GB2025385A - Activated carbon and apparatus for hemoperfusion - Google Patents

Abstract

A method and apparatus for hemoperfusion comprising a vessel packed with a spherical active carbon having pores of substantially not larger than 500 ANGSTROM in radius, said spherical active carbon being produced by polymerising an ethylenically unsaturated aromatic compound, making the resulting spherical polymer infusible, calcining the resulting infusible polymer and activating, and the use thereof. The apparatus is useful for the treatment of patients with chronic renal failure, acute intoxication, liver failure, hepatoreal syndrome or the like, particularly as an artificial kidney.

Description

SPECIFICATION Activated carbon and apparatus for hemoperfusion The present invention relates to activated carbon and to apparatus and methods for hemoperfusion. More particularly, it relates to an apparatus for hemoperfusion wherein an active carbon consisting of spherical particles having no surface-coating is used as an adsorbing agent.

It is well known that in the treatment of patients with chronic renal failure, acute intoxication, liver failure, hepatoreal syndrome or the like, it is effective to purify blood by removing injurious materials such as the poisons, metabolic wastes or the like. In the treatment of patients with chronic renal failure, the purification of blood has hitherto been done by using a dialysis membrane. This method, however, is effective in removing materials having a molecular weight of about 300 to about 3000, so-called middle molecules, which are said to be uremic toxins. Attempts have been made to remove the middle molecules by contacting blood with active carbon or by separating blood plasma from the blood by filtration or centrifugation and then contacting the separated blood plasma with active carbon.In this treatment, when the active carbon is used without surface-coating, there are some problems, such as adsorption of blood platelets and leukocytes onto the active carbon, blood coagulation, and occurrence of thrombus due to fine powders released from the active carbon. Accordingly, the active carbon has usually been used after coating of its surface with a hydrophilic high molecular weight compound such as poly(2-hydroxyethyl methacrylate), collodion, albumin, or the like. However, such coated active carbons also have their drawbacks. They are difficult to sterilize and have side effects such as induction of allergy due to the coating material, lowering of adsorptivity due to the coating, difficult coating processes, or the like.

As a result of the present inventors' extensive studies on absorbing agents useful for the blood purification, it has surprisingly been found that a specific spherical active carbon can be used as an adsorbing agent for blood purification without a surface coating of a hydrophilic high molecular weight compound.

The invention provides activated carbon suitable for use as an adsorbent in hemoperfusion in the form of substantially spherical pore containing particles, substantially all the pores being 500A or less in radius, the carbon being produced by polymerising or copolymerising one or more ethylenically unsaturated aromatic compounds to provide substantially spherical, pore containing polymer beads, rendering the polymer beads infusible, calcining the infusible beads to carbon and activating the carbon, the polymerising and calcining conditions being such as to provide the said pores of not more than 500 A radius.

The invention includes a method for producing activated carbon for use in hemoperfusion, comprising polymerising or copolymerising one or more ethylenically unsaturated aromatic compounds to provide substantially spherical, pore containing polymer bead's, rendering the polymer infusible, calcining the infusible beads to carbon and activating the carbon, wherein the polymerising conditions and the calcining conditions are chosen such that the pores in the activated carbon substantially all have a radius of 500 A or less.

Although the present active carbon is used without surface-coating, the preferred active carbons do not suffer from the same drawbacks as conventional uncoated active carbon, such as blood coagulation during the flowing of blood, and further, the decrease of blood platelet and leukocyte counts produced by the new active carbon is as little or even smaller than that found using the known coated active carbon. Also, the undesirable release of fine powders of the active carbon is negligible.

In the present invention, it is essential that substantially all of the pore volume of the present active carbon is due to pores of not substantially larger than 500 A in radius. The preferred pore radius of the present active carbon is not larger than 200 A. With such a pore radius, no thrombus occurs because high molecular weight materials such as blood serum protein are hardly adsorbed onto the active carbon, and further the active carbon has a high mechanical strength and hence almost no undesirable fine powders are produced. it is to be understood that, the present active carbon may contain some pores having larger than 500 A making up a few or several percent of the total pore volume, e.g. 10% or 5%.

The radius of pores of the spherical active carbon may be measured, in case of carbon having pores of less than 50 A, according to the adsorption isotherms of nitrogen which may be measured by Sorptomatic 1800 (made by Carbo Erba), and in case of carbon having pores of 50 to 75,000 A, according to the mercury penetration method using porosimeter 1500 (made by Carbo Erba).

Preferred methods for obtaining the active carbon of the invention are as follows.

The ethylenically unsaturated aromatic compounds used as starting monomer for the preparation of active carbon include styrene, a-methylstyrene, vinyltoluene, ethylvinylbenzene, vinylpyridine, or the like.

The spherical particle polymer is preferably produced by copolymerising an ethylenically unsaturated aromatic compound and one or more other ethylenically unsaturated compounds including a compound having a plurality of ethylenically unsaturated groups which preferably have no conjugated relation with the ethylenically unsaturated aromatic compound. Suitable examples of such compounds having a plurality of ethylenically unsaturated groups are aromatic compounds such as divinylbenzene, divinylnaphthalene, diallyl phthalate, divinylpyridine and aliphatic compounds such as ethyleneglycol diacrylate, ethyleneglycol dimethacrylate, trimethylolpropane trimethacrylate; or the like.

The ethylenically unsaturated aromatic compound may also be copolymerized with a small amount of another ethylenically unsaturated compound. Suitable examples of this other ethylenically unsaturated compound are acrylonitrile, methacrylonitrile, esters of acrylic acid or methacrylic acid with methyl, ethyl, propyl, butyl, cyclohexyl, hydroxyethyl or the like, acrylamide, methacrylamide, vinyl acetate, butadiene, isoprene, chloroprene, or the like.

A preferred spherical particle polymer is a copolymer of styrene and divinylbenzene.

The spherical particle polymer may be produced by conventional methods of suspension polymerisation of an ethylenically unsaturated aromatic compound or a mixture thereof with other comonomer as mentioned above.

Generally, the pore size of the final product is mainly determined by the pore size of the polymer.

The monomer proportions and other polymerisation conditions should therefore be chosen so as to obtain pores of suitable size. Generally the pore size and distribution changes somewhat on calcination, the distribution becoming sharper and the pore size smaller.

The polymer has preferably a macroreticular (macroporous) structure. Macroreticular polymers can be produced by known processes as disclosed in British Patent Specification No. 1,525,420 and Japanese Patent publication Nos. 13792/1962,40431/1971, 888/1972 and 40315/1972.

The preparation of active carbon from macroreticular resin beads is described in United States Patent Specification No. 4040990 and the use of the carbon for removing barbiturates from blood is mentioned. However, the preparation of carbon having the pore size characteristic of this invention is not disclosed.

A polymer comprising spherical particles having a macroreticular structure can, for example, be produced by the following processes.

A A mixture of the ethylenically unsaturated aromatic compound such as styrene and the other ethylenically unsaturated compound such as divinylbenzene is subjected to a suspension polymerisation in an aqueous medium in the presence of a precipitating agent. Said precipitating agent is a substantially water-insoluble liquid and functions as a solvent of these monomers and does not swell the produced polymer and is used in an amount of 20 to 50% by weight on the basis of whole weight of the monomers and the precipitating agent. Suitable examples of the precipitating agent are butanol, heptane, or the like. A conventional radical initiator is used in the above suspension polymerisation.

Generally, it may be said that the pore size in the polymer product tends to be larger when more precipitatìng agent, or a more pbtent precipìtating agent, is used. The pores also tend to be larger when a lesser amount of monomers are used and particularly when the amount of the other, e.g:' the iion- aromatic and/or polyunsaturated monomer, is reduced.

It may therefore be stated generally that it is preferred to produce the polymer beads by aqueous suspension polymerisation of ethylenically unsaturated aromatic monomer and another ethylenically unsaturated monomer, which may be polyunsaturated, in the presence of a precipitating agent, the proportions of monomers and precipitating agent being so chosen as to produce polymer beads containing pores, substantially all of which are less than 500 A in radius.

The spherical polymer thus obtained can be made infusible by known methods using oxygen, ozone, sulfur trioxide, sulfur dioxide, sulfuric acid, chlorosulfonic acid, nitrogen dioxide, chlorine, bromine, hydrogen peroxide, or the like. Preferably, the polymer is made infusible by sulfonation or chlorosulfonation thereof by treating it with sulfuric acid, chlorosulfonic acid or sulfur trioxide, by which the polymer can be made infusible in a high carbon yield within a short period of time. A particularly preferred method for making the polymer infusible is to contact the polymer with vapor of sulfur trioxide.The sulfur trioxide is diulted with dry air, nitrogen, helium, argon or the like and is used in a concentration of not higher than 50% by volume, more preferably not higher than 30% by volume, by which the sulfonation can be done without undesirable disintegration of the spherical polymer.

The infusible spherical polymer thus obtained may then be calcined in an inert gas at a temperature of 500 to 30000C, preferably 800 to 1200 C, more preferably 1000 to 12800C. The calcined spherical polymer may be further activated by known methods, for example, by heating it in steam at a temperature of 700 to 1 0000C to give the desired spherical particles of active carbon.

The surface area of the active carbon thus obtained is preferably 500 m2/g or more, more preferably 800 to 2000 m2/g. When the surface area is smaller than 500 m2/g an undesirably large amount of active carbon is required for obtaining the desired purification effect, which means that too large a column volume is required. On the other hand when the active carbon has a too large surface area, unfavourably fine powders of the active carbon are produced. The spherical active carbon has preferably an average particle size of 500 y or more, but less than 2 mm. When the average particle size is smaller than 500 , undesirable blood coagulation occurs, which induces an unfavourable pressure loss in the column.

The preferred active carbon can be used, without coating with a hydrophilic polymer, for purification of blood without any pressure loss during flowing of blood (e.g. hemoperfusion), and with little lowering of blood platelet and leukocyte counts, and with far less occurrence of fine powder of active carbon in comparison with the conventional coated active carbon.

The apparatus of the present invention comprises a vessel which is packed wholly or partIally with the spherical active carbon without coating, through which blood passes. The vessel may be in any form, but is usually in the form of column.

Purification of blood by the present apparatus may, for example, be carried out by the flow as shown in the accompanying Figure 1.

As is shown in Figure 1 , the blood is introduced into a bubble trap 3 equipped with a pressure gauge 4 through a line 2 by means of a pump 1. In this bubble trap 3, bubbles are removed from the blood. Thus treated blood is taken out from the bubble trap 3 and is sent through a line 5 to a column 6 which is packed with the spherical active carbon. In this column 6, the blood is contacted with the spherical active carbon, and thereby, the injurious materials are adsorbed onto the active carbon. The blood after subjected to the adsorption treatment is then sent to a bubble trap 8 equipped with a pressure gauge 9 and therein it is again subject to removal of bubbles.

The apparatus of the present invention is used in the same manner as with conventional spherical active carbon from petroleum pitch which is coated with a hydrophilic polymer (cf. Kidney International, Vol.10, pages 305-311(1976) and Trans Amer. Soc. Artif. Int. Organs, Vol. XXI, pages 502-509 (1 975)). The flow rate of the blood may vary depending on ihe kind and amount of packed active carbon and other factors well known in this art, but is usually in the range of 100 to 300 mi/min.

The apparatus of the present invention is useful for the treatment of patients with chronic renal failure, acute intoxication, liver failure, hepatoreal syndrome or the like by passing the blood of the patients through the apparatus, wherein the blood is directly contacted with the active carbon packed within the apparatus, or the blood is firstly filtered or centrifuged and the resulting blood plasma is then contacted with the active carbon. For instance, the apparatus may be used as an artificial kidney.

The present invention is illustrated by the following Examples, but is not limited thereto.

EXAMPLE 1 (1) Preparation of spherical active carbon A mixture of styrene (55 g), divinylbenzene (purity: 55%, 145 g), n-heptane (100 g) and benzoyl peroxide (1 g) was added to a solution of gum arabic (2 g) in distilled water (1.0 litre), and the mixture was suspension-polymerised with agitation at 800C for 6 hours. The spherical polymer thus obtained (100 g) was contacted with agitation with sulfur trioxide having a concentration of 30% by volume in nitrogen gas (carrier gas) at 6000 for 5 hours, and then, the temperature was raised to 100000 at a rate of 1 0O00/hour under nitrogen gas to give spherical carbon (85 g). The spherical carbon thus obtained was activated by treating with steam (1200 g) at B00 C.

The spherical active carbon thus obtained had a surface area of 1200 m2/g and had an average pore radius of 100 A and further had 1.0 cc/g of pores of not more than 200 A in radius and less than 0.03 cc/g of pores of more than 500 A in radius. Said pore radius was measured by mercury porosimeter.

The spherical active carbons were classified into those of particle size of 0.5 to 1.0 mm 9 and those of a particle size of 0.7 to 1.4 mm sb and were used for the experiments disclosed hereinafter.

Reference Example 1 In a manner similar to that described in Example 1, a mixture of styrene (145 g), divinylbenzene (55 g) and secbutanol (160 g) was subjected to suspension polymerisation, followed by making infusible, calcining and activating. The spherical active carbon thus obtained had an average pores of 600 A and contained 0.32 cc/g of pores of more than 500 .

Reference Example 2 The spherical active carbons having a particle size of 0.34 to 0.50 mm Q were separated from those obtained in Example 1.

Reference Example 3 Spherical active carbon particles obtained from petroleum pitch (BAC-MU grade, made by Taiyo Kaken, particle size: 0.7-1.4 mm #, 750 g) was immersed in a 0.1% solution of poly(2-hydroxyethyl me+hacrylate) (hereinafter, referred to as "PHEMA") in ethanol for 10 minutes, filtered, dried at 8000 for 20 hours, and then was again immersed in a 1% PHEMA solution, filtered and dried in the same manner as above to give spherical active carbon particles coated with PHEMA.

(2) Measurement of adsorptivity (a) Adsorption of middle molecules and of materials having lower molecular weight than middle molecules.

To a solution of creatinine (uremictoxins, concentration: 20 mg/dl) in saline (100 ml) was added the active carbon to be tested (0.5 g).

Separately, to a solution of Vitamin B12 (representative substance of middle molecules, concentration: 20 mg/dl) in saline (100 ml) was added the active carbon to be tested (2.5 g).

Both solutions as prepared above were shaken at 3700, and the variation of the concentration of remaining substrate was measured with the lapse of time. The results are shown in the following Table 1.

Table 1 Concentration of remaining substrate (mg/dl)

Time Active Active carbon of Active carbon of carbon of petoleum pitch of the present shaking petroleum coated with PHEMA invention Substrate (minute) pitch (Ref. Ex. 3) (Example 1) 20 10 13 8 Creatinine 60 6 8 4 20 4.8 6.4 4.0 Vitamine B12 60 1.0 2.0 0.4 As is clear from the above test results, the spherical active carbon of the present invention had superior adsorptivity to the conventional spherical active carbon of petroleum pitch and the product coated with PHEMA.

(b) Adsorption of blood serum proteins To a solution of albumin (concentration: 14 Hg/ml) in phosphate buffer (pH: 7.4, 100 ml) was added active carbon to be tested (2 g), and the mixture was shaken at 370C for 3 hours, and thereby, the amount of adsorbed albumin per 1 g of active carbon was measured. The test was repeated in respect to y-globulin and fibrinogen. The results are shown in Table 2.

Table 2 Adsorption of blood serum proteins per 1 g of active carbon

Active carbon Active carbon of Active of the present petroleum pitch carbon of invention coated with PHEMA petroleum (Example 1) (Ref. Ex. 3) pitch Content of pores of more than 0.03 > 0.12 0.12 500 A (cc/g) particle size (mm 0.7-1.4 0.7-1.4 0.7-1.4 Adsorption of albumin (CrS/S) 90 140 320 adsorption of vglobul in 120 120 280 (crsls) Adsorption of fibrinogen 120 120 270 As is clear from the above test results, the spherical acive carbon of the present invention shows far lower adsorptivity of blood serum proteins than the conventional spherical active carbon particles derived from petroleum pitch and shows similar lower adsorptivity than the conventional spherical particles of active carbon from petroleum pitch coated with PHEMA.

It is well known that when fibrinogen or glopulin is adhered onto surface of material, it induces thrombosis (cf. S. W. Kim et al, Trans, Amer. Soc. Artif. Int. Organs, Vol XX, 1974, page 449).

Accordingly, the above test results suggest that the spherical particles of active carbon of the present invention are better than the conventional active carbons from petroleum pitch regarding prevention of thrombosis.

Also, it may be assumed that the reason for the smaller adsorption of blood serum proteins by the present active carbon may be the fact that the spherical active carbon of the present invention has almost no pore volume attributable to pores of more than 500 A or less and hence the huge molecules of the blood serum proteins can hardly enter into the fine pores. On the other hand, the conventional active carbon of petroleum pitch has a pore radius of up to 1000 A and hence the blood serum proteins can enter into the pores.

(c) Adsorption of blood platelets Test blood was collected from hepatic vein of HLA male rats weighing 400-500 g. The blood passed through a column of silicon tube (5 mm ) packed with 0.5 of active carbon to be tested in a flow rate of 1 my/1.5 minute. The number of blood platelets in the passed blood was measured by a coulter counter (made by Coulter Electronic Inc.), and the adsorptivity for blood platelets of the active carbon was shown by the reduced number of blood platelets in the blood which passed through the column, the loss of platelets being expressed as a percentage of the number of platelets in the blood originally. The test results are shown in Table 3.

Table 3 Percentage Loss platelets

Active carbon Active carbon having average Active carbon Active carbon having pores particle size of petroleum of the present of more than of less than pitch coated Active carbon invention 500 0.5 mm# with PHEMA of petroleum (Example 1) (Ref. Ex. 1) (Ref. Ex. 2) (Ref. Ex. 3) pitch Content of pores of more than 0.03 > 0.03 > 0.32 0.03 > 0.12 0.12 500 (cc/g) Particle size (mm #) 0.7-1.4 0.5-1.0 0.7-1.4 0.35-0.45 0.7-1.4 0.7-1.4 Reducing rate of blood 21 23 Blood was Blood was 21 40 platelet (%) coagulated coagulated As is clear from the above test results, the spherical active carbon of the present invendon.shows far less adsorptivity for blood platelets in comparison with the conventional spherical active carbon of petroleum pitch and the active carbon having pores of more than 500 A and has similar adsorptivity to that of the spherical active carbon of petroleum pitch coated with PHEMA. Also, even if the active carbon has no pore of more than 500 A but has an average particle size of less than 500 , it it not preferable because of occurrence of blood coagulation. It is well known that thrombus is induced by adsorption of blood platelets, and hence it is preferable to show lower adsorption of blood platelets.

(3) Hemoperfusion test The spherical active carbon of the present invention was packed into a column (inside diameter: 50 mm , inner volume: 400 ml), which was sterilised at 121 0C for 30 minutes.

By using adult dog weighing 10 kg, a circulation system was provided outside of the body, said circulation system being connected between the femoral artery and femoral vein. The column obtained above was connected in the circulation system. The test dog was treated with 3000 units of heparin and then blood was perfused through the circulation system at a flow rate of 150 ml/minute while administering continuously 100 units/kg/hr of heparin to the dog.

During the hemoperfusion, there were measured the change of pressure loss in the column, and also the numbers of blood platelets, leukocytes and erythrocytes were measured before and after the hemoperfusion. The pressure loss in the column was 5 mmHg which did not change during the hemoperfusion for 2 hours. No thrombosis was observed.

The number of blood platelets was reduced by about 1 5% by the hemoperfusion for 2 hours. The number of leukocytes and erythrocytes was not reduced by the hemoperfusion.

When spherical active carbon of petroleum pitch with no coating was used instead of the active carbon of the present invention in the above test, thrombus was observed in the column. When spherical active carbon of petroleum pitch with PHEMA-coating was used, the reduction in the number of blood platelets was similar to the case of using the active carbon of the present invention.

(4) Test of occurrence of fine powder of active carbon Active carbon to be tested (1.5 g) was added to water (10 ml) and the mixture was shaken at 180 r.p.m. for 2 hours. When spherical active carbon of petroleum pitch was used, occurrence of fine powder was observed by the naked eye, but in case of spherical active carbon of the present invention, no fine powder was observed.

After shaking, the mixture was filtered with 0.5 zb Millipore filter. Fine powders of carbon were wholly adhered onto the filter in case of active carbon of petroleum pitch with no coating and a little fine powder was observed in the case of active carbon of petroleum pitch with PHEMA-coating, but in case of active carbon of the present invention, no fine powder was observed, as if as pure water was being filtered.

Furthermore, spherical active carbon of petroleum pitch with PHEMA-coating and spherical active carbon of the present invention (1.5 g) were each added to water (10 ml), and the mixture was treated with ultrasonics for 10 minutes. As a result, it was observed that in case of active carbon of petroleum pitch with PHEMA-coating there was an occurrence of fine powder, but in case of active carbon of the present invention, no fine powder was observed by the naked eye. After the ultrasonic treatment, the amount of fine powder was measured by a coulter counter. As a result, in the case of active carbon of petroleum pitch with PHEMA-coating, fine powders of 1 .0.0 y in particle size were produced in an amount of 500 > 10,000 grainsiml and fine powders of larger than size in particle size were produced in an amount of about 200 grains/mi. On the other hand, in case of active carbon of the present invention, only 1 S50 grains/ml of fine powders of 1.0-4.0 in particle size were counted and no fine powder of larger than 4.0 y in particle size was counted.

Claims (26)

1. Activated carbon suitable for use as an adsorbent in hemoperrusion in the form of substantially spherical pore containing particles, substantially all the pores being 500 A or less in radius, the carbon being produced by polymerising or copolymerising one or more ethylenically unsaturated aromatic compounds to provide substantially spherical, pore containing polymer beads, rendering the polymer beads infusible, calcining the infusible beads to carbon and activating the carbon, the polymerising and calcining conditions being such as to provide the said pores of not more than 500 A radius.

2. Activated carbon as claimed in claim 1, having an average particle size of 500 y to 2 mm.

3. Activated carbon as claimed in claim 1 or claim 2, having a surface area of 500 m2/g or more.

4. Activated carbon as claimed in claim 3, having a surface area of 800 to 2000 m2/g.

5. Activated carbon as claimed in any preceding claim, wherein pores having a radius of more than 500 A make up no more than 10% of the total pore volume.

6. Activated carbon as claimed in claim 5, wherein pores having a radius of more than 500 A make up no more than 5% of the total pore volume.

7. Activated carbon substantially as hereinbefore described in Example 1.

8. A method for producing activated carbon for use in hemoperfusion, comprising polymerising or copolymerising one or more ethylenically unsaturated aromatic compounds to provide substantially spherical, pore containing polymer beads, rendering the polymer infusible, calcining the infusible beads to carbon and activating the carbon, wherein the polymerising conditions and the calcining conditions are chosen such that the pores in the activated carbon substantially all have a radius of 500 A or less.

9. Activated carbon as claimed in claim 8, the polymer beads from which the carbon is produced being obtained by copolymerising an ethylenically unsaturated aromatic compound and at least one other ethylenically unsaturated and optionally aromatic compound.

10. Activated carbon as claimed in claim 9, the polymer beads from which the carbon is produced being obtained by copolymerising a monoethylenically unsaturated aromatic compound with an ethylenically unsaturated compound having a plurality of ethylenic groups.

11. A method as claimed in any one of claims 8 to 10, wherein the or an ethylenically unsaturated compound is styrene, a-methylstyrene, vinyltoluene, ethylvinylbenzene or vinylpyridine.

12. A method as claimed in any one of claims 8 to 11, wherein an ethylenically unsaturated compound is copolymerised with divinylbenzene, divinylnaphthalene, diallylphthalate, divinylpyridine, ethyleneglycol diacrylate, ethyleneglycol dim eth acryl ate or trimethylolpropanetrimeth acryl ate.

13. A method as claimed in claim 12, wherein styrene is copolymerised with divinylbenzene.

14. A method as claimed in any preceding claim, wherein the polymer beads are rendered infusible by treatment with oxygen, ozone, sulfur trioxide, sulfur dioxide, sulfuric acid, chlorosulfonic acid, nitrogen dioxide, chlorine, bromine or hydrogen peroxide.

15. A 5. A method.as claimed in any preceding claim, wherein the infusible beads are calcined at from 5000 to 3O000C.

16. A method as claimed in claim 15, wherein the calcination temperature is from 10000 to 1 2000C.

17. A method as claimed in any preceding claim, wherein the carbon is activated by heating in steam to from 700 to 10000 C.

18. A method for producing activated carbon substantially as hereinbefore described in Example 1.

1 9. Activated carbon produced by a method as claimed in any preceding claim.

20. An apparatus for hemoperfusion comprising a vessel packed with a spherical active carbon in the form or spherical particles having pores substantially all of which are not larger than 500 A in radius, said activated carbon being produced by polymerising or copolymerising one or more ethylenically unsaturated aromatic compounds to form substantially spherical pore containing polymer beads, making the resulting spherical polymer beads infusible, calcining the resulting infusible polymer beads to carbon and activating the carbon.

21. Apparatus as claimed in claim 20, wherein the activated carbon is as claimed in any one of claims 1 to 7 or claim 19.

22. Apparatus as claimed in claim 20 or 21, wherein the said vessel is a column.

23. Apparatus for hemoperfusion substantially as hereinbefore described with reference to the accompanying drawing.

24. A method for purification of blood, which comprises passing blood through a zone packed with activated carbon as claimed in any one of claims 1 to 7 or claim 8.

25. A method for purification of blood as claimed in claim 10, wherein the blood is passed through the zone at a flow rate of 100 to 300 ml/min.

26. A method for hemoperfusion as claimed in claim 24 and substantially as hereinbefore described.