DE2617822C3 - Verfahren zur Herstellung eines für die intravenöse Injektion geeigneten Hämoglobinpräparates mit erhöhter Sauerstoffabgabe gegenüber Erythrozyten - Google Patents
Verfahren zur Herstellung eines für die intravenöse Injektion geeigneten Hämoglobinpräparates mit erhöhter Sauerstoffabgabe gegenüber ErythrozytenInfo
- Publication number
- DE2617822C3 DE2617822C3 DE19762617822 DE2617822A DE2617822C3 DE 2617822 C3 DE2617822 C3 DE 2617822C3 DE 19762617822 DE19762617822 DE 19762617822 DE 2617822 A DE2617822 A DE 2617822A DE 2617822 C3 DE2617822 C3 DE 2617822C3
- Authority
- DE
- Germany
- Prior art keywords
- hemoglobin
- erythrocytes
- solution
- oxygen
- treated
- 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.)
- Expired
Links
- 108010054147 Hemoglobins Proteins 0.000 title claims description 34
- 102000001554 Hemoglobins Human genes 0.000 title claims description 34
- 210000003743 erythrocyte Anatomy 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 title claims description 18
- 239000001301 oxygen Substances 0.000 title claims description 18
- 229910052760 oxygen Inorganic materials 0.000 title claims description 18
- 238000000034 method Methods 0.000 title claims description 8
- 238000010253 intravenous injection Methods 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 239000000243 solution Substances 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 29
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 claims description 14
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 claims description 14
- 229960001327 pyridoxal phosphate Drugs 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000007792 addition Methods 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 6
- 206010018910 Haemolysis Diseases 0.000 claims description 5
- 229960001031 glucose Drugs 0.000 claims description 5
- 230000008588 hemolysis Effects 0.000 claims description 5
- 239000013049 sediment Substances 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 150000001768 cations Chemical class 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000007859 condensation product Substances 0.000 claims description 4
- 239000003792 electrolyte Substances 0.000 claims description 4
- 210000002381 plasma Anatomy 0.000 claims description 4
- 230000001698 pyrogenic effect Effects 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 229960000380 propiolactone Drugs 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims 2
- 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 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 4
- OSNSWKAZFASRNG-WNFIKIDCSA-N (2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol;hydrate Chemical compound O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O OSNSWKAZFASRNG-WNFIKIDCSA-N 0.000 description 3
- XOHUEYCVLUUEJJ-UHFFFAOYSA-I 2,3-Diphosphoglycerate Chemical compound [O-]P(=O)([O-])OC(C(=O)[O-])COP([O-])([O-])=O XOHUEYCVLUUEJJ-UHFFFAOYSA-I 0.000 description 3
- CEEQUQSGVRRXQI-UHFFFAOYSA-N Pyridoxal 5-phosphate monohydrate Chemical compound O.CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O CEEQUQSGVRRXQI-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XOHUEYCVLUUEJJ-UWTATZPHSA-N 2,3-bisphospho-D-glyceric acid Chemical compound OP(=O)(O)O[C@@H](C(=O)O)COP(O)(O)=O XOHUEYCVLUUEJJ-UWTATZPHSA-N 0.000 description 2
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 239000003978 infusion fluid Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 238000007865 diluting Methods 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
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000001295 genetical effect Effects 0.000 description 1
- 108010047477 hemoglobin P Proteins 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 1
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000003415 peat Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011046 pyrogen test Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/795—Porphyrin- or corrin-ring-containing peptides
- C07K14/805—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19762617822 DE2617822C3 (de) | 1976-04-23 | 1976-04-23 | Verfahren zur Herstellung eines für die intravenöse Injektion geeigneten Hämoglobinpräparates mit erhöhter Sauerstoffabgabe gegenüber Erythrozyten |
| FR7711719A FR2348703A1 (fr) | 1976-04-23 | 1977-04-19 | Preparation d'hemoglobine appropriee pour l'injection intraveineuse et son procede d'obtention |
| JP4459377A JPS52154515A (en) | 1976-04-23 | 1977-04-20 | Hemoglobin preparation strengthening oxygen release property |
| US05/789,759 US4136093A (en) | 1976-04-23 | 1977-04-21 | Hemoglobin preparation with increased oxygen release |
| GB1681677A GB1576752A (en) | 1976-04-23 | 1977-04-22 | Haemoglobin preparation |
| CH504577A CH638401A5 (en) | 1976-04-23 | 1977-04-22 | Process for the preparation of haemoglobin preparations having an increased oxygen delivery |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19762617822 DE2617822C3 (de) | 1976-04-23 | 1976-04-23 | Verfahren zur Herstellung eines für die intravenöse Injektion geeigneten Hämoglobinpräparates mit erhöhter Sauerstoffabgabe gegenüber Erythrozyten |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2617822A1 DE2617822A1 (de) | 1977-10-27 |
| DE2617822B2 DE2617822B2 (de) | 1980-04-30 |
| DE2617822C3 true DE2617822C3 (de) | 1981-01-08 |
Family
ID=5976043
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19762617822 Expired DE2617822C3 (de) | 1976-04-23 | 1976-04-23 | Verfahren zur Herstellung eines für die intravenöse Injektion geeigneten Hämoglobinpräparates mit erhöhter Sauerstoffabgabe gegenüber Erythrozyten |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE2617822C3 (enExample) |
| FR (1) | FR2348703A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3144705C2 (de) * | 1981-11-11 | 1983-12-08 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | Verfahren zur Herstellung eines lagerstabilen, vernetzten Hämoglobinpräparates mit hoher Sauerstoff-Transportkapazität, sowie das nach diesem Verfahren hergestellte Hämoglobinpräparat |
| DE3501349A1 (de) * | 1985-01-17 | 1986-07-17 | Battelle-Institut E.V., 6000 Frankfurt | Blutersatz |
| US4826811A (en) * | 1986-06-20 | 1989-05-02 | Northfield Laboratories, Inc. | Acellular red blood cell substitute |
-
1976
- 1976-04-23 DE DE19762617822 patent/DE2617822C3/de not_active Expired
-
1977
- 1977-04-19 FR FR7711719A patent/FR2348703A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| DE2617822B2 (de) | 1980-04-30 |
| FR2348703A1 (fr) | 1977-11-18 |
| FR2348703B1 (enExample) | 1981-06-19 |
| DE2617822A1 (de) | 1977-10-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| AG | Has addition no. |
Ref country code: DE Ref document number: 2714252 Format of ref document f/p: P |
|
| 8327 | Change in the person/name/address of the patent owner |
Owner name: BIOTEST AG, 6000 FRANKFURT, DE |