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Encapsulating biological active substances into erythrocytes
| Details |
Inventors: Ropars, Claude; Nicolau, Yves C.; Chassaigne, Maurice;
Assignee: Centre National de la Recherche Scientifique (CNRS) (Paris, FR); Centre Hospitalier Regional de Tours (Tours, FR); Studiengesellschaft Kohle MBH (Muelheim/Ruhr, DE)
Primary Examiner: Rosen; Sam
Assistant Examiner:
Attorney, Agent or Firm: Sprung, Horn, Kramer & Woods
This invention relates to a process for the encapsulation in human or animal erythrocytes of at least one substance having a biological activity, characterized in that the primary compartment of at least one dialysis element is continuously supplied with an aqueous suspension of erythrocytes, the secondary compartment of the dialysis element contains an aqueous solution which is hypotonic with respect to the erythrocyte suspension in order to lyse the erythrocytes, the erythrocyte lysate is in contact with said substance having a biological activity and, in order to reseal the membrane of the erythrocytes, the osmotic and/or oncotic pressure of the erythrocyte lysate is increased after it has been brought into contact with said substance having a biological activity. |
|
DETAILED DESCRIPTION We claim: 1.
A process for the encapsulation in human or animal erythrocytes of at least one substance having a biological activity utilizing a dialysis element having a primary compartment and a secondary compartment comprising continuously supplying the primary compartment of the dialysis element with an aqueous suspension of erythrocytes, and supplying the secondary compartment of the dialysis element with an aqueous solution which is hypotonic with respect to the erythrocyte suspension in order to lyse the membranes of the erythrocytes and form an erythrocyte lysate, the erythrocyte lysate being contacted with the substance having a biological activity and increasing the osmotic pressure of the erythrocyte lysate in order to reseal the membranes of the erythrocytes.
2.
A process according to claim 1, wherein the osmotic pressure of the erythrocyte lysate is increased by passing it into the primary compartment of the dialysis element, the secondary compartment of the dialysis element containing a solution which is hypertonic with respect to the lysate and the resealed lysate being continuously recovered.
3.
A process according to claim 1, characterised in that the osmotic pressure of the lysate is increased by mixing it with a solution which is hypertonic with respect to said lysate.
4.
A process according to claim 1, characterised in that lysis is carried out at a temperature between 0.
degree.
and 10.
degree.
C.
5.
A process according to claim 1, characterised in that resealing is carried out at a temperature between 20.
degree.
and 40.
degree.
C.
6.
A process according to claim 1, characterised in that the substance having a biological activity is added before or during lysis.
7.
A process as claimed in claim 1, wherein a first dialysis element is continuously fed with an aqueous erythrocyte suspension having an isotonic strength of from 180 to 220 mos.
8.
A process as claimed in claim 1, characterized in that the isotonic strength of the aqueous erythrocyte suspension is adjusted to between 180 and 220 mos by continuously feeding the primary compartment of an additional dialysis element with an aqueous erythrocyte suspension, the secondary compartment of this additional dialysis element being fed with an aqueous solution which is hypotonic in relation to the erythrocyte suspension in order to adjust the isotonic strength of the primary compartment to between 180 and 220 mos
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