DD266099A1 - METHOD FOR PRODUCING STABLE WAESSER VITAMIN D SOLUTIONS - Google Patents
METHOD FOR PRODUCING STABLE WAESSER VITAMIN D SOLUTIONS Download PDFInfo
- Publication number
- DD266099A1 DD266099A1 DD30731887A DD30731887A DD266099A1 DD 266099 A1 DD266099 A1 DD 266099A1 DD 30731887 A DD30731887 A DD 30731887A DD 30731887 A DD30731887 A DD 30731887A DD 266099 A1 DD266099 A1 DD 266099A1
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- solutions
- vitamin
- waesser
- polyethylene glycol
- producing stable
- Prior art date
Links
- 229940088594 vitamin Drugs 0.000 title description 4
- 239000011782 vitamin Substances 0.000 title description 4
- 229930003231 vitamin Natural products 0.000 title description 3
- 235000013343 vitamin Nutrition 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000003722 vitamin derivatives Chemical class 0.000 title 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims abstract description 12
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 10
- 229930003316 Vitamin D Natural products 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 7
- 235000019166 vitamin D Nutrition 0.000 claims abstract description 7
- 239000011710 vitamin D Substances 0.000 claims abstract description 7
- 150000003710 vitamin D derivatives Chemical class 0.000 claims abstract description 7
- 229940046008 vitamin d Drugs 0.000 claims abstract description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims 1
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 abstract description 5
- 229960002061 ergocalciferol Drugs 0.000 abstract description 5
- 235000001892 vitamin D2 Nutrition 0.000 abstract description 5
- 239000011653 vitamin D2 Substances 0.000 abstract description 5
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 abstract description 5
- 235000005282 vitamin D3 Nutrition 0.000 abstract description 5
- 239000011647 vitamin D3 Substances 0.000 abstract description 5
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 abstract description 5
- 229940021056 vitamin d3 Drugs 0.000 abstract description 5
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 230000002411 adverse Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 229940068917 polyethylene glycols Drugs 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000001795 light effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 229940093430 polyethylene glycol 1500 Drugs 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- VUYXVWGKCKTUMF-UHFFFAOYSA-N tetratriacontaethylene glycol monomethyl ether Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO VUYXVWGKCKTUMF-UHFFFAOYSA-N 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Die Erfindung betrifft ein Verfahren zur Herstellung von stabilen, waessrigen Vitamin-D-Loesungen. Erfindungsgemaess werden polare Loesungen des Ergocalciferols und Colecalciferols mit Polyethylenglykol einer definierten Molekuelgroesse oder mit einem Gemisch verschiedener Polyethylenglykole versetzt. Der Wirkstoff zeigt in Gegenwart des Polyethylenglykols eine signifikant hoehere Stabilitaet.The invention relates to a process for the preparation of stable, aqueous vitamin D solutions. According to the invention, polar solutions of ergocalciferol and colecalciferol are mixed with polyethylene glycol of a defined molecular size or with a mixture of different polyethylene glycols. The active ingredient shows in the presence of polyethylene glycol a significantly higher stability.
Description
Anwendungsgebiet der ErfindungField of application of the invention
Die Erfindung betrifft ein Verfahren zur Herstellung von wäßrigen Vitamin-D-Lösungen mit verlängerter Haltbarkeit.The invention relates to a process for the preparation of aqueous vitamin D solutions with extended shelf life.
Charakteristik des bekannten Standes der TechnikCharacteristic of the known state of the art
Varschiedene Vitamine sind dadurch gekennzeichnet, daß sie sich sehr reaktiv verhalten und demzufolge ihre Verarbeitung zu haltbaren Präparaten besondere Schwierigkeiten bereitet.Varied vitamins are characterized by the fact that they behave very reactive and consequently their processing into durable preparations causes particular difficulties.
Zu ihnen gehören die D-Vitemine Ergocalciferol und Cotecalciferol. Die Lagenähigkeit von Arzneimitteln wie PolyVitaminpräparaten wird durch diese Wirkstoffe begrenzt. Daher sind Vei fahren zur Stabilisierung der D-Vitamine seit langem von Interesse und Gegenstand galenischer Entwicklungsarbeiten.These include the D-vitemine ergocalciferol and cotecalciferol. The layerability of drugs such as polyVitaminpräparaten is limited by these drugs. Therefore, vaccines for stabilizing D-vitamins have long been of interest and have been the subject of Galenic developmental work.
Ergocalciferol und Cholecalciferol werden durch photokatalytische Oxidation abgebaut, so doß neben dem Sauerstoff- auch der Lichteinfluß zu beachten ist. Während aber die Lichtwirkung in sehr einfacher Weise durch einen Lichtschutz wie Glasfärbung herabgesetzt werden kann, sind die Möglichkeiten zur Beschränkung der Sauerstoffreaktion bisher relativ gering. In erster Linie werden Antioxidantien eingesetzt, die kompetitiv den Sauerstoff binden (P. Schuler und V. Bühler in D. Essig, J. Hofer, P. C.Ergocalciferol and cholecalciferol are degraded by photocatalytic oxidation, so in addition to the oxygen and the light influence is observed. But while the light effect can be reduced in a very simple manner by a light protection such as glass staining, the possibilities for limiting the oxygen reaction are so far relatively low. Primarily antioxidants are used which competitively bind the oxygen (P. Schuler and V. Bühler in D. Essig, J. Hofer, P.C.
Schmidt, H. Stumpf (Ed.], Stabilisierungstechnologie, Wege zur haltbaren Arzneiform, S. 65 bis 91 (1986)).Schmidt, H. Stumpf (Ed.], Stabilization Technology, Pathways to Durable Drug Form, pp. 65 to 91 (1986)).
Über die bisher eingesetzter. Antioxidantien wurde eine internationale Diskussion über die Anwendbarkeit und auftretende nachteilige Nebenwirkungen gefühlt.About the previously used. Antioxidants have been an international discussion on the applicability and adverse effects occurring.
Einen anderen Weg stellt der Zusatz geringer Tensidmengen dar iR. Hüttenrauch, S. Fricke. P. Zielko, WP DD 239804 A1Another way is the addition of small amounts of surfactant iR. Hut smoke, S. Fricke. P. Zielko, WP DD 239804 A1
Um eine größere Variationsbreite der Stabilisierungsmethodon zu erreichen, wurde nach weiteren Faktoren gesucht. Dabei kam auch eine synergistische Wirkung und Addition verschiedener Effekte in Betracht (L. Klotz, R. Hüttenra· cn, W. Müller, Pharmazie 20,β0β|1965|).In order to achieve a wider variation of the stabilization methodon, further factors were searched for. A synergistic effect and addition of various effects were also considered (Klotz, R. Hüttenra · cn, W. Müller, Pharmacie 20, β0β | 1965 |).
Ziel der ErfindungObject of the invention
Ziel der Erfindung ist di6 Schaffung eines Verfahrens zur Herstellung von waßiigen Vitamin-D-Lösungen mit verbesserter Stabilität gegenüber Sauerstoffeinfluß und mit geringeren nachteiligen Nebenwirkungen.The aim of the invention is to provide a process for the preparation of aqueous vitamin D solutions with improved stability against oxygen influence and with less adverse side effects.
Darlegung des Wesens der ErfindungExplanation of the essence of the invention
Die Aufgabe der Erfindung ist die Bereitstellung eines Verfahrens zur Gewinnung von stabilen wäßrigen Vitamin-D-Lösungen mittels Zusatz eines pharmazeutischen Hilfsstoffes.The object of the invention is to provide a process for obtaining stable aqueous vitamin D solutions by adding a pharmaceutical excipient.
Erfindungsgemäß worden polare Lösungen des Ergocalciferol« und Colecalciferols mit Polyethylenglykol einer definierten Molekülgröße oder mit einem Gemisch verschiedener Polyothylenglykole vercetzt.According to the invention, polar solutions of ergocalciferol and colecalciferol have been crosslinked with polyethylene glycol of a defined molecular size or with a mixture of different polyethyleneglycols.
Bei der Serienuntersuchung verschiedener Hilfsstoffe war überraschend gefunden worden, daß Polyethylonglykole (PEG) die fettlöslichön Vitamine stabilisieren. Von der Struktur der eingesetzten Hilfsstoffe hör, war die stabilisierende Wirkung nicht zu orwarten. In wäßrigen Lösungen mit Imgl- 40000IE) Colecalcifeiol in 100ml wurde folgender Einfluß auf den Zersetzungsverlauf beobachtet:In the serial investigation of various excipients, it had surprisingly been found that polyethylenglycols (PEG) stabilize the fat-soluble vitamins. Listen to the structure of the excipients used, the stabilizing effect was not to be expected. In aqueous solutions with Imgl-40000IE) colecalcifeiol in 100 ml the following influence on the course of decomposition was observed:
Der Wirkstoff besaß in Gegenwart des Polyethylenolykols signifikant höhere Stabilität. Ein Vergleich verschiedener Polyethylenglykole zeigte, daß der Effekt von der Molekülgröße des Hilfsetoffs unabhängig ist. Ebenso spielt der Lichtfluß keine wesentliche Rolle, die Stabilisierung war auch bei Aufbewahrung im Dunkeln deutlich nachweisbar.The active ingredient had significantly higher stability in the presence of polyethylene glycol. A comparison of various polyethylene glycols showed that the effect is independent of the molecular size of the Hilfsetoffs. Likewise, the light flux plays no essential role, the stabilization was clearly detectable even when stored in the dark.
1 g Colecalciferol oder Ergocalciferol wird in 500 ml Ethanol gelöst und mit 9,5 Liter einer Lösung verdünnt, Ίίβ 30% Polyethylenglykol 1500 in Wasser enthält.1 g of colecalciferol or ergocalciferol is dissolved in 500 ml of ethanol and diluted with 9.5 liters of a solution containing 30% polyethylene glycol 1500 in water.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD30731887A DD266099A1 (en) | 1987-09-28 | 1987-09-28 | METHOD FOR PRODUCING STABLE WAESSER VITAMIN D SOLUTIONS |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD30731887A DD266099A1 (en) | 1987-09-28 | 1987-09-28 | METHOD FOR PRODUCING STABLE WAESSER VITAMIN D SOLUTIONS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD266099A1 true DD266099A1 (en) | 1989-03-22 |
Family
ID=5592562
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD30731887A DD266099A1 (en) | 1987-09-28 | 1987-09-28 | METHOD FOR PRODUCING STABLE WAESSER VITAMIN D SOLUTIONS |
Country Status (1)
| Country | Link |
|---|---|
| DD (1) | DD266099A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0588539A1 (en) * | 1992-09-18 | 1994-03-23 | Teva Pharmaceutical Industries, Ltd. | Stabilized pharmaceutical compositions containing derivatives of vitamins D2 and D3 |
-
1987
- 1987-09-28 DD DD30731887A patent/DD266099A1/en not_active IP Right Cessation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0588539A1 (en) * | 1992-09-18 | 1994-03-23 | Teva Pharmaceutical Industries, Ltd. | Stabilized pharmaceutical compositions containing derivatives of vitamins D2 and D3 |
| US5565442A (en) * | 1992-09-18 | 1996-10-15 | Teva Pharmaceutical Industries Ltd. | Stabilized pharmaceutical compositions containing derivatives of vitamins D2 and D3 |
| US5804573A (en) * | 1992-09-18 | 1998-09-08 | Teva Pharmaceutical Industries Ltd. | Stabilized pharmaceutical composition containing derivative of vitamins D2 and D3 |
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| ENJ | Ceased due to non-payment of renewal fee |