DE2435664A1 - Mikrokuegelchen, verfahren zu ihrer herstellung und anwendung bei der herstellung von injizierbaren arzneimitteln - Google Patents
Mikrokuegelchen, verfahren zu ihrer herstellung und anwendung bei der herstellung von injizierbaren arzneimittelnInfo
- Publication number
- DE2435664A1 DE2435664A1 DE19742435664 DE2435664A DE2435664A1 DE 2435664 A1 DE2435664 A1 DE 2435664A1 DE 19742435664 DE19742435664 DE 19742435664 DE 2435664 A DE2435664 A DE 2435664A DE 2435664 A1 DE2435664 A1 DE 2435664A1
- Authority
- DE
- Germany
- Prior art keywords
- microspheres
- polymer
- agent
- aqueous phase
- methacrylic acid
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 8
- 229940126601 medicinal product Drugs 0.000 title description 3
- 239000004005 microsphere Substances 0.000 claims description 45
- 239000008346 aqueous phase Substances 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 12
- 239000000178 monomer Substances 0.000 claims description 12
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 9
- 229920000642 polymer Polymers 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 239000003995 emulsifying agent Substances 0.000 claims description 7
- 239000000839 emulsion Substances 0.000 claims description 7
- -1 alkyl methacrylate Chemical compound 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 5
- 238000004132 cross linking Methods 0.000 claims description 4
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 4
- 125000005395 methacrylic acid group Chemical group 0.000 claims description 4
- 239000004014 plasticizer Substances 0.000 claims description 4
- 238000006116 polymerization reaction Methods 0.000 claims description 4
- 229920001519 homopolymer Polymers 0.000 claims description 3
- 239000003981 vehicle Substances 0.000 claims description 3
- 239000002685 polymerization catalyst Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000012907 medicinal substance Substances 0.000 claims 2
- 238000004581 coalescence Methods 0.000 claims 1
- DJPZSBANTAQNFN-UHFFFAOYSA-N Testosterone acetate Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(OC(=O)C)C1(C)CC2 DJPZSBANTAQNFN-UHFFFAOYSA-N 0.000 description 13
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 12
- DJPZSBANTAQNFN-PXQJOHHUSA-N testosterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)C)[C@@]1(C)CC2 DJPZSBANTAQNFN-PXQJOHHUSA-N 0.000 description 12
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 8
- 229920002125 Sokalan® Polymers 0.000 description 8
- 229920002689 polyvinyl acetate Polymers 0.000 description 7
- 239000011118 polyvinyl acetate Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 239000007900 aqueous suspension Substances 0.000 description 5
- 239000011049 pearl Substances 0.000 description 5
- 229940068968 polysorbate 80 Drugs 0.000 description 5
- 241001440269 Cutina Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- MPMBRWOOISTHJV-UHFFFAOYSA-N but-1-enylbenzene Chemical compound CCC=CC1=CC=CC=C1 MPMBRWOOISTHJV-UHFFFAOYSA-N 0.000 description 4
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 4
- 229960001076 chlorpromazine Drugs 0.000 description 4
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000011325 microbead Substances 0.000 description 4
- 210000002307 prostate Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 239000002518 antifoaming agent Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229920001688 coating polymer Polymers 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 229940102213 injectable suspension Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 229940116351 sebacate Drugs 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- 239000004160 Ammonium persulphate Substances 0.000 description 1
- OKJCFMUGMSVJBG-ABEVXSGRSA-N Delta(1)-dihydrotestosterone Chemical compound C1C(=O)C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 OKJCFMUGMSVJBG-ABEVXSGRSA-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
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 1
- 235000019395 ammonium persulphate Nutrition 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- MIMDHDXOBDPUQW-UHFFFAOYSA-N dioctyl decanedioate Chemical compound CCCCCCCCOC(=O)CCCCCCCCC(=O)OCCCCCCCC MIMDHDXOBDPUQW-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
Classifications
-
- 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
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
- B01J13/18—In situ polymerisation with all reactants being present in the same phase
- B01J13/185—In situ polymerisation with all reactants being present in the same phase in an organic phase
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7327577A FR2238477B1 (https=) | 1973-07-27 | 1973-07-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2435664A1 true DE2435664A1 (de) | 1975-02-06 |
Family
ID=9123241
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19742435664 Pending DE2435664A1 (de) | 1973-07-27 | 1974-07-24 | Mikrokuegelchen, verfahren zu ihrer herstellung und anwendung bei der herstellung von injizierbaren arzneimitteln |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS5076223A (https=) |
| BE (1) | BE818154A (https=) |
| DE (1) | DE2435664A1 (https=) |
| DK (1) | DK404274A (https=) |
| FR (1) | FR2238477B1 (https=) |
| GB (1) | GB1482663A (https=) |
| LU (1) | LU70619A1 (https=) |
| NL (1) | NL7409978A (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4464434A (en) * | 1978-03-13 | 1984-08-07 | Celanese Corporation | Microencapsulated alkaloidal material and method of producing same |
| EP0143608B1 (en) * | 1983-11-25 | 1992-07-22 | Ciba Specialty Chemicals Water Treatments Limited | Manufacture and use of polymeric beads |
| GB8331546D0 (en) * | 1983-11-25 | 1984-01-04 | Exxon Research Engineering Co | Polymeric compositions |
| JPS6187734A (ja) * | 1984-10-03 | 1986-05-06 | Japan Synthetic Rubber Co Ltd | 中空ポリマ−粒子の製造方法 |
| US4690825A (en) * | 1985-10-04 | 1987-09-01 | Advanced Polymer Systems, Inc. | Method for delivering an active ingredient by controlled time release utilizing a novel delivery vehicle which can be prepared by a process utilizing the active ingredient as a porogen |
| US5840293A (en) * | 1988-11-16 | 1998-11-24 | Advanced Polymer Systems, Inc. | Ionic beads for controlled release and adsorption |
| DE4015753A1 (de) * | 1990-05-16 | 1991-11-21 | Basf Ag | Farbbildner enthaltende mikrokapseln |
| EP1315777B1 (en) | 2000-09-06 | 2007-10-31 | AP Pharma, Inc. | Degradable polyacetal polymers |
| US6590059B2 (en) | 2001-05-11 | 2003-07-08 | Ap Pharma, Inc. | Bioerodible polyorthoesters from dioxolane-based diketene acetals |
| US6524606B1 (en) | 2001-11-16 | 2003-02-25 | Ap Pharma, Inc. | Bioerodible polyorthoesters containing amine groups |
| GB202307501D0 (en) * | 2023-05-19 | 2023-07-05 | Lawley Pharmaceuticals Pty Ltd | Process for preparing dispensable testosterone cream |
-
1973
- 1973-07-27 FR FR7327577A patent/FR2238477B1/fr not_active Expired
-
1974
- 1974-07-24 DE DE19742435664 patent/DE2435664A1/de active Pending
- 1974-07-24 NL NL7409978A patent/NL7409978A/xx unknown
- 1974-07-25 JP JP8468674A patent/JPS5076223A/ja active Pending
- 1974-07-26 LU LU70619A patent/LU70619A1/xx unknown
- 1974-07-26 BE BE147003A patent/BE818154A/xx unknown
- 1974-07-29 GB GB3338074A patent/GB1482663A/en not_active Expired
- 1974-07-29 DK DK404274A patent/DK404274A/da not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5076223A (https=) | 1975-06-21 |
| DK404274A (https=) | 1975-04-01 |
| FR2238477A1 (https=) | 1975-02-21 |
| NL7409978A (nl) | 1975-01-29 |
| LU70619A1 (https=) | 1975-05-21 |
| GB1482663A (en) | 1977-08-10 |
| FR2238477B1 (https=) | 1976-12-03 |
| BE818154A (fr) | 1975-01-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OHJ | Non-payment of the annual fee |