Jenapharm
Encyclopedia
Jenapharm is a pharmaceutical company from Jena
Jena
Jena is a university city in central Germany on the river Saale. It has a population of approx. 103,000 and is the second largest city in the federal state of Thuringia, after Erfurt.-History:Jena was first mentioned in an 1182 document...

, Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...

. Founded in 1950 in East Germany, the company focused from the beginning on the production and development of steroids. Due to the economic circumstances of the Eastern Bloc
Eastern bloc
The term Eastern Bloc or Communist Bloc refers to the former communist states of Eastern and Central Europe, generally the Soviet Union and the countries of the Warsaw Pact...

, the company initially used a unique process of steroid synthesis
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...

 starting from hog bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

, however this method was abandoned a decade later in favor of total synthesis
Total synthesis
In organic chemistry, a total synthesis is, in principle, the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes. In practice, these simpler pieces are commercially available in bulk and semi-bulk quantities, and are often...

. Initially the company produced a wide range of generic steroids, including corticosteroids, but later on it focused on anabolic steroids, estrogens and progestins.

Prior to Germany's reunification Jenapharm was the only supplier of hormonal contraceptives in East Germany. It successfully marketed a number of drugs it had developed in collaboration with other East German chemists. Perhaps the most well known of these is Valette, which sold well in Germany in the 1990s. After the reunification, Jenapharm eventually became a subsidiary of Schering
Schering
Schering AG was a research-centered German pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering and merged with Bayer's pharma sector in December 2006. The company's headquarters was in Berlin-Wedding, Germany...

 AG, which sold its generic therapeutics businesses to Dermapharm AG in 2004, and a year later restructured the marketing and distribution of Jenapharm into an independent subsidiary while integrating the research and development branch with its own laboratories.

East Germany had been running a state-sponsored mass doping program for its athletes with anabolic steroids, mostly with Oral Turinabol, a product that Jenapharm had developed. In 2005 the company was sued or threatened with lawsuits by hundreds of athletes who were forced to take these drugs. The company settled the lawsuits by contributing to the creation of a $4.1 million fund that compensated former athletes.

History

During the occupation of Germany at the end of World War II, all pharamaceutial companies from Nazi Germany were located in the Western-occupied areas. Jena, which fell in the Soviet-controlled area, had an Institute for Microbiology — the Schott-Zeiss Institute — that had the prerequisites for small scale pharmaceutical production. Although the institute had been founded in 1944 with just 9 employees, Hans Knöll
Hans Knöll
Hans Knöll was a German physician and microbiologist. He was the director of the Central Institute of Microbiology and Experimental Therapy in Jena from 1953 to 1976, a member of the Academy of Sciences of the German Democratic Republic , and professor of bacteriology at the University of Jena...

 produced there the first batch of penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

 made in Germany, right before the end of the war. In 1948 the institute was producing 10 billion IU
International unit
In pharmacology, the International Unit is a unit of measurement for the amount of a substance, based on biological activity or effect. It is abbreviated as IU, as UI , or as IE...

s of penicillin per month.

In the late 1940s rickets
Rickets
Rickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...

 was rampant amongst the children in the Soviet-occupied zone. In 1949 Alfred Schubert, who first developed a method of synthesis of vitamin D2 at the Friedrich-Schiller University, set up and industrial process that produced about 10 kg/year of Vitamin D2. (Vitamin D2 was superseded by vitamin D3 10 years later). In the same year the institute was tasked to synthesize steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...

 hormones, in particular cortisone
Cortisone
Cortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...

. At the end of 1949 it received official permission to manufacture and market pharmaceuticals, and the public company VEB Jenapharm was founded on January 1, 1950. At the time the company already had about 600 employees.

Diosgenin
Diosgenin
Diosgenin, a steroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of Dioscorea wild yam, such as the Kokoro...

 and hecogenin, which were commonly used in the West as precursors for steroid synthesis, were not available in East Germany, and for political and economic reasons, these substances could not be imported. Jenapharm developed an alternate process starting from hyodesoxycholic acid extracted from hog bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

, from which they first produced pregnenolone
Pregnenolone
Pregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. As such it is a prohormone. Pregnenolone sulfate is a GABAA antagonist and increases neurogenesis in the hippocampus.-Chemistry:Like other steroids,...

, and subsequently progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

 and desoxycorticosterone acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...

 in 1954/1955. In that decade research and production continued to be closely intertwined at Jenapharm. Alfred Schubert was both Research Director and manager of the plant that produced steroids.

Between 1957 and 1962 Gerhard Langbein further expanded the gamut of steroids that Jenapharm produced using its unique process to include testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

, 4-chlorotestosterone
Clostebol
Clostebol , usually as the ester clostebol acetate, is a synthetic anabolic androgenic steroid. Clostebol is the 4-chloro derivative of the natural hormone testosterone....

, cortexolone, cortisone
Cortisone
Cortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...

, cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

 and prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

. Chlormadinone
Chlormadinone
Chlormadinone is a progestagen.-Synthesis:Bruckner, K.; Hampel, B.; Johnson, V.; Chem. Ber. 1961, 94, 1225.http://dx.doi.org/10.1002/cber.19610940510...

 acetate was the first oral contraceptive produced by Jenapharm. It was sold under the name Ovosiston starting in 1964, and was also produced from hog bile.

In the 1960s East German scientists tried to find an alternative to hog bile as the precursor for steroid synthesis by cultivating Solanum auriculatum, but these efforts failed to achieve industrial scale. Attempts to use sugar cane wax
Wax
thumb|right|[[Cetyl palmitate]], a typical wax ester.Wax refers to a class of chemical compounds that are plastic near ambient temperatures. Characteristically, they melt above 45 °C to give a low viscosity liquid. Waxes are insoluble in water but soluble in organic, nonpolar solvents...

 from Cuba or cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 from animal spinal cords also proved uneconomical. To remain competitive on the steroids market Jenapharm moved towards total synthesis. They used Igor Torgov
Igor Torgov
Igor Vladimirovich Torgov was a Soviet chemist and a corresponding member of the Soviet Academy of Sciences ....

's synthesis scheme, which was not patented in the GDR, and ironically was ignored by other Soviet chemists. Initially Jenapharm managed to produce only 25–75 kg of entirely synthetic steroids annually, but after tuning the process through more than 100 patented improvements, production reached about 5 tons per year in the 1980s. The move to total synthesis forced however Jenepharm to abandon the corticosteroids market.

At the end of 1980s Jenapharm had sales of around DM200m ($112m) and 1700 employees, and was amongst eastern Germany's three largest pharmaceuticals producers with production plants at Jena, Erfurt
Erfurt
Erfurt is the capital city of Thuringia and the main city nearest to the geographical centre of Germany, located 100 km SW of Leipzig, 150 km N of Nuremberg and 180 km SE of Hannover. Erfurt Airport can be reached by plane via Munich. It lies in the southern part of the Thuringian...

, Naumburg
Naumburg
Naumburg is a town in Germany, on the Saale River. It is in the district Burgenlandkreis in the Bundesland of Saxony-Anhalt. It is approximately southwest of Leipzig, south-southwest of Halle, and north-northeast of Jena....

 and Magdeburg
Magdeburg
Magdeburg , is the largest city and the capital city of the Bundesland of Saxony-Anhalt, Germany. Magdeburg is situated on the Elbe River and was one of the most important medieval cities of Europe....

. It produced a wide range of products, but 50% of sales were in hormone products. In 1991 Jenapharm was privatized and sold to Gehe AG, a subsidiary of Franz Haniel & Cie GmbH, after an initial bid by Schering
Schering
Schering AG was a research-centered German pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering and merged with Bayer's pharma sector in December 2006. The company's headquarters was in Berlin-Wedding, Germany...

 AG failed, but by October 2001 Schering had acquired 100% ownership of Jenapharm stock.

Original products

In the 1960s Jenapharm had fewer than 40 employees working on developing new products. This lack of dedicate resources translated in few original products. The first original product developed at Jenapharm was 4-chlorodehydromethyltestosterone, an anabolic steroid
Anabolic steroid
Anabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...

 which was marketed under the name Oral Turinabol. This product later became infamous for being the most often used AAS
AAS
Aas may refer to:* Aas * Aas, Pyrénées-Atlantiques, a village in FranceAAS, as an acronym or initialism, may refer to:-Businesses:*Ateliers Aéronautiques de Suresnes, a defunct French aircraft manufacturing company...

 in doping East German athletes under a state-sponsored program.

In 1967 Jenapharm, using mechanisms of the centralized East German economy, initiated a collaboration with other chemists from the East German Academy of Sciences to synthesize strongly active estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

s with a depot effect. This effort bore fruit a decade later. In 1978 the company brought to market the first once-a-week oral contraceptive Deposiston, a combination of ethinylestradiol
Ethinylestradiol
Ethynylestradiol , also ethynyl estradiol , is a derivative of estradiol. Ethynyl estradiol is an orally bio-active estrogen used in almost all modern formulations of combined oral contraceptive pills...

 3-isopropylsulfonate and norethisterone
Norethisterone
Norethisterone is a molecule used in some combined oral contraceptive pills, progestogen only pills and is also available as a stand-alone drug...

 acetate. The other product that resulted from this collaboration was Turisteron (ethinylestradiol propanesulphonate) that proved efficacious in treating androgen-dependent carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

 of the prostate.

In 1975 Kurt Ponsold, in cooperation with Jenapharm, synthesized a new progestin — dienogest
Dienogest
Dienogest is an orally active synthetic progesterone . It is available for use as an oral contraceptive in combination with ethinylestradiol. It has antiandrogenic activity and as a result can improve androgenic symptoms. It is a non-ethinylated progestin which is structurally related to testosterone...

. The combination ethinyl estradiol/dienogest was efficacious as oral contraceptive. It was marketed initially as Certostat, and later as Valette). After sales debuted in 1990, within only a few years Valette become the most sold oral contraceptive on the German market. Jenapharm managed to take the top spot in German market share for oral contraceptives with 18%, compared with Schering's 13-14%. In 1996 Valette had annual sales of DM40m. This was a compelling reason to Schering to acquire Jenapharm.

Doping and lawsuits

Starting from 1966 East Germany ran a vast state-sponsored program of doping. The state gave grants and organized symposia where scientists and physicians who served as unofficial collaborators for the Ministry for State Security ("Stasi
Stasi
The Ministry for State Security The Ministry for State Security The Ministry for State Security (German: Ministerium für Staatssicherheit (MfS), commonly known as the Stasi (abbreviation , literally State Security), was the official state security service of East Germany. The MfS was headquartered...

"), including top-ranking professors, collaborated on doping research and methods of drug administration that would evade detection by international doping controls. GDR physicians administered prescription drugs as well as unapproved experimental drug preparations to several thousand athletes every year, including to minors of both sexes. Special emphasis was placed on administering androgens to women and adolescent girls because this practice proved to be particularly effective for improving sports performance.

In the 1980s doping tests at Olympic events became more widespread and effective. A symposium to face this problem was held in Leipzig
Leipzig
Leipzig Leipzig has always been a trade city, situated during the time of the Holy Roman Empire at the intersection of the Via Regia and Via Imperii, two important trade routes. At one time, Leipzig was one of the major European centres of learning and culture in fields such as music and publishing...

 on June 24, 1981. In the ensuing years nasal spray preparations containing testosterone or androstenedione
Androstenedione
Androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...

 were developed in collaboration with Jenapharm, tested, and used in top athletes—some of whom did not like this mode of application. Doping tests at the time used the T:E (testosterone:epitestosterone
Epitestosterone
Epitestosterone is a natural steroid, an inactive epimer of the hormone testosterone. Structurally, it differs from testosterone only in the configuration at the OH-bearing carbon, C17...

) ratio. Since 1983, Jenapharm had produced preparations of epitestosterone
Epitestosterone
Epitestosterone is a natural steroid, an inactive epimer of the hormone testosterone. Structurally, it differs from testosterone only in the configuration at the OH-bearing carbon, C17...

 propionate
Propionate
The propanoate or propionate ion is C2H5COO− .A propanoic or propionic compound is a salt or ester of propanoic acid....

, a biologically inactive compound that had no commercial value but was prepared exclusively for the governmental doping system. It was used simultaneously or sequentially with testosterone injections to bring the T:E ratio back into the normal range, but only for athletes participating in international competitions. This protocol made it possible for female athletes to receive high testosterone dosages and still pass doping tests, but it had strong virilizing effects, in particular hirsutism
Hirsutism
Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...

 and voice changes. Concomitant consumption of alcohol or contraceptive pills led to severe and sometimes life-threatening liver damage. In male weight lifters cases of gynecomastia
Gynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...

 had to be resolved by surgery. All these side effects, as well the athletic improvements were meticulously documented in reports to the Stasi.

In 2005 some 160 former athletes, facing spiraling medical costs from the long term side effects of anabolic steroids, sued Jenapharm. Some of the female athletes had suffered multiple miscarriage
Miscarriage
Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...

s. Many of the former athletes did not qualify for state medical insurance because they have been too ill to work. Initially Jenapharm denied responsibility for their condition, arguing that Oral Turinabol had been legally approved in the GDR and available on the market, but was misused by sports physicians and trainers. Lawyers representing the athletes argued that research from files left behind by Stasi secret police showed that Jenapharm also passed non-approved substances to trainers and withheld information about their side effects, thereby breaking the law. Another argument brought by the athletes was that Jenapharm manufactured substances that had no use other than doping, and that the government pressure in East Germany was not so great that company were unable to refuse engaging in doping-related activities. Eventually, the German Olympic Sports Federation (DOSB), the legal successor to the former East German National Olympic Committee, compensated each athlete with 9,250€ ($12,200). Jenapharm contributed to the $4.1 million fund. About $500,000 were set aside for future claims.
The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK