WO2000064875A1 - Procede de pulverisation - Google Patents
Procede de pulverisation Download PDFInfo
- Publication number
- WO2000064875A1 WO2000064875A1 PCT/JP2000/002616 JP0002616W WO0064875A1 WO 2000064875 A1 WO2000064875 A1 WO 2000064875A1 JP 0002616 W JP0002616 W JP 0002616W WO 0064875 A1 WO0064875 A1 WO 0064875A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- particle diameter
- present
- compound
- pulverization
- pulverizer
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/02—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of powders
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- 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
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
Definitions
- the present invention relates to a known (E) -4— [2— [2— [N—ylcetyl-1-N— (4—methoxybenzenesulfonyl) amino] phenyl] ethenyl) having an excellent anticancer effect.
- Pyridin 1 This method relates to the pulverization of one-year-old oxide (hereinafter referred to as “the compound”).
- the pulverization method for making the particles fine is roughly classified into an open circuit pulverization method and a closed circuit pulverization method.
- the open circuit pulverization method is a method in which an object to be pulverized is passed through the pulverization processing section several times within one minute, or substantially] times, for example, and pulverized.
- a product is pulverized by passing it through a pulverizing section many times in a relatively long time.
- a drug is present in a crystalline state more stably thermodynamically than in an amorphous form.
- the drug after pulverization is It is considered desirable to provide it in a crystalline state.
- An object of the present invention is to provide a method for pulverizing the compound while maintaining the crystal form of the compound, a finely powdered form of the compound maintaining the crystalline state, and the like.
- the present inventors have conducted intensive studies and found that the present compound was pulverized by an open-circuit pulverization method.
- the inventors have found that the above object can be solved by finely pulverizing with a machine, and thus completed the present invention.
- the present invention includes a method of pulverizing the compound, which is characterized by pulverizing the compound with an open-circuit pulverizer.
- Examples of the open-circuit pulverizer that can be used in the present invention include a high-speed rotary impact pulverizer and an airflow pulverizer.
- the pulverization of the present compound is suitably performed until the average particle diameter is in the range of l to 25 m and the particle diameter of 50 m or more is 2% or less. It is preferable to carry out the treatment until the particle diameter of the particles in the range of 50 / m or more becomes 1% or less or 0%. From this, the average particle diameter is in the range of 1 to 25 zm, the particle diameter of 50 m or more is 2% or less, preferably the average particle diameter is in the range of 5 to 20 m. Crystalline compounds of the present invention having a particle diameter of 50% or more and 1% or less or 0% (hereinafter referred to as “the finely divided product of the present invention”) can also be mentioned as the present invention.
- a high-speed rotary impact pulverizer When using a high-speed rotary impact pulverizer, it is appropriate to perform pulverization at a rotational speed of 10,000 rpm or more, although it depends on the model used and drug lot, etc., and at a rotational speed of 20, OOOrpm or more. Pulverization is preferred.
- a gas Nagareshiki grinder When using a gas Nagareshiki grinder is appropriate to pulverization treatment at a pressure in the range of 3 ⁇ 7 kg / cm 2 in air weight in the range of 0.5 ⁇ 50m 3 / niin, 10 ⁇ 45 m It is preferable to carry out the pulverization treatment with an air volume in a tartan of 3 / inin and a pressure in a range of 5 to 6 kg / cm 2 .
- the pulverization of the present invention can be easily performed by, for example, supplying the present compound to an open-circuit pulverizer at a suitable supply rate (eg, 10 g to 1,0001 ig / hr) and performing a pulverization treatment.
- a suitable supply rate eg, 10 g to 1,0001 ig / hr
- micronized product of the present invention can be used as a medicament similarly to the present compound.
- Pharmaceutical compositions containing the micronized product of the present invention as an active ingredient include, for example, lung cancer, breast cancer, gastrointestinal cancer, prostate cancer, and blood cancer. Use as an anticancer drug against etc. be able to.
- a pharmaceutical composition containing the micronized product of the present invention as an active ingredient (hereinafter, referred to as “the composition of the present invention”) is prepared by adding the micronized product of the present invention as it is or in a pharmaceutically acceptable non-toxic and inert carrier, for example, 0.1%. To 99.5%, preferably 0.5% to 90%, and can be administered to animals including humans.
- composition of the present invention is desirably administered in a dosage unit form.
- the composition of the present invention can be administered orally, intraosseously, topically (transdermally, instilled, nasally, etc.) or rectally, and oral administration is particularly preferred. Needless to say, it is administered in a dosage form suitable for these administration methods.
- the dosage of the micronized product of the present invention as a medicament is preferably adjusted in consideration of the patient's condition such as age and weight, the administration route, the nature and degree of the disease, the indications, etc.
- capsules containing the micronized product of the present invention were prepared according to the physical mixture formulation shown in Table 2, (Male, 6-9 years old) Oral administration to 4 animals, blood collection over time, and metabolites of this compound in plasma ([E)- 4- (2— [2—CN- (4-methoxybenzenesulfonyl) amino] phenyl] ethenyl] pyridine 1-oxide) concentration was measured by HPLC method.
- Figure 4 shows the results.
- the plasma concentration of the compound was significantly increased by pulverizing the compound.
- FIG. 1 shows an X-ray diffraction pattern according to Example 1.
- the upper part shows the X-ray diffraction pattern after pulverization
- the lower part shows the X-ray diffraction pattern before pulverization.
- the horizontal axis indicates the diffraction angle (.)
- the vertical axis indicates the intensity (cps).
- FIG. 2 shows an X-ray diffraction pattern according to Example 2.
- the upper part shows the X-ray diffraction pattern after pulverization
- the lower part shows the X-ray diffraction pattern before pulverization.
- the horizontal axis indicates the diffraction angle (°)
- the vertical axis indicates the intensity (cps).
- FIG. 1 shows an X-ray diffraction pattern according to Example 1.
- the upper part shows the X-ray diffraction pattern after pulverization
- the lower part shows the X-ray diffraction pattern before pulverization.
- FIG 3 shows an X-ray diffraction pattern according to Comparative Example 1.
- the bottom row shows the X-ray diffraction pattern before grinding
- the second row from the bottom shows the X-ray diffraction pattern 30 minutes after grinding
- the second row from the top shows the X-ray diffraction pattern 60 minutes after grinding.
- the horizontal axis indicates the diffraction angle (°), and the vertical axis indicates the intensity (cps).
- FIG. 4 shows the change in the plasma concentration of the metabolite of the present compound.
- - ⁇ - represents the results for the compound of the present invention pulverized according to the present invention (the pulverized product of the present invention), and-and-represent the results for the compound before pulverization.
- the horizontal axis represents time (hours), and the vertical axis represents the concentration of metabolites in plasma (ig / ml).
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/069,192 US6994283B1 (en) | 1999-04-23 | 2000-04-21 | Method for pulverizing to fine powder |
JP2000613828A JP3849428B2 (ja) | 1999-04-23 | 2000-04-21 | 微粉化法 |
EP00917408A EP1174427A4 (en) | 1999-04-23 | 2000-04-21 | pulverization |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP11681099 | 1999-04-23 | ||
JP11/116810 | 1999-04-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000064875A1 true WO2000064875A1 (fr) | 2000-11-02 |
Family
ID=14696222
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2000/002616 WO2000064875A1 (fr) | 1999-04-23 | 2000-04-21 | Procede de pulverisation |
Country Status (4)
Country | Link |
---|---|
US (1) | US6994283B1 (ja) |
EP (1) | EP1174427A4 (ja) |
JP (1) | JP3849428B2 (ja) |
WO (1) | WO2000064875A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001044195A1 (fr) * | 1999-12-14 | 2001-06-21 | Nippon Shinyaku Co., Ltd. | Dérivés hétérocycliques et médicaments |
WO2002087578A1 (fr) * | 2001-04-10 | 2002-11-07 | Nippon Shinyaku Co., Ltd. | Agent therapeutique pour rhumatisme articulaire chronique |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2460915B (en) | 2008-06-16 | 2011-05-25 | Biovascular Inc | Controlled release compositions of agents that reduce circulating levels of platelets and methods therefor |
TW201613888A (en) | 2014-09-26 | 2016-04-16 | Helsinn Healthcare Sa | Crystalline forms of an NK-1 antagonist |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0754682A1 (en) * | 1994-04-06 | 1997-01-22 | Nippon Shinyaku Company, Limited | Aminostilbazole derivative and medicine |
-
2000
- 2000-04-21 US US10/069,192 patent/US6994283B1/en not_active Expired - Fee Related
- 2000-04-21 JP JP2000613828A patent/JP3849428B2/ja not_active Expired - Fee Related
- 2000-04-21 WO PCT/JP2000/002616 patent/WO2000064875A1/ja not_active Application Discontinuation
- 2000-04-21 EP EP00917408A patent/EP1174427A4/en not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0754682A1 (en) * | 1994-04-06 | 1997-01-22 | Nippon Shinyaku Company, Limited | Aminostilbazole derivative and medicine |
Non-Patent Citations (1)
Title |
---|
See also references of EP1174427A4 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001044195A1 (fr) * | 1999-12-14 | 2001-06-21 | Nippon Shinyaku Co., Ltd. | Dérivés hétérocycliques et médicaments |
US6787546B2 (en) * | 1999-12-14 | 2004-09-07 | Nippon Shinyaku Co., Ltd. | Heterocycle derivatives and drugs |
WO2002087578A1 (fr) * | 2001-04-10 | 2002-11-07 | Nippon Shinyaku Co., Ltd. | Agent therapeutique pour rhumatisme articulaire chronique |
US6967211B2 (en) * | 2001-04-10 | 2005-11-22 | Nippon Shinyaku Co. Ltd. | Remedial agent for chronic articular rheumatism |
KR100801121B1 (ko) * | 2001-04-10 | 2008-02-05 | 니뽄 신야쿠 가부시키가이샤 | 만성 관절 류마티즘 치료제 |
Also Published As
Publication number | Publication date |
---|---|
EP1174427A4 (en) | 2002-07-10 |
EP1174427A1 (en) | 2002-01-23 |
US6994283B1 (en) | 2006-02-07 |
JP3849428B2 (ja) | 2006-11-22 |
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