Perfluorochemicals (PFCs) highly dissolve oxygen and can function as an oxygen carrying agent in an emulsified from. However, these substances must be used as a fine and stable emulsion with the particles below 0.2 microm in an average diameter, because the particle size is closely related to both toxicity and efficacy, the larger particle, the more toxic and the less effective. In addition, the PFCs to be used as the material for artificial blood must be rapidly eliminated from the body after completing the role as an oxygen carrying agent. From many kinds of PFCs, Perfluorodecalin (FDC) and perfluorotripropylamine (FTPA) were selected as acceptable materials for artificial blood substitute and an emulsion was prepared by using the mixture of both PFCs. This preparation, tentatively named Fluosol-DA, has been made iso-tonic and iso-oncotic with proper amounts of electrolytes and colloidal substance, respectivery. Fluosol-DA has been manifested to cover the most parts of indispensable properties of blood substitute. It is low toxic and stable. Animals displaced over 90% of their own blood with this preparation survived well and were kept in good condition for subsequent long periods. From the results of clinical trials, over 70 cases in Japan and U. S. A., Fluosol-DA has been proved to be safe and effective as artificial blood substitute. The present paper includes the following contents; Needs for artificial blood substitutes, History of PFC-artificial blood, Development of Fluosol-DA, Expected uses and limits of Fluosol-DA and Prospect of Fluosol-DA in future.
1- (Tetrahydro-2-furanyl) -5-fluorouracil (Futraful®, FT-207) was synthesized by S.A. Hiller, et al. in 1967. In this 5-fluorouracil (5-FU) derivative, a tetrahydrofuran group replace the sugar on the nucleoside. FT-207 is an antimetabolite, anti-tumor agent, and is well absorbed from the intenstine. It is gradually metabolized to substances such as 5-FU, 5-fluorouridine (FUR) and 5-Fluorouridine monophosphate (FUMP), which exhibit anti-tumor activity. These active substances are maintained in the blood and tissues for a long time, and thus FT-207 shows significant anti-tumor activity. FT-207 has less effect than other anti-tumor agents on antibody production, the blood picture and the functions of the liver, spleen and kidney. Thus since it has only side effects, it can be used for a long-term therapeutic treatment. It is effective when given intravenously, orally or intrarectally and has been employed clinically to induce tumor regression and to maintain regression and inhibit metastases.
In Japan, almost 80 % of annual consumption of sugar is depend on import. On this account, the technique for production of such sweetenings as millet jelly and glucose from starch have long been developed. Since the saccharification of starch by enzymes was introduced in 1959, the isomerization of glucose to fructose have been seriously studied for the new application of glucose. Under the situations, author began to study on the enzymatic method of isomerization of glucose to fructose and succeeded in developing first in the world an industrial production technique of glucose isomerase in 1966. At present, the technique is being developed on a world-wide scale. In Japan, the present production of fructose syrup amounts to about 10 % of the total sugar consumption and is expected to develop further in the future. In the present literature, the process of development of the enzyme and present status of the technique were described.
In 1964, slender-spikerush was received major attention as weeds in paddy field because of revelation resistance to the effect of herbicide hithertofore in use. Authors aimed at search of herbicide for controlling slender-spikerush. A large number of compounds have synthesized, laying stress on S-benzyl thiolcarbamates. These compounds were evaluated for especially slender-spikerush in addition to barnyard grass and broad leaf plant as usual. From the results, S-4-chlorobenzyl N, N-diethylthiolcarbamate (Benthiocarb) was selected as a compound having most effectiveness. On the other hand, the preparation process of carbonyl sulfide was established and has been applied to the synthesis of Benthiocarb. By this process, Benthiocarb was obtained with high-purity and high-yield.
In the studies on the application of organic sulfur compounds in agricultural fungicides, some derivatives of ketene thioacetals were found to be effective for the control of rice blast. This original, serendipitous discovery prompted an extensive synthetic and screening program, which shed considerable light on the relationship between chemical structure, and biological activity. As a result, isoprothiolane, diisopropyl 1, 3-dithiolan-2-ylidenemalonate, 5e was selected as being the most potent compound for the control of rice blast. During the research program, this fungicide was found to be able to control the several species of planthoppers in paddy field. Isoprothiolane was developed as a new systemic pesticide for the control of rice blast and planthoppers. This paper descrives the discovery and development of isoprothiolane.
A series of butadiene oligomers consisting of liquid 1, 2-polybutadiene and deriving dicarboxylic acid and glycol having molecular weight of 1, 0004, 000 with narrow molecular weight distribution were commercialized by use of living polymerization technique. The process comprises intiation with sodium dispersion, living polymerization at low temperature and termination with proton, carbon dioxide or ethylene oxide. Continuous process is adopted for the commercial plant of which production capacity is 7, 200 tons/year. The products including their derivatives are used in wide range of application such as electrodeposition paint, emulsion paint; insulating varnish, casting resin, molding compound, adhesive, sealant and modifier for plastics. As an example of research and development of a new product prepared by a new process, the background of the research and the procedure of the development including application research works were mentioned.
In 1967, our company, Lion Fat & Oil Co., Ltd. at that time, marketed a heavy-duty powder detergent with AOS, the pioneer product in this line in the world, which was developed by intensive research works triggered by the social demand of switchover to so-called soft-type detergent. Since the first commercialization of AOS-base detergent, it took about one decade to develop a specially designed sulfonater by our own technology for manufacturing of AOS with improved color and performance properties. Taking the most advantage of high quality AOS having rapid biodegradability, excellent detergency, and good foamability and anti-caking property, low-phosphated heavy-duty detergents, shampoos and other some products have been developed and marketed successively. Recently, many inquiries have been brought about the sulfonater as well as AOS application technology. The lincensings to the big firms in Europe were already materialized. The development works on AOS in our company and the background are historically reviewed, and it is also suggested that AOS will play more important role in detergent materials in near future.
Oxychlorination is the key reaction for the manufacture of vinyl chloride monomer (VCM) starting from ethylene. Research and development of the Mitsui Toatsu Chemicals' oxychlorination process is described. Characteristic features are “Fluidized-bed reactor” and “Oxygen based total recycle gas system”. The fluidized-bed technology using the catalyst, prepared by mixed-gel process, with high performance and selectivity for EDC, enables efficient heat-removal and use of oxygen, not air, which in turn realizes the excess ethylene recycling process, compact facilities and low investment cost. The operation is run within non-flammable region throughout the reaction and after-treatment, so the process is highly safe though pure oxygen is used as the oxidant. The process is almost care-free for pollution problem because of the negligibly small amount of off-gas compared with the air-based process. Processes for producing VCM other than Mitsui Toatsu Chemicals' are also outlined.
Butadiene and isoprene are important raw materials for synthetic rubbers, resins and other products. Nippon Zeon developed unique processes to recover high quality butadiene and isoprene monomer respectively by extractive distillation using non aqueous dimethylformamide as selective solvent with a special polymerization inhibitor from C4 stream and C5 stream, respectively (GPB and GPI process). The characteristics of these processes are quite low energy consumption, high recovery rate, high product quality, no environmental problem, easy operation and maintenace-free processes. GPB process has been licensed all over the world and more than thirty plants are now under construction or operation. Recently, attention is being focused on the solvent conversion in existing plants for energy saving and operation improvement. GPI process has no chemical treatment which seems necessary in other processes, and other useful C5 components such as dicyclopentadiene and pentadienes can be easily recovered with additional equipment. These components can be used for various new products in synthetic rubber, resin and fine chemicals industries.