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107-493: It is mainly agricultural with the main crops being wheat and maize (corn). Its major industry is a pharmaceutical company (Dongfeng Yaoye), after which the county town's main street is named. Deer are also raised for their meat and antlers, which are used in Chinese medicine . It is a relatively poor county with salaries starting at Y300. Many people in the county town are unemployed and rely on riding "daoqilu" (pedicabs where

214-560: A compound annual growth rate (CAGR) of 1.8% given the results of recent events (which includes the COVID-19 pandemic ). In historical terms, a pharmaceutical industry as an intellectual concept arose within the middle to late 1800s inside of certain nation-states with developed economies such as Germany , Switzerland , and the United States given that multiple businesses engaging in synthetic organic chemistry , such as

321-492: A 20% drop in those for which antibiotics were not effective. The report concluded that "it appears that the use of antibiotics, early diagnosis, and other factors have limited the epidemic spread and thus the number of these diseases which have occurred". The study further examined mortality rates for eight common diseases for which antibiotics offered effective therapy (syphilis, tuberculosis, dysentery, scarlet fever, whooping cough, meningococcal infections, and pneumonia), and found

428-517: A 56% decline over the same period. Notable among these was a 75% decline in deaths due to tuberculosis. During the years 1940–1955, the rate of decline in the U.S. death rate accelerated from 2% per year to 8% per year, then returned to the historical rate of 2% per year. The dramatic decline in the immediate post-war years has been attributed to the rapid development of new treatments and vaccines for infectious disease that occurred during these years. Vaccine development continued to accelerate, with

535-411: A Japanese biochemist working for the pharmaceutical company Sankyo, identified mevastatin (ML-236B), a molecule produced by the fungus Penicillium citrinum , as an inhibitor of HMG-CoA reductase, a critical enzyme used by the body to produce cholesterol. Animal trials showed very good inhibitory effect as in clinical trials , however a long-term study in dogs found toxic effects at higher doses and as

642-536: A Korean Township. However, the local media do not have any Korean language programmes or newspapers to cater for them and many of the Koreans in Dongfeng have lost their Korean language skills even though there is a Korean language secondary school and a Korean church available to them. The county administers 12 towns, one township, and one ethnic township. Towns: Townships: This Jilin location article

749-595: A commercial scale. Early industrialization was conducted by J. Pullar and Sons in Scotland. The first synthetic dye, mauve , was discovered serendipitously by William Henry Perkin in 1856. The discovery of mauveine started a surge in synthetic dyes and in organic chemistry in general. Other aniline dyes followed, such as fuchsine , safranine , and induline . Many thousands of synthetic dyes have since been prepared. The discovery of mauve also led to developments within immunology and chemotherapy . In 1863

856-414: A compound is identified as a potential drug in order to establish its suitability as a medication. Objectives of drug development are to determine appropriate formulation and dosing , as well as to establish safety . Research in these areas generally includes a combination of in vitro studies, in vivo studies, and clinical trials . The cost of late stage development has meant it is usually done by

963-472: A drug could be sold, and explicitly prohibited false therapeutic claims. The aftermath of World War II saw an explosion in the discovery of new classes of antibacterial drugs including the cephalosporins (developed by Eli Lilly based on the seminal work of Giuseppe Brotzu and Edward Abraham ), streptomycin (discovered during a Merck-funded research program in Selman Waksman's laboratory ),

1070-558: A heart attack were reduced by 42%. In 1995, Zocor and Mevacor both made Merck over US$ 1 billion. Endo was awarded the 2006 Japan Prize , and the Lasker-DeBakey Clinical Medical Research Award in 2008. For his "pioneering research into a new class of molecules" for "lowering cholesterol," Since several decades, biologics have been rising in importance in comparison with small molecules treatments. The biotech subsector, animal health and

1177-507: A highly toxic solvent that is now widely used as antifreeze. Under the laws extant at that time, prosecution of the manufacturer was possible only under the technicality that the product had been called an "elixir", which literally implied a solution in ethanol. In response to this episode, the U.S. Congress passed the Federal Food, Drug, and Cosmetic Act of 1938 , which for the first time required pre-market demonstration of safety before

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1284-439: A living body - administered by injection or other means (intravital staining) - as the latter is (for instance) subject to higher safety standards, and must typically be a chemical known to avoid causing adverse effects on any biochemistry (until cleared from the tissue), not just to the tissue being studied, or in the short term. The term "vital stain" is occasionally used interchangeably with both intravital and supravital stains,

1391-406: A microscope). As the visibility is meant to allow study of the cells or tissues, it is usually important that the dye not have other effects on the structure or function of the tissue that might impair objective observation. A distinction is drawn between dyes that are meant to be used on cells that have been removed from the organism prior to study (supravital staining) and dyes that are used within

1498-469: A number of companies developed products based on adrenal extracts containing varying purities of the active substance. In 1897, John Abel of Johns Hopkins University identified the active principle as epinephrine , which he isolated in an impure state as the sulfate salt. Industrial chemist Jōkichi Takamine later developed a method for obtaining epinephrine in a pure state, and licensed the technology to Parke-Davis . Parke-Davis marketed epinephrine under

1605-479: A number of firms generating dyestuffs derived from coal tar on a large scale, sought out new applications of their artificial materials in terms of human health . This trend to increased capital investment occurred in tandem with the scholarly study of pathology as a field advancing significantly, and a variety of businesses set up cooperative relationships with academic laboratories evaluating human injury and disease. Examples of industrial companies with

1712-413: A person. Buses also link Dongfeng with Liaoyuan, Siping, Changchun, Shenyang, and other cities and counties. Temperatures range from up to 30 C in the short summer to minus 30 or even minus 40 C in the long winter, during which snow covers the ground and the rivers and drains are iced up. Most of the people living in Dongfeng are Han Chinese , but there are also scattered ethnic Korean communities, and

1819-493: A pharmaceutical focus that have endured to this day after such distant beginnings include Bayer (based out of Germany) and Pfizer (based out of the U.S.). The modern era of pharmaceutical industry began with local apothecaries that expanded for their traditional role of distributing botanical drug s such as morphine and quinine to wholesale manufacture in the mid-1800s, and from discoveries resulting from applied research. Intentional drug discovery from plants began with

1926-499: A protocol to discontinue their use. A series of experiments performed from the late 1800s to the early 1900s revealed that diabetes is caused by the absence of a substance normally produced by the pancreas. In 1869, Oskar Minkowski and Joseph von Mering found that diabetes could be induced in dogs by surgical removal of the pancreas. In 1921, Canadian professor Frederick Banting and his student Charles Best repeated this study and found that injections of pancreatic extract reversed

2033-467: A push for revisions of the FD&;C Act emerged from Congressional hearings led by Senator Estes Kefauver of Tennessee in 1959. The hearings covered a wide range of policy issues, including advertising abuses, questionable efficacy of drugs, and the need for greater regulation of the industry. While momentum for new legislation temporarily flagged under extended debate, a new tragedy emerged that underscored

2140-504: A reduction in initial public offerings being floated. A 2022 article articulated this notion succinctly by saying "In the business of drug development, deals can be just as important as scientific breakthroughs", typically referred to as pharmaceutical M&A (for mergers and acquisitions). It highlighted that some of the most impactful of the remedies of the early 21st Century were only made possible through M&A activities, specifically noting Keytruda and Humira . Drug discovery

2247-400: A result mevastatin was believed to be too toxic for human use. Mevastatin was never marketed, because of its adverse effects of tumors, muscle deterioration, and sometimes death in laboratory dogs. P. Roy Vagelos , chief scientist and later CEO of Merck & Co , was interested, and made several trips to Japan starting in 1975. By 1978, Merck had isolated lovastatin (mevinolin, MK803) from

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2354-431: A series of such compounds, and was found to exhibit partially selective toxicity. Arsphenamine proved to be the first effective treatment for syphilis , a disease untl then had been incurable and led inexorably to severe skin ulceration, neurological damage, and death. Ehrlich's approach of systematically varying the chemical structure of synthetic compounds and measuring the effects of these changes on biological activity

2461-568: A sleep aid beginning in 1904. Systematic investigations of the effect of structural changes on potency and duration of action led to the discovery of phenobarbital at Bayer in 1911 and the discovery of its potent anti-epileptic activity in 1912. Phenobarbital was among the most widely used drugs for the treatment of epilepsy through the 1970s, and as of 2014, remains on the World Health Organizations list of essential medications. The 1950s and 1960s saw increased awareness of

2568-492: A small fraction are eventually approved in most nations by government-appointed medical institutions or boards, who have to approve new drugs before they can be marketed in those countries. In 2010 18 NMEs (New Molecular Entities) were approved and three biologics by the FDA, or 21 in total, which is down from 26 in 2009 and 24 in 2008. On the other hand, there were only 18 approvals in total in 2007 and 22 back in 2006. Since 2001,

2675-561: A third of the global pharmaceutical market, with $ 340 billion in annual sales followed by the EU and Japan. Emerging markets such as China, Russia, South Korea and Mexico outpaced that market, growing a huge 81 percent. The top ten best-selling drugs of 2013 totaled $ 75.6 billion in sales, with the anti-inflammatory drug Humira being the best-selling drug worldwide at $ 10.7 billion in sales. The second and third best selling were Enbrel and Remicade, respectively. The top three best-selling drugs in

2782-568: Is a stub . You can help Misplaced Pages by expanding it . Pharmaceutical company The pharmaceutical industry is an industry involved in medicine that discovers, develops, produces, and markets pharmaceutical goods for use as drugs that function by being administered to (or self-administered by) patients using such medications with the goal of curing or preventing disease (as well as possibly alleviating symptoms of illness or injury ). Pharmaceutical companies may deal in " generic " medications and medical devices without

2889-454: Is a very large study of efficacy in the intended patient population. Following the successful completion of phase III testing, a New Drug Application is submitted to the FDA. The FDA reviews the data and if the product is seen as having a positive benefit-risk assessment, approval to market the product in the US is granted. A fourth phase of post-approval surveillance is also often required due to

2996-559: Is added to the dye bath to help the uptake of the dye onto the fiber. Basic dyes are also used in the coloration of paper . Direct or substantive dyeing is normally carried out in a neutral or slightly alkaline dye bath, at or near boiling point , with the addition of either sodium chloride (NaCl) or sodium sulfate (Na 2 SO 4 ) or sodium carbonate (Na 2 CO 3 ). Direct dyes are used on cotton , paper, leather , wool, silk and nylon . They are also used as pH indicators and as biological stains . Laser dyes are used in

3103-454: Is not associated with cancer in people. Other notable new vaccines of the period include those for measles (1962, John Franklin Enders of Children's Medical Center Boston, later refined by Maurice Hilleman at Merck), Rubella (1969, Hilleman, Merck) and mumps (1967, Hilleman, Merck) The United States incidences of rubella, congenital rubella syndrome, measles, and mumps all fell by >95% in

3210-486: Is the food dye . Because food dyes are classed as food additives , they are manufactured to a higher standard than some industrial dyes. Food dyes can be direct, mordant and vat dyes, and their use is strictly controlled by legislation . Many are azo dyes, although anthraquinone and triphenylmethane compounds are used for colors such as green and blue . Some naturally occurring dyes are also used. A number of other classes have also been established, including: By

3317-430: Is the core guide for pharmacists and clinicians. In many non-US western countries, a 'fourth hurdle' of cost effectiveness analysis has developed before new technologies can be provided. This focuses on the 'efficacy price tag' (in terms of, for example, the cost per QALY ) of the technologies in question. In England and Wales NICE decides whether and in what circumstances drugs and technologies will be made available by

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3424-498: Is the most important risk factor for cardiovascular morbidity and mortality , in industrialized countries . Prior to 1940 approximately 23% of all deaths among persons over age 50 were attributed to hypertension. Severe cases of hypertension were treated by surgery. Early developments in the field of treating hypertension included quaternary ammonium ion sympathetic nervous system blocking agents, but these compounds were never widely used due to their severe side effects, because

3531-595: Is the process by which potential drugs are discovered or designed. In the past, most drugs have been discovered either by isolating the active ingredient from traditional remedies or by serendipitous discovery. Modern biotechnology often focuses on understanding the metabolic pathways related to a disease state or pathogen , and manipulating these pathways using molecular biology or biochemistry . A great deal of early-stage drug discovery has traditionally been carried out by universities and research institutions. Drug development refers to activities undertaken after

3638-415: Is the value of the publicly traded companies. Small Molecules modality had 58.2% of the valuation share down from 84.6% in 2003. Biologics was up at 30.5% from 14.5%. The valuation share of Chinese Pharma grew from 2003 to 2021 from 1% to 12% overtaking Switzerland who is now ranked number 3 with 7.7%. The United States had still by far the most valued pharmaceutical industry with 40% of global valuation. 2023

3745-463: Is used. The very fine particle size gives a large surface area that aids dissolution to allow uptake by the fiber. The dyeing rate can be significantly influenced by the choice of dispersing agent used during the grinding. Azoic dyeing is a technique in which an insoluble Azo dye is produced directly onto or within the fiber. This is achieved by treating a fiber with both diazoic and coupling components . With suitable adjustment of dyebath conditions

3852-519: The Nobel Prize in Medicine for this discovery. Nonetheless, the dramatic decrease in deaths from infectious diseases that occurred prior to World War II was primarily the result of improved public health measures such as clean water and less crowded housing, and the impact of anti-infective drugs and vaccines was significant mainly after World War II. In 1928, Alexander Fleming discovered

3959-571: The Republic of Georgia in a prehistoric cave dated to 36,000 BP . Archaeological evidence shows that, particularly in India and Phoenicia , dyeing has been widely carried out for over 5,000 years. Early dyes were obtained from animal , vegetable or mineral sources, with no to very little processing. By far the greatest source of dyes has been from the plant kingdom , notably roots, berries, bark, leaves and wood, only few of which are used on

4066-577: The birth control movement and the efforts of activists Margaret Sanger , Mary Dennett , and Emma Goldman . Based on fundamental research performed by Gregory Pincus and synthetic methods for progesterone developed by Carl Djerassi at Syntex and by Frank Colton at G.D. Searle & Co. , the first oral contraceptive, Enovid , was developed by G.D. Searle & Co. and approved by the FDA in 1960. The original formulation incorporated vastly excessive doses of hormones, and caused severe side effects. Nonetheless, by 1962, 1.2 million American women were on

4173-477: The opportunity cost of investing capital many years before revenues are realized (see Time-value of money ). Because of the very long time needed for discovery, development, and approval of pharmaceuticals, these costs can accumulate to nearly half the total expense. A direct consequence within the pharmaceutical industry value chain is that major pharmaceutical multinationals tend to increasingly outsource risks related to fundamental research, which somewhat reshapes

4280-458: The Center for Drug Evaluation and Research has averaged 22.9 approvals a year. This approval comes only after heavy investment in pre-clinical development and clinical trials , as well as a commitment to ongoing safety monitoring . Drugs which fail part-way through this process often incur large costs, while generating no revenue in return. If the cost of these failed drugs is taken into account,

4387-494: The Chinese pharmaceutical sector have also grown substantially. On the organisational side, big international pharma corporations have experienced a substantial decline of their value share. Also, the core generic sector (substitutions for off-patent brands) has been downvalued due to competition. Torreya estimated the pharmaceutical industry to have a market valuation of US$ 7.03 trillion by February 2021 from which US$ 6.1 trillion

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4494-518: The Institute of Experimental Therapy in Berlin. The drug was given the commercial name Salvarsan. Ehrlich, noting both the general toxicity of arsenic and the selective absorption of certain dyes by bacteria, hypothesized that an arsenic-containing dye with similar selective absorption properties could be used to treat bacterial infections. Arsphenamine was prepared as part of a campaign to synthesize

4601-791: The NHS, whilst similar arrangements exist with the Scottish Medicines Consortium in Scotland, and the Pharmaceutical Benefits Advisory Committee in Australia. A product must pass the threshold for cost-effectiveness if it is to be approved. Treatments must represent 'value for money' and a net benefit to society. There are special rules for certain rare diseases ("orphan diseases") in several major drug regulatory territories. For example, diseases involving fewer than 200,000 patients in

4708-820: The Orange Book site. In the UK, the Medicines and Healthcare products Regulatory Agency approves and evaluates drugs for use. Normally an approval in the UK and other European countries comes later than one in the USA. Then it is the National Institute for Health and Care Excellence (NICE), for England and Wales, who decides if and how the National Health Service (NHS) will allow (in the sense of paying for) their use. The British National Formulary

4815-458: The US market. The FDA received authority to regulate advertising of prescription drugs and to establish good manufacturing practices . The law required that all drugs introduced between 1938 and 1962 had to be effective. An FDA - National Academy of Sciences collaborative study showed that nearly 40 percent of these products were not effective. A similarly comprehensive study of over-the-counter products began ten years later. In 1971, Akira Endo ,

4922-589: The United States in 2013 were Abilify ($ 6.3 billion,) Nexium ($ 6 billion) and Humira ($ 5.4 billion). The best-selling drug ever, Lipitor , averaged $ 13 billion annually and netted $ 141 billion total over its lifetime before Pfizer's patent expired in November 2011. IMS Health publishes an analysis of trends expected in the pharmaceutical industry in 2007, including increasing profits in most sectors despite loss of some patents, and new 'blockbuster' drugs on

5029-690: The United States, or larger populations in certain circumstances are subject to the Orphan Drug Act. Because medical research and development of drugs to treat such diseases is financially disadvantageous, companies that do so are rewarded with tax reductions, fee waivers, and market exclusivity on that drug for a limited time (seven years), regardless of whether the drug is protected by patents. In 2011, global spending on prescription drugs topped $ 954 billion, even as growth slowed somewhat in Europe and North America. The United States accounts for more than

5136-495: The addictive properties and abuse potential of barbiturates and amphetamines and led to increasing restrictions on their use and growing government oversight of prescribers. Today, amphetamine is largely restricted to use in the treatment of attention deficit disorder and phenobarbital in the treatment of epilepsy . In 1958, Leo Sternbach discovered the first benzodiazepine , chlordiazepoxide (Librium). Dozens of other benzodiazepines have been developed and are in use, some of

5243-560: The addition of salt to produce a lake pigment . Textile dyeing dates back to the Neolithic period. Throughout history, people have dyed their textiles using common, locally available materials. Scarce dyestuffs that produced brilliant and permanent colors such as the natural invertebrate dyes Tyrian purple and crimson kermes were highly prized luxury items in the ancient and medieval world. Plant-based dyes such as woad , indigo , saffron , and madder were important trade goods in

5350-401: The antibacterial effects of penicillin , but its exploitation for the treatment of human disease awaited the development of methods for its large scale production and purification. These were developed by a U.S. and British government-led consortium of pharmaceutical companies during the world war. There was early progress toward the development of vaccines throughout this period, primarily in

5457-476: The biological effects of these structural changes. By the 1890s, the profound effect of adrenal extracts on many different tissue types had been discovered, setting off a search both for the mechanism of chemical signalling and efforts to exploit these observations for the development of new drugs. The blood pressure raising and vasoconstrictive effects of adrenal extracts were of particular interest to surgeons as hemostatic agents and as treatment for shock, and

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5564-404: The cost of developing a successful new drug ( new chemical entity , or NCE), has been estimated at US$ 1.3 billion (not including marketing expenses ). Professors Light and Lexchin reported in 2012, however, that the rate of approval for new drugs has been a relatively stable average rate of 15 to 25 for decades. Industry-wide research and investment reached a record $ 65.3 billion in 2009. While

5671-590: The cost of research in the U.S. was about $ 34.2 billion between 1995 and 2010, revenues rose faster (revenues rose by $ 200.4 billion in that time). A study by the consulting firm Bain & Company reported that the cost for discovering, developing and launching (which factored in marketing and other business expenses) a new drug (along with the prospective drugs that fail) rose over a five-year period to nearly $ 1.7 billion in 2003. According to Forbes, by 2010 development costs were between $ 4 billion to $ 11 billion per drug. Some of these estimates also take into account

5778-455: The data supporting the safety of thalidomide was incomplete. The firm continued to pressure Kelsey and the FDA to approve the application until November 1961, when the drug was pulled off the German market because of its association with grave congenital abnormalities. Several thousand newborns in Europe and elsewhere suffered the teratogenic effects of thalidomide. Without approval from the FDA,

5885-409: The development of tricyclic antidepressants in the 1960s. In 1903, Hermann Emil Fischer and Joseph von Mering disclosed their discovery that diethylbarbituric acid, formed from the reaction of diethylmalonic acid, phosphorus oxychloride and urea, induces sleep in dogs. The discovery was patented and licensed to Bayer pharmaceuticals , which marketed the compound under the trade name Veronal as

5992-429: The driver is seated at the back and the passengers at the front) and tuk tuks to make a living. The county is linked by a single track railway to Liaoyuan and Siping in one direction and Meihekou in the other, with trains running to Beijing , Tonghua and Changchun amongst other places. There is also a frequent bus service to Meihekou, the nearest large town, which can also be reached by shared taxi for Y20 or Y5

6099-410: The dyeing of cellulose acetate , and are water-insoluble. The dyes are finely ground in the presence of a dispersing agent and sold as a paste, or spray-dried and sold as a powder. Their main use is to dye polyester , but they can also be used to dye nylon, cellulose triacetate , and acrylic fibers. In some cases, a dyeing temperature of 130 °C (266 °F) is required, and a pressurized dyebath

6206-513: The economies of Asia and Europe. Across Asia and Africa, patterned fabrics were produced using resist dyeing techniques to control the absorption of color in piece-dyed cloth. Dyes from the New World such as cochineal and logwood were brought to Europe by the Spanish treasure fleets, and the dyestuffs of Europe were carried by colonists to America. Dyed flax fibers have been found in

6313-448: The extent that such laws did exist, enforcement was lax. In the United States, increased regulation of vaccines and other biological drugs was spurred by tetanus outbreaks and deaths caused by the distribution of contaminated smallpox vaccine and diphtheria antitoxin. The Biologics Control Act of 1902 required that federal government grant premarket approval for every biological drug and for the process and facility producing such drugs. This

6420-500: The fabric in a solution of an organic compound, typically a nitrophenol derivative, and sulfide or polysulfide . The organic compound reacts with the sulfide source to form dark colors that adhere to the fabric. Sulfur Black 1, the largest selling dye by volume, does not have a well defined chemical structure. Some dyes commonly used in Staining: One other class that describes the role of dyes, rather than their mode of use,

6527-425: The fact that even the largest clinical trials cannot effectively predict the prevalence of rare side-effects. Postmarketing surveillance ensures that after marketing the safety of a drug is monitored closely. In certain instances, its indication may need to be limited to particular patient groups, and in others the substance is withdrawn from the market completely. The FDA provides information about approved drugs at

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6634-454: The fiber is attributed, at least partly, to salt formation between anionic groups in the dyes and cationic groups in the fiber. Acid dyes are not substantive to cellulosic fibers. Most synthetic food colors fall in this category. Examples of acid dye are Alizarine Pure Blue B, Acid red 88 , etc. Basic dyes are water-soluble cationic dyes that are mainly applied to acrylic fibers , but find some use for wool and silk. Usually acetic acid

6741-448: The fiber substrate. The covalent bonds that attach reactive dye to natural fibers make them among the most permanent of dyes. "Cold" reactive dyes, such as Procion MX , Cibacron F , and Drimarene K , are very easy to use because the dye can be applied at room temperature. Reactive dyes are by far the best choice for dyeing cotton and other cellulose fibers at home or in the art studio. Disperse dyes were originally developed for

6848-686: The firm distributed Kevadon to over 1,000 physicians there under the guise of investigational use. Over 20,000 Americans received thalidomide in this "study," including 624 pregnant patients, and about 17 known newborns suffered the effects of the drug. The thalidomide tragedy resurrected Kefauver's bill to enhance drug regulation that had stalled in Congress, and the Kefauver-Harris Amendment became law on 10 October 1962. Manufacturers henceforth had to prove to FDA that their drugs were effective as well as safe before they could go on

6955-418: The first vaccine against Japanese Encephalitis . Hilleman later moved to Merck , where he played a key role in the development of vaccines against measles , mumps , chickenpox , rubella , hepatitis A , hepatitis B , and meningitis . Prior to the 20th century, drugs were generally produced by small scale manufacturers with little regulatory control over manufacturing or claims of safety and efficacy. To

7062-401: The forerunner to Bayer AG was formed in what became Wuppertal , Germany . In 1891, Paul Ehrlich discovered that certain cells or organisms took up certain dyes selectively. He then reasoned that a sufficiently large dose could be injected to kill pathogenic microorganisms, if the dye did not affect other cells. Ehrlich went on to use a compound to target syphilis , the first time a chemical

7169-407: The form of academic and government-funded basic research directed toward the identification of the pathogens responsible for common communicable diseases. In 1885, Louis Pasteur and Pierre Paul Émile Roux created the first rabies vaccine . The first diphtheria vaccines were produced in 1914 from a mixture of diphtheria toxin and antitoxin (produced from the serum of an inoculated animal), but

7276-535: The fungus Aspergillus terreus , first marketed in 1987 as Mevacor. In April 1994, the results of a Merck-sponsored study, the Scandinavian Simvastatin Survival Study , were announced. Researchers tested simvastatin , later sold by Merck as Zocor, on 4,444 patients with high cholesterol and heart disease. After five years, the study concluded the patients saw a 35% reduction in their cholesterol, and their chances of dying of

7383-577: The horizon. Dye A dye is a colored substance that chemically bonds to the substrate to which it is being applied. This distinguishes dyes from pigments which do not chemically bind to the material they color. Dye is generally applied in an aqueous solution and may require a mordant to improve the fastness of the dye on the fiber. The majority of natural dyes are derived from non-animal sources such as roots, berries, bark, leaves, wood, fungi and lichens . However, due to large-scale demand and technological improvements, most dyes used in

7490-401: The immediate aftermath of widespread vaccination. The first 20 years of licensed measles vaccination in the U.S. prevented an estimated 52 million cases of the disease, 17,400 cases of mental retardation , and 5,200 deaths. Hypertension is a risk factor for atherosclerosis, heart failure , coronary artery disease , stroke , renal disease , and peripheral arterial disease , and

7597-911: The industry ecosystem with biotechnology companies playing an increasingly important role, and overall strategies being redefined accordingly. Some approved drugs, such as those based on re-formulation of an existing active ingredient (also referred to as Line-extensions) are much less expensive to develop. In the United States, new pharmaceutical products must be approved by the Food and Drug Administration (FDA) as being both safe and effective. This process generally involves submission of an Investigational New Drug filing with sufficient pre-clinical data to support proceeding with human trials. Following IND approval, three phases of progressively larger human clinical trials may be conducted. Phase I generally studies toxicity using healthy volunteers. Phase II can include pharmacokinetics and dosing in patients, and Phase III

7704-565: The involvement of intellectual property , in " brand " materials is specifically tied to a given company's history, or in both within different contexts. The industry's has various subdivisions (which include distinct areas such as manufacturing biologics ) are all subject to a variety of laws and regulations that govern entire financial processes including the patenting , efficacy testing, safety evaluation , and marketing of these drugs. The global pharmaceuticals market produced treatments worth $ 1,228.45 billion in 2020, in total, and this showed

7811-509: The isolation between 1803 and 1805 of morphine – an analgesic and sleep-inducing agent – from opium by the German apothecary assistant Friedrich Sertürner , who named this compound after the Greek god of dreams, Morpheus . Multinational corporations including Merck , Hoffman-La Roche , Burroughs-Wellcome (now part of Glaxo Smith Kline ), Abbott Laboratories , Eli Lilly and Upjohn (now part of Pfizer ) began as local apothecary shops in

7918-436: The isolation of tuberculosis-infected people were an ubiquitous feature of cities in developed countries, with 50% dying within 5 years of admission. A Federal Trade Commission report issued in 1958 attempted to quantify the effect of antibiotic development on American public health. The report found that over the period 1946–1955, there was a 42% drop in the incidence of diseases for which antibiotics were effective and only

8025-462: The larger pharmaceutical companies. The pharmaceuticals and biotechnology industry spends more than 15% of its net sales for Research & Development which is in comparison with other industries by far the highest share. Often, large multinational corporations exhibit vertical integration , participating in a broad range of drug discovery and development, manufacturing and quality control, marketing, sales, and distribution. Smaller organizations, on

8132-413: The law to prosecute manufacturers for making unsupported claims of efficacy were undercut by a Supreme Court ruling restricting the federal government's enforcement powers to cases of incorrect specification of the drug's ingredients. In 1937 over 100 people died after ingesting " Elixir Sulfanilamide " manufactured by S.E. Massengill Company of Tennessee. The product was formulated in diethylene glycol ,

8239-513: The long-term health consequences of high blood pressure had not yet been established, and because they had to be administered by injection. In 1952 researchers at Ciba discovered the first orally available vasodilator, hydralazine . A major shortcoming of hydralazine monotherapy was that it lost its effectiveness over time ( tachyphylaxis ). In the mid-1950s Karl H. Beyer, James M. Sprague, John E. Baer, and Frederick C. Novello of Merck and Co. discovered and developed chlorothiazide , which remains

8346-453: The mid-1800s. By the late 1880s, German dye manufacturers had perfected the purification of individual organic compounds from tar and other mineral sources and had also established rudimentary methods in organic chemical synthesis . The development of synthetic chemical methods allowed scientists to systematically vary the structure of chemical substances, and growth in the emerging science of pharmacology expanded their ability to evaluate

8453-559: The modern world are synthetically produced from substances such as petrochemicals. Some are extracted from insects and/or minerals . Synthetic dyes are produced from various chemicals. The great majority of dyes are obtained in this way because of their superior cost, optical properties (color), and resilience (fastness, mordancy). Both dyes and pigments are colored, because they absorb only some wavelengths of visible light . Dyes are usually soluble in some solvent, whereas pigments are insoluble. Some dyes can be rendered insoluble with

8560-524: The more popular drugs being diazepam (Valium), alprazolam (Xanax), clonazepam (Klonopin), and lorazepam (Ativan). Due to their far superior safety and therapeutic properties, benzodiazepines have largely replaced the use of barbiturates in medicine, except in certain special cases. When it was later discovered that benzodiazepines, like barbiturates, significantly lose their effectiveness and can have serious side effects when taken long-term, Heather Ashton researched benzodiazepine dependence and developed

8667-452: The most notable achievement of the period being Jonas Salk 's 1954 development of the polio vaccine under the funding of the non-profit National Foundation for Infantile Paralysis . The vaccine process was never patented but was instead given to pharmaceutical companies to manufacture as a low-cost generic . In 1960 Maurice Hilleman of Merck Sharp & Dohme identified the SV40 virus, which

8774-439: The most widely used antihypertensive drug today. This development was associated with a substantial decline in the mortality rate among people with hypertension. The inventors were recognized by a Public Health Lasker Award in 1975 for "the saving of untold thousands of lives and the alleviation of the suffering of millions of victims of hypertension". A 2009 Cochrane review concluded that thiazide antihypertensive drugs reduce

8881-718: The nature of their chromophore , dyes are divided into: Dyes produced by the textile, printing and paper industries are a source of pollution of rivers and waterways. An estimated 700,000 tons of dyestuffs are produced annually (1990 data). The disposal of that material has received much attention, using chemical and biological means. A "vital dye" or stain is a dye capable of penetrating living cells or tissues without causing immediate visible degenerative changes. Such dyes are useful in medical and pathological fields in order to selectively color certain structures (such as cells) in order to distinguish them from surrounding tissue and thus make them more visible for study (for instance, under

8988-462: The need for more comprehensive regulation and provided the driving force for the passage of new laws. On 12 September 1960, an American licensee, the William S. Merrell Company of Cincinnati, submitted a new drug application for Kevadon ( thalidomide ), a sedative that had been marketed in Europe since 1956. The FDA medical officer in charge of reviewing the compound, Frances Kelsey , believed that

9095-500: The other hand, often focus on a specific aspect such as discovering drug candidates or developing formulations. Often, collaborative agreements between research organizations and large pharmaceutical companies are formed to explore the potential of new drug substances. More recently, multi-nationals are increasingly relying on contract research organizations to manage drug development. Drug discovery and development are very expensive; of all compounds investigated for use in humans only

9202-429: The pH of the extract allowed a relatively pure grade of insulin to be produced. Under pressure from Toronto University and a potential patent challenge by academic scientists who had independently developed a similar purification method, an agreement was reached for non-exclusive production of insulin by multiple companies. Prior to the discovery and widespread availability of insulin therapy the life expectancy of diabetics

9309-401: The pill, and by 1965 the number had increased to 6.5 million. The availability of a convenient form of temporary contraceptive led to dramatic changes in social mores including expanding the range of lifestyle options available to women, reducing the reliance of women on men for contraceptive practice, encouraging the delay of marriage, and increasing pre-marital co-habitation. In the U.S.,

9416-474: The production of some lasers, optical media ( CD-R ), and camera sensors ( color filter array ). Mordant dyes require a mordant , which improves the fastness of the dye against water, light and perspiration . The choice of mordant is very important as different mordants can change the final color significantly. Most natural dyes are mordant dyes and there is therefore a large literature base describing dyeing techniques. The most important mordant dyes are

9523-486: The risk of death ( RR 0.89), stroke (RR 0.63), coronary heart disease (RR 0.84), and cardiovascular events (RR 0.70) in people with high blood pressure. In the ensuring years other classes of antihypertensive drug were developed and found wide acceptance in combination therapy, including loop diuretics (Lasix/ furosemide , Hoechst Pharmaceuticals , 1963), beta blockers ( ICI Pharmaceuticals , 1964) ACE inhibitors , and angiotensin receptor blockers . ACE inhibitors reduce

9630-479: The risk of new onset kidney disease [RR 0.71] and death [RR 0.84] in diabetic patients, irrespective of whether they have hypertension. Prior to the Second World war, birth control was prohibited in many countries, and in the United States even the discussion of contraceptive methods sometimes led to prosecution under Comstock laws . The history of the development of oral contraceptives is thus closely tied to

9737-654: The safety of the inoculation was marginal and it was not widely used. The United States recorded 206,000 cases of diphtheria in 1921, resulting in 15,520 deaths. In 1923, parallel efforts by Gaston Ramon at the Pasteur Institute and Alexander Glenny at the Wellcome Research Laboratories (later part of GlaxoSmithKline ) led to the discovery that a safer vaccine could be produced by treating diphtheria toxin with formaldehyde . In 1944, Maurice Hilleman of Squibb Pharmaceuticals developed

9844-528: The symptoms produced by pancreas removal. Soon, the extract was demonstrated to work in people, but development of insulin therapy as a routine medical procedure was delayed by difficulties in producing the material in sufficient quantity and with reproducible purity. The researchers sought assistance from industrial collaborators at Eli Lilly and Co. based on the company's experience with large scale purification of biological materials. Chemist George B. Walden of Eli Lilly and Company found that careful adjustment of

9951-532: The synthetic mordant dyes, or chrome dyes, used for wool; these comprise some 30% of dyes used for wool, and are especially useful for black and navy shades. The mordant potassium dichromate is applied as an after-treatment. It is important to note that many mordants, particularly those in the heavy metal category, can be hazardous to health and extreme care must be taken in using them. Vat dyes are essentially insoluble in water and incapable of dyeing fibres directly. However, reduction in alkaline liquor produces

10058-418: The tetracyclines (discovered at Lederle Laboratories, now a part of Pfizer ), erythromycin (discovered at Eli Lilly and Co.) and their extension to an increasingly wide range of bacterial pathogens. Streptomycin, discovered during a Merck-funded research program in Selman Waksman's laboratory at Rutgers in 1943, became the first effective treatment for tuberculosis. At the time of its discovery, sanitoriums for

10165-494: The trade name Adrenalin . Injected epinephrine proved to be especially efficacious for the acute treatment of asthma attacks, and an inhaled version was sold in the United States until 2011 ( Primatene Mist ). By 1929 epinephrine had been formulated into an inhaler for use in the treatment of nasal congestion. While highly effective, the requirement for injection limited the use of epinephrine and orally active derivatives were sought. A structurally similar compound, ephedrine ,

10272-404: The two components react to produce the required insoluble azo dye. This technique of dyeing is unique, in that the final color is controlled by the choice of the diazoic and coupling components. This method of dyeing cotton is declining in importance due to the toxic nature of the chemicals used. Sulfur dyes are inexpensive dyes used to dye cotton with dark colors. Dyeing is effected by heating

10379-408: The underlying concept in either case being that the cells examined are still alive. In a stricter sense, the term "vital staining" means the polar opposite of "supravital staining." If living cells absorb the stain during supravital staining, they exclude it during "vital staining"; for example, they color negatively while only dead cells color positively, and thus viability can be determined by counting

10486-565: The visible region (some examples are nitro , azo , quinoid groups) and an auxochrome which serves to deepen the color. This theory has been superseded by modern electronic structure theory which states that the color in dyes is due to excitation of valence π-electrons by visible light. Dyes are classified according to their solubility and chemical properties. Acid dyes are water - soluble anionic dyes that are applied to fibers such as silk , wool , nylon and modified acrylic fibers using neutral to acid dye baths. Attachment to

10593-412: The water-soluble alkali metal salt of the dye. This form is often colorless, in which case it is referred to as a Leuco dye , and has an affinity for the textile fibre. Subsequent oxidation reforms the original insoluble dye. The color of denim is due to indigo , the original vat dye. Reactive dyes utilize a chromophore attached to a substituent that is capable of directly reacting with

10700-439: Was a year of layoffs for at least 10,000 people across 129 public biotech firms globally, albeit most small firms; this was a significant increase in reductions versus 2022 was in part due to worsening global financial conditions and a reduction in investment by "generalist investors". Private firms also saw a significant reduction in venture capital investment in 2023, continuing a downward trend started in 2021, which also led to

10807-531: Was developed by Smith, Kline and French as a nasal decongestant under the trade name Benzedrine Inhaler. Amphetamine was eventually developed for the treatment of narcolepsy , post-encephalitic parkinsonism , and mood elevation in depression and other psychiatric indications. It received approval as a New and Nonofficial Remedy from the American Medical Association for these uses in 1937, and remained in common use for depression until

10914-459: Was followed in 1906 by the Pure Food and Drugs Act , which forbade the interstate distribution of adulterated or misbranded foods and drugs. A drug was considered misbranded if it contained alcohol, morphine, opium, cocaine, or any of several other potentially dangerous or addictive drugs, and if its label failed to indicate the quantity or proportion of such drugs. The government's attempts to use

11021-481: Was identified by Japanese chemists in the Ma Huang plant and marketed by Eli Lilly as an oral treatment for asthma. Following the work of Henry Dale and George Barger at Burroughs-Wellcome , academic chemist Gordon Alles synthesized amphetamine and tested it in asthma patients in 1929. The drug proved to have only modest anti-asthma effects but produced sensations of exhilaration and palpitations. Amphetamine

11128-496: Was later shown to cause tumors in many mammalian species. It was later determined that SV40 was present as a contaminant in polio vaccine lots that had been administered to 90% of the children in the United States. The contamination appears to have originated both in the original cell stock and in monkey tissue used for production. In 2004 the National Cancer Institute announced that it had concluded that SV40

11235-448: Was only a few months. The development of drugs for the treatment of infectious diseases was a major focus of early research and development efforts; in 1900, pneumonia, tuberculosis, and diarrhea were the three leading causes of death in the United States and mortality in the first year of life exceeded 10%. In 1911 arsphenamine , the first synthetic anti-infective drug, was developed by Paul Ehrlich and chemist Alfred Bertheim of

11342-535: Was pursued broadly by industrial scientists, including Bayer scientists Josef Klarer, Fritz Mietzsch, and Gerhard Domagk . This work, also based on the testing of compounds available from the German dye industry, led to the development of Prontosil , the first representative of the sulfonamide class of antibiotics . Compared to arsphenamine, the sulfonamides had a broader spectrum of activity and were far less toxic, rendering them useful for infections caused by pathogens such as streptococci . In 1939, Domagk received

11449-448: Was used in order to selectively kill bacteria in the body. He also used methylene blue to target the plasmodium responsible for malaria . The color of a dye is dependent upon the ability of the substance to absorb light within the visible region of the electromagnetic spectrum (380–750 nm). An earlier theory known as Witt theory stated that a colored dye had two components, a chromophore which imparts color by absorbing light in

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