JPS6216770A - Carbon blood sorbent and its production - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to medicine, and more particularly to carbon hemosorbents and methods for making such hemosorbents. Such blood sorbents are used to treat symptoms caused by endogenous and exogenous poisoning.
on) to remove toxins from the blood.

[Conventional technology]

Blood sorption is currently widely used to treat a variety of conditions, and the recommended range of applications is increasing each year. In this context, the issue of sorbent quality has become the focus of attention; the sorbent should provide effective clearance of toxins with minimal damage to the fluid. The latter becomes especially important when the patient has to undergo several types of blood sorption, or even is a normal criterion in chronic patients. The blood sorbent should be compatible with blood, ie should leave blood components intact, and should be highly thromboresistant. Furthermore, active particles and dust particles of the hemosorbent itself should not be allowed to enter the bloodstream during the hemosorption process.

Heterogeneous charcoals are often used as blood sorbents because their adsorption spectra cover a wide range of toxic substances. This causes fibrin to deposit on the charcoal surface and clog the pores.The sorption capacity gradually declines as more toxic substances are cleared.Furthermore, charcoal is easily crushed. and form dust particles, the penetration of which into the flow can cause embolization of internal organs and their malfunction.

Various coating or encapsulation methods have recently been developed in which charcoal granules are coated with different polymeric substances to protect blood particles from damage, impart antithrombotic properties to the charcoal, and eliminate dust formation. There is.

Charcoal blood sorbents, which are cellulose-coated granular activated carbon, are widely used (e.g., V. G., Nikolaev, V. V., Strelko, Gemosorbtaly).
ana Aktivirovannykh Ugla
kh (activated charcoal hemosorption), Naukoba Dumka
Publ.

Kiev, /q79, pages g0 to g7).

Among cellulose coatings, albumin cellulose coatings are also popular in amounts suitable for use as a base for ACAC systems (albumin coated activated carbon).

This carbon blood sorbent with albumin cellulose coating is manufactured as follows.

The granular activated carbon is washed with water, autoclaved at a temperature of 120°C, washed in athermal water for 2 hours to remove dust, and dried in a stream of air at a temperature of 9°C for several hours. The charcoal was then flushed with cellulose nitrate solution.
ood), stirred, spread in a shallow tray and dried at a temperature of 30°C, and flushed with athermal water to remove dust. After washing, transfer the charcoal to a perfusion chamber filled halfway with athermal water. Wrap the perfusion chamber in cotton cloth and heat to 12/℃.
Autoclave for 30 minutes at a temperature of . The perfusion chamber is then cooled and then injected with 20 ql of cold sterile physiological saline solution.
Wash at a flow rate of 0 m11 min.

When the temperature of the perfusion chamber drops to 10"C, the physiological saline solution is replaced by the thialbumin solution and the contents are kept at a temperature of 15"C for 15 hours. In this condition, the ACAC system can be stored for a month. Yes, immediately before use, flush the ACAC system with physiological saline solution without exposing it to air (see literature above).

The carbon blood sorbent based on the ACAC system obtained as described above has a small proportion (g
%), has good thrombotic resistance, and is a suitable sorbent for low-molecular substances. However, sorption declines as the molecular weight of the toxin increases. A similar phenomenon occurs in other hemoperfusions with any coatings.
) system has also been observed. This is due to the fact that the sorption process becomes secondary to the diffusion of the toxic substance through the semipermeable membrane of the coating. This feature makes blood clearance by such blood perfusion systems very similar to dialysis. Detoxification efficiency is lower because dialyzable toxins are removed.

The sorption capacity of coated or encapsulated charcoal is rather low for medium molecular organic substances (V, G, Nikolaev, V, V,
Strelco, Activated Charcoal Blood Sorption, Naukova Dum
ka Publ, Kiev, 1979, page g7~
(See page 90).

Moreover, the sorption capacity of such blood sorbents diminishes over time, in other words the clearance deteriorates, although slower than that of uncoated charcoal. The degradation of the clearance of coated charcoal is due to the clogging of the pores of the coating during the sorption process.

The complex encapsulation method of sorbent granules, such as charcoal granules, used to manufacture the ACAC System carbon blood sorbent reduces the efficiency of the sorption process (less toxins are scavenged from the replacement fluid). , and produces platelet depletion of approximately 30 t.

[Problems to be solved by the invention and means for solving them]
The object of the invention is to eliminate the above-mentioned drawbacks.

This invention is based on low and medium molecular weight: carbon which has a high and constant sorption capacity regarding toxins, has a destructive effect on blood formed components, and does not form dust particles that get into the replacement fluid. It is an object of the present invention to provide a blood sorbent and also to provide a method for producing the carbon blood sorbent.

Granular activated carbon and having polymer particles applied thereon, containing fluoroplastic particles as polymer particles, and a portion (in the so-gO% range) of the surface of the activated carbon granules having fluoroplastic particles applied thereon. remains free of plastic particles, with a weight ratio of activated carbon granules to fluoroplastics of 10-99 to J
A carbon blood sorbent that is ~99 to 20-1 is provided.

Also, in preparing a carbon blood sorbent by washing the activated carbon granules with water and treating them with a polymer, the polymer is a fluoroplastic particle with a size of 0.3 to 7 μm. The fluoroplastic is a 26% water suspension, the exposure of the granular activated carbon is carried out for 30-120 minutes, and the granular activated carbon with the fluoroplastic particles applied thereon is 100-. A method of manufacturing a carbon blood sorbent that is dried at a temperature of 200°C is provided.

Carbon blood sorbents made in accordance with the present invention are made of fluoroplastics in such a way that the fluoroplastic particles are distributed in individual islands on the sorbent surface, leaving virtually all pores uncovered. coated. The sorption capacity of the blood sorbent remains virtually unchanged compared to the capacity of the initial charcoal after fluoroplastic particles are applied thereon and is very high for low and medium molecular weight substances. Furthermore, the sorption capacity of the blood sorption agent according to the present invention is
It shows virtually no degradation in the process of blood sorption, and the clearance remains at a virtually constant level.

The fluoroplastic particles applied onto the granular activated carbon prevent any contact between blood particles and the activated carbon surface that would destroy the blood particles. Fluoroplastics are known to be compatible with blood, so contact of blood particles with fluoroplastics does not cause damage.

Moreover, the blood sorbent as proposed in this invention is highly thromboresistant, does not affect blood gas drainage, is dust-free and is easily sterilized by any known method. Ru.

It is important that the carbon blood sorbent is heat resistant and its properties remain unaffected up to tso''c and therefore can be sterilized at high temperatures.

Another advantage of the manufacturing method of carbon blood sorbent as proposed in this invention is that the manufacturing process is not complicated;
and that the required equipment is sufficiently simple.

Operation The carbon blood sorbent according to the present invention is manufactured as follows.

The granulated activated carbon is washed with water, flushed with an aqueous fluoroplastic (particle size 0.3-/μm) suspension and kept for 30-120 minutes. The solution is then drained and the activated carbon with fluoroplastic particles coated thereon is placed in a drying oven where the ioo-
, 20°C.

The particle size of the fluoroplastic is determined by the pore size of the activated carbon. The fluoroplastic particles are placed on the surface of the activated carbon so that the fluoroplastic does not penetrate into the micro- or mega-pores within the activated carbon material and interfere with the sorption of low and medium molecular weight substances to be removed from the blood. should be applied. The micropore or mesa cell size of activated carbon granules is 0.00
It is known to be in the range of /~0.3 μm. Therefore, the fluoroplastic particles have a size between 0.3 and 7μ.
It should be m.

The optimum content of fluoroplastic in the suspension is determined by the following considerations. If the suspension contains more than u)% fluoroplastic, the blood sorbent becomes too hydrophobic and its sorption capacity deteriorates.

When the suspension contains less than /% fluoroplastics, blood particles tend to be destroyed during blood sorption.

When the amount of fluoroplastic in the suspension is /~0, the resulting carbon blood sorbent has a weight ratio of carbon to fluoroplastic of ~99 to M~/. In this case, 30-10% of the surface of the granular activated carbon is
Remains free of fluoroplastic particles.

The treatment time of the granular activated carbon with the fluoroplastic suspension is selected to ensure that all fluoroplastic particles have time to settle onto the surface of the activated carbon granules. When activated carbon granules are treated with a concentrated suspension containing ~J% of fluoroplastic material, the treatment time should exceed 30 minutes, while with a lower concentration of fluoroplastic containing ~/~S%. Treatment with the suspension should last 720 minutes. Longer exposures produce no additional effects.

The method according to the invention allows the use of different types of granular activated carbon, for example peat carbon, synthetic carbon or carbon produced from baking coke.

Fluoroplastics used for processing a wide range of materials, namely polytetrafluoroethylene, polytetra 7
/I/ may be chosen from olopropylene, hexafluoropropylene or a copolymer of perfluoropropyl-vinyl ether and tetrafluoroethylene.

Blood sorbents obtained illegally can be used immediately;
Or it can be stored dry in a closed container for several years. When used after long-term storage, blood sorbents should be sterilized by conventional methods.

EXAMPLES For a better understanding, the invention will be described in detail with reference to specific examples thereof.

Example/ Granular activated carbon is obtained by carbonization of peat. Granular activated carbon is
Total capacity of mesa pores and macro pores: 0.4: 1 cf
IL''/, !i'.
Flush with water suspension for 30 minutes.

Drain and dry the activated carbon with polytetrafluoroethylene particles at a temperature of 200''C.

The resulting carbon blood sorbent is a granular activated carbon with polytetrafluoroethylene particles applied on its surface. The weight ratio of granular activated carbon to polytetrafluoroethylene is go to w theal. Approximately SO 1 of the activated carbon surface remains uncovered by polymer particles.

This carbon blood sorbent does not destroy the formed components in the blood,
It is highly thromboresistant, dust-free, and its adsorption capacity remains virtually unchanged compared to the initial activated carbon.

Example Calcinate the polyvinyl chloride and then go the product.

Granular synthetic activated carbon is obtained by carbonization at ~900°C. The activated carbon thus produced has micropores of 0,9 tyn"/9. The activated carbon has a particle size of 0.
．． Flush for 60 minutes with a 10% water suspension of 3 μm polytetrafluoroethylene. The activated carbon with polytetrafluoroethylene particles is then drained and dried at a temperature of 200°C.

The carbon blood sorbent thus obtained is granular activated carbon with polytetrafluoroethylene particles applied thereon. The weight ratio of granular activated carbon to polytetrafluoroethylene is 90:10. Approximately 70% of the surface of the activated carbon granules remains uncovered by polymer particles.

The properties of this carbon blood sorbent are similar to those of the blood sorbent of Example/.

Example 3 Granular activated carbon is obtained from recoked coal by carbonization at a temperature of 'yoo-too'c. The total capacity of mesa pores and macropores in this activated carbon is 0. l 13/g
It is. It is immersed for 720 minutes in a suspension of polytetrafluoroethylene (activated carbon particle size/μm) in water. The activated carbon with polytetrafluoroethylene particles applied thereon is then drained and dried at a temperature of 100°C.

The carbon blood sorbent thus obtained is granular activated carbon with polytetraethylene particles applied thereon. The weight ratio of particulate active agent to polytetrafluoroethylene is qq:99:20-1. Approximately gO% of the activated carbon surface remains free of polymer particles.

The properties of the carbon blood sorbent are similar to those of the blood sorbent of Example 1.

For example, using granular activated carbon. Granular activated carbon with particle size O8S
Flush with a µm polytetrafluoropropylene/theta water suspension for 0 minutes. The activated carbon with the polytetrafluoropropylene particles coated thereon is then drained and dried at a temperature of 200°C.

The carbon blood sorbent thus obtained is a granular activated carbon with polytetrafluoropropylene particles coated thereon. The weight ratio of granular activated carbon to polytetrafluoropropylene is qO to 10. Approximately 62% of the surface of the active granules remains uncovered by polymer particles.

The carbon blood sorbent thus obtained is similar in properties to the blood sorbent of Example/.

For example, use granular activated carbon. Particle size/μm of granular activator
Flushing for 60 minutes with a 70% suspension of tetrafluoroethylene-hexafluoropropylene copolymer in water. Then drain and dry the activated carbon with particles of said copolymer at a temperature of 100°C.

The carbon blood sorbent thus obtained is a granular activated carbon with copolymer particles coated thereon.

The weight ratio of granular activated carbon to copolymer is 90:10. Approximately 60 inches of the surface of the activated carbon granules remain uncovered by polymer particles.

The properties of the carbon blood sorbent thus obtained are as follows:
Similar to the properties of the blood sorbent described in Example/.

EFFECTS OF THE INVENTION The carbon blood sorbent and raw coal according to the invention are tested for their sorption capacity on a comparative basis. Ultraswept fluid/l was obtained from uremic patients by so-called "dry" ultraswab in a capillary dialyzer.

The column contained 10 ml of blood sorbent. The infiltration rate of the ultrafluid fluid was 200 rnl 1 min, and the sorption period was 7 hours.

The sorption capacity was determined by finding the rate of decrease of the sorbed substances in the ultrafluid after clearance and sorption/time of different substances according to the formula devised by T. Nealon.

The results are shown in Table/.

As can be seen from /ZANOMOTO/, the sorption capacity of the blood sorbent according to the present invention is virtually equal to the sorption capacity of raw coal.

The destructive effect of this blood sorbent on blood components, such as blood solids, was evaluated in animal experiments (mongrel dogs).

The evaluation study was conducted as follows. The sorbent was placed in a 10 ml cylindrical column. Femoral containers were used for intravenous injection of heparin in an amount of ooME/kg. Blood sorption method in appropriate animal bloodstream/lo
-sooml/min.

The results of the evaluation of red blood cell and hemoglobin destruction are shown in Table 2. The results of the evaluation of platelet destruction are shown in Table 3. Blood samples for assessment of platelet destruction were drawn before heparin injection, 3 minutes after heparin injection, and every 30 minutes during the blood sorption process.

/ to It should be noted that hematocrit remained unchanged before and after blood sorption.

Toxicological tests on animals demonstrate that the proposed blood sorbent has no toxic effects.

The dust formation of the proposed hemosorbent was evaluated by the turbidity of the supernatant after the heparin-containing hemosorbent was vigorously shaken. Turbidity was not observed in any case.

The proposed blood sorbent was also subjected to clinical trials. Blood sorption instructions were as follows.

Urine toxic or purulent powder Urine toxicity and septic toxicity urinary sepsis Fifteen hemosorptions were performed on seven patients.

Each patient underwent 7 to 3 hemosorptions depending on the condition. All blood sorption was uneventful.

The technique of the clinical trial was as follows. A quantity of 300 ml of carbon blood sorbent was added at a temperature of 120"C, i.
Sterilization was performed by autoclaving under atmospheric pressure for 90 minutes. Patients were given heparin, 2r prior to blood sorption.
o Had an intravenous injection of ME/kg.

This amount is on the order of half the amount normally used when uncoated charcoal is used as a sorbent.

The blood sorbent column was connected to the patient by a venous-venous or arterial-venous system. Blood flow rate was regulated by a roller pump. The volume velocity of blood flow is ioo~/left oml
/minute.

Efficiency of blood sorbent was evaluated by biochemical blood tests before and after column, 70 minutes, 60 minutes and 120 minutes after no blood sorption. The clearance of the toxin was found based on these data. Results of the trial q Urea 77, g 7A, 0 7 Otsu, 3 uric acid g
t, /gJ gt, left creatinine gt,
Og2.3 g/,! r Medium molecular substance (MW /, 000 ~ Ko, ooo) /2θ, / 12g, 0
//9. As the table shows, the clearance of low molecular weight substances at the onset of sorption and after 2 hours remains virtually unchanged. The difference is only 2-3-7 minutes and the clearance of medium molecule substances is the same or even higher.

Significantly, the clearance of medium-molecular substances by known ACAC systems drops from 120 to 90 m11 min by J within an hour (e.g. C11nical
Nephrology, Vol, //,! ,2
, /9 Kude, (v) It is mechanically simple.

(See T., M., S., Chunk, Evaluation of a Clinical Trial of Charcoal Blood Perfusion in Uremic Patients, Page 1/Left).

Studies conducted to evaluate the amount of blood formed elements during clinical trials of the proposed hemosorbent showed that no changes were observed when comparing the numbers before and after hemosorption. It has been proven.

It should be noted that in animal experiments and clinical trials of the proposed blood sorbent, the gas composition of the blood also remained unchanged. The blood sorbent granules showed no clot-forming properties, demonstrating the high anti-thrombotic properties of the hemosorbent according to the invention.

In conclusion, the carbon blood sorbent produced according to the present invention has a very high sorption capacity in pair with the source charcoal, and the sorption capacity of the proposed blood sorbent is significant in the process of blood sorption. Shows no deterioration.

Furthermore, the proposed blood sorbent does not destroy blood solids, is highly thromboresistant, does not disturb blood gas balance, is dust-free and can be sterilized by any convenient method. obtain. The method for producing the blood sorbent according to this invention is technically difficult: (Left)

Claims (1)

[Scope of Claims] 1. A carbon blood sorbent which is granular activated carbon and has polymer particles coated thereon, which contains fluoroplastic particles as the polymer particles,
A carbon blood sorbent characterized in that about 50-80% of the surface of the granular activated carbon remains free of fluoroplastic particles and the mass ratio of granular activated carbon to fluoroplastic is 80-99 to 20-1. 2. By washing the granular activated carbon with water and treating it with a polymer, a carbon blood sorbent which is a granular activated carbon and has polymer particles coated thereon, with fluoroplastic as the polymer particles. particles, about 50-80% of the surface of the granular activated carbon remains free of fluoroplastic, and the mass ratio of granular activated carbon to fluoroplastic is 80-99 to 20-1. In manufacturing, the polymer content is 1-20%
The fluoroplastic is used as a water suspension (the size of the fluoroplastic shall be 0.3-1 μm), and the treatment of granular activated carbon with the fluoroplastic suspension lasts 30-120 minutes, and the fluoroplastic The temperature of granular activated carbon coated with particles is 100-200℃
A method for producing a carbon blood sorbent, characterized in that the carbon blood sorbent is dried at a temperature of .