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Attempts to purify FVIII by isoelectric precipitation were promising. drugs from human plasma has resulted in the improvements in purity of products, higher safety, and yield noticeably. Still, the backbone of the modern plasma fractionation technique is mainly based on cold ethanol fractionation of the human plasma that is almost the same as fractionation of crude oil, breaking it down into its components. The demand for IgG for treating immune deficiencies and coagulation factor VIII for hemophilia A determines how to design the plasma fractionation industry in terms of capacity. Nowadays, cold ethanol fractionation has followed by chromatographic methods, since they offer higher purity. In this review, we describe different methods of plasma fractionation such as cold ethanol fractionation, gel filtration, fractionation by salt, and fractionation by polyethylene glycol. There is no doubt VHL that the four main products of human plasma are albumin, IgG, coagulation factor VIII, and IX, which their methods of separation from human plasma have been explained in this paper. == Conclusions == It can be concluded that plasma fractionation with ethanol at low temperature for the preparation of the main human plasma biological components including albumin, IgG, coagulation factors VIII, and IX is still the most widely used method at an industrial scale. Nowadays, LY2835219 (abemaciclib) this method is being used in combination with different chromatographic techniques in order to achieve a higher quality and the yield. Keywords: Human plasma, Proteins, IgG, Coagulation factors, Fractionation == 1 . Background == Nowadays, biological drugs medicines prepared from the human plasma play a vital role in the treatment of patients with different diseases (1-3). By the beginning of the new century, about 500, 000 kg of human serum albumin (HAS) and 40, 000 kg of intravenous immunoglobulin (IVIG) is being produced per year. For the production of such amounts of albumin and IVIG, more than 20 million liters of the starting material which is human plasma is needed. If we notice to more than $7 billion annual productions of these human plasma products, it can be concluded that implementation of new technology in the production of such biological drugs is a necessity (4, 5) with respect to Good Manufacturing Practice (6). Also, virus inactivation should be carried out during the procedure of production (7-9). Treatment of more than thousands casualties from world war II was a trigger for the preparation of biological drugs such LY2835219 (abemaciclib) as albumin and immunoglobulin from human plasma (10-12). For these reasons different studies on developing procedures for the preparation of human plasma derived biological drugs were carried out (13, 14). One of the methods introduced for proteins separation from human plasma is salting out. For this purpose, ammonium sulfate as a salt can be added at different concentrations to the solution of human plasma for precipitation of the protein. The addition of ammonium sulfate should be repeated with different concentrations in order to obtain specific protein after each addition of the salt. Lactate of 2-ethoxy-6, 9-diamino-acridine is another compound which can be used to decrease the solubility of proteins in human plasma, following to the addition of which insoluble protein can be separated by LY2835219 (abemaciclib) centrifugation. The additional technique for plasma derived proteins separation is definitely fractionation of plasma simply by polyethylene glycol. In all methods of plasma derived natural drugs planning, virus inactivation is an important step (15). In our examine, by this technique, intermediate resources for planning of fibrinogen, 1-antitrypsin, albumin, IgG, IgA, and IgM were accomplished (16). Affinity and ion exchange chromatography are suitable for splitting up of labile protein including coagulation factors. These methods are suitable for the preparation of plasminogen and coagulation factors IX, VII, and immunoglobulin from man plasma (12, 13, 17-20). The main LY2835219 (abemaciclib) execution of LY2835219 (abemaciclib) plasma derived natural drugs has been shown in (Table 1). == Table 1 . Usage of plasma derived natural medicines. == The most important natural medicines that can be prepared by human plasma are albumin, Immunoglobulin G, coagulation component VIII, and coagulation component IX. There are several other items which can be separated from bloodstream but with significantly less importance meant for patients treatment, due to fewer numbers of sufferers with particular deficiency of that compoundsuch while 1-antitrypsin, anti thrombin III, ceruloplasmin, and plasminogen (13, 21, 22). The amount required for these substances is much lower than albumin and IgG. That is why, a method having a higher capability of planning and chance of implementation in an industrial size is the most important component. Development of a.