THE CHEMflCAL WORLD THIS WEEK
Specialized eciuipmenl features Mercks* cortisone production, which continues to rise as broad activity results in .
New Drugs for Arthritis Ά. NEW, potentially low-cost drug which promises relief in 6()r/r of arthritis cases will appear on the market next week. This announcement came rapidly on the heels of a preliminary report from Sweden indicate that a combined treatment with a cortisone precursor and vitamin C gives the same results as cortisone in rheumatoid arthritis. The precursor employed is desoxycorticosterone, which lacks oxygen in the difficult 11-position and is much more readily available than cortisone.
The new antirheumatic agent to be introduced the week of Jan. 9 is glucuronic acid, which is being manufactured on a pilot plant scale by Corn Products Refining Co. The product will be marketed by CSC Pharmaceuticals, a division of Commercial Solvents Corp., under the name, Clueurone, which is the company's abbreviation of glucuronolaetone, the anhydride of glucuronic acid.
Although the selling price of Clueurone has not yet been set, it is less expensive tha».· the hormone-type drugs but is still not cheap. It will be offered in the form of 0.5- gram tablets for oral administra
tion; dosage is about 2 grams per day. While it i s probable that it will later be soid over the counter, Glucurone will at first be sold only under prescription.
Clinical trials of glucuronic acid over a period o f several years and involving several hundred physicians have been revealed t o average about 60% effectiveness depending on the type and cause of the artlxritic condition. About 30% of the results have been dramatic, 25 to W/f bave been good, with no effect on the remainder of the eases. The clinical investigations have been conducted by CSC Pharmaceuticals under the supervision of L . W. Smith, medical director.
The V/eek's Events Casey Receives Iowa Award . . . 4 8 British Fluorine Symposium . . . . 5 1 ACS Award Nominations Asked . . 5 2 C ^ to Co "ver Nuclear Phenomena . . 5 2 Brookhaven Tracer Conference Program 5 4 Finnish Chemists Receive Gadolin Award 57 C&EN Expands Chemical Market Prices
Section 6 9
In a recent announcement of preliminary results of one group of clinical trials (Journal· Lancet y pages 3 8 5 - 8 ) , Joseph H. Hodas, Harvey Brandon, and John F. Maloney of New York reported 9 complete remissions, 19 major improvements, and 14 minor improvements out of 50 cases studied.
In the series reported the comparatively early eases of osteo-arthritis responded best. In addition to lessening of pain and swelling in the joints, the general feeling of well-being and the gain of weight were outstanding symptoms. In rheumatoid arthritis and its subdivisions, the results were less effective and at times equivocal, reported the investigators.
Another field for the use of glucuronic acid, according to these clinicians, appears to be in the treatment of sciatica. Satisfactory results were obtained with two cases of sciatica in this series, but dramatic response has been observed in 10 cases not included in the present report.
Glucuronic acid is an oxidative derivative of D-glucose in which all of the features of the glucose molecule are preserved except for conversion of the primary hydroxyl group to carboxyl. Polysaccharides of plant gums, such as gum arabic, contain glucuronic acid, but its isolation is difficult. It occurs naturally in the
44 C H E M I C A L A N D E N G I N E E R I N G N E W S
Team that produced commercial glucuronic acid: S. W. Kapranos , R. A. Reiners. A. L . Wilson, Har ry Gehman, N. E . Artz, E . W . Kaiser, and E. M . Osman
body as a constituent of connective tissue and collagen, particularly the carti lage, periosteum, nerve sheath, joint capsule, tendon, and joint fluid. I t is also contained in the intercellular cement sub stance and in blood vessel walls. An important function of this agent is in detoxification reactions in which many normally toxic substances are cxcreied as conjugates of glucuronic acid.
Amazement has been expressed tha t a compound which has aroused so much interest and the probable function of which has been used to explain data presented in over 400 technical papers has not received more attention at the hands of the chemist. Medical investigators have had to rely upon the expensive biosynthetic route for the small amounts of glucuronic acid used in past studies. Dogs fed such compounds as camphor and phenol in sublethal doses excrete these as conjugated derivatives of glucuronic acid in quantities significant to the organism but qui te insignificant chemically and in a form difficult to recover.
A wide variety of toxic organic compounds, some of which are carcinogenic, have been observed to be excreted as conjugates of glucuronic acid. Examples are aromatic hydrocarbons, sulfonamides, salicylates, chloral hydrate, terpenes, a n d sex hormones.
A Detroit physician, E . A. Pe tennan , suggested in 1947 (Journal-Lancet, pages 4 5 1 - 3 ) that the destruction of carti lage and bone may be due to deficiency of glucuronic acid required for body metabolism. I t is thought that such a metabolic disturbance might also involve the cement substance of the collagen diseases, which includes arthritis. The cause of t h e d e ficiency has not been ascertained.
Following this thesis, Pe tennan and others commenced to treat arthritis as a deficiency disease. The low yields of glucuronic acid obtainable from niitural
A. L. Elder, director of Research for the Corn Products Refining Co .
gums or by the use of laboratory animals made it apparent that a completely synthetic source was needed, and they approached Corn Products for aid in synthesizing glucuronic acid in clinical amounts.
Research Program
A program was started under A. L. Elder, director of research for Corn Products, with the intent of producing the desired glucuronic acid from corn starch or starch derivatives. T h e first basic studies in this difficult field were undertaken by Elizabeth M. Osman. As in any research organization where emphasis is placed on the rapid solution of a problem, many members of the staff worked together as a team. Under the supervision of ass:.stunt directors of research Harry Gehman and A. L. Wilson, many proposed methods of synthesis were explored.
For some time the immediate laboratory work has been headed by Neal E. Artz, formerly professor of biochemistry in the school of medicine, Syracuse University. Major contributions to an efficient synthetic process, pilot plant construction, and manufacture of glucuronic acid have been made possible through the efforts of R. A. Reiners, S. W. Kapranos, E. \V. Kaiser, and their associates.
Pure glucuronic acid, usually crystallized as the gamma lactone, is being produced by the chemical division of Corn Products. Although production facilities have been expanded several times during the past year, the output is still on a pilot-plant scale. Clinical investigators no longer lack for all of the glucuronic acid needed for their work, company spokesmen revealed.
If increased future demand for glucuronic acid warrants it, production facilities will be erected to supply the general demand. No difficulty is anticipated in a transition from pilot plant to production scale operation. T h e ultimate price of glucuronic acid cannot l»c established until demands are more definitely known. Since glucuronic acid is produced from inexpensive and easily available raw materials, quanti ty production would be expected to result in an ultimate price level sufficiently low to assure general availability.
Desoxycorticosterone
T h e report fiom Gothenburg, Sweden {Lancet, Nov. 26, p . 993) indicates that the injection of both desoxycorticosterone acetate and ascorbic acid appear to give the same results as cortisone in the treatment of rheumatoid arthritis. E. Lewin and YV. Wassen have recorded the same dramatic cessation of articular pain and return, of joint motility after injections of 2.5 mg. and 500 mg . of the agents, respectively, as experienced with cortisone.
T h e effect lasts from 2 to 6 hours, occasionally more than 24 hours and appears to last longer with each further injection. In some acute cases one or two injections have been enough to banish pain for 2 to 3 weeks, report physicians.
T h e significance in this report lies in the fact that both desoxycorticosterone and ascorbic acid are readily available in quanti ty and do not involve expensive syntheses.
Cortisone Progress Brings Lower Prices
Meanwhile, Merck & Co., Inc. , is continuing to increase its output of cortisone and reflected this in a 2 5 % price reduction recently. It is now selling for $150 per gram. Production has reached a point where allocation is not the problem that it was dur ing the summer, and the committee of the National Academy of Sciences that was supervising the distribution of cortisone for Merck (C&EN. Aug. 15, p . 2366) was disbanded on Dec. 3 1 . From now on Merck will operate its own system of priorities, but since cortisone has not yet been passed by the Food and Drug Administration, it will stilî be restricted to experimental use.
No further progress has been reported to da le on efforts to obtain cortisone intermediates from plant sources. Three expeditions are still in Africa searching for varieties of Strophanthus that might yield sarmentogenin. Merck is sponsoring one expedition, S. B. Penick & Co. another, and the third is jointly sponsored b> the U. S. Public Health Service and th<-U. S. Depar tment of Agriculture (C&EN Aug. 29, p. 2 4 8 8 ) .
T h e latter expedition, headed by John T. Baldwin of the Division of Plant Ex·
V O L U M E 2 8, N O . 1 » » J A N U A R Y 2, 1 9 5 0 45
Pipe Line or Absorption Column...
" "™ PYREX BRAND
GLASS PIPE
ADAPTABLE FOR MANY USES
When Corning announced 6" PYREX brand glass pipe recently, chemical engineers
saw that it had real "gadgeteering" potential. Out of this came the absorption column illustrated
above as well as bubble cap columns and reaction vessels.
More and more, PYREX brand glass N o . 7740 is becoming a useful tool in many phases of plant processing. For the transfer of corrosive or easily contaminated liquids, PYREX brand glass pipe is first choice. Balanced stocks of 1", 1>£", 2", 3", 4", and 6" diameter pipe are maintained at all t imes, including a full line of fittings. Adaptors make i t easy to connect PYREX brand glass pipe to metal pipe lines or other equipment.
Whether you use PYREX brand glass N o . 7740 in pipe lines or for special equipment, you can depend on its high chemical stability plus exceptional resistance to thermal and physical shock. That's what makes PYREX pipe the most practical and economical solution to difficult process problems.
If you have a process or product that would benefit from the advantages PYREX brand glass N o . 7740 affords, ask Corning engineers for ideas.
C O R N I N G GLASS W O R K S
ploration and Introduction, USDA, has visited Liberia, Gold Coast, and Nigeria and is now in Cameroons. Varieties of Strophanihus are being located for return visits to collect seeds during the fruiting season in the spring.
Jn the meantime, Baldwin κ, collecting stems, roots, and leaves of Strophanthine varieties for shipment to the National Institutes of Health in Bethesda, Md., io search for a useful precursor of sarmento-genin, which, according to reports from Switzerland, is elusive. Chemists there have found that authentic seeds from S. sarmentosus sometimes do not contain sarmentogenin.
It is indicated that stocks of seeds wiD be received and analyses begun by the end of March and that the useful varieties, if any, may soon be identified. Eric Mosettig, research chemist at Bethesda in charge of evaluation, will be assisted in this aspect of the project by A. Katz, a co-worker of T. Reichstein's, who wiB come here from Switzerland on a Public Health Service special fellowship in February. It is emphasized, however, that ever* if a suitable source of sarmentogenin is found, the agricultural phases of its production from plant sources will have to-be conducted in tropical countries and will probably be a long term proposition.
Among other plant materials, the division of plant exploration is bringing in Mexican yams (C&EN, Sept. 5, page 2548) for investigation of their sapogenin content. Yams are also being investigated at the Eastern Regional Research Laboratory of USDA where a review of the sterol content of all agricultural commodities-being produced commercially in this country is also being undertaken.
ACTH Progress has also been made in the
commercial production of adrenocorticotropic hormone (ACTH), the pituitary agent which is considered to control the formation of cortisone in the adrenal cortex. Armour & Co. has announced that ACTH will be sold to research organizations as of this week. The price, which has not been disclosed, is not to be profit-making but will attempt only to-cover current manufacturing costs, it is stated.
Production of ACTH is still very small, about 30 days are required for its isolation and preparation for administration. Ten or 11 chemical control tests are necessary in the course of production. About 45 clinics are currently investigating the application of this hormone.
Present information indicates that the new agents for arthritis will complement rather than supplant ACTH and cortisone. For example, glucuronic acid is apparently of doubtful value in rheumatoid arthritis, in which cortisone is most effective. Thus, all of these drugs will have their place in the treatment of special types of arthritis and other conditions in which new applications are constantly being found.
46 C H E M I C A L A N D E N G I N E E R I N G N E W S
CORNING, N. Y.
£&z*€4>cf /?ceœ^/ze<feazc/C £>t> &Î&44
Technical Products Division: Glass Pipe, Laboratory Glassware, Plant Equipment, Lightingware, S ignalware , G a u g e Glasses, Opt ica l Glass, Glass Components