DK2459176T3 - Krystallisationsfremgangsmåde og biotilgængelighed - Google Patents
Krystallisationsfremgangsmåde og biotilgængelighed Download PDFInfo
- Publication number
- DK2459176T3 DK2459176T3 DK10805109.5T DK10805109T DK2459176T3 DK 2459176 T3 DK2459176 T3 DK 2459176T3 DK 10805109 T DK10805109 T DK 10805109T DK 2459176 T3 DK2459176 T3 DK 2459176T3
- Authority
- DK
- Denmark
- Prior art keywords
- zoledronic acid
- lysine
- complex
- water
- zoledronic
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 22
- 238000002425 crystallisation Methods 0.000 title description 3
- 230000008025 crystallization Effects 0.000 title description 3
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims description 253
- 229960004276 zoledronic acid Drugs 0.000 claims description 162
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- DDLVWJKPGCPJKJ-UHFFFAOYSA-N (1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid;trihydrate Chemical compound O.O.O.OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 DDLVWJKPGCPJKJ-UHFFFAOYSA-N 0.000 description 13
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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
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- 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
- A61K31/66—Phosphorus compounds
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- 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
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Claims (10)
1. Krystallinsk molekylekompleks omfattende zoledronsyre eller et salt deraf og et hjælpestof udvalgt blandt lysin og glycin.
2. Molykylekompleks udvalgt fra gruppen bestående af: et krystallinsk zoledronsyre-, vand- og L-lysin-kompleks; et krystallinsk zoledronsyre-, vand- og DL-lysin-kompleks; et krystallinsk zoledronsyre-, vand- og glycin-kompleks; et krystallinsk zoledronsyre-, L-lysin- og vand-kompleks kendetegnet ved et røntgenpulverdiffraktionsmønster med toppe ved cirka 9,0, 14,4, 18,1, 26,0 og 29,6 ±0,2 0 2Θ; et krystallinsk zoledronsyre-, L-lysin- og vand-kompleks kendetegnet ved et røntgenpulverdiffraktionsmønster med toppe ved cirka 9,6, 10,7, 14,3, 21,4, 23,5 ±0,2 0 2Θ; et krystallinsk zoledronsyre-, DL-lysin- og vand-kompleks kendetegnet ved et røntgenpulverdiffraktionsmønster med toppe ved cirka 8,3, 11,8, 12,3, 15,8 og 20,8 ±0,2 ° 2Θ; et krystallinsk zoledronsyre-, DL-lysin- og vand-kompleks kendetegnet ved et røntgenpulverdiffraktionsmønster med toppe ved cirka 9,1, 14,7, 18,0, 21,2 og 26,0 ±0,2 0 2Θ; et krystallinsk zoledronsyre- og glycin-kompleks kendetegnet ved et røntgenpulverdiffraktionsmønster med toppe ved cirka 10,2, 17,8, 19,9, 22,9 og 28,1 ±0,2 ° 2Θ; et krystallinsk zoledronsyre-, DL-lysin- og vand-kompleks kendetegnet ved et røntgenpulverdiffraktionsmønster med toppe ved cirka 9,7, 10,8, 14,4, 18,9, 21,4 ±0,2 ° 2Θ; et krystallinsk zoledronsyre-, DL-lysin-, ethanol- og vand-kompleks kendetegnet ved et røntgenpulverdiffraktionsmønster med toppe ved cirka 8,8, 9,7, 17,6, 23,1 og 26,5 ±0,2 ° 2Θ; når røntgenpulverdiffraktionsmønstre indsamles over et vinkelspand på 3° til 40° 2Θ under anvendelse af Cu Κα-stråling med λ = 1,540562 Å.
3. Sammensætning omfattende det krystallinske molekylkompleks omfattende zoledronsyre eller et salt deraf og lysin ifølge krav 1 eller krav 2, og et overskud af glycin, lysin eller blandinger deraf, fortrinsvis et overskud af lysin.
4. Sammensætning omfattende det krystallinske molekylkompleks omfattende zoledronsyre eller et salt deraf og lysin ifølge krav 1 eller krav 2, og et overskud af glycin, lysin eller blandinger deraf, fortrinsvis et overskud af glycin.
5. Farmaceutisk sammensætning omfattende det krystallinske molekylkompleks ifølge krav 1 eller krav 2, eller sammensætningen ifølge krav 3 eller krav 4, og en farmaceutisk acceptabel excipiens.
6. Farmaceutisk sammensætning ifølge krav 5, hvor sammensætningen er en oral fast doseringsform.
7. Farmaceutisk sammensætning ifølge krav 6, hvor sammensætningen er en oral doseringsform udvalgt blandt en tablet, en kapsel og en flydende opslæmning af det faste molekylekompleks.
8. Molekylekompleks ifølge krav 1 eller krav 2, sammensætning ifølge krav 4 eller krav 5 eller farmaceutisk sammensætning ifølge et hvilket som helst af kravene 6 til 8 til anvendelse som lægemiddel.
9. Molekylekompleks ifølge krav 1 eller krav 2, sammensætning ifølge krav 3 eller krav 4, eller farmaceutisk sammensætning ifølge et hvilket som helst af kravene 5 til 6 til anvendelse i behandling og/eller forebyggelse af sygdomstilstande forbundet med osteoporose, hypercalcæmi, cancerfremkaldt knoglemetastase, Pagets knoglesygdom eller adjuvans- eller neoadjuvans-cancerbehandlinger.
10. Molekylekompleks ifølge krav 1 eller krav 2, sammensætning ifølge krav 3 eller krav 4, eller farmaceutisk sammensætning ifølge et hvilket som helst af kravene 5 til 7 til anvendelse til fremme af biotilgængeligheden eller permeabiliteten af zoledrinsyre eller et salt deraf hos en patient med behov derfor.
Applications Claiming Priority (7)
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