Ukrain

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Ukrain - the structure shown here and claimed by the manufacturer could not be reproduced in independent studies.

Ukrain is a “special liquid celandine root extract ” distributed by the Viennese company Nowicky Pharma , which it claims . Despite the lack of approval as a drug in EU countries, Switzerland or other western industrialized countries, Nowicky Ukrain propagates the treatment of various forms of cancer . In Austria, an application for approval made in 1986 was rejected by the then responsible Federal Ministry for Health and Consumer Protection in June 1995. In 2011 the Federal Office for Safety in Health Care (BASG) warned against the use of Ukrain, which is illegally marketed in various EU countries. In 2013, the Federal Institute for Drugs and Medical Devices (BfArM) classified Ukrain as a questionable drug, which is why its marketing and use on patients in Germany are prohibited without exception.

ingredients

Greater celandine ( Chelidonium majus )

According to one patent , it should in the drug to a semi-synthetic conjugation of thiotepa and celandine alkaloids act. An entry in the PubChem database shows a conjugation product of thiotepa with three chelidonin molecules. A mass spectrometric analysis at the University of Tübingen found neither thiotepa nor thiotepa compounds in Ukrain. Rather, the product consisted of a mixture of alkaloids from celandine ( Chelidonium majus ): the main components were protopine , chelidonine, allocryptopine , sanguinarine and chelerythrine . A similar assumption was made in 2000 by a South African working group. A reply from Nowicky Pharma did not take place.

It is not known whether standardized celandine extracts are used for the production of Ukrain. It is also not known whether the composition of Ukrain has remained constant since it was first described.

Attributed Effects

Mechanism of action

Based on the work of the Tübingen working group, it can be assumed that the effects of Ukrain can be ascribed to the celandine alkaloids as known mitotic toxins , especially chelidonin.

The mixture of substances led to programmed cell death ( apoptosis ) with and without involvement of caspases in cell lines of solid human tumors and lymphomas . Other sources also immunomodulatory and anti-be angiogenic mechanisms described.

The selective effectiveness of Ukrain against tumor cells, emphasized by the manufacturer, while avoiding damage to healthy cells, could not be reproduced by an independent working group.

toxicity

In studies on mice and rats in 1992, oral, intravenous and intraperitoneal administration of Ukrain produced eye disorders, tremors and twitching as well as reduced height growth. The LD 50 values ​​were in the range between 190 mg / kg (mouse, intraperitoneal) and 1,000 mg / kg (rat, oral).

Clinical effects

There are only a few controlled studies . The authors of a literature review found that all available studies have serious methodological deficiencies. They concluded that further, methodologically good studies had to be carried out before a risk-benefit assessment could be carried out.

A study carried out at the University of Ulm , in which the patients treated with Ukrain and a cytostatic agent are said to have survived almost twice as long as those who had only received the cytostatic agent (see controversy ), was of particular importance .

Possible side effects are fever and possibly inflammation of the liver ( hepatitis ), as this disease has been described after taking other celandine preparations.

Other Information

Development history

Ukrain is said to have been developed in 1978 and has been manufactured in Vienna and the Netherlands ever since. The inventor, the chemist Wassil Jaroslaw Nowicky, named it after his country of birth. It was first described in accessible literature in 1987.

An application for approval made in Austria in 1986 was refused in 1995 because product quality, content analyzes, efficacy, toxicity and shelf life tests, clinical tests, pharmaceutical preparations , labeling and instructions for use by Ukrain do not meet the requirements of the pharmaceutical law.

According to the manufacturer, Ukrain should be approved as a medicinal product in the Ukraine , Mexico and the United Arab Emirates . The approval in Ukraine has been suspended since November 2011.

Ukrain was granted the status of a possible development candidate for rare diseases ( orphan drugs ) in the USA in 2003 and in Australia in 2004 . Such registration does not constitute approval as a medicinal product. A corresponding classification for the EU was rejected by the European Commission at the end of 2007, and Nowicky's lawsuit against this rejection was rejected on all points by the ECJ .

Effectiveness evaluation

The study group Methods with Unproven Effectiveness in Oncology of the Swiss Cancer League wrote in 1995 that there was no evidence of the effectiveness of Ukrain against cancer. The group advises against its use in cancer therapy. The drug commission of the German medical profession , the German Cancer Society eV, and the Federal Institute for Drugs and Medical Devices (BfArM) came to the same conclusion in 2001.

The Swiss Study Group for Complementary and Alternative Methods in Cancer (SKAK) published a detailed assessment of Ukrain in 2006 and came to the conclusion that meaningful studies on the effectiveness of Ukrain are still pending.

The health insurance companies do not cover the costs of treatment. Even civil servants do not receive any allowance for treatment with Ukrain. In the gray pharmaceutical market, treatment costs are around 3,000 euros per week.

controversy

The BfArM accused Hans Beger , the former director of the department for general surgery at Ulm University Hospital, of scientific manipulation in a serious case. The German Federal Ministry of Health commissioned the BfArM to examine studies on Ukrain. In two works by Beger, the BfArM identified “14 critical and 8 serious deficiencies”. Several researchers had influenced the data “specifically in favor of the superiority of the Ukrain”. The manufacturer supplied considerable material and third-party funds. The accused denies this. However, the credibility of the 2002 study had previously been called into question.

Legal consequences

In connection with Ukrain, house searches were carried out in Vienna in September 2012, several people, including the managing director of Nowicky Pharma, were arrested and 200,000 ampoules of Ukrain were confiscated. The allegation was serious commercial fraud. The presumption of innocence applies .

In connection with a damages proceedings it became known that z. T. miraculous healings are promised. A patient from the vicinity of Munster was promised by the operator of a private clinic that "almost all patients recovered surprisingly well as a result of the treatment with this drug". The patient suffered from an advanced tumor disease with metastases in the liver and lungs. He died a few months after the Ukrain was given. The fee claim of the private clinic in the amount of 16,500 euros was rejected by the Hamm Higher Regional Court.

On January 27, 2015, the Viennese Regional Court began the trial of the indictment of serious commercial fraud against the chemist from Ukraine. According to the indictment, he had relabelled ampoules to a later expiration date. His ex-wife and secretary are also accused of minor involvement. On May 23, 2016, the accused chemist was sentenced to an unconditional imprisonment of 3 ½ years by a jury in Vienna.

Trivia

The inventor of Ukrain and owner of the manufacturing company, Wassil Nowicky, attributes the fact that Ukrain is still pending approval to a conspiracy. He has filed numerous lawsuits and complaints. He claims that the Israeli intelligence service Mossad attempted to murder him in 1996, and in 2004 he might have been killed. a. when the Nobel Prize for Chemistry was awarded in favor of Israeli scientists. On September 4, 2012, several people were arrested in Austria in connection with the distribution of the unapproved drug.

Web links

Individual evidence

  1. ↑ a b c d D. Habermehl, B. Kammerer, R. Handrick u. a .: Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway. In: BMC Cancer. 6, 2006, p. 14. PMID 16417634
  2. ↑ a b A. Panzer, AM Joubert, JN Eloff a. a .: Chemical analyzes of Ukrain, a semi-synthetic Chelidonium majus alkaloid derivative, fail to confirm its trimeric structure. In: Cancer Lett . 160, 2000, pp. 237-241. PMID 11053654
  3. ↑ a b Federal Ministry for Health and Consumer Protection. Decision of June 2, 1995. Gz 2.921.726 / 7-II / C / 16b / 95. Accessed October 3, 2008.
  4. ↑ Ukrain (celandine extract) ( memento from July 20, 2012 in the web archive archive.today ). News from November 18, 2011.
  5. ↑ Ukrain: New findings regarding the harmful effects of the drug. BfArM , February 9, 2012, accessed January 6, 2018 .
  6. ^ W. Nowicky: Process for reacting alkaloids and use of reaction products in the preparation of medicaments. 2002, WO 03/041721
  7. ↑ Entry on Ukrain in the ChemIDplus database of the United States National Library of Medicine (NLM)
  8. ↑ a b Swiss Study Group for Complementary and Alternative Methods in Cancer (SKAK): The “cancer drug” Ukrain: high costs, questionable effect ( memento of October 26, 2007 in the Internet Archive ).
  9. ↑ a b J. Nowicky, M. Greif, F. Hamler u. a .: Biological activity of ukrain in vitro and in vivo. In: Chemioterapia. 6 (2 Suppl), 1987, pp. 683-685. PMID 3334662
  10. ↑ SN Kurochkin, SL Kolobkov, II Votrin, IV Voltchek: Induction of apoptosis in cultured Chinese hamster ovary cells by Ukrain and its synergistic action with etoposide. In: Drugs Exp Clin Res. 26, 2000, pp. 275-278. PMID 11345038
  11. ↑ IN Roublevskaia, AR Haake, JW Ludlow, BV Polevoda: Induced apoptosis in human prostate cancer cell line LNCaP by Ukrain. In: Drugs Exp Clin Res. 26, 2000, pp. 141-147. PMID 11345020
  12. ↑ JW Nowicky, W. Hiesmayr, A. Liepins: Influence of Ukrain on immunological blood parameters in vitro and in vivo. In: Drugs Exp Clin Res. 22, 1996, pp. 163-165. PMID 8899322
  13. ↑ Y. Koshelnick, E. Moskvina, BR Binder, JW Nowicky: Ukrain (NSC-631570) Inhibits angiogenic differentiation of human endothelial cells in vitro. 17th International Cancer Congress, Rio de Janeiro, 24.-28. August 1998. Monduzzi Editore, pp. 91-95.
  14. ↑ A. Panzer, E. Hamel, AM Joubert a. a .: Ukrain (TM), a semisynthetic Chelidonium majus alkaloid derivative, acts by inhibition of tubulin polymerization in normal and malignant cell lines. In: Cancer Lett. 160, 2000, pp. 149-157. PMID 11053644
  15. ↑ Z. Kleinrok, E. Jagiełło-Wójtowicz, B. Matuszek, A. Chodkowska: Basic central pharmacological properties of thiophosphoric acid alkaloid derivatives from Chelidonium majus L. In: Pol J Pharmacol Pharm . 44, 1992, 227-239. PMID 1470561
  16. ^ A b E. Ernst, K. Schmidt: Ukrain - a new cancer cure? A systematic review of randomized clinical trials. In: BMC Cancer . 5, 2005, p. 69. PMID 15992405
  17. ↑ a b c F. Gansauge, M. Ramadani, J. Pressmar u. a .: NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial. In: Langenbecks Arch Surg. 386, 2002, pp. 570-574. PMID 11914932
  18. ↑ J. Benninger, HT Schneider, D. Schuppan a. a .: Acute hepatitis induced by Greater Celandine (Chelidonium majus). In: Gastroenterol. 117, 1999, pp. 1234-1237. PMID 1180428
  19. ^ Nowicky Pharma (Dubai). Ukrain and its potential. Accessed October 3, 2008.
  20. ↑ Ukrain: BfArM warns against the application. BfArM , November 28, 2011, accessed on January 6, 2018 .
  21. ↑ Food and Drug Administration: Orphan Drug Designations and Approvals - Search result , accessed May 9, 2019.
  22. ↑ Therapeutic Goods Administration: Orphan drug designation prior to July 1, 2017 - NSC-631570 , accessed May 9, 2019.
  23. ↑ European Commission (December 4, 2007). Rejection of the designation of the medicinal product “Special liquid celandine root extract” as a medicinal product for orphan diseases. (PDF; 17 kB) Ref. K (2007) 6132.
  24. ↑ EGC, judgment of 9 September 2010 - T-74/08 (Lexetius.com/2010,3009)
  25. ↑ Drugs Commission of the German Medical Association. For the use of the preparation “UKRAIN” in cancer therapy. In: Dtsch Arztebl. 98, 2001, pp. A-418.
  26. ↑ BfArM warns of Galavit and Ukrain ( Memento of March 16, 2010 in the Internet Archive ), press release 16/2001.
  27. ↑ T. Ufer: No eligibility for treatment with “Ukrain”. ( Memento of the original from August 16, 2011 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. August 18, 2006; Accessed October 3, 2008. @1@ 2Template: Webachiv / IABot / www.medizinrecht-aktuell.de
  28. ↑ G. Hopf: Ukrain ® - progress or regression in drug therapy for oncological diseases? In: Dtsch Z Onkol. 34, 2002, pp. 31-36.
  29. ↑ The Medicines Letter. 33/1999, No. 8.
  30. ^ F. Gansauge, M. Ramadani et al. a .: The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer. In: Hepato-gastroenterology. Volume 54, Number 75, Apr-May 2007, ISSN  0172-6390 , pp. 917-920. PMID 17591092 .
  31. ↑ Famous surgeon is said to have manipulated scientific studies. ( Memento from October 23, 2008 in the Internet Archive ) In: Der Spiegel. 39/2008.
  32. ↑ Hans G. Beger: Counterstatement . In: Der Spiegel . No. 3 , 2009, p. 117 ( online - 12 January 2009 ).
  33. ↑ Phase II study for the treatment of advanced, inoperable pancreatic carcinoma with Ukrain. (No longer available online.) In: der-arzneimittelbrief.de. Archived from the original on May 18, 2015 ; accessed on May 11, 2015 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.der-arzneimittelbrief.de
  34. ↑ a b Cancer patients deceived: arrests. on: orf.at , September 4, 2012.
  35. ↑ Karin Pollack: From false promises of salvation. In: derstandard.at . September 10, 2012, accessed May 11, 2015 .
  36. ↑ Hamm Court: 3 U 197/00 OLG Hamm.
  37. ↑ Chemist in court for cancer drug. In: wien.orf.at. January 27, 2015, accessed May 11, 2015 .
  38. ↑ Cancer remedies sold: 3.5 years for the manufacturer of "Ukrain". Der Standard, May 23, 2016.
  39. ↑ a b Nowicky Pharma. Homepage. Accessed October 3, 2008.