Sterling-Winthrop Research Articles

Comparative study of specific activity of rectal suppositories with clopidogrel

One of the most effective platelet antiaggregants is clopidogrel, inhibiting platelet activation by selectively binding adenosine diphosphate (ADP) with specific receptors. However, in a number of clinical situations it is necessary to have a pronounced antithrombotic effect in the shortest possible time which gives rise to interest in the transmucose use of the drug, in particular, rectal route. The theoretical preconditions for the development of a rectal administration of clopidogrel are based on the data that the anti-aggregation effect of a substance is carried out by its main metabolite formed after “first hepatic passage”, while clopidogrel itself in this aspect is inactive. On the base of complex physico-chemical, pharmaceutical, biopharmaceutical, rheological and microbiological investigations, the rational composition of clopidogrel rectal dosage form – suppository on a hydrophilic base to prevent atherothrombotic events in patients with myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral arterial occlusion, is proposed by the employees of the Department of Technology of Medications of the Zaporizhzhia State Medical University. The aim of the work is to investigate the specific activity of rectal suppositories with clopidogrel. Materials and methods. Experimental suppositories with clopidogrel 0,075 g for rectal administration were used as the objects in pre-line studies. The ability of clopidogrel to reduce the inhibitory effect of ADP on adenylate cyclase activity and decrease the number of binding sites for 2-methylthio-ADP (analogue of ADP) without altering the receptor topography is used as a base of the method of comparative study of its specific activity in the rectal dosage form (suppository) and in comparison with the reference medication Plavix (SANOFI WINTHROP INDUSTRIE, France) in the tablet form. Studies were performed on white non-linear rats of different sexes with different mass 150–210 g, aged 3.5–5.0 months. Results. Statistically significant differences in the inhibition of induced platelet aggregation were registered after 6 hours of rectal administration of clopidogrel and gastric administration of the reference medication, indicating the effectiveness of the rectal applicative transmucosal route for this active pharmaceutical ingredient (API). On the 5th day of administration, inhibition of induced platelet aggregation significantly increased, and that is supported by literature on the cumulative effect of clopidogrel in daily life. When comparing the digital material of the table, it is obvious that the rectal administration of clopidogrel is more effective in comparison with oral route which is probably due to the rapid delivery of API to the liver and the formation of an active metabolite of clopidogrel inhibiting the induction and spontaneous aggregation of platelets in human’s and animal’s blood. Obtained data provide with sound arguments for development of rectal suppositories with clopidogrel because in clinical care faster achievement of an anti-aggregation effect in patients with acute coronary syndrome is the primary task of clinical pharmacology and pharmacy. Conclusions. Using the biochemical model of pathology, it was established that the applicative semisolid medication of clopidogrel in the form of rectal suppository exhibited inductive anti-aggregation activity and its administration didn’t reveal any side effects and undesirable events. Rectal suppositories with clopidogrel have been shown to exhibit faster reliable anti-aggregation effect in comparison with intragastric administration.

William F. Johns

William F. Johns, 89, died on Sept. 22, 2019, in Bonita Springs, Florida. “He once told me that he got started in chemistry because he liked all the colored liquids in flasks. He was a bit disappointed to learn that most of the compounds he worked with, especially after crystallization, were plain white powders.”—Mitrick A. Johns, son Most recent title: Senior director, Sterling Drug Education: PhB, chemistry, 1948, and MS, chemistry, 1950, University of Chicago; PhD, chemistry, University of Wisconsin–Madison, 1955 Survivors: Wife, Patricia; daughter, Sue Johns-Morgan; sons, Mitrick and Daniel; four grandchildren; five great-grandchildren To recognize your late loved one or colleague, submit obituary information at cenm.ag/obits.

Pain and Profits: The History of the Headache and Its Remedies in America

Pain and Profits is an accessible social history of headache that aims to answer the question of why headache treatment remains in popular hands. It is also a highly readable history of jurisdictional disputes among the pharmaceutical industry, dispensing druggists, and clinical practitioners that is suitable for undergraduate courses. Bringing the history of drug supply (and demand) to bear upon the history of headache, Jan R. McTavish interweaves the history of commerce with the history of medicine. She uses patient accounts of this most everyday complaint to supplement those of the trade press, which portray ongoing professional disputes over prescription, distribution, advertising, and marketing but largely ignore sufferers. The book is also a history of intellectual property and direct-to-consumer pharmaceutical advertising, a much-contested policy blamed for everything from the com-modification of medicine to its democratization. This book reminds us that both are far from new phenomena. At times the book falls prey to the very trivialization of the headache it protests; it is sometimes more anecdotal and engaging than substantive. The final chapter on headache research is somewhat unsatisfying. McTavish is at her best when she recounts how aspirin became inextricably linked to the headache, given that it was not so introduced or marketed by either Bayer or Sterling Drug, the American company that bought the property at auction when it was confiscated by the U.S. Office of the Alien Property Custodian at the outset of World War I. McTavish ultimately settles upon “laypeople” as responsible for keeping headaches within the realm of self-medication, yet she acknowledges gaps both in the credibility of the laity and in physicians' sympathy toward them (p. 172). The people are attributed great sway, yet their outlines are but vaguely delineated. There is little attempt to specify populations and thus the public is represented as a somewhat homogenous and stubborn actor.

Managing the Gray Market in the European Union: The Case of the Pharmaceutical Industry

The emergence of significant trade blocks, such as the European Union (EU) and the North American Free Trade Agreement, has established the need for studies on managerial strategies to effectively circumvent gray markets in these regional marketplaces. Therefore, this article reviews the necessary market conditions required to foster gray markets by specifically exploring the regulated price and legal environments of the pharmaceutical industry in the EU. The article addresses the significance of, and relationship between, Articles 30 (promoting the free movement of goods within the EU) and 36 (permitting limits on imports and exports in certain cases) of the EU Treaty. Relevant decisions of the European Court of Justice are summarized and analyzed, with particular emphasis on those applying the Exhaustion of Rights Doctrine established in the 1974 landmark case of Centrafarm v. Sterling Drug. The article also examines the limits that the European courts have placed on the doctrine and suggest possible tactics that may be employed by pharmaceutical managers attempting to curtail the distribution of gray market pharmaceuticals. Also addressed are managerial perceptions regarding gray markets in the EU by means of personal interviews with 13 multinational pharmaceutical firms. Four principal themes emerged in the interviews on the topic of parallel imports: the degree to which a firm's exposure to gray markets varies in the EU; the current consolidation of wholesalers to bolster parallel imports; national governments’ overt or covert condonation of parallel imports to reduce the national drug bill; and the lack of managerial control to prevent gray markets. In this connection, the article concludes with a discussion of various anti-gray marketing strategies to facilitate managerial control in this trade block. In general, the manager must employ strategic links between the regulated price and legal framework governing the pharmaceutical marketing environment in the EU with various anti-gray marketing strategies such as supply interference, product differentiation, and marketing information systems.

Science and Technology Scouting at Elf Aquitaine

Let us be clear at the outset: Those who believe that it is not easy for a company to look for help in science and technology outside its own organization are right. Nothing that has been said about the difficulties of overcoming the Not Invented Here syndrome, or initiating a dialogue between two worlds as different as those of academic research and industry, is inaccurate. All of this is almost obvious. We experienced it in the past, and are still experiencing it every day at Elf Aquitaine. However, we are also experiencing the emergence of an irreversible process: an opening of our company to the outside world in all its activities. The people in the divisions have put this process into action through such agreements as the one that links Elf Sanofi, our pharmaceutical subsidiary, and Sterling Drug to develop and market new products; or the one linking Rohm and Haas with Elf Atochem, our chemicals subsidiary, concerning polymethyl methacrylate plastics. We in the RD meaningful experiments are costly, and must be carefully considered in advance and correctly interpreted afterward. What is required is a better understanding (cynics would say some understanding) of our processes and products. A scientific approach is thus perceived as an increasingly useful tool for our industrial developments. On the other hand, the integration of new technologies is most often closely linked with good access to science. Often, new technologies are born in the academic world before they are transplanted into industry for development. At a time when everyone is looking for advanced information, close relationships with university laboratories bring us in direct contact with emerging technologies that may have a relevance for our markets in the medium to long term. Last but not Least, educational institutions and, to a lesser extent, government research centers are training grounds for industry staff, especially in RD thus, competition for scientifically trained personnel is a real concern for our company, and a continuous interaction with the best universities is an excellent support for our recruiting. To sum up, we are convinced that industry must include science as one of its strategic tools, and we ensure that our R&D organization provides access to it in an efficient way. FROM A NATIONAL TO A WORLDWIDE EFFORT Elf Aquitaine has always tried to benefit to the fullest from what we call in France research, that is to say, research performed in the French universities or government-funded research centers. Indeed, we are one of the two or three companies in France that have the most interaction with that public research. We decided nearly 20 years ago to implement this policy simply because, unlike IBM or the former AT&T, we could not make the considerable long-term financial commitment necessary to set up our own basic research facilities. When this policy was launched in the late 1970s, it seemed to be a pioneering venture at a time when industry and academia were barely talking to each other, especially in France. …

Hydroxychloroquine Retinopathy

We analyzed ocular findings from two patients (aged 49 and 60 years) with hydroxychloroquine (Plaquenil, Winthrop Pharmaceuticals, Division of Sterling Drug, Inc., New York, New York) retinopathy. Both patients were treated for systemic lupus erythematosus; one patient was treated with 400 to 800 mg of hydroxychloroquine per day (6.1 to 12.2 mg/kg of body weight/day) over a ten-year period. Cumulative doses were 1,788 and 2,920 g, respectively. Neither patient had ever been treated with chloroquine. One patient complained of glare and difficulty in adjusting to changes in illumination, whereas the other was asymptomatic. Both had bilateral visual acuities of 20/25, pericentral scotomata, and increased final dark-adapted rod thresholds in the two retinal areas that were tested. Fullfield electroretinograms were reduced and delayed, and focal cone electroretinography showed abnormal foveal responses as well. Ophthalmoscopy and fluorescein angiography showed a bull's-eye maculopathy in both eyes of one patient and perifoveal depigmentation in both eyes of the other patient. Retinal function remained stable at follow-up examinations 18 to 24 months after the cessation of hydroxychloroquine treatment. These two cases demonstrate that peripheral retinopathy, as well as maculopathy, can develop in patients who are treated with hydroxychloroquine for systemic lupus erythematosus, and that retinal function may remain stable after discontinuation of hydroxychloroquine treatment.

Bayer reorganizes U.S. operations as Miles Inc.

The U.S. operations of Germany's Bayer A.G. will be completely restructured and also get a new name, the firm announced last week. Helge H. Wehmeier, president and chief executive officer of Bayer USA, told a press conference at the company's Pittsburgh headquarters that the company will drop the Bayer name. It also will cease use of the name Mobay for its chemical operations, terminate its organization as a holding company, and reorganize all existing operations on Jan. 1 as divisions of a new North American operating company called Miles Inc. The reorganization marks maturation of an active acquiring organization into an operating company with projected sales of $6 billion in North America. It also is an acknowledgment that operating in the U.S. under the Bayer name would require too high a price to pay for nostalgia. Bayer paid in excess of $20 million to Sterling Drug in 1986 for use of the name for the ...

Development of enzyme-based assays to detect circulating levels of IL7 in serum and to detect the immune response to IL7 injected into a xenogeneic species: [formula omitted] Sterling Drug, Inc., Malvern, PA 19355-1314

Development of enzyme-based assays to detect circulating levels of IL7 in serum and to detect the immune response to IL7 injected into a xenogeneic species: [formula omitted] Sterling Drug, Inc., Malvern, PA 19355-1314

Development of a chemiluminescent enzyme-linked immunosorbant assay (ELISA) for the quantitation of recombinant human interleukin-4 (RHUIL-4) in human serum and comparison of assay sensitivity with colorimetric methods: [formula omitted]. Sterling Drug Inc., Rensselaer, NY and Malvern, PA

Development of a chemiluminescent enzyme-linked immunosorbant assay (ELISA) for the quantitation of recombinant human interleukin-4 (RHUIL-4) in human serum and comparison of assay sensitivity with colorimetric methods: [formula omitted]. Sterling Drug Inc., Rensselaer, NY and Malvern, PA

Building a global team at Sterling Drug

Describes the two‐core management development programmes. Featuring internationally known business school faculty and consultants the first core stressed global strategic thinking: achieving world class excellence. Describes the integration of the International Division corporate strategy. Concludes that the key lessons include leadership, informed planning and eventual in‐house ownership of the programmes.

Kodak restructures, to cut 3000 employees

As part of a corporate restructuring, Eastman Kodak last week announced its fourth work force reduction in the past eight years. Kodak plans to reduce its imaging and information systems employment base by 3000, mostly through early retirement. It will take a onetime charge against earnings that will reduce third-quarter earnings $375 million. It is consolidating all its operations into three business units—Eastman Chemical, a new Imaging Group that includes information systems, and a Health Group. And it has named new heads for two of the units and retained a third, Earnest W. Deavenport Jr., as president of Eastman Chemical. The charge Kodak plans to take against earnings also includes costs for its Sterling Drug unit's alliance with French drugmaker Sanofi (C&EN, Jan. 14, page 15), and rationalization of operations for film manufacturing and photo processing outside the U.S. ...

Effects of Calcium-phosphate-based Materials on Proliferation and Alkaline Phosphatase Activity of Newborn Rat Periosteal Cells in vitro

The effects of dental materials, intended for bone substitution, on cell growth and alkaline phosphatase activity of newborn rat periosteal cells have been studied in vitro. Confluent periosteal cells were exposed to three apatite-based materials (400 micrograms/mL) with different physico-chemical properties. The materials were a beta-tricalcium phosphate with a microporous granular structure obtained by sinterization (Synthograft, Johnson & Johnson, East Windsor, NY), a 40-60-mesh microporous durapatite ceramic (Periograf, Sterling Drug, Inc., Rensselaer, NY), and a 1-2-mm-diameter hydroxyapatite ceramic (Osprovit, Feldmuhle Aktiengeselschaft, Plochingen, Germany) with macropores larger than 100 microns. Cell proliferation and alkaline phosphatase activity were assessed by incorporation of 3H-thymidine into trichloroacetic-acid-precipitable material and by a fluorimetric method, respectively. Cell viability and compatibility with the materials were determined by morphology in phase-contrast microscopy. Periosteal cells showed increased proliferation following exposure to Synthograft, but were unaffected by Osprovit, whereas Periograf caused significantly reduced cell growth. Alkaline phosphatase activity was unaffected by Osprovit, but was decreased by both Synthograft and Periograf. The results indicated a differential response of periosteal cells to bone-substituting materials with heterogeneous physico-chemical characteristics.

4978664 3-arylcarbonyl- and 3-cycloalkyl-carbonyl 1-aminoalkyl-1H indole pharmaceutical compositions: Malcolm R Bell assigned to Sterling Drug Inc

4978664 3-arylcarbonyl- and 3-cycloalkyl-carbonyl 1-aminoalkyl-1H indole pharmaceutical compositions: Malcolm R Bell assigned to Sterling Drug Inc

Eicosanoids and heart disease

The discovery of prostaglandins over 5 decades ago heralded a new era in the study of mediators or factors involved in physiological and pathophysiological processes. Prostaglandins, however, do not represent the sole products derived from arachidonic acid or other fatty acid precursors; instead these fatty acids can undergo metabolism to numerous bioactive compounds derived from cyclooxygenase, lipoxygenase, as well as the recently discovered epoxygenase cytochrome P-450 dependent pathways. Collectively, these products are commonly referred to as eicosanoids and have been implicated in numerous biological phenomena. It has long been hypothesized that the prostaglandins play an important role in cardiovascular regulation. For instance, the concept of a balance between the vasoconstrictor, prothrombotic properties of some arachidonic acid derived products and the opposing actions of others led to the development of drug therapies against thromboembolic disorders. Aspirin, for example, a well-known cyclooxygenase inhibitor, has been shown to be efficacious against myocardial infarction and stroke of embolic origin. Moreover, cyclooxygenase- and lipoxygenase-derived products have been implicated in various types of cardiac dysfunction including coronary constriction, arrhythmogenesis, anaphylactic reactions, or ischemic and reperfusion injury.In view of the evolving complexity of arachidonic acid metabolism and increasing evidence that eicosanoids, either alone, or through interaction with other substances, represent important mediators in either the development of heart disease or the myocardial response to injury, we organized this symposium entitled Eicosanoids and Heart Disease concurrent with the 31st Annual Meeting of the Canadian Federation of Biological Societies. A one-half day symposium precludes the possibility of detailed coverage of the many areas in cardiovascular disease in which eicosanoid participation could be implicated and which ideally one would hope to cover. The organizers' aim was to address, in the form of research presentations or reviews, current areas of investigation dealing with selected topics in heart disease.The success of this symposium was made possible by the participation of several distinguished scientists. We would also like to thank the Pharmacological Society of Canada, the Canadian Heart Foundation, Upjohn Canada, Sterling Drug, and Ciba-Geigy U.S. A. for financial support. The organizers thank Dr. J. Burka for serving as Guest Editor and Mrs. L. Hendrickson of this Journal for coordinating the submission of the manuscripts.

Sterling plans major R&D staff relocation

Sterling Drug plans to move 800 scientists and support staff of 950 employed at its research operations in Rensselaer, N.Y., to Providence Township in Pennsylvania, 20 miles northwest of Philadelphia, over the next four years. About 150 positions at the former Sterling-Winthrop Research Institute, established in 1950, will be eliminated. Sterling intends to employ 2000 scientists and support staff at the Pennsylvania site by the year 2000. Acquired by Eastman Kodak in early 1988 and now operated as an independent subsidiary, Sterling also plans to close its nearby East Greenbush, N.Y., manufacturing plant, with 260 employees, within the next two years. Leo J. Thomas, Sterling's chairman, says, Consolidation of our U.S. research operations into a single cohesive unit in state-of-the-art facilities should improve significantly our capabilities in drug discovery and development. Thomas, a career Kodak employee, was named to head Sterling in August 1988. A generous relocation allowance will be granted to ...

Comparison of Drug Information Practice in Hospitals and Industry

To assess the type of information requested of a pharmaceutical manufacturer, requests received over a 12 month period in the Professional Services Department of Sterling Drug Inc were reviewed. To compare drug information services of Sterling Drug with those of pharmacist-operated drug information centers (DICs), requests were classified as to the nature of the question, category of requestor, and patient specificity. Questions regarding dosage or administration, drug identification, and adverse drug events were common in both DICs and industry. At Sterling Drug Inc the largest number of requests were for literature reprints or physician drug samples and dosage or administration. This contrasts with hospital-based DICs, where the largest number of requests pertained to therapeutic use and drug efficacy or adverse drug events. At Sterling and DICs few questions pertained to pharmacology, toxicology or poisoning, and pharmacokinetics. Physicians comprised the largest group of requestors in DICs. Profession...

CHEMICAL ACQUISITIONS: Kodak wins fight for Sterling

Sterling Drug has given up its fight to remain independent and accepted a proposal to merge with Eastman Kodak. The deal is worth $89½ a share, or $5.1 billion. Sterling's sales of close to $2 billion would put Kodak's sales in the range of $14 billion annually. Sterling successfully managed to spurn the advances of Hoffmann-La Roche, the Swiss-based pharmaceuticals giant that made three bids for Sterling, the last one for $81 a share, or $4.8 billion (C&EN, Jan. 25, page 4). Roche withdrew its bid almost immediately after Kodak's higher offer. The Kodak bid does seem to guarantee Sterling a measure of operational independence that management feared it might lose if Roche had succeeded in the takeover. Kodak indicated it does not plan to sell any of Sterling's nondrug operations to pay for the acquisition. Those operations include Minwax and Formby's wood-finishing products as well as household products such as Lysol pine cleaner ...

Sterling files suit to prevent takeover

Hostilities are escalating in the attempted $4.2 billion takeover of Sterling Drug Co. by Swiss-based Hoffmann-La Roche, in which Roche has proposed to purchase 59 million shares of Sterling stock ...

Sterling Drug target for hostile takeover

Swiss pharmaceuticals giant Hoffmann-La Roche has launched an unfriendly takeover bid for New York City-based Sterling Drug valued at $4.2 billion. Hoffmann-La Roche says it now owns 57,900 shares of Sterling's approximately 159 million outstanding shares and adds that it seeks a majority of Sterling Drug shares by Feb. 2. At press time, Sterling failed to publicly respond to the offer, but its chairman, John M. Pietruski, is expected to resist any takeover. In his only public statement on the matter to date he has castigated investment bank Morgan Stanley, which is providing investment banking service to Hoffmann-La Roche on the deal, for its unethical conduct in aiding and abetting a surprise raid on [Sterling Drug,] one of its long-time clients. Pharmaceutical stocks closed higher on Jan. 5, spurred by speculation of other takeovers. Rorer was ahead $1½ for the day at $37½; Schering-Plough, up $2¼ to $49¼; and Warner-Lambert, up $2½ ...

4717569 Unit dosage form of sparingly soluble medicaments: Paul Harrison, John R Langridge, Christopher J Potter, Alnwick, United Kingdom assigned to Sterling Drug Inc

4717569 Unit dosage form of sparingly soluble medicaments: Paul Harrison, John R Langridge, Christopher J Potter, Alnwick, United Kingdom assigned to Sterling Drug Inc