Method and system for externally treating human blood

• US 4,321,919 A
• Filed: 12/11/1979
• Issued: 03/30/1982
• Est. Priority Date: 12/11/1979
• Status: Expired due to Term

• Current Assignee: Eleanor F. Bourke, Frederic A. Bourke, Jr., Richard L. Edelson, Ruth C. Edelson
• Original Assignee: Leukocyte Research Incorporated
• Inventors: Edelson, Richard L.
• Primary Examiner(s): Michell, Robert W.
• Assistant Examiner(s): Swisher, Nancy A. B.
• Application Number:
  US06/102,553
• Time in Patent Office: 840 Days
• Field of Search: 128/214 B, 128/275.1, 128/207.22, 128/214 R, 128/214.2, 128/1.1, 128/1 R, 128/395, 128/DIG. 3
• US Class Current: 604/6.08
• CPC Class Codes: A61M 1/3616 Batch-type treatment
• CPC Class Codes: A61M 1/3681 by irradiation
• CPC Class Codes: A61M 1/3686 by removing photoactive agents after irradiation
• CPC Class Codes: Y10S 128/03 Heart-lung

Abstract

A method and system are disclosed for externally treating human blood, with the objective of reducing the functioning lymphocyte population in the blood system of a human subject. According to the method, blood is withdrawn from the subject and passed through an ultraviolet radiation field in the presence of from about 1 nanogram to 100 micrograms per ml of blood, of a dissolved psoralen capable of forming photoadducts with DNA, to thereby effect covalent bonding between the psoralen and the nucleic acid of the lymphocytes, thereby altering the said nucleic acid and inhibiting the metabolic processes of the lymphocytes; and thereupon returning the irradiated blood to the subject. The withdrawn blood may be formed into an extracorporeal stream and flowed through a treatment station whereat the irradiation is effected, as for example by exposure to UV energy in the wave length range of from about 3200 to 4000 Angstroms; and such flow process may be conducted on a continuous basis. If desired, at least portions of the treated blood may then be separated, as for example by a continuous centrifuge, before returning the remaining diverted blood to the subject.

Claims

1. A method for reducing the population of lymphocytes with intense metabolic activity in the blood supply of a human subject, comprising the steps of:

withdrawing whole blood from said subject, forming said whole blood into an extracorporeal stream, flowing said stream through a treatment station which comprises a thin chamber substantially transparent to UV radiation, irradiating said withdrawn whole blood in said treatment station with UV radiation in the presence of about 1 nanogram to 100 micrograms of a dissolved psoralen capable when activated by said UV radiation to effect chemical bonding between said psoralen and said lymphocytes, thereby selectively inhibiting the metabolic processes of said lymphocytes; and

returning the irradiated whole blood to said subject.

2. A method in accordance with claim 1, wherein said psoralen comprises 8-MOP.

3. A method in accordance with claim 1, wherein said withdrawing of said whole blood, passage to such treatment station, and return of said whole blood to said subject, is carried out as a continuous operation.

4. A method in accordance with claim 3, wherein the flow rate of said extracorporeal bloodstream is in the range of from about 10 to 75 ml/min.

5. A method in accordance with claim 3, including the further step of separating at least portions of said lymphocyte population before returning said whole blood to said subject, by passing said bloodstream through a continuous flow centrifuge.

6. A method in accordance with claim 5, wherein excess quantities of said psoralen are removed from the extracorporeal stream by withdrawing blood plasma at said centrifuge and replacing same with fresh psoralen-free plasma.

7. A method in accordance with claim 1, including the further step of separating at least portions of said lymphocyte population before returning said whole blood to said subject.

8. A method in accordance with claim 1, wherein said whole blood is irradiated with photoenergy in the UVA wavelength range, and at a radiation dose level of from about 0.1 to 100 joules/cm².

9. A method in accordance with claim 1, wherein said psoralen is dissolved in said whole blood by mixing same with said whole blood subsequent to withdrawing the whole blood from said subject.

10. A method in accordance with claim 1, wherein said psoralen is dissolved in said whole blood by administering said psoralen orally to said subject.

11. A method in accordance with claim 1, wherein said psoralen is methyl or methoxy substituted.

12. A method in accordance with claim 11, wherein said psoralen is methyl-substituted at one or more of the 4, 4'"'"', 5'"'"' and 8 positions.

13. A method in accordance with claim 12, wherein said psoralen comprises 4, 5'"'"',8-trimethylpsoralen.

14. A method for reducing the population of lymphocytes with intense metabolic activity in the blood supply of a human subject, comprising the steps of:

withdrawing whole blood from said subject, forming said whole blood into an extracorporeal stream, flowing said stream through a treatment station which comprises a thin chamber substantially transparent to UV radiation, irradiating said withdrawn whole blood in said treatment station with UV radiation in the presence of an effective amount of 8-methoxypsoralen within the range of from about 1 nanogram to 100 micrograms per ml of blood capable when activated by said UV radiation to effect chemical bonding between said 8-methoxypsoralen and said lymphocytes, thereby selectively inhibiting the metabolic processes of said lymphocytes; and

returning the irradiated whole blood to said subject, wherein said process is carried out continuously.

15. The process of claim 14 wherein said chamber is a UV-transparent plastic.

16. The process of claim 14 wherein the psoralen, is an isotonic solution, is introduced into the extracorporeal stream.