This paper is intended to provide some of the history of the development of nerium oleander extract as a novel medicinal product. The extract evolved to a stable, purified product (ANVIRZEL™) under the direction of Ozelle Pharmaceuticals and has completed Phase I clinical trials.

Who is Dr Ozel

Dr. H. Ziya Ozel, the creator of Nerium Oleander Extracts (NOE), is a Turkish surgeon who has dedicated his life to helping patients who suffer from various diseases. He has used forms of NOE for the treatment of cancer, AIDS, and immune system disorders for more than thirty years.

Dr. Ozel was born in 1927 in Kurkcu/Mut, a small village in the southern province of Turkey. During his middle school years he stayed with a family friend in a nearby city as he continued his education. He took exams for government financial aid and was found eligible to attend Kayseri High School as a boarding student under a government grant. He attended the Military Medical School from 1946 thru 1952. After graduating he served in the army for another five years as a military physician. From 1957 until 1961, he attended Gulhane Military Medical Academy and specialized in general surgery. In 1962, after resigning from the military, he was assigned to Mugla State Hospital. He became well known in Western Turkey for his innovative surgical techniques and specialized treatments – but also for his kindness and generosity in the local community. He served there until 1974, at first as the general surgeon and later as the Chief Doctor of the Mugla State Hospital. When he was retired, Dr. Ozel moved to Istanbul with his family. He continued practicing medicine in his private clinic until 1988. Today, Dr. Ozel and his wife still spend most of their time caring for patients who seek help, while looking forward to the days which they both can really retire.

Dr. & Mrs. Ozel have a son and a daughter who both reside with their families in the U. S. 

Nerium Oleander (N.O.) - History

Dr. Ozel began his work on NOE [Nerium Oleander Extract] in 1966 when he was a physician at Mugla State Hospital. What brought his attention to Nerium Oleander? Over the years, this question has been generously answered by many individuals, most of whom have no knowledge of the subject and who certainly do not know Dr. Ozel. The claims of “Dr. Zima(sic) Ozel” watching some villagers drink nerium oleander juice to get healthy or of his trying to find a cure for his sick pet, are mere fictions to juice up the story of discovery of nerium oleander’s effectiveness and its development into a safe product. Nothing needs to be juiced up if the readers learn the whole truth.

Dr. H. Ziya Ozel made an observation that the majority of cancer patients referring to him were coming from an altitude above 600 meters. He thought that there should be a correlation between the rate of cancer occurrence and some environmental influence. He reviewed a number of environmental factors, but also studied folkloric remedies and discovered that poultices made of crushed oleander leaves and flour were applied topically to wounds and produced amazingly fast healing of the wounds. Further research showed that Nerium Oleander was most abundant in lower altitudes and practically did not exist at high altitude. He became intrigued with the plant. His preliminary studies on live animals determined the toxicology and effects of NOE. After further experimentation he developed his treatment in different forms and eventually started tests on terminal human cases.

After initial success in treating human cancer patients with NOE, Dr. Ozel began to discussing his findings with other professionals in his field. He sought analysis of the extract from various Turkish laboratories to understand the empirical results. They were unable to characterize the extracted compounds. In hope of gaining assistance from the government or research organizations, he prepared a paper to present his first human cases at the Fourth Balkanic Medical Days Symposium held in Ankara on 20 September 1973.

The cases presented were all considered terminal cases when the patients came to Dr. Ozel. By law, he could not treat patients with an experimental drug, such as NOE, unless they had exhausted all other conventional treatment methods with no response or were diagnosed as advanced stage, terminal cases. At the symposium he was able to call the attention of the scientific community to NOE and how the extract had shown to be efficacious on cancer cases of different varieties. He was sure that his presentation would trigger serious and abundant research on NOE, and that it finally could be put into service for mankind.

The response from the scientific community was less than overwhelming. The skepticism centered mainly on the fact that the presentation contradicted what little literature there was on oleander species. Clearly the results presented could not be explained as an extension of prior art but Turkish scientists strongly denied the facts that Dr. Ozel had presented without any further research. To conclude, the medical community was reluctant to accept the results. Dr. Ozel was undaunted by the criticism and lack of support for the ideas presented. He continued his research and patients continued to seek treatment.

In 1974, he published additional case reports in the Turkish Medical Journal “Dirim”. Dr. Ozel resigned from his position as Chief Doctor at Mugla State Hospital that same year in order to be able to work on NOE and initiate research on the subject,

Dr. Ozel contacted various universities in Istanbul. Years passed and he realized that no serious scientific research could be performed in any of the local universities. In the meantime, his old patients referred new ones to him, and more cancer patients presented to him as word of the results of the treatment spread.

In 1985 he started to look for research facilities abroad. During 1986-1987 some tests performed in Europe proved the effect of NOE on the immune system as well as cancer tumors. The studies showed that it was at least twice as potent as lipopopolysaccharide (LPS), the most active stimulator known at the time.

LPS was first discovered in the 1920s by a U.S. Surgeon, Dr. Colley. He had obtained LPS from bacteria. Dr. Colley treated some inoperable and advanced cancer patients with LPS. Although some of Dr. Colley’s patients were still in regression five years later, further treatment of humans was stopped because of the unpredictable and frequent toxic effects of LPS. It is still used in laboratories to compare new immune-stimulant compounds. The most active commercially available immune-stimulants were patented by the Japanese in the early 1980s. These are Schizophylan, Krestin and Lentinan, which have activities of 40% as compared to LPS. The activity of NOE is approximately 240% compared to LPS, but without the unpredictable results of LPS in human use.

In 1988, a research team was formed at Munich University Pharmacology Institute to isolate the active components contained in the NOE. Several polysaccharides were identified that might be responsible for some part of the immune activity. On 17-22 July 1990, the initial results were presented as a poster at the symposium of Biology and Chemistry of Active Natural Substances (BACANS) which was held in Bonn, Germany. The presentation was published in Planta Medica 1990-56:66. However, no single component of the extract was found to be the sole source of its benefits. Instead, the activity is induced by a complex mixture of components contained in the extract, acting synergistically to modulate the immune system. 

Dr. Ozel continued his research and was granted patents in the U.S. (# 5,135,745) and other countries for his extract of nerium oleander. In 1995 a U.S. venture capital firm, Pharmaceutical Ventures Trust, today known as Ozelle Pharmaceuticals, Inc. (OPI)) signed an agreement with Dr. Ozel to complete the necessary steps to gain FDA approval in order to bring NOE to market. OPI has developed an FDA approved protocol for manufacturing the drug and has successfully completed Phase I clinical trials. OPI continues its work today to bring its product, ANVIRZEL™, to market. Since Dr. Ozel joined forces with the company, Ozelle Pharmaceuticals Inc. has moved its operations to Illinois under the presidency of Mr. Douglas Crawford and has no affiliations with any other domestic or non-domestic companies. Today Ozelle Pharmaceuticals Inc. of Illinois is the only entity that has FDA permission to use ANVIRZEL™ on a compassionate use basis.