EP1861406A2 - Hydrocodone polymorphs - Google Patents
Hydrocodone polymorphsInfo
- Publication number
- EP1861406A2 EP1861406A2 EP06738095A EP06738095A EP1861406A2 EP 1861406 A2 EP1861406 A2 EP 1861406A2 EP 06738095 A EP06738095 A EP 06738095A EP 06738095 A EP06738095 A EP 06738095A EP 1861406 A2 EP1861406 A2 EP 1861406A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- hydrocodone bitartrate
- peaks
- following xrpd
- filtering
- solution
- 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- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
- C07D489/04—Salts; Organic complexes
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Hydrocodone bitartrate forms are disclosed which are useful as analgesic agents either in combination with or as replacements for hydrocodone bitartrate.
Description
HYDROCODONE POLYMORPHS
BACKGROUND OF THE INVENTION
Hydrocodone (4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1 :1) hydrate (2:5), dihydrocodeinone) is a semi synthetic opioid structurally related to codeine and is approximately equipotent to morphine in producing opiate-like effects.
It is also known as hydrocodone bitartrate. Hydrocodone bitartrate is well known as an antitussive agent and an effective analgesic for mild to moderate pain control. In its most usual product forms hydrocodone bitartrate is combined with acetaminophen, aspirin, ibuprofen, and antihistamines. It is commercially available in tablet, capsule, and liquid forms. Hydrocodone bitartrate is available as Vicodin®, Lortab®,
Vicoprofen®, Tussionex®, Hycomine®, and many other products. The drug is most often administered orally, typically in dosage forms of 5, 7.5, and 10 mg.
SUMMARY OF THE INVENTION
The present invention is directed to ten novel forms of hydrocodone bitartrate. These are identified herein as Forms N-X and an amorphous form. The known form of hydrocodone bitartrate is referred to hereinafter as hydrocodone bitartrate Form I.
DETAILED DESCRIPTION
All ten forms are derived directly or indirectly from hydrocodone bitartrate (hydrocodone bitartrate Form I) and are characterized by physical data, most notable by their X-ray powder diffraction XRPD patterns expressed in terms of °2Θ and the relative intensities of the X-ray diffraction peaks. One aspect of the invention is the novel forms of hydrocodone bitartrate.
Another aspect of this invention is processes to make these novel forms. These novel forms of hydrocodone bitartrate can be used instead of or in combination with hydrocodone bitartrate for its pharmacological effects. The novel forms may be produced and used as the pure form, or the forms may be produced and used in combination with the other novel forms and/or hydrocodone bitartrate Form I. Another aspect of the invention is compositions comprising therapeutically effective amounts of one or more of these novel forms, optionally in combination with hydrocodone bitartrate Form I, and pharmaceutically acceptable carriers therefor. Another aspect is a method of providing a therapeutic (e.g., analgesic) effect to a mammal, preferably a human, in need thereof which comprises administering to said mammal a therapeutic amount of one or more of a novel form of the invention, optionally in combination with
hydrocodone bitartrate. Hydrocodone bitartrate, its therapeutic uses and dose ranges, modes of administration, etc. are all well known in the art.
By pure is meant that each form of the invention is about 90-100%, preferably
95-100%, more preferably 98-100% (wt./wt.) pure; e.g. free of other hydrocodone bitartrate forms, solvents, and/or other undesirable non-hydrocodone bitartrate impurities. A preferred form of the invention is one that is free of other hydrocodone bitartrate forms, preferably 98-100% free.
One embodiment of the invention is the forms of hydrocodone bitartrate made by the processes such as recited in the examples. Another embodiment of the invention is the forms of hydrocodone bitartrate as identified by the X-ray powder diffraction patterns shown below.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG 1 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form I expressed in terms of °2Θ.
FIG 2 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form Il expressed in terms of °2Θ.
FIG 3 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form III expressed in terms of °2Θ. FIG 4 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form IV expressed in terms of °2Θ.
FIG 5 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form V expressed in terms of °2Θ.
FIG 6 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form Vl expressed in terms of °2θ.
FIG 7 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form VII expressed in terms of °2θ.
FIG 8 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form VIII expressed in terms of °2Θ. FIG 9 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form IX expressed in terms of °2Θ.
FIG 10 is an X-ray powder diffraction pattern of hydrocodone bitartrate Form X expressed in terms of °2Θ.
FIG 11 is an X-ray powder diffraction pattern of hydrocodone bitartrate, amorphous form expressed in terms of °2Θ.
Tables I and Il summarize the prominent peaks of the X-ray powder diffraction patterns of each hydrocodone bitartrate form. The relative intensity (R.I.) (l/lo > 10) of each peak is shown, wherein R.I. is the ratio of the height of each peak compared to the highest peak, which is designated as 100%. The data were generated using a Shimadzu v 4.1 X-ray powder diffractometer using Cu Ka radiation, fitted with a fine-focus X-ray tube, set at 40 kV and 40 mA. The divergence and scattering slits were set at 1 ° and the receiving slit was set at 0.15 mm. Diffracted radiation was detected by a NaI scintillation detector. A theta-two theta continuous scan was used at 37min (0.4sec/0.02° step) from 2.5 to 40 °2Θ.
TABLES I & Il
HYDROCODONE XRPD °2Θ PEAKS AND RELATIVE INTENSITIES
TABLE I
TABLE
Table III summarizes the peaks of the X-ray powder diffraction patterns of each hydrocodone bitartrate form that are unique (peaks that are not shared with other forms within +0.20 °2Θ) and/or four additional intense peaks to make up a unique set for each form.
TABLE III
* Denotes the peak of greatest intensity for each form 0
Table IV summarizes the peaks of the X-ray powder diffraction patterns of the amorphous hydrocodone bitartrate form as generated by a Shimadzu v 4.1 X-ray powder diffractometer.
5 TABLE IV
Amorphous Hydrocodone Bitartrate XRPD Peak Ranges
0
5
The forms of the invention may be further defined by other physical properties such as those in Table V.
TABLE V
Unique Properties of Hydrocodone Bitartrate Polymorphs
* Differential scanning calorimetry
One of skill in the art will know how to determine "Hot stage Melt" temperature. Briefly, hot stage melt is determined by placing a sample of the compound on a glass microscope stage and slowly increasing the temperature of the stage until melting of the compound is observed.
As used herein the term "hydrocodone bitartrate" when used alone and without modifiers, refers to the known form or Form I of hydrocodone bitartrate.
The invention is further defined by reference to the following examples, which are intended to be illustrative and not limiting.
EXAMPLE 1
Preparation of Form Il
755 mg of hydrocodone bitartrate was dissolved in 13 ml_ of a 9:1 (v/v) water: ethanol. 2 ml_ of the solution was filtered through a 0.2-μm nylon syringe filter, placed in a fume hood uncapped for evaporation to dryness to yield the title form.
EXAMPLE 2
Preparation of Form III
1000 mg of hydrocodone bitartrate was dissolved in 17 mL of water. ~2 mL of the solution was filtered through a 0.2 μm nylon syringe filter, 16 mL of acetone was added to the filtrate. The solution was placed in a refrigerator at ~4 0C for 4 days, then placed in a freezer (-20 °C) for 1 day. The solid formed was vacuum filtered to afford the title form.
EXAMPLE 3
Preparation of Form IV 1000 mg of hydrocodone bitartrate was dissolved in 17 mL of water. 2 mL of the solution was filtered through a 0.2 μm nylon syringe filter, placed in a fume hood uncapped for evaporation to dryness, and dried under vacuum for 4 days to yield the title form.
EXAMPLE 4
Preparation of Form V
338 mg of hydrocodone bitartrate was dissolved in 7.5 mL of water. The solution was filtered through a 0.2 μm nylon syringe filter, added acetone (72.5 mL) to the filtrate. The solution was covered and placed in a freezer (-20 0C) for 5 days. The title form was then collected through vacuum filtration.
EXAMPLE 5
Preparation of Form Vl
80 mg of hydrocodone bitartrate was dissolved in 20 ml_ of tetrahydrofuran at
60 0C. The solution was filtered while warm and allowed to cool slowly to room temperature. After several hours of cooling, the sample was placed in a refrigerator (4 0C) for 3 days, and a freezer (-20 0C) for 8 days. The solids formed were collected through vacuum filtration, and dried under vacuum to yield the title form.
EXAMPLE 6
Preparation of Form VII 81 mg of hydrocodone bitartrate was dissolved in13 ml_ of methanol and filtered through a 0.2 μm nylon syringe filter, The solution was placed in a freezer (-20 0C) for 9 days the solids formed were removed by vacuum filtration. Seven (7) mL of cooled ethyl ether was added to the filtered solution, covered and placed back into the freezer (-20 0C) for 39 days. The solid formed was vacuum filtered to yield the title form.
EXAMPLE 7
Preparation of Form VIII
95 mg of hydrocodone bitartrate was dissolved in 20 mL of acetonitrile. 5 mL of the solution was filtered through a 0.2 μm nylon syringe filter, left loosely capped in a fume hood to dryness to yield the title form.
EXAMPLE 8
Preparation of Form IX 802 mg of hydrocodone bitartrate was dissolved in 200 mL of tetrahydrofuran at 60 °C. Half the solution was poured into a pre-warmed beaker, which was then placed in a dry ice/acetone bath. The beaker was then covered and placed in a freezer (-20 0C) for 26 days. The solids formed were removed by vacuum filtration. The filtrate was left uncovered in a fume hood to dryness to yield the title form.
EXAMPLE 9
Preparatϊoi. Jf Form X
104 mg of hydrocodone bitartrate was dissolved in 20 ml_ of acetonitrile. The solution was filtered through a 0.2 μm nylon syringe filter and covered with a foil lid containing 5 pinholes, and left in a fume hood to dryness to yield the title form.
EXAMPLE 10
Preparation of Amorphous Form
43 mg of hydrocodone bitartrate was dissolved in 10 ml_ of tetrahydrofuran and 2 ml_ water. Half the solution was filtered through a 0.2-micrometer nylon syringe filter and the solution was allowed to evaporate without a cover (completely evaporated after 1 day) to yield the title form.
Claims
1. A form of hydrocodone bitartrate which is selected from the group consisting of forms; II, III, IV, V1 Vl, VII, VIII, IX, X, and an amorphous form.
2. Form Il of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities (l/lo ):
3. Form III of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities:
4. Form IV of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities:
5. Form V of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities:
6. Form Vl of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities:
7. Form VII of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities:
8. Form VIII of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities:
9. Form IX of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities:
10. Form X of claim 1 which is characterized by the following XRPD °2Θ peaks and relative intensities:
11. The amorphous form of claim 1 which is characterized by a single broad peak from 7.28- 30.76 XRPD °2Θ.
12. Form Il of claim 1 , which is characterized by the following XRPD °2Θ peaks; 10.39, 17.13, 18.32, 20.86, 21.37, 23.01 , 30.24 and 33.55.
13. Form III of claim 1 , which is characterized by the following XRPD °2Θ peaks; 4.86, 6.74, 8.82, 10.40, 26.76 and 36.40.
14. Form IV of claim 1 , which is characterized by the following XRPD °2Θ peaks: 7.54, 11.21 , 19.21 , 22.80 and 25.02.
15. Form V of claim 1 , which is characterized by the following XRPD °2Θ peaks: 6.57, 12.16, 14.54 and 20.76.
16. Form Vl of claim 1 , which is characterized by the following XRPD °2Θ peaks: 12.54, 12.92, 18.01 , 26.15, 28.91 , and 32.74.
17. Form VII of claim 1 , which is characterized by the following XRPD °2Θ peaks: 13.08, 21.64, 21.98 and 28.70.
18. Form VIII of claim 1 , which is characterized by the following XRPD °2Θ peaks: 7.35, 14.70, 25.50 and 26.54.
19. Form IX of claim 1 , which is characterized by the following XRPD °2Θ peaks: 8.21 , 12.66, 17.78, 19.74, and 22.22.
20. Form X of claim 1 , which is characterized by the following XRPD °2Θ peaks: 8.75, 10.56, 18.07 and 22.87.
21. A form of claim 1 which is 90-100 % pure (wt./wt).
22. A form of claim 21 that is 95-100% pure.
23. A form of claim 22 that is 98-100% pure.
24. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in a 9:1 (v/v) wateπethanol mix, filtering the solution, and leaving the mixture uncapped to evaporate to dryness to yield Form II.
25. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in water, filtering the solution and adding acetone, cooling to 4 C for 4 days then reducing the temperature to -20 C for 1 day and vacuum filtering the solid formed to yield Form III.
26 . A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in water, filtering the solution through a nylon syringe filter, leaving the mixture uncapped to evaporate to dryness, and drying under vacuum to yield Form IV.
27. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in water, filtering the solution through a nylon syringe filter and adding acetone to the filtrate and then placing mixture in a freezer at minus 20 degrees C for 5 days and recovering solids by vacuum filtration to yield Form V.
28. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in tetrahydrofuran at 60 degrees C, filtering the solution while warm, cooling to room temperature followed by cooling to 4 degrees C for 3 days followed by cooling to minus 20 degrees C for 8 days, collecting the solids by vacuum filtration, and drying under vacuum to yield Form Vl.
29. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in methanol, filtering the solution through a nylon syringe filter, cooling mixture to minus 20 degrees C for 9 days and removing solids by filtration and then adding ethyl ether to the filtered solution and cooling the resulting mixture to minus 20 degrees C for 39 days and filtering the solids to yield Form VII.
30. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in acetonitrile, filtering the solution through a nylon syringe filter and leaving the mixture loosely capped to evaporate to dryness to yield Form VIII.
31. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in tetrahydrofuran at 60 degrees C, cooling quickly to the temperature of a dry ice acetone mixture and maintaining at a temperature of minus 20 for 26 days, then removing solids through filtration, and leaving uncovered to evaporate to dryness to yield Form IX.
32. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in acetonitrile, filtering the solution through a nylon syringe filter and leaving the mixture under a foil lid containing 5 pinholes to evaporate to dryness to yield Form X
33. A process to make a form of hydrocodone bitartrate of claim 1 , which comprises: dissolving hydrocodone bitartrate in a 5:1 tetrahydrofuran/water (v/v) mixture, filtering the solution through a nylon syringe filter and leaving the mixture uncapped to evaporate to dryness to yield the Amorphous Form.
34. A form of hydrocodone bitartrate made by the process of claim 24.
35. A form of hydrocodone bitartrate made by the process of claim 25.
36. A form of hydrocodone bitartrate made by the process of claim 26.
37. A form of hydrocodone bitartrate made by the process of claim 27.
38. A form of hydrocodone bitartrate made by the process of claim 28.
39. A form of hydrocodone bitartrate made by the process of claim 29.
40. A form of hydrocodone bitartrate made by the process of claim 30.
41. A form of hydrocodone bitartrate made by the process of claim 31.
42. A form of hydrocodone bitartrate made by the process of claim 32.
43. A form of hydrocodone bitartrate made by the process of claim 33.
44. A composition comprising therapeutically effective amounts of one or more of the Forms of claim 1 , optionally in combination with hydrocodone bitartrate, and pharmaceutically acceptable carriers therefor.
45. A method of providing an analgesic effect to a person in need thereof which comprises administering to said person a therapeutic amount of one or more of a Form of claim 1 , optionally in combination with hydrocodone bitartrate.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US66064505P | 2005-03-11 | 2005-03-11 | |
PCT/US2006/008990 WO2006099351A2 (en) | 2005-03-11 | 2006-03-08 | Hydrocodone polymorphs |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1861406A2 true EP1861406A2 (en) | 2007-12-05 |
Family
ID=36685874
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP06738095A Withdrawn EP1861406A2 (en) | 2005-03-11 | 2006-03-08 | Hydrocodone polymorphs |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP1861406A2 (en) |
JP (1) | JP2008533049A (en) |
KR (1) | KR20070119672A (en) |
CN (1) | CN101171253A (en) |
AU (1) | AU2006223129A1 (en) |
CA (1) | CA2621943A1 (en) |
IL (1) | IL185801A0 (en) |
MX (1) | MX2007011192A (en) |
WO (1) | WO2006099351A2 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB201419454D0 (en) * | 2014-10-31 | 2014-12-17 | Cambrex Charles City Inc | New process |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2577947A (en) * | 1951-12-11 | Manufacture of dihydrocodeinone | ||
US2544291A (en) * | 1949-04-05 | 1951-03-06 | New York Quinine And Chemical | Alkaloid manufacture |
GB9717629D0 (en) * | 1997-08-21 | 1997-10-22 | Johnson Matthey Plc | Removal of residual organic solvents |
SK286047B6 (en) * | 2004-04-13 | 2008-01-07 | Zentiva, A. S. | Method for the preparation of 4,5alpha-epoxy-6-oxomorphinane derivatives |
US7692013B2 (en) * | 2004-10-27 | 2010-04-06 | Mallinkrodt Inc. | Method for separation and purification of hydrocodone by preparative chromatography |
-
2006
- 2006-03-08 WO PCT/US2006/008990 patent/WO2006099351A2/en active Application Filing
- 2006-03-08 AU AU2006223129A patent/AU2006223129A1/en not_active Abandoned
- 2006-03-08 CA CA002621943A patent/CA2621943A1/en not_active Abandoned
- 2006-03-08 KR KR1020077023157A patent/KR20070119672A/en not_active Application Discontinuation
- 2006-03-08 MX MX2007011192A patent/MX2007011192A/en unknown
- 2006-03-08 EP EP06738095A patent/EP1861406A2/en not_active Withdrawn
- 2006-03-08 CN CNA2006800153424A patent/CN101171253A/en active Pending
- 2006-03-08 JP JP2008501047A patent/JP2008533049A/en active Pending
-
2007
- 2007-09-06 IL IL185801A patent/IL185801A0/en unknown
Non-Patent Citations (1)
Title |
---|
See references of WO2006099351A2 * |
Also Published As
Publication number | Publication date |
---|---|
AU2006223129A1 (en) | 2006-09-21 |
JP2008533049A (en) | 2008-08-21 |
IL185801A0 (en) | 2008-01-06 |
KR20070119672A (en) | 2007-12-20 |
CN101171253A (en) | 2008-04-30 |
WO2006099351A3 (en) | 2007-02-22 |
AU2006223129A2 (en) | 2006-09-21 |
MX2007011192A (en) | 2007-11-21 |
WO2006099351A2 (en) | 2006-09-21 |
CA2621943A1 (en) | 2006-09-21 |
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