Rutin, a New Drug from Buckwheat

Rutin, a New Drug From In 1942 chemists at the Eastern Regional Research Laboratory wx^re studying the constituents of tobacco in a search for compounds that might be Buckwheat useful in some way other than smoking. In the course of the investigations, James F. Couch rutin was isolated from flue-cured tobacco; a Japanese chemist had found rutin in tobacco 10 years previously and the discovery had been confirmed by two German chemists in 1936. The The story of rutin begins in 1842, finding of rutin in tobacco raised the when it was first prepared by a phar- question : What use can be made of the macist-chemist of Nuremberg, Ger- glycoside? Its only known utility, that many, named August Weiss, who of a dyestufiP, did not appear promising, obtained it from garden rue, Ruta and no other use was apparent. graveolens. As time went on, chemists As a result of a complicated train of found rutin in a number of plants. reasoning, coupled wîth previous ex- Rutin is a yellow, crystalline powder perience, it occurred to me that rutin with the formula CîKnO^^/dKÔ. It might possess a "vitamin P" action— is only slightly soluble in water, more in fact, it might be the long-sought soluble in alcohol, acetone, and alka- vitamin itself. "Vitamin P" had been line solutions, and insoluble in chloro- postulated in 1936 by a Hungarian bio- form, ether, and the hydrocarbons. chemist, Albert Szent-Györgyi, to ac- Rutin is a glycosidc, which is hydro- count for certain medical eflccts pro- lyzed to form one molecule each of duced by citrus extracts that could not quercetin, glucose, and rhamnose when be explained by reference to ascorbic it is boiled with 2 percent sulfuric acid. acid or vitamin G. Szent-Györgyi and Quercetin is a well-known chemical his coworkers attempted unsuccessfully substance belonging to the class of to isolate from citrus fruits and red flavonols, a class whose representatives peppers the substance that had this are widely distributed in the plant antihcmorrhagic action. They did, kingdom. Rutin is reasonably stable in however, obtain a mass of chemical in- boiling wâter and may be recrystallized formation on it; the data pointed to from that medium for purification. It the flavonols. has been the subject of many chemical To test whether rutin had the same studies and its chemical nature is action, it was necessary to cooperate thoroughly understood. Extensive stu- wdth some scientist who was already dies by pharmacologists at the Western wôrking in the field and who could Regional Research Laboratory and by conduct the tests properly. Dr, John Q. others have shown that rutin is Griffith, Jr., and Dr. M. A. Lindauer, nontoxic. then of the Medical School of the Uni- For a century after its discovery, versity of Pennsylvania, had been rutin remained without any known studying the problem for several years use, although plants containing it were and were using a citrus preparation sometimes used as dycstuffs. This use known as crude hesperidin, which con- disappeared with the advent of the tained the unidentified "vitamin P." synthetic coal-tar colors. Arrangements were made for them to 742 R U T I N, A NEW DRUG FROM BUCKWHEAT 743 test the activity of rutin. Within a year The extraction of rutin from thc Dr. Griffith was satisfied that rutin did, leaf meal or the fresh plant was ex- indeed, possess the antihemorrhagic haustively studied in the Eastern Labo- activity characteristic of "vitamin P" ratory, and the findings were made preparations. The result was an- available to industry. After many trials, nounced in 1943 before the Medical a process was developed in which hot Society of the State of Pennsylvania dilute isopropyl alcohol, a cheap and and published in May 1944 in the Pro- efficient solvent for rutin, is employed. ceedings of the Society for Experimen- By distilling the alcohol from the ex- tal Biology and Medicine. Drs. Griffith tract and straining ofT the fats, which and Lindauer continued their study of settle out, a watery solution is obtained rutin wdth special reference to its use from which crude rutin crystallizes on for increased capillary fragility in standing and cooling. hypertensive patients. A great deal of Refining the crude rutin to a com- interest was aroused by the work, and pound pure enough for medicinal use other physicians began experimenting presented many difficulties. We had to with rutin in their practices. They remove impurities, some of which found that rutin is effective in a variety stuck tenaciously to the glycoside; re- of hemorrhagic conditions. crystallizations caused appreciable losses of material and had to be re- As THE DEMAND for thc glycosidc in duced in number; contact wdth iron or medical circles grew, it became appar- copper vessels discolored the rutin; and ent that tobacco was too expensive a the operations had to be conducted in source of rutin to permit its extensive stainless-steel tanks, stills, and filter use. A search began for a cheaper jDresses, although for some operations source. A thorough survey was made of we could use wooden tanks. Industry plants reported to contain rutin and has adopted the successful solutions of others likely to contain it. Eventually the many problemas involved in the the green buckwheat j^lant was discov- prejâration of pure rutin from the ered to be nearly ideal as a source. It crude product. contained several times as much rutin Some 15 chemical firms now prepare as did tobacco, and it was cheap; the rutin of medicinal grade. Their esti- material cost of rutin could be cut to mated annual output is 15,000 to 20,- about 1 percent by changing from to- 000 pounds. Many pharmaceutical bacco to buckwheat. Buckwheat is now laboratories are marketing dosage the chief American source of rutin for forms of rutin, principally tablets, for commercial purposes, although much sale in drug stores. is now being made from a Chinese drug. Wai Fa, the flower buds of the THE FIRST APPLICATION of rutin me- Chinese scholartree. dicinally wâs in the treatment of in- Rutin may be obtained from dried or creased capillary fragility, a condition green buckwheat in several ways. If in which the smallest blood vessels be- dried plant is to be used, the. fresh come abnormally fragile and rupture, buckwheat must be dehydrated under so that small hemorrhages occur. The special conditions ; otherwise there may correction of the capillary fault is be a large loss of thc glycosidc. Proc- known as the "vdtamin P" action. The esses for conducting this drying were cause of the fragility is not definitely studied in the laboratory and pilot known. Some think that the vessel wâlls plant and also in actual commercial become weakened and no longer can operations. There was finally devel- withstand pressure exerted upon them oped a process for dehydrating fresh by the blood. Sometimes the capillary buckwheat and producing a leaf meal walls do not rupture but become ab- rich in rutin and stable under ordinary normally permeable, so that they allow storage conditions. substances to pass from the blood into 744 1950-1 9 í5 1 YEARBOOK OF AGRICULTURE the tissue spaces in larger quantities or tective action has recently been de- of diíTcrent kinds than normally filter veloped. The fact of protection against through the capillary wall. The condi- irradiation led to the thought that rutin tion is referred to as increased capillary may be of some use as a defense against permeability. Where either of these injuiy by radiations from atomic faults is present, danger increases of bombs, particularly in borderline^ cases. retinal hemorrhage or apoplexy, par- Rutin has been of great benefit in a ticularly in people with high blood disease known as hereditary hemor- pressure. rhagic telangiectasia, in which numer- Medical studies have shown that ous small hemorrhages occur, with rutin, taken by mouth, will correct bleeding from the gums and nose, into these capillary faults in a large pro- the stomach and intestines, and en- portion of cases. Accompanying this gorgement of small skin blood vessels. return of the capillary condition to The loss of blood leads to anemia; normal is a decrease in the tendencies sometimes the number of the red blood to apoplexy and retinal hemorrhage, corpuscles goes down to 2 million. Up so that patients show only the same to the present, no satisfactory treat- tendency to these accidents as is shown ment has been found for this disease, by patients w^ho have not had a capil- which usually persists throughout life. lary fault. Se\Tral cases in which rutin has been Diabetics frequently have complica- used with benefit have been reported. tions of this sort, with more or less loss The hemorrhages have been controlled of vision and often blindness. Eye doc- and the patient's health restored suffi- tors who have studied the use of rutin ciently to permit his n^turn to work. in such conditions feel that, while there An interesting application of rutin has not been a positive cure, the use of in strengthening the capillaries was re- rutin has resulted in arresting the prog- ported by Drs. Frederick Fuhrman and ress of the loss of sight and sometimes JefTcrson M. Crismon, of Stanford an improvement in vision, especially in University. They were studying the young patients. efifects of frostbite on animals, with the Other applications to eye diseases aim of developing a method for pro- have been studied. Physicians report tecting persons exposed to low tem- that the use of rutin in conjunction peratures from injury due to cold.

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