Analysis of medical use of carbon adsorbents in China and additional possibilities in this field achieved in Ukraine

Abstract

The review is devoted to analysis of the use of carbon sorbents for medicinal purposes in China and description of some innovative technologies in this field in Ukraine. The review underlines the presence of common roots of sorption therapy development in these two countries determined by pioneer works of Prof. T.M.S. Chang, created to the concept of artificial cells. High level of works of Chinese scientists on sorption purification of blood and combined extracorporeal methods has been mentioned. At the same time, by author's opinion, two other methods of sorption therapy, namely enterosorption and sorption therapy of wounds and burns, has not been properly developed in China. In the review, there are also described the essential results of Ukrainian scientists in the field of blood purification from protein-bound toxins and other harmful compounds what is important for treatment of many serious human pathologies, and also the important data on the use of oral sorbents and dressings from activated carbon materials, which could be considered as a useful addition to achievements of Chinese scientists in the field of the development and use of sorbents for medicinal purposes.

Keywords::

• adsorptive therapy
• enterosorption
• haemoperfusion
• wound dressings

Introduction

It is known that there are at least three main types of sorption therapy based on the use of activated carbons, namely, hemosorption (hemocarboperfusion), enterosorption, i.e. oral administration of special types of carbon sorbents, and application-sorption therapy of wounds and burns.

Hemocarboperfusion

The development of this line of research in China and Ukraine (and earlier – in USSR) has a lot in common what could be explained by an influence of distinguished Canadian scientist, the creator of the concept of artificial cells (Chang et al. 1972, 1973, Chang 1975, 2007), respected expert in the field of extracorporeal detoxification and artificial blood, Officer of the Order of Canada, professor of McGill University Thomas Ming Swi Chang. For many decades Prof. Chang was a guiding hand for many PhD students and postdoctoral fellows from China and also gave comprehensive support to Ukrainian scientists in international scientific community and readily published their innovative reports in his journal “Artificial Cells, Blood Substitute and Immobilization Technology”.

Thanks in no small part to this, in 80th-90th in China there have been developed different materials for hemosorption, including synthetic resins and their carbon derivatives designed for removal of uremic metabolites, “middle weight” molecules, barbiturates, and bilirubin; DNA-containing hemoimmunosorbents on the basis of carbonic and cellulose carriers have demonstrated their efficacy in the treatment of severe forms of systemic lupus erythematosus and rheumatoid arthritis (Yang et al. 1988, Yu and Chen 1990, Chen et al. 1991, Gao et al. 1995, Kong et al. 1998, Fu et al. 2000). Some of these hemosorbents are still being used in Chinese hospitals and show good curative results (Wang and Yu 2011). In the last 10–12 years the field of development, research, and practical use of hemoperfusion in China has been extended significantly. The method of hemosorption has been widely used for treatment of acute poisonings, in particular, poisonings with phosphoorganic insecticides (Talbot 1989, Peng et al. 2004, Dehua et al. 2006, Karalliedde et al. 2006, Gao et al. 2007, Zhao et al. 2008, Song et al. 2010, Zhou et al. 2010, Lu et al. 2011, Lai et al. 2011, Liu et al. 2012, Zhang et al. 2012, Qiu et al. 2012, Lai et al. 2012, Shi et al. 2012, Hsu et al. 2012, He et al. 2012). The peculiarity of these works is a rational combination of extracorporeal detoxification, careful attention to molecular mechanisms of exotoxicosis development, attempts to use hemosorption for treatment of somatogenous phase of acute poisonings as well as to combine it with original methods of mobilization of hydrophobic poisons from extravascular space.

The studies of Chinese scientists in the field of removal of “hepatic” toxins and treatment of liver failure are of interest, too. Having in one's disposition the newest foreign means for removal of protein-bound compounds, including albumin dialysis, systems MARS, and Medisorba BL-300 (Awad et al. 1997, Nakaji and Hayashi 2003, Abe et al. 2004, Wu and Wang 2004, Churchwell et al. 2009), Chinese professionals develop a number of innovative methods for removal of bilirubin and other hydrophobic metabolites (Zhang and Jin 2005, Guo et al. 2010, 2009, Yu et al. 2010, Tang et al. 2011, Duan et al. 2006). In China a adaptable liver support system (ALSS) has been proposed, which includes the methods of plasmapheresis, hemodialysis, hemodiafiltration, hemo- and plasma-sorption, and the their uses are deemed necessary. The use of such universal set has significantly reduced the mortality rates in the case of severe subacute and chronic hepatitis (Li et al. 2004, 2006, He et al. 2004). A number of works of Chinese authors (Song et al. 2010, Qiao et al. 2010, Chen et al. 2011, Zhu et al. 2013, Chen et al. 2013) are devoted to the use of hemoperfusion in the treatment of kidney diseases, and among those an important 2-year study has demonstrated significant benefits of combination of chronic dialysis with hemosorption compared to convenient hemodialysis, for improvement of quality of life, normalization of biochemical parameters, and decrease of mortality rates in the patients with terminal renal failure (Chen et al. 2011).

Among other works one should mention the studies on the use of neutral resins for the treatment of sepsis (Huang et al. 2010), the attempts to combine sulfonated carbons with multilayer nanotubes for removal of “middle weight” molecules and low-density lipoproteins description of some cases on the use of hemoperfusion for treatment of acute pancreatitis, crush-syndrome, and severe influenza (Li et al. 2011, Lu et al. 2011, Tang et al. 2012, Hong et al. 2012, Hui et al. 2013). It is necessary to note that in 2–3 years the number of publications of Chinese authors about hemoperfusion has increased significantly which shows the growing interest on this method.

Such interest to hemoperfusion makes, especially the perspective, the development of bilateral Chinese-Ukrainian cooperation in this field, including implementation of newest means and methods of hemoperfusion developed by Ukrainian scientists, first deliganding carbon adsorbents and combined hemoimmunosorbents on their basis, in China. These hemosorbents known in Ukraine and SIC countries under HSGD trade mark—HemoSorbents Granulated Deliganding—are synthetic activated carbons with mass-fractal inner structure, higher in orders by capacity toward protein-bound compounds that convenient activated carbons used for hemosorption (Sarnatskaya et al. 2007). For example, this property allows removal of bilirubin quantity equal to its tertian production from a body in 5 hours, using only 10 g of HSGD. Maximal capacity of HSGD hemosorbents by unconjugated bilirubin adsorbed at constant concentration of 20 mg% from 3% albumin solution is higher than 150 mg per 1 g of carbon matrix, and the quantity of immobilized albumin achieves 1200 mg per 1000 mg of carbon material (Sarnatskaya et al. 2002). The use of HSGD hеmоsorbents for the treatment of polyorganic insufficiency in children caused by severe poisoning with death-cup (Sarnatskaya et al. 2007) allows nearly 6-fold decrease of mortality compared with traditional therapy, including hemosorption on activated synthetic carbons of previous generation known under SCN trade mark.

HSGD hemosorbents could be used as a proper matrix for coating with proteins, lipids, nucleic acids, and polysaccharides (Bardakhivskaya and Nikolaev 2001, Snezhkova et al. 2004., Sarnatskaya et al. 2005). As an example one could mention a case of a patient with severe form of idiopathic dilated cardiomyopathy who underwent six sessions of hemoperfusion through HSGD coated with heparin and 3 weeks of the treatment had left ventricular ejection fraction increased from 14 to 36%, final diastolic volume of left ventricle decreased from 273 ml to 177 ml, and final systolic volume from 234 ml to 112 ml. Along with this drastic improvement of histologic picture of myocardium bioptates taken before and after therapy has been recorded. In general, in 34 patients with dilated cardiomyopathy who were treated at an average with four extracorporeal procedures, ejection fraction increased by 2.2 fold, diastolic volume was reduced by 27%, and systolic volume by 33%. Such therapy is especially effective in the case of DCMP developed as a late complication of cancer chemotherapy with high-dose doxorubicine (Todurov and Kovtun 2011).

Also, it is necessary to note that in a number of cases convenient synthetic SCN hemosorbents demonstrate high clinical efficacy and, for example, increase survival of dogs upon severe irradiation from 3 to 60–70%, decrease mortality caused by diffuse purulent peritonitis by three times, and demonstrate an expressed curative effect upon exacerbation of chronic glomerulonephritis (Ternovoy et al. 1983, Nikolaev 1984b, Nikolaev et al. 1985).

Enterosorption

Internet search did not reveal the reports of Chinese authors in the field of enterosorption on activated carbons. Meanwhile, this noninvasive and relatively cheap method of sorption therapy, proposed in our laboratory in 1982 and firstly described in foreign scientific press in China (Nikolaev et al. 1982, Nikolaev 1984a), provides a whole number of important therapeutic data. In particular, enterosorption used as monotherapy in patients with leptospirosis (Nikolaev 1984b) results in quick jugulation of hepato-renal syndrome, and in patients with cholera with medium severity form—to significant (2.2 fold) decrease of stool volume, and, consequently, to decreased volume of required transfusion media (Nikolaev et al. 1998). Administration of enterosorbents to cancer patients treated with intense polychemotherapy, results in nearly 4-fold increase of patients free from manifestations of acute toxic reactions (nausea, vomiting, headache, etc.) (Ponomareva et al. 2008). It has been shown also that carbon enterosorbents possess an expressed reno-protective action upon administration of cisplatin—one of the most toxic anticancer preparations (Sakhno et al. 2013). According to our newest results, by the intensity of their myeloprotective action some enterosorbents are comparable or even better than gene-engineered granulocyte colony-stimulating factor (G-CSF) widely used for therapy of myelodepression caused by irradiation or intense chemotherapy. It is necessary to note that therapy with G-CSF costs 3000–5000 EU for one patient (Lin et al. 2012), what is more than by two orders costive than enterosorption course.

One should also take into account that the production of modern enterosorbents could be organized in China using its raw material base. Chinese-Ukrainian cooperation in this field could be very important for elevation of quality of treatment of many serious diseases and pathological states.

Application-sorption therapy of wounds and burns

The reports on the use of this method in China are rare (Pat. # 1726782; Pat. # 2652362). Meanwhile, carbon-activated tissues are successfully used in different countries for therapy of various phases of wound process upon mechanical or thermal trauma (Sakhno et al. 1991, Eretskaya et al. 1999, Fernandez Ospina et al. 2009). An efficacy of application-sorption therapy could be demonstrated on a model of its influence on the duration of healing of experimental burn of stage 3А. Here the barrier function of epithelium is out of the question, that is why the placement of potent sorption system here is capable to exert significant effect on the development of local manifestations of burn disease via formation of common diffusion space. It is important to note that carbon tissue “Borisfen” of Ukrainian production is the most potent (with highest capacity) sorbents among all tissue sorption materials produced worldwide.

Significant differences in the state of experimental burn wound (stage 3А) caused by water steam could be observed just in 24 and 48 hours at visual and histologic levels. In the case of early use of dressing “Borisfen”, complete healing of burn wound occurs in 7–8 days versus 18–24 days in the control group. The differences in histological picture of burn wound after 1, 3, and 7 days in experimental and control groups are clearly seen. This result could be of essential commercial and social value in the case of market promotion of carbon dressings in the home sets, first aiders of drivers, resquers, firemen, etc. This method is especially important for treatment of home burn in children at the stage of first premedical aid when moisten carbon dressing is placed on injured lesion in the first minutes of burn trauma.

So, the newest developments of Ukrainian scientists in the field of sorption therapy could be a useful addition to the already existing practice of Chinese scientists and create the grounds for significant extension of effective use of carbon sorbents for medicinal purpose in China. An accent could be made on creation of facilities for production of new highly effective means of sorption therapy directly in China, from Chinese raw materials, and with maximally low cost of production.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.