CS209458B2 - Method of making the complex of the insuline salt with the protamine - Google Patents

Method of making the complex of the insuline salt with the protamine Download PDF

Info

Publication number: CS209458B2
Authority: CS; Czechoslovakia
Prior art keywords: insulin; protamine; salt; complex; sodium
Prior art date: 1971-04-30

Application number

CS722923A

Other languages

Czech (cs)

English (en)

Inventor

Richard L Jackson

Original Assignee

Richard L Jackson

Priority date (The priority date 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 date listed.)

1971-04-30

Filing date

1972-04-28

Publication date

1981-12-31

1972-04-28 Application filed by Richard L Jackson filed Critical Richard L Jackson

1981-12-31 Publication of CS209458B2 publication Critical patent/CS209458B2/cs

Links

229940048914 protamine Drugs 0.000 title claims abstract description 38
102000007327 Protamines Human genes 0.000 title claims abstract description 35
108010007568 Protamines Proteins 0.000 title claims abstract description 35
150000003839 salts Chemical class 0.000 title abstract description 7
238000004519 manufacturing process Methods 0.000 title description 3
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class 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 abstract description 155
102000004877 Insulin Human genes 0.000 claims abstract description 77
108090001061 Insulin Proteins 0.000 claims abstract description 77
229940125396 insulin Drugs 0.000 claims abstract description 72
239000000725 suspension Substances 0.000 claims abstract description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
239000012736 aqueous medium Substances 0.000 claims abstract description 10
229910052783 alkali metal Inorganic materials 0.000 claims abstract description 8
-1 alkali metal salt Chemical class 0.000 claims abstract description 7
150000003863 ammonium salts Chemical class 0.000 claims abstract description 7
239000000644 isotonic solution Substances 0.000 claims abstract description 7
238000002360 preparation method Methods 0.000 claims description 24
229910052725 zinc Inorganic materials 0.000 claims description 13
239000011701 zinc Substances 0.000 claims description 13
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 12
238000000034 method Methods 0.000 claims description 12
229910001385 heavy metal Inorganic materials 0.000 claims description 3
230000000694 effects Effects 0.000 abstract description 16
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 abstract description 8
229910052708 sodium Inorganic materials 0.000 abstract description 8
239000011734 sodium Substances 0.000 abstract description 8
230000002035 prolonged effect Effects 0.000 abstract description 7
230000002218 hypoglycaemic effect Effects 0.000 abstract description 5
150000001340 alkali metals Chemical class 0.000 abstract description 4
229910001413 alkali metal ion Inorganic materials 0.000 abstract description 3
238000002425 crystallisation Methods 0.000 abstract description 3
230000008025 crystallization Effects 0.000 abstract description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 abstract description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 abstract description 2
229910052792 caesium Inorganic materials 0.000 abstract description 2
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 abstract description 2
229910052744 lithium Inorganic materials 0.000 abstract description 2
229910052700 potassium Inorganic materials 0.000 abstract description 2
239000011591 potassium Substances 0.000 abstract description 2
150000008044 alkali metal hydroxides Chemical class 0.000 abstract 1
239000008280 blood Substances 0.000 description 22
210000004369 blood Anatomy 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000002609 medium Substances 0.000 description 15
239000000203 mixture Substances 0.000 description 15
241000283973 Oryctolagus cuniculus Species 0.000 description 13
239000007788 liquid Substances 0.000 description 13
159000000000 sodium salts Chemical class 0.000 description 11
239000000243 solution Substances 0.000 description 11
101001011741 Bos taurus Insulin Proteins 0.000 description 10
IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound 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)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](CC=3NC=NC=3)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)=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(C)C)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)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 10
238000002347 injection Methods 0.000 description 9
239000007924 injection Substances 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
239000003085 diluting agent Substances 0.000 description 7
239000000047 product Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
239000013078 crystal Substances 0.000 description 6
230000007935 neutral effect Effects 0.000 description 6
101000993800 Sus scrofa Insulin Proteins 0.000 description 5
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 5
238000001914 filtration Methods 0.000 description 5
229950008679 protamine sulfate Drugs 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
239000003708 ampul Substances 0.000 description 3
229910003002 lithium salt Inorganic materials 0.000 description 3
159000000002 lithium salts Chemical class 0.000 description 3
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
238000003860 storage Methods 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
102000005237 Isophane Insulin Human genes 0.000 description 2
108010081368 Isophane Insulin Proteins 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
238000009472 formulation Methods 0.000 description 2
230000005923 long-lasting effect Effects 0.000 description 2
230000007774 longterm Effects 0.000 description 2
239000000463 material Substances 0.000 description 2
210000000496 pancreas Anatomy 0.000 description 2
229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 2
229940119528 pork insulin Drugs 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
229910021653 sulphate ion Inorganic materials 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
206010048909 Boredom Diseases 0.000 description 1
244000265913 Crataegus laevigata Species 0.000 description 1
102000051325 Glucagon Human genes 0.000 description 1
108060003199 Glucagon Proteins 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
101710123026 High molecular weight antigen Proteins 0.000 description 1
108050008546 Hyperglycemic hormone Proteins 0.000 description 1
108010005991 Pork Regular Insulin Proteins 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000032683 aging Effects 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
238000005275 alloying Methods 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
238000009826 distribution Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000012847 fine chemical Substances 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
231100000989 no adverse effect Toxicity 0.000 description 1
230000003334 potential effect Effects 0.000 description 1
238000004321 preservation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000005406 washing Methods 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

Landscapes

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)
Peptides Or Proteins (AREA)

CS722923A 1971-04-30 1972-04-28 Method of making the complex of the insuline salt with the protamine CS209458B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US13912071A	1971-04-30	1971-04-30

Publications (1)

Publication Number	Publication Date
CS209458B2 true CS209458B2 (en)	1981-12-31

Family

ID=22485216

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS722923A CS209458B2 (en)	1971-04-30	1972-04-28	Method of making the complex of the insuline salt with the protamine

Country Status (23)

Country	Link
US (1)	US3758683A (de)
JP (1)	JPS5735185B1 (de)
BE (1)	BE782651A (de)
CA (1)	CA976085A (de)
CH (1)	CH566784A5 (de)
CS (1)	CS209458B2 (de)
DD (1)	DD100708A5 (de)
DE (1)	DE2219635C3 (de)
DK (1)	DK131760C (de)
ES (1)	ES402176A1 (de)
FI (1)	FI49773C (de)
FR (1)	FR2134658B1 (de)
GB (1)	GB1385086A (de)
HU (1)	HU166989B (de)
IL (1)	IL39181A (de)
NL (1)	NL178258C (de)
NO (1)	NO137178C (de)
PL (1)	PL86966B1 (de)
RO (1)	RO64387A (de)
SE (1)	SE378066B (de)
SU (1)	SU508162A3 (de)
YU (1)	YU36155B (de)
ZA (1)	ZA722243B (de)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK140801B (da) *	1975-01-15	1979-11-19	Nordisk Insulinlab	Fremgangsmåde til fremstilling af et stabilt langtidsvirkende insulinpræparat.
NL193099C (nl) *	1981-10-30	1998-11-03	Novo Industri As	Gestabiliseerde insuline-oplossing.
WO1988002633A1 (en) *	1986-10-20	1988-04-21	Novo Industri A/S	Protamine zinc insulin preparations
ES2053723T3 (es) *	1987-02-25	1994-08-01	Novo Nordisk As	Nuevos derivados de insulina.
DE19726167B4 (de) *	1997-06-20	2008-01-24	Sanofi-Aventis Deutschland Gmbh	Insulin, Verfahren zu seiner Herstellung und es enthaltende pharmazeutische Zubereitung
US6624141B1 (en) *	1999-03-17	2003-09-23	The Regents Of The University Of Michigan	Protamine fragment compositions and methods of use
DE10114178A1 (de) *	2001-03-23	2002-10-10	Aventis Pharma Gmbh	Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität
DE10227232A1 (de) *	2002-06-18	2004-01-15	Aventis Pharma Deutschland Gmbh	Saure Insulinzubereitungen mit verbesserter Stabilität
PT3228320T (pt)	2008-10-17	2020-03-26	Sanofi Aventis Deutschland	Combinação de uma insulina e de um agonista do glp-1
PH12011502708B1 (en)	2009-07-06	2017-11-10	Sanofi Aventis Deutschland	Insulin preparations containing methionine
SG10201500871TA (en)	2009-11-13	2015-04-29	Sanofi Aventis Deutschland	Pharmaceutical composition comprising a glp-1 agonist and methionine
JP5832439B2 (ja)	2009-11-13	2015-12-16	サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング	Ｇｌｐ−１アゴニスト、インスリン及びメチオニンを含む薬学的組成物
CN103179978A (zh)	2010-08-30	2013-06-26	赛诺菲-安万特德国有限公司	Ave0010用于制造供治疗2型糖尿病用的药物的用途
US9821032B2 (en)	2011-05-13	2017-11-21	Sanofi-Aventis Deutschland Gmbh	Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
JP6367115B2 (ja)	2011-08-29	2018-08-01	サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング	２型糖尿病患者の血糖コントロールに使用する組合せ医薬
TWI559929B (en)	2011-09-01	2016-12-01	Sanofi Aventis Deutschland	Pharmaceutical composition for use in the treatment of a neurodegenerative disease
CN107206058A (zh)	2014-12-12	2017-09-26	赛诺菲-安万特德国有限公司	甘精胰岛素/利西拉来固定比率配制剂
TWI748945B (zh)	2015-03-13	2021-12-11	德商賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患治療
TW201705975A (zh)	2015-03-18	2017-02-16	賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患之治療
BR112020002804A2 (pt)	2017-08-24	2020-07-28	Novo Nordisk A/S	composição farmacêutica líquida, e, kit
IL294521A (en)	2020-02-18	2022-09-01	Novo Nordisk As	glp-1 compounds and their uses
CN122005837A (zh) *	2023-08-07	2026-05-12	浙江大学	一种糖响应鱼精蛋白胰岛素及其制备方法和应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR5038E (fr) *	1904-03-09	1905-12-02	Georges Frederic Brade	Perfectionnements dans la fabrication des organes du métronome
GB889769A (en) *	1957-07-18	1962-02-21	Nordisk Insulinlab	Slowly acting insulin preparation in crystalline form

1971
- 1971-04-30 US US00139120A patent/US3758683A/en not_active Expired - Lifetime
1972
- 1972-04-04 ZA ZA722243A patent/ZA722243B/xx unknown
- 1972-04-10 IL IL39181A patent/IL39181A/en unknown
- 1972-04-17 FI FI721077A patent/FI49773C/fi active
- 1972-04-20 DD DD162448A patent/DD100708A5/xx unknown
- 1972-04-21 DE DE2219635A patent/DE2219635C3/de not_active Expired
- 1972-04-24 NO NO1423/72A patent/NO137178C/no unknown
- 1972-04-26 SU SU1778186A patent/SU508162A3/ru active
- 1972-04-26 BE BE782651A patent/BE782651A/xx not_active IP Right Cessation
- 1972-04-26 JP JP4209072A patent/JPS5735185B1/ja active Pending
- 1972-04-27 DK DK209472A patent/DK131760C/da not_active IP Right Cessation
- 1972-04-27 PL PL1972155003A patent/PL86966B1/pl unknown
- 1972-04-27 ES ES402176A patent/ES402176A1/es not_active Expired
- 1972-04-28 CH CH633872A patent/CH566784A5/xx not_active IP Right Cessation
- 1972-04-28 CA CA140,826A patent/CA976085A/en not_active Expired
- 1972-04-28 NL NLAANVRAGE7205865,A patent/NL178258C/xx not_active IP Right Cessation
- 1972-04-28 HU HUEI419A patent/HU166989B/hu unknown
- 1972-04-28 GB GB1974172A patent/GB1385086A/en not_active Expired
- 1972-04-28 FR FR7215270A patent/FR2134658B1/fr not_active Expired
- 1972-04-28 YU YU1142/72A patent/YU36155B/xx unknown
- 1972-04-28 SE SE7205698A patent/SE378066B/xx unknown
- 1972-04-28 CS CS722923A patent/CS209458B2/cs unknown
- 1972-04-29 RO RO7270743A patent/RO64387A/ro unknown

Also Published As

Publication number	Publication date
IL39181A0 (en)	1972-06-28
DK131760B (da)	1975-09-01
NO137178C (no)	1978-01-18
YU114272A (en)	1981-06-30
JPS5735185B1 (de)	1982-07-27
CA976085A (en)	1975-10-14
DE2219635C3 (de)	1981-10-15
US3758683A (en)	1973-09-11
ZA722243B (en)	1973-11-28
NO137178B (no)	1977-10-10
HU166989B (de)	1975-07-28
SU508162A3 (ru)	1976-03-25
NL7205865A (de)	1972-11-01
NL178258B (nl)	1985-09-16
RO64387A (fr)	1979-07-15
DE2219635A1 (de)	1972-11-09
FI49773B (de)	1975-06-30
DD100708A5 (de)	1973-10-05
FR2134658B1 (de)	1975-10-17
PL86966B1 (de)	1976-06-30
BE782651A (fr)	1972-10-26
FI49773C (fi)	1975-10-10
IL39181A (en)	1974-09-10
DK131760C (da)	1976-02-02
ES402176A1 (es)	1975-03-01
GB1385086A (en)	1975-02-26
CH566784A5 (de)	1975-09-30
YU36155B (en)	1982-02-25
NL178258C (nl)	1986-02-17
SE378066B (de)	1975-08-18
DE2219635B2 (de)	1980-11-27
FR2134658A1 (de)	1972-12-08

Publication	Publication Date	Title
DE3880346T2 (de)	1993-07-29	Insulinderivate.
US3758683A (en)	1973-09-11	Insulin product
EP0306824B1 (de)	1992-06-24	Stabilisierte Humanprotein-Präparate
DE69106549T2 (de)	1995-06-22	Thrombin-Zusammensetzung zur oralen Verabreichung.
DE69810755T2 (de)	2003-08-07	Verfahren und zusammensetzungen zur herstellung getrockneter, lagerungsstabiler blutplättchen
RU2108341C1 (ru)	1998-04-10	Способ получения кристаллов гр или производных гр, кристаллы человеческих гр или производных человеческих гр и фармацевтический препарат
EP0516704B1 (de)	1993-11-10	Neue zusammensetzungen auf insulinbasis
CZ445199A3 (cs)	2000-07-12	Stabilní inzulínové prostředky
US5028587A (en)	1991-07-02	Mixed crystals of insulin and insulin derivatives
SU1514240A3 (ru)	1989-10-07	СПОСОБ ПОЛУЧЕНИЯ СТАБИЛЬНЫХ ЦИКЛОДЕКСТРИН-РОМАШКОВЫХ КОМПЛЕКСОВ, включения
DE60009926T2 (de)	2005-04-07	Stabilisierung von gefriergetrocknetem kuchen
US5489577A (en)	1996-02-06	Semi-solid pharmaceutical agent and process for producing the same
JPH08505617A (ja)	1996-06-18	インシュリン状成長因子を含有する安定溶液
CS240957B2 (en)	1986-03-13	Production method of stabile solution containing iron and selenium
DE2920020C2 (de)	1988-09-01
Wycoff	1970	Production of fibrinogen following an endotoxin injection
US5780599A (en)	1998-07-14	Growth hormone crystals and a process for production of growth hormone crystals
US4698361A (en)	1987-10-06	Tris-chydroxymethyl) aminomethane salt of 4-chloro-N-furfuryl-5-sulfamoyl anthranilic acid and diuretic compositions containing the same
EP0012495B1 (de)	1983-06-22	Pharmazeutische Zusammensetzung enthaltend ein wasserlösliches Salz von Amoxycillin und Polyvinylpyrrolidon, und eine Ampulle die eine Einheitsdosis dieser Zusammensetzung enthält
DE69018438T2 (de)	1995-08-24	Methode zur Herstellung einer getrockneten Mischung vom insulinähnlichen Wachstumsfaktor-I (IGF-I).
CZ20011998A3 (cs)	2001-10-17	Troferutin s vysokým obsahem trihydroxietylrutinu a způsob jeho výroby
US2793156A (en)	1957-05-21	Repository penicillin products
US2192386A (en)	1940-03-05	Insulin preparation and process
CA1107647A (en)	1981-08-25	Stable secretin composition, process for its preparation and its use
Trading et al.	1969	Biological and chemical properties of two glucagon preparations with prolonged action