BE512305A - - Google Patents

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Publication number: BE512305A
Authority: BE; Belgium
Prior art keywords: insulin; amorphous; suspension; solution; process according
Prior art date

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English (en)

French (fr)

Publication of BE512305A publication Critical patent/BE512305A/fr

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NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 355
102000004877 Insulin Human genes 0.000 claims description 180
108090001061 Insulin Proteins 0.000 claims description 180
229940125396 insulin Drugs 0.000 claims description 179
239000011701 zinc Substances 0.000 claims description 53
239000000725 suspension Substances 0.000 claims description 50
229910052725 zinc Inorganic materials 0.000 claims description 49
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 47
238000002360 preparation method Methods 0.000 claims description 43
229910052751 metal Inorganic materials 0.000 claims description 42
239000002184 metal Substances 0.000 claims description 42
239000000243 solution Substances 0.000 claims description 41
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
238000000034 method Methods 0.000 claims description 32
239000000203 mixture Substances 0.000 claims description 28
150000002739 metals Chemical class 0.000 claims description 26
239000012153 distilled water Substances 0.000 claims description 20
239000000126 substance Substances 0.000 claims description 19
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 18
239000000872 buffer Substances 0.000 claims description 13
238000007792 addition Methods 0.000 claims description 12
238000001556 precipitation Methods 0.000 claims description 11
230000002035 prolonged effect Effects 0.000 claims description 10
229910052759 nickel Inorganic materials 0.000 claims description 9
239000003755 preservative agent Substances 0.000 claims description 9
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
239000007900 aqueous suspension Substances 0.000 claims description 8
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 7
229910052802 copper Inorganic materials 0.000 claims description 7
239000010949 copper Substances 0.000 claims description 7
239000012928 buffer substance Substances 0.000 claims description 6
230000002335 preservative effect Effects 0.000 claims description 6
230000007935 neutral effect Effects 0.000 claims description 5
239000007858 starting material Substances 0.000 claims description 5
PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 4
229910052793 cadmium Inorganic materials 0.000 claims description 4
BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 claims description 4
229910017052 cobalt Inorganic materials 0.000 claims description 4
239000010941 cobalt Substances 0.000 claims description 4
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 4
229910052742 iron Inorganic materials 0.000 claims description 4
229910052748 manganese Inorganic materials 0.000 claims description 4
239000011572 manganese Substances 0.000 claims description 4
150000002736 metal compounds Chemical class 0.000 claims description 4
239000003929 acidic solution Substances 0.000 claims description 3
230000002378 acidificating effect Effects 0.000 claims description 3
150000002500 ions Chemical class 0.000 claims description 3
238000002156 mixing Methods 0.000 claims description 2
230000001105 regulatory effect Effects 0.000 claims description 2
230000001954 sterilising effect Effects 0.000 claims description 2
238000004659 sterilization and disinfection Methods 0.000 claims description 2
102000016261 Long-Acting Insulin Human genes 0.000 claims 1
108010092217 Long-Acting Insulin Proteins 0.000 claims 1
229940100066 Long-acting insulin Drugs 0.000 claims 1
239000000463 material Substances 0.000 claims 1
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 45
239000011550 stock solution Substances 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
235000011187 glycerol Nutrition 0.000 description 17
235000011121 sodium hydroxide Nutrition 0.000 description 17
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 16
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
239000002609 medium Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
238000011017 operating method Methods 0.000 description 5
239000002994 raw material Substances 0.000 description 5
239000001632 sodium acetate Substances 0.000 description 5
235000017281 sodium acetate Nutrition 0.000 description 5
235000005074 zinc chloride Nutrition 0.000 description 5
239000011592 zinc chloride Substances 0.000 description 5
FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 4
229960002319 barbital Drugs 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
238000007705 chemical test Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
238000011146 sterile filtration Methods 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000011976 maleic acid Substances 0.000 description 3
229910021586 Nickel(II) chloride Inorganic materials 0.000 description 2
102000007327 Protamines Human genes 0.000 description 2
108010007568 Protamines Proteins 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
229910021538 borax Inorganic materials 0.000 description 2
239000006172 buffering agent Substances 0.000 description 2
238000001311 chemical methods and process Methods 0.000 description 2
230000007012 clinical effect Effects 0.000 description 2
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000010790 dilution Methods 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000012530 fluid Substances 0.000 description 2
239000007951 isotonicity adjuster Substances 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 2
229940048914 protamine Drugs 0.000 description 2
239000004328 sodium tetraborate Substances 0.000 description 2
235000010339 sodium tetraborate Nutrition 0.000 description 2
238000003860 storage Methods 0.000 description 2
238000010254 subcutaneous injection Methods 0.000 description 2
239000007929 subcutaneous injection Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
150000003751 zinc Chemical class 0.000 description 2
UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 2
229940007718 zinc hydroxide Drugs 0.000 description 2
229910021511 zinc hydroxide Inorganic materials 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
241000282412 Homo Species 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
241001465754 Metazoa Species 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
230000004308 accommodation Effects 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
244000052616 bacterial pathogen Species 0.000 description 1
229940125717 barbiturate Drugs 0.000 description 1
239000002585 base Substances 0.000 description 1
239000003637 basic solution Substances 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3N=CN=C3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 1
239000003518 caustics Substances 0.000 description 1
239000007979 citrate buffer Substances 0.000 description 1
229960003280 cupric chloride Drugs 0.000 description 1
238000011461 current therapy Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
-1 diethyl barbiturate Chemical compound 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
235000019800 disodium phosphate Nutrition 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
238000009472 formulation Methods 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
239000008103 glucose Substances 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
230000007794 irritation Effects 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000007774 longterm Effects 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
239000000047 product Substances 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
230000006920 protein precipitation Effects 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
229960001763 zinc sulfate Drugs 0.000 description 1
229910000368 zinc sulfate Inorganic materials 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins

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Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Epidemiology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

BE512305D BE512305A (2)

Publications (1)

Publication Number	Publication Date
BE512305A true BE512305A (2)

Family

ID=150800

Family Applications (1)

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BE512305D BE512305A (2)

Country Status (1)

Country	Link
BE (1)	BE512305A (2)

0
- BE BE512305D patent/BE512305A/fr unknown

Publication	Publication Date	Title
US5898067A (en)	1999-04-27	Crystallization of proteins
US2882203A (en)	1959-04-14	Injectable insulin preparation with protracted effect
FR2751875A1 (fr)	1998-02-06	Nouvelles formulations liquides stables a base de paracetamol et leur mode de preparation
US2849370A (en)	1958-08-26	Injectable insulin preparations with protracted effect and process of producing same
US8188005B2 (en)	2012-05-29	Liquid composition for promoting plant growth containing titanium dioxide nanoparticles
CN1134213C (zh)	2004-01-14	含银杀菌剂的制备方法
EP2723774B1 (en)	2019-04-03	Method for manufacturing hydroxyethyl starch derivatives
EP2821393B1 (fr)	2016-04-06	Procédé de synthèse de composés azo
CA1155439A (en)	1983-10-18	Insulin crystal suspension and process for the preparation thereof
DE2614092B2 (de)	1978-02-23	Aminosaeureloesungen zur parenteralen verabreichung
US4849215A (en)	1989-07-18	Pharmaceutical iodophor preparations with controlled iodine:iodide ratio and method of producing the same
EP0966482B1 (en)	2005-04-27	Crystallisation of proteins
EP2747756B1 (de)	2015-07-29	Metabolisierbare salze und deren verwendung in diagnostik und therapie
WO2025060397A1 (zh)	2025-03-27	一种手性二氧化锰纳米颗粒及其制备方法与应用
CH309033A (fr)	1955-08-15	Procédé de fabrication d'une préparation d'insuline injectable, avec effet retard.
CH326787A (fr)	1957-12-31	Procédé de fabrication de préparations injectables d'insuline à effet prolongé
DE950595C (de)	1956-10-11	Verfahren zur Herstellung eines injizierbaren Insulinpraeparates mit verzoegerter Wirkung
BE529315A (2)
BE533298A (2)
BE842679A (fr)	1976-10-01	Procede de preparation de nitrate d'argent
CH301951A (fr)	1954-09-30	Procédé de fabrication d'une préparation d'insuline injectable, avec effet retard.
BE568417A (2)
BE857769A (fr)	1978-02-13	Agents antimicrobiens et leur application
Johnson	1887	VIII. On kreatinins. I. On the kreatinin of urine, as distinguished from that obtained from flesh-kreatin. II. On the kreatiuins derived from the dehydration of urinary kreatin
BE550641A (2)

BE512305A - - Google Patents

Info

Links

Classifications

Landscapes

Publications (1)

Family

ID=150800

Family Applications (1)

Country Status (1)

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