inntil det samlede virksomme stoff er fordelt jevnt på kjerneover-flaten. Glibenclamide is powdered in a mixture with excipients on one core evenly moistened with adhesive solution and the thus coated cores are dried with blowing air. This process is thus repeated until the total active substance is distributed evenly on the core surface.
Sammensetning av glibenclamid- innstrøblanding.Composition of glibenclamide bedding mixture.
De med glibenclamid belagte drasjekjerner drasjeres til avslutning på vanlig måte. The coated cores coated with glibenclamide are coated to finish in the usual way.
Claims (9)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19732347531 DE2347531A1 (en) | 1973-09-21 | 1973-09-21 | MEDICINAL PREPARATIONS FOR ORAL DIABETES TREATMENT |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO743394L true NO743394L (en) | 1975-04-14 |
Family
ID=5893251
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO743394A NO743394L (en) | 1973-09-21 | 1974-09-20 |
Country Status (12)
| Country | Link |
|---|---|
| JP (1) | JPS5053521A (en) |
| AU (1) | AU7349374A (en) |
| BE (1) | BE820222A (en) |
| DE (1) | DE2347531A1 (en) |
| DK (1) | DK496774A (en) |
| FI (1) | FI274174A (en) |
| FR (1) | FR2244481A1 (en) |
| IL (1) | IL45690A0 (en) |
| NL (1) | NL7412254A (en) |
| NO (1) | NO743394L (en) |
| SE (1) | SE7411852L (en) |
| ZA (1) | ZA745981B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61260013A (en) * | 1985-05-14 | 1986-11-18 | Katsumi Takada | Multi-layer tablet consisting of three parts |
| US5985843A (en) * | 1995-04-03 | 1999-11-16 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical composition containing sucralfate |
| MY125516A (en) * | 1999-11-16 | 2006-08-30 | Smithkline Beecham Plc | Novel composition based on thiazolidinedione and metformin and use |
| FR2816841B1 (en) * | 2000-11-22 | 2004-02-06 | Lipha | NOVEL PHARMACEUTICAL COMPOSITIONS WITH ANTIDIABETIC ACTION AND PROCESS FOR THEIR PREPARATION |
| US7964216B2 (en) * | 2001-01-12 | 2011-06-21 | Sun Pharma Advanced Research Company Limited | Spaced drug delivery system |
| ITFI20010230A1 (en) * | 2001-11-29 | 2003-05-29 | Menarini Int Operations Lu Sa | PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF TYPE II DIABETES |
-
1973
- 1973-09-21 DE DE19732347531 patent/DE2347531A1/en active Pending
-
1974
- 1974-09-16 NL NL7412254A patent/NL7412254A/en unknown
- 1974-09-19 AU AU73493/74A patent/AU7349374A/en not_active Expired
- 1974-09-19 FI FI2741/74A patent/FI274174A/fi unknown
- 1974-09-20 DK DK496774A patent/DK496774A/da unknown
- 1974-09-20 ZA ZA00745981A patent/ZA745981B/en unknown
- 1974-09-20 SE SE7411852A patent/SE7411852L/ not_active Application Discontinuation
- 1974-09-20 NO NO743394A patent/NO743394L/no unknown
- 1974-09-21 JP JP49108328A patent/JPS5053521A/ja active Pending
- 1974-09-22 IL IL45690A patent/IL45690A0/en unknown
- 1974-09-23 FR FR7432021A patent/FR2244481A1/en not_active Withdrawn
- 1974-09-23 BE BE148792A patent/BE820222A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NL7412254A (en) | 1975-03-25 |
| FI274174A (en) | 1975-03-22 |
| DE2347531A1 (en) | 1975-04-30 |
| AU7349374A (en) | 1976-03-25 |
| FR2244481A1 (en) | 1975-04-18 |
| ZA745981B (en) | 1975-10-29 |
| DK496774A (en) | 1975-05-26 |
| SE7411852L (en) | 1975-03-24 |
| IL45690A0 (en) | 1974-11-29 |
| BE820222A (en) | 1975-03-24 |
| JPS5053521A (en) | 1975-05-12 |
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