1
266 CI~c~CHO II PATENT ABSTRACTS (,v~ 4526714 CONJUGATES OF ANTICOAGULANT AND PROTEIN Jan Feijen, Wilhelmus E Hennink. Hengelo, Netherlands assigned to Cordis Europa N V CH2OR21 I C=O RII , ,OH O ~ ~ 16 ' R6 tv) Disclosed and claimed is an improved microbial bioconversion to produce 1, 2-dehydro steroids from their corresponding 1,2-saturated derivatives. 4525349 PROCESS FOR THE LARGE- SCALE PRODUCTION OF A VACCINE AGAINST POLIOMYELITIS AND THE RESULTING VACCINE Conjugates are provided which are covalently bonded conjugates of an anticoagulant and pro- tein that are prepared in the presence of a coupling agent that forms amide linkages bet- ween the anticoagulant and the protein. Such amide linking coupling agents exclude highly toxic coupling agents such as CNBr. These con- jugates are useful for enhancing the blood com- patibility of certain surfaces of a prosthetic device, a surgical apparatus, or an extra- corporeal medical device. Bernard J Montagnon, Bernard J C Fanget, L'Arbresle, France assigned to Societe Anonyme dite: lnstitut Merueux A process for large-scale production of poliomyelitis vaccine separately entails, for each type of poliomyelitis virus used, the following steps. A cell strain, using a cell stock, is multi- plied by culturing the same in a liquid nutritive medium on microcarriers in suspension and by successive passages into biogenerator of in- creasing volumes. The last biogenerator is one having a capacity of at least 150 liters and the nutritive medium contains serum. This opera- tion is carried out with stirring at a rate not greater than 40 rpm. At the end of the final pas- sage the liquid nutritive medium is withdrawn and replaced by one that is serum-free. The bio- generator used for the last passage is then inoculated with virus which is permitted to develop, again with stirring at a rate not greater than 40 rpm. After virus culture, the liquid suspension is withdrawn, filtered, concentrated at least 150 times by ultrafiltration, subjected first to gel filtration and then to ion exchange chromatography. The resulting concentrated suspension is diluted with a serum-free medium and then inactivated. The suspensions of the respective types used are mixed from which in- dividual dosages are prepared 4526715 METHOD OF PREPARING HIGHLY PURIFIED, STROMA- FREE, NON-HEPATITIC HUMAN AND ANIMAL HEMOGLOBIN SOLUTIONS Norbert Kothe, Bertra Eichentopf, Kronberg, Federal Republic Of Germany assigned to Bio- test Pharma GmbH To provide a method that allows the prepara- tion, not only from human blood but also from animal blood and in quantities large enough for clinical applications, of highly purified hemoglobin solutions that can be employed for the treatment of humans and that are free of plasma proteins and residual stroma lipids (a) a starting material that contains erythrocytes is pumped over a filter unit that has a pore size bet- ween 0.1 and 1.2 mum in circulation against an isotonic washing solution, (b) the product of (a) is hemolyzed and pumped over an ultrafiltration unit that has a permeability of 80,000 to 100,000 D in circulation against water, and (c) the ul- trafiltrate obtained in stage (b) is pumped and diafiltered over an ultrafiltration unit that has a

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Page 1: 4526714 Conjugates of anticoagulant and protein

266

C I ~ c ~ C H O

II

PATENT ABSTRACTS

(,v~ 4 5 2 6 7 1 4

C O N J U G A T E S O F A N T I C O A G U L A N T A N D P R O T E I N

Jan Feijen, Wilhelmus E Hennink. Hengelo, Netherlands assigned to Cordis Europa N V

CH2OR21 I C = O

RII , ,OH

O ~ ~ 16' R6

tv)

Disclosed and claimed is an improved microbial bioconversion to produce 1, 2-dehydro steroids from their corresponding 1,2-saturated derivatives.

4 5 2 5 3 4 9

P R O C E S S F O R T H E L A R G E - S C A L E P R O D U C T I O N O F A

V A C C I N E A G A I N S T P O L I O M Y E L I T I S A N D T H E

R E S U L T I N G V A C C I N E

Conjugates are provided which are covalently bonded conjugates of an anticoagulant and pro- tein that are prepared in the presence of a coupling agent that forms amide linkages bet- ween the anticoagulant and the protein. Such amide linking coupling agents exclude highly toxic coupling agents such as CNBr. These con- jugates are useful for enhancing the blood com- patibility of certain surfaces of a prosthetic device, a surgical apparatus, or an extra- corporeal medical device.

Bernard J Montagnon, Bernard J C Fanget, L'Arbresle, France assigned to Societe Anonyme dite: lnstitut Merueux

A process for large-scale production of poliomyelitis vaccine separately entails, for each type of poliomyelitis virus used, the following steps. A cell strain, using a cell stock, is multi- plied by culturing the same in a liquid nutritive medium on microcarriers in suspension and by successive passages into biogenerator of in- creasing volumes. The last biogenerator is one having a capacity of at least 150 liters and the nutritive medium contains serum. This opera- tion is carried out with stirring at a rate not greater than 40 rpm. At the end of the final pas- sage the liquid nutritive medium is withdrawn and replaced by one that is serum-free. The bio- generator used for the last passage is then inoculated with virus which is permitted to develop, again with stirring at a rate not greater than 40 rpm. After virus culture, the liquid suspension is withdrawn, filtered, concentrated at least 150 times by ultrafiltration, subjected first to gel filtration and then to ion exchange chromatography. The resulting concentrated suspension is diluted with a serum-free medium and then inactivated. The suspensions of the respective types used are mixed from which in- dividual dosages are prepared

4 5 2 6 7 1 5

M E T H O D O F P R E P A R I N G H I G H L Y P U R I F I E D , S T R O M A -

F R E E , N O N - H E P A T I T I C H U M A N A N D A N I M A L H E M O G L O B I N

S O L U T I O N S

Norbert Kothe, Bertra Eichentopf, Kronberg, Federal Republic Of Germany assigned to Bio- test Pharma G m b H

To provide a method that allows the prepara- tion, not only from human blood but also from animal blood and in quantities large enough for clinical applications, of highly purified hemoglobin solutions that can be employed for the treatment of humans and that are free of plasma proteins and residual stroma lipids (a) a starting material that contains erythrocytes is pumped over a filter unit that has a pore size bet- ween 0.1 and 1.2 mum in circulation against an isotonic washing solution, (b) the product of (a) is hemolyzed and pumped over an ultrafiltration unit that has a permeability of 80,000 to 100,000 D in circulation against water, and (c) the ul- trafiltrate obtained in stage (b) is pumped and diafiltered over an ultrafiltration unit that has a