Discovered by Pliva’s research team in Zagreb in 1980, with Azithromycin or Sumamed Croatia became one of only nine countries in the world with an original antibiotic
| Azithromycin or Sumamed is one of the world’s best-selling antibiotics, used to treat or prevent certain bacterial infections, most often those causing middle ear infections, strep throat, pneumonia, typhoid, bronchitis and sinusitis. It has been discovered Croatia’s capital Zagreb in 1980, by a team of researchers at the Croatian pharmaceutical company Pliva: Gabrijela Kobrehel, Gorjana Radobolja-Lazarevski, and Zrinka Tambura1ev, led by Dr. Slobodan Dokiae. They are recipients of the 2000 award Heroes of Chemistry by the American Chemical Society in Washington, USA. The patent rights expired in 1999. The first roots of Pliva go to 1921. Croatian Nobel Prize winner Vladimir Prelog (1975 for chemistry) worked in a company preceding Pliva in 1935. The earnings from selling Azitromycin or Sumamed are estimated to 1.5 billon US$ per year! Azitromycin or Sumamed is the most important pharmaceutical product ever produced in Croatia. Croatia is one of only nine countries in the world with its own antibiotic product. |
| Azithromycin or Sumamed Azithromycin is one of the world’s best-selling antibiotics, used to treat or prevent certain bacterial infections, most often those causing middle ear infections, strep throat, pneumonia, typhoid, bronchitis and sinusitis. In recent years, it has been used primarily to prevent bacterial infections in infants and those with weaker immune systems. A team of researchers at the Croatian pharmaceutical company Pliva – Gabrijela Kobrehel, Gorjana Radobolja-Lazarevski, and Zrinka Tambura1ev, led by Dr. Slobodan Dokiae – discovered azithromycin in 1980. It was patented in 1981. In 1986, Pliva and Pfizer signed a licensing agreement, which gave Pfizer exclusive rights for the sale of azithromycin in Western Europe and the United States. Pliva put its azithromycin on the market in Central and Eastern Europe under the brand name of Sumamed in 1988. Pfizer launched azithromycin under Pliva’s license in other markets under the brand name Zithromax in 1991. Pfizer’s exclusive rights have since lapsed and Pliva-manufactured azithromycin is also marketed in the United States by generic drug maker Teva Pharmaceuticals (which now owns Pliva). After several years, the U.S. Food and Drug Administration (FDA) approved AzaSite, an ophthalmic formulation of azithromycin, for the treatment of eye infections. AzaSite is marketed in the U.S. and Canada by Inspire Pharmaceuticals, a wholly owned subsidiary of Merck.[22] Source http://en.wikipedia.org/wiki/Azithromycin |
Two Pliva buildings in Zagreb, arial view
| SUMMARY of an article published in Croatian The Story of Azithromycin Z. Banić Tomišić The invention of azithromycin, the active pharmaceutical ingredient of the antibiotic Sumamed (Croatian brand name by PLIVA; Zithromax by Pfizer in the USA) belongs among the great achievements in the history of science in Croatia. From the viewpoint of commercialization of research results, it may have been one of the greatest. In addition to contributing to science and to medicine, azithromycin has also brought about an improvement in the quality of life on the global level. Owing to its exceptional therapeutic properties, it has come to be one of the most successful antibiotics worldwide. Marking the 30th anniversary of the azithromycin Yugoslav patent application, this paper gives an overview of the research that led to its discovery and comes with a list of papers and patents through which the drug has been made known to the public. The invention was due to the scientists from the Research Institute of the pharmaceutical company PLIVA in Zagreb, Croatia, D. Sc. S. Dokiae, M. Sc. G. Kobrehel, D. Sc. G. Lazarevski, and D. Sc. Z. Tambura1ev. Azithromycin became the first representative of the new class of 15-membered macrolides known as azalides after the introduction of nitrogen in the macrocycle of erythromycin A. Its synthesis involved several steps: oximation of erithromycin A, Beckmann rearrangement of erythromycin A oxime with aromatic sulphochlorides, reduction of the produced erithromycin A iminoether, and final methylation of the nitrogen introduced in the macrocycle of erythromycin A. Because of inadequate analytical support in the late 1970s and early 1980s, the precise structure of the LD product in the Beckmann rearrangement step of azithromycin synthesis was confirmed only later as 7 and not 6 as assumed. Today, azithromycin is known under the common chemical name of 9-deoxo-9a-aza-9a-methyl-homoerythromycin A. This paper also deals with the negotiations and signing of a contract between PLIVA, Croatian pharmaceutical company, the patent holder, and Pfizer, one of the world largest pharmaceutical companies in the field of proprietary research. The dihydrate form of azithromycin is also discussed. The azithromycin (i.e. Sumamed and Zithromax) story, which dates from the second half of the last century, can be considered as the first and foremost example of successful knowledge and technology transfer in Croatia ever. On their web pages, the World Intellectual Property Organization (WIPO) reports the PLIVA azithromycin story as a case study and excellent example of proactive licensing strategy. For the discovery of azithromycin, in addition to receiving numerous awards, in the year 2000, PLIVA’s scientists D. Sc. S. Dokiae and M. Sc. G. Kobrehel, together with the representatives from the US-based Pfizer, were granted the honorable titles of “Heroes of Chemistry 2000” by the American Chemical Society (ACS), a non-profit association of American chemists and chemical engineers, and the largest association of scientists in the world. This high award is rightly taken to be also recognition of the achievement of PLIVA’s entire team working on azithromycin. The success of azithromycin has placed PLIVA among the few pharmaceutical companies in the world that have developed their own blockbuster drug, and has entitled Croatia to join a small group of nations that have developed a new antibiotic. Zrinka BANIĆ TOMIŠIĆ: Priea o azitromicinu, Kem. Ind. 60 (12) 603–617 (2011) |
| PLIVA Company Info  With 90 years of successful pharmaceutical experience, PLIVA is today a member of the Teva Group, one of the largest global pharmaceutical companies. We at PLIVA are dedicated to providing our customers with high quality, affordable medicines for a better quality of life.PLIVA is the largest pharmaceutical company in Croatia and one of the leading companies in Southeast Europe thanks to its highly competent employees, innovative technologies and continuous investments in production. PLIVA is also one of the major exporters in Croatia with over 80% of products intended for exports, and its major markets are Croatia, the USA and Russia. PLIVA’s production portfolio includes a high number of finished dosage forms covering almost all therapeutic groups and active pharmaceutical ingredients. Focused on development of generic and niche products, PLIVA has the broadest portfolio of generic medicines in Central and Eastern Europe. Thanks to the approvals by the US Food and Drug Administration (FDA), the British Medicines and Healthcare Products Regulatory Agency (MHRA) and those of other relevant European agencies, PLIVA is one of the manufacturers complying with the highest global quality standards required for international markets. PLIVA’s success and status may be largely attributed to its in-house research and development of finished dosage forms and active pharmaceutical ingredients, and Zagreb is therefore today one of the leading R&D centres in the Teva Group. Source www.pliva.com (En), www.pliva.hr (Hr) Croatian pharmaceutical companies that precede Pliva were founded already in 1921. In 1935 distinguished Croatian scientist Vladimir Prelog (1906-1998), winner of the Nobel Prize for chemistry in 1975, started his work there. |
| IZUMITELJI SUMAMEDA DOBILI NAGRADU AMERIEKOG KEMIJSKOG DRUŠTVA 23. kolovoza 2000. – Azitromicin, lijek poznatiji pod tržišnim imenom Sumamed, jedan je od najuspje1nijih hrvatskih izvoznih proizvoda. Da je doista rijee o iznimnom otkriću, pokazala je 20-ogodišnja uporaba, a potvrdilo Amerieko kemijsko društvo, koje je nagradu Heroji kemije 2000 dodijelilo Plivinim znanstvenicima – Gabrijeli Kobrehel i pokojnom Slobodanu Đokiću. Prestižna nagrada ameriekog kemijskog društva godinama se dodjeljuje iskljueivo znanstvenicima zaslužnim za globalnu dobrobit. Izumitelji Azitromicina, unatoe skromnosti, svjesni su da je nagrada dospjela u prave ruke.  To je otkriaee svjetskog nivoa jer su Plivini istraživači otkrili jednu potpuno novu grupu makrolidnih antibiotika koju su nazvali Azalidi i koja je predstavljala prekretnicu u pristupu kemiji makrolida, rekla je mr. Gabrijela Kobrehel, dobitnica nagrade Heroji kemije 2000. |
| PLIVINI znanstvenici – Heroji kemije 2000 U Washingtonu, SAD, 20. kolovoza 2000, u organizaciji amerieke neprofitne organizacije ACS (American Chemical Society), strukovne udruge ameriekih kemiËara i kemijskih inženjera, održana je sveeanost proglaπenja “Heroja kemije 2000”. Za otkriaee azitromicina, prvog predstavnika azalidnih antibiotika, uz predstavnike kompanije Pfizer eiji su znanstvenici također pridonijeli uspjehu Sumameda (PLIVA), odnosno Zithromaxa (Pfizer), herojima kemije proglašeni su dr. Slobodan Dokiae i mr. Gabrijela Kobrehel, PLIVINI znanstvenici. U ime pok. dr. Đokića svečaanosti proglašenja prisustvovali su njegova supruga Lidija i sin, dr. Darije Dokiae.  Tim istra 3/4 ivaea PLIVE koji je otkrio azitromicin:
mr. Gabrijela Kobrehel, dr. Slobodan Dokiae, mr. Gorjana Radobolja-Lazarevski i dr. Zrinka Tambura1ev. Priznanje “Heroji kemije 2000” jedna je od brojnih nagrada kojima se uvijek iznova potvrđuje trajan doprinos tima PLIVINIH znanstvenika svjetskoj znanosti, medicini i globalnom poboljπanju kvalitete života. Ovo je priznanje dodatna potvrda vrijednosti i rezultata rada cijeloga tima istra 3/4 ivaea PLIVE koji je otkrio azitromicin, a koji osim dr. Slobodana Dokiaea i mr. Gabrijele Kobrehel Ëine dr. Zrinka Tamburaπev i mr. Gorjana Radobolja-Lazarevski. Otkriaee azitromicina najveaei je dogadaj u povijesti PLIVE i hrvatske farmaceutske industrije u cjelini. Kao rezultat trajnog, sustavnog i predanog istržćivačkog rada, 1980. godine PLIVINI su znanstvenici otkrili i patentirali novi originalni makrolidni antibiotik – azitromicin. Zahvaljujući iznimnim terapeutskim svojstvima, azitromicin, koji PLIVA prodaje pod imenom Sumamed, izazvao je revoluciju u dotadašnjem načinu liječenja, postao jedan od najuspje1nijih lijekova u svijetu te uvrstio PLIVU medu malobrojne farmaceutske kompanije u svijetu koje imaju svoj vlastiti lijek, a Hrvatsku medu devet zemalja u svijetu koje imaju vlastiti antibiotik.  Nagrada “Heroji kemije 2000” ACS-a (American Chemical Society)
Alan Vojvodić i Renata Valentić |
| “Heroji kemije” Istraživački tim kemieara iz PLIVE koji je sintetizirao novi antibiotik pod nazivom azitromicin koji se na hrvatskom tržištu prodaje pod nazivom Sumamed zaslužuje svoje posebno mjesto u pregledu najboljih hrvatskih izumitelja. Tim stručnjaka predvođen doktorom Slobodanom Đokićem u sastavu Gorjana Radoboja-Lazarevski, Zrinka Tambura1ev i Gabrijela Kobrehel je 1980. otkrio formulu kemijskog spoja azitromicina koji se pokazao izrazito efikasnim pri terapijskom lijeeenju bakterijskih infekcija. 1981. spoj je patentiran i praktieki baeen u ladicu da bi ga Pfizerovi znanstvenici ponovno pronašli prelistavajući dokumentaciju patentiranih kemijskih spojeva. Već 1986.Pliva i Pfizer su potpisali ugovor koji je Pfizeru dao ekskluzivna prava za prodaju azitromicina na tržištima SAD-a i Zapadne Europe, dok je Pliva 1988. na tr 3/4 i1te Centralne i Istoene Europe lansirala svoj azitromicin pod imenom Sumamed, razvojem tržišta na bazi istog spoja 1991. izdaje Pfizer Zithromax i Zentiva Azitrox. Djelovanje azitromicina Azitromicin je antibiotik širokog spektra djelovanja, prvi predstavnik nove podskupine makrolidnih antibiotika nazvane azalidi. Spriječavajući sintezu bakterijskih bjelaneevina, uklanja sposobnost bakterije da raste i da se razmnožava. Azitromicin ciljano djeluje na mjestu infekcije zahvaljujući prenošenju putem bijelih krvnih stanica. Azitromicin u upalno promijenjenim tkivima postiže visoku koncentraciju te terapija ostaje djelotvorna još pet do sedam dana nakon prestanka uzimanja lijeka. Zarada od 1,6 milijardi dolara Azitromicin je Plivin originalni antibiotik koji je tijekom posljednja dva desetljeća bio najprodavaniji proizvod kompanije. Godišnji prihod od prodaje originalnog oblika lijeka – Sumamed i Zitromax tableta – iznosio je, prije isteka patenta prošle godine, vi1e od 1,6 milijardi dolara. Izum: Azitromicin (Sumamed) Zbog iznimnih terapijskih svojstava azitromicin je izazvao revoluciju u lijeeenju antibioticima, postavši tako jedan od najuspje1nijih lijekova u cijelom svijetu. Azitromicin je sintetiziran i patentno za1tiaeen osamdesetih godina te je postao “zlatni standard” za makrolidne antibiotike, a cijela je klasa poslije nazvana azalidima. Otkriaee azitromicina najveaei je dogadaj u povijesti PLIVE i hrvatske farmaceutske industrije u cjelini, a njegov uspjeh uvrstio je Hrvatsku medu samo desetak zemalja u svijetu i PLIVU medu malobrojne farmaceutske kompanije koje su otkrile vlastiti lijek. Heroji kemije U Washingtonu 20. kolovoza 2000. Američko društvo kemičara – neprofitna udruga ameriekih kemieara i kemijskih in 3/4 enjera te najveća udruga svjetskih znanstvenika – organiziralo je sveeanost “Heroji kemije 2000”. U povodu otkriaea azitromicina njegovi tvorci imenovani su “Herojima kemije”. “Proglašavajući vas veeeras herojima, mi prepoznajemo va1 kreativni duh, znanstveni talent, vašu posvećenost izvrsnosti, prepoznajemo korist koju su vaši proizvodi donijeli ljudima te korporativno vodstvo koje je poticalo vaša znanja i usmjeravalo va1u inovativnost. Vi ste heroji zbog svojih izvanrednih doprinosa znanstvenoj zajednici i ljudskom društvu u cjelini”, izjavio je Daryle H. Busch, predsjednik American Chemical Society, na sveeanosti u Washingtonu. Put do velikog otkriaea 1980. – Patentiran i za1tiaeen PLIVIN vlastiti originalni makrolidni antibiotik – azitromicin. 1986. – Sklopljen licencni ugovor s ameriekom tvrtkom PFIZER, kojom PFIZER dobiva ekskluzivno pravo na prodaju lijeka u SAD-u, zapadnoj Europi i Japanu. 1988. – Azitromicin uveden na tr 3/4 i1te pod za1tiaeenim imenom SUMAMED. 1991. – Azitromicin uveden na tr 3/4 i1te SAD-a i zapadne Europe pod za1tiaeenim imenom Zithromax – tvrtke PFIZER. Izvor genius-croatia.com  |
Formated for CROWN by Darko Žubrinić
Distributed by www.Croatia.org . This message is intended for Croatian Associations/Institutions and their Friends in Croatia and in the World. The opinions/articles expressed on this list do not reflect personal opinions of the moderator. If the reader of this message is not the intended recipient, please delete or destroy all copies of this communication and please, let us know!
