Two Potent Analgesics Await FDA Approval Sterling Drug files its nonaddictive drug; Lederle filed on similar drug previously Sterling Drug's application to FDA for permission to market its nonaddictive painkiller, pentazocine, makes it the second drug company to file on such a drug. The drug is about as strong an analgesic as morphine on a dose-per-dose basis. Unlike morphine and other powerful analgesics, however, pentazocine (C&EN, March 23, 1964, page 37) doesn't seem to be addictive after prolonged use. Sterling would market its drug under the trade name Talwin. First to file a new drug application (NDA) on a powerful nonaddictive analgesic with the U.S. Food and Drug Administration was Lederle Laboratories division of American Cyanamid. Lederle applied early last year to FDA for clearance on its methotrimeprazine. According to the company, FDA has asked for additional information on the drug and Lederle is currently supplying the data. Similar drugs are being studied by Wyeth Laboratories, a division of American Home Products Corp., and by a group at the University of Rochester. Market. Target of this search for potent nonaddictive analgesics is the medical market now dominated by morphine and other opium-derived drugs. Sterling estimates this market at about $38 million annually at the manufacturers' level. Such analgesics could also take a share of the much larger market for mild painkillers. Today, the only potent analgesics marketed are opium-derived drugs such as morphine and codeine, and related synthetics such as meperidine.
All of these drugs, however, are habitforming and have some adverse side effects. In addition, a tolerance to morphine and similar drugs develops, and increasingly larger doses must be given to obtain the same analgesic effect. The new drugs, however, promise to overcome these disadvantages. Pentazocine. Sterling's pentazocine is 2-dimethylallyl-5,9-dimethyl-2'hydroxy-6,7-benzomorphan. At dose levels that give the same analgesic activity as morphine, pentazocine is tolerated as well as moiphine, says Sterling. Also, pentazocine does not produce any disturbing psychotic effects, the company adds. In its NDA, Sterling says pentazocine has been tested on more than 7000 patients by about 150 clinical investigators in the U.S. and Canada. It has been used to relieve postoperative pain, pain during childbirth, and pain associated with heart ailments, cancers, renal colic, migraine and tension headaches, and rheumatoid arthritis. According to Sterling, more than 90% of the patients experienced effective pain relief with the drug.
dl - Hexahydro -1,3 - dimethyl - 4 - phenyl azepine-4-carboxylic acid ethyl ester hydrochloride (Wyeth's Wy-535)
10- (3-Dimethylamino - 2 - methylpropyl) -2methoxyphenothiazine (Lederle's methotrimetrazine)
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2 - Dimethylallyl-5,9 - dimethyl - 2'-hydroxy6,7-benzomorphan (Sterling Drugs pentazocine)
Another big advantage of pentazocine is that it relieves pain over an extended period of time without increasing dosage, says Dr. Robert W. Ballard, v.p. and director of medical research for Sterling's Winthrop Laboratories division. Several dozen patients have been taking pentazocine continuously for about a year, and the drug has remained effective without any dosage increase. Pentazocine does have some of the side effects common to narcotics. These include respiratory depression, nausea, and drowsiness. However, these side effects are mild, Dr. Ballard says. Methotrimeprazine. Lederle's methotrimeprazine is a synthetic variation of the chlorpromazine tranquilizers, used widely for mental illness. Methotrimeprazine is 10-(3-dimethylamino-2-methylpropyl) - 2 - methoxyphenothiazine. No signs of addiction to this compound, which is about as potent as codeine, have been reported after more than eight years of u s e mainly as a tranquilizer—in Europe and Canada, says Lederle. Lederle would market methotrimeprazine under the trade name Levoprome. Related structurally to meperidine, Wyeth's Wy-535 is dZ-hexahydro-1,3- dimethyl-4-phenylazepine-4-carboxylic acid ethyl ester hydrochloride. According to Wyeth v.p. B. J. Gray, the compound has the analgesic properties of morphine without any of morphine's addictive qualities. Clinical tests for the first several months indicate so far that side effects are mild. At this time, says Wyeth, it is still too early to say how the tests will come out. Morphine Antagonists. Work on morphine antagonists that are potent analgesics is also going on at the University of Rochester. One of the promising compounds being studied is cyclorphan (C&EN, March 23, 1964, page 37). Cyclorphan, 3-hydroxy-Ncyclopropylmethylmorphinan, is one of a series of -cyclopropylmethylmoiphinan and morphine derivatives synthesized by Rochester's Dr. Marshall Gates and Dr. Thomas A. Montzka (now at Bristol Laboratories). Cyclophan is currently undergoing clinical testing. Some undesirable psychotic side effects, primarily of a hallucinatory nature, have shown up, but it is still too early to tell if they are serious enough to disqualify the drug for medical use, Dr. Gates says.
Carbide Organizes Detergent Department FROM
Firm, now producing nonionic detergent intermediates, plans strong move into biodegradables Union Carbide is integrating its entire detergent intermediate and chemical specialties operations. William C. Morro, Jr., has been appointed vice president and general manager of the new detergent and chemical specialties department. He was formerly general manager in the olefins division responsible for Carbide's alkylate business activities. According to Mr. Morro, the management reorganization means that Carbide plans to earn a bigger place as a supplier to the detergents industry. Carbide already has a plant to produce linear alkyl sulfonates in Institute, W.Va., and this month has been readying its new nonionic detergent intermediates plant in Texas City, Tex., for full production. Carbide plans to move strongly into the biodegradable detergent market. The plant in Texas City will be able to produce more than 100 million pounds a year of biodegradable nonionic detergent intermediates, which are derived from linear secondary alcohols. These nonionics are used for light-duty liquid detergents as well as for industrial and chemical specialties. Production of nonionics will complement Carbide's line of biodegradable linear alkyl sulfonates, the main detergent material for heavy-duty use. Over a year ago, Carbide started producing soft linear alkylate to replace
William C. Morro, Jr. Aims for "bigger place as a supplier"
hard alkylbenzene for anionic detergents at its 150 million pound-a-year plant in Institute (C&EN, March 9, 1964, page 19). Both the alkylate and the nonionic detergent intermediates are derived from paraffins produced at Carbide's paraffin separation plant in Texas City. This plant, having a capacity of more than 200 million pounds per year, went on stream over a year ago (C&EN, May 25, 1964, page 28). Soon, a 100 million pound-per-year addition will be in operation. In the new setup, long-range development of Carbide's business with the detergent industry will be directed by George A. Trigaux, formerly manager of new product development for the olefins division. His activities will emphasize the development of products. Dr. L. W. Newton has been appointed technology manager for research and development of new products and for customer service. Domestic marketing will be managed by Dale F. Swartz, Jr. He will coordinate all detergent intermediates sales, promotional, and market development activities. He will be assisted by three market development managers. R. C. Thies will be responsible for detergent manufacturers, Dr. E. A. Lawrence for detergent intermediate manufacturers, and J. R. Howell for all of Carbide's interests in the chemical specialties field. Before the reorganization, the development of Carbide's two detergent intermediates—Ucane R alkylate and Tergitol R nonionics—had been handled by separate divisions of the complex Carbide family. Carbide felt that the fastest way to develop biodegradables that would perform reliably was to take advantage of research strength which the company already had in its olefins and chemicals divisions. The olefins division assumed responsibility for alkylates, since it was experimenting with the use of molecular sieves in the separation of paraffin from kerosine. The chemical division was selected to develop a soft nonionic detergent intermediate because of its experience with ethoxylation reactions.
ENGELHARD...
What's New in Platinum Laboratory Ware?
To meet the advancing requirements of science and industry, Engelhard constantly adds new types of dishes, crucibles and vessels to its already extensive line of standard laboratory apparatus. Examples of recent additions are: • Trilay® Platinum Crucibles and Dishes (for longer life under corrosive and high temperature conditions). • Polygon Crucibles (for easier pickup and pouring). • Pure Iridium and Pure Rhodium Crucibles (for growing crystals for lasers and masers). For complete Laboratory Ware Catalogs and Data Sheets, write to Technical Service Dept.
ij.ijjjiij.i.j.j BAKER P L A T I N U M
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113 Astor Street • Newark 14, New Jersey
MAR. 2 9, 196 5 C & E N 29
Hooker Joins National Lead, H-K in Salt Lake Venture National Lead and H-K Corp. have enlisted a third partner in their effort to exploit the mineral resources of the Great Salt Lake. The third partner is Hooker Chemical. Hooker and National Lead each own a 44.5% interest in the venture. H-K, whose exclusive rights to magnesium in the lake extend till 1969, owns the remainder. The three-firm joint venture has a large-scale experimental facility, at Lakepoint, Utah, for extracting magnesium chloride and other salts from the lake. Among the other chemicals recoverable as coproducts are potassium sulfate, magnesium oxide, and hydrochloric acid. The joint venture is also building, at Henderson, Nev., a prototype, fullscale cell for the electrolytic conversion of magnesium chloride into magnesium and chlorine. The companies expect to complete pilot plant investigations and begin building solar evaporation ponds this year. Eventually, the companies plan to spend $37 million to build a chemical processing plant and a large-scale electrolytic plant for converting the magnesium chloride into magnesium and chlorine. The electrolytic plant will be built in the Pacific Northwest, where an expanding pulp and paper industry would provide a market for the chlorine. The chemical processing plant is to be built on the shore of the lake. H-K has leases and options to 150,000 acres around the lake.
Mobil Builds High-Purity Terephthalic Acid Plant Construction is now under way at Mobil Chemical's high-purity terephthalic acid plant at Beaumont, Tex. (C&EN, Nov. 30, 1964, page 1 7 ) . The multimillion-dollar plant will produce more than 50 million pounds a year of Mobil's high-purity TPA A-900. The plant is scheduled to begin commercial production next January. John D. Fennebresque, president of Mobil Chemical Co., says the expansion of the firm's semicommercial TPA plant at Beaumont is complete. The plant now produces high-purity TPA at a 5 million pound-a-year rate. Speaking of both plants, he says, "Both the new plant and the scaled-up semicommercial unit incorporate a unique 30
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purification process developed by Mobil Chemical after two years of research." High-purity TPA is used for direct esterification with ethylene glycol to produce polyester fiber or film. Lower purity (technical grade) TPA must be converted first to dimethylterephthalate and then undergo transesterification to produce the polyester. Highpurity TPA may also be used in lubricant additives, plasticizers, adhesives, and herbicides.
Manufacturing Injury Rates Decline in Last-Quarter 1964 The work-injury frequency rate for the nation's manufacturing industry declined somewhat in the last half of 1964. Preliminary figures compiled by the Labor Department's Bureau of Labor Statistics show a drop in rates from 13.2 to 12.2 between the third and fourth quarters—about usual for the season. The rates refer to the number of disabling injuries per million employee-hours worked. On an annual basis, the average frequency rate in manufacturing was 12.7 —a 5c/c increase over 1963. The rate for each quarter of 1964 was higher than for the comparable periods of 1963. In contrast to the national average, the rate in chemicals and allied products was lower (7.6) in 1964 than in 1963 (8.0). Disabling injuries include deaths, permanent impairments of any kind, and temporary injuries which cause an employee's inability to perform his regular job for one work shift on the day following the injury. The preliminary figures were derived from replies to questionnaires, and represent about 29% of the working force in manufacturing industries.
Mass., producer of thermoplastic food containers. Rexall bought the fixed assets and working capital of the company from Atlantic Refining Co., Philadelphia, Pa. The purchase price was not disclosed. Massachusetts Plastics will operate under Rexall's subsidiary, Rexall Chemical Co., Paramus, N.J.
Belding Hem in way Co.'s board of directors has approved the proposed acquisition of Virginia Dyeing Corp., Emporia, Va., subject to a Belding's shareholders' vote on April 28. The New York, N.Y., firm makes silk and synthetic threads.
Pittsburgh Plate Glass Co.'s coatings and resins division has a new department for appliance, container, and drill coatings. After mid-1965, the department will have its headquarters at Delaware, Ohio, where PPG is building an automobile refinishes plant.
American Roland Corp. will set up a process chemicals department to market industrial chemicals, intermediates, and chemical specialties. The new department will be at coiporate headquarters, New York, N.Y.
Martin Metals Co., Wheeling, 111., has closed its metal technology laboratory in Portland, Ore. The operations were transferred to Wheeling.
Purex Corp., Ltd., Lakewood, Calif., has acquired Wallace Chemical Co., Tampa, Fla. Wallace makes household cleaning products and plastic containers. It will become part of Purex's grocery products group.
BRIEFS NEW FACILITIES Syntex Laboratories, Inc., Palo Alto, Calif., has set up an animal health division to staff a marketing unit for the U.S. and Canada. The division will introduce anti-inflammatory and fertility agents to veterinarians. Later this year it will begin building an experimental farm at Morgan Hill, Calif.
Chemical Construction Corp., New York, N.Y., will build nitric acid and ammonium nitrate plants near Hannibal, Mo., for American Cyanamid (C&EN, Dec. 7, 1964, page 19). The plants will be in operation early in 1966.
Rexall Drug & Chemical Co., Los Angeles, Calif., has acquired Massachusetts Plastics Corp., a Ludlow,
International Minerals & Chemical Corp., Skokie, 111., has taken an option on 80 acres of land on the Penobscot
FOR ULTIMATE PURITY...
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flffi ADSORPTION?
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Minerals & Chemicals Philipp Corporation I OPiAl Essex Turnnike. Menlo Park. N. J .
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MINERALS & CHEMICALS PHILIPP CORPORATION 2647 Essex Turnpike, Menlo Park, New Jersey 0 8 8 3 7
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River in Maine as a possible site for a chlorine and caustic soda plant. If the option is exercised, a highly automated, multimillion-dollar operation would be planned.
Goodyear is expanding its polyester resin plant at Point Pleasant, W.Va., again. Last year the original capacity of the six-year-old plant was doubled. The present $1.5 million expansion will be completed later this year.
Harris Laboratories, Inc., of Lincoln, Neb., has expanded its research farm division, El Rancho Micro. The expansion provides independent research and development services, such as tissue residue problems, toxicity testing, and clinical evaluations.
Firestone Tire & Rubber Co. will double the capacity of its coated fabrics plant in Magnolia, Ark. At the same time, the company's coated fabrics division will become Firestone Coated Fabrics Co. with Don L. Weihe, the division's former sales manager, as president.
Borden Chemical Co. has begun construction of a $15 million complex at Plant City, Fla. As part of Florida's expanding phosphate industry (C&EN, March 15, page 2 4 ) , the facility will produce 140,000 tons of phosphoric acid, 184,000 tons of fertilizers, and 385,000 tons of sulfuric acid per year when it is operating in mid-1966.
American Cyanamid will soon complete construction of a unit to recover sodium sulfate from waste water at Fort Worth, Tex. The project, planned in cooperation with the Texas Water Pollution Control Board, has two puiposes: to help clean up waste water discharged into the local river, and to recover a salable material. Sodium sulfate is used in making paper, glass, and detergents.
MARKETS Enjay Chemical Co., a division of Humble Oil & Refining, has reduced prices on two of its four neoacids to compete with imported materials. Enjay is the only U.S. producer of 32
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Gulf Adds Hydrocracker at Port Arthur Refinery This 500-ton hydrocracker unit is being lifted into place at Gulf Oil Corp.'s refinery at Port Arthur, Tex. The 100-foot-long reactor will be able to convert 15,000 barrels a day of furnace oil into naphtha, gasoline, isobutane, ethane, propane, and fuel gas. The unit is scheduled to be in operation in May. Fluor Corp., Los Angeles, Calif., is the prime contractor for the plant, although the reactor itself was made by Chicago Bridge & Iron Co. at Birmingham, Ala.
neoacids. The new prices, effective March 15, are 40 cents per pound for carload drum lots of neopentanoic acid, and 41.5 cents for neodecanoic acid. These are reductions of 2.5 cents per pound on each acid.
Goodrich-Gulf Chemicals has established a new sales division called national and special accounts. It will be managed by Samuel D. Morgan, former manager of the company's domestic rubber sales division.
Union Carbide's chemicals division has discontinued handling charges on small orders and substituted price increases. Prices of chemicals in 5-gallon quantities were raised by 20 cents per pound, and in 1-gallon quantities by 60 cents per pound.
FINANCIAL Southern Nitrogen Co., Inc., Savannah, Ga., will seek stockholders' approval to increase common stock from 1.75 million shares to 3 million. Voting will take place at an annual meeting on April 30.
Standard Oil Co. of Indiana's sales of chemicals last year reached $100 million, a 37% increase over the 1963 figure. Among the factors contributing to the increase were large boosts in capacity for chemical raw materials at the company's Joliet, 111., plant. The company doubled its ammonia sales to almost 210,000 tons. It also introduced new products, including an automotive finish solvent, an antifoulant for refinery cooling systems, and a new high-temperature coating.
