In recent years, cancer has become, of the major diseases, a most serious threat to human health. The World Health Organization (WHO) 2008 statistics show that the global number of cancer deaths worldwide is about 11 million new cases of cancer each year, with the Asia-Pacific region accounting for 45 percent of new cases of cancer worldwide, and through new cases of cancer each year, up to 7 million patients die. In the past 30 years, the rate of cancer incidence has grown by 3%-5% annually, with three out of four new cases occurring in the newly industrialized and developing countries, with the number of cancer deaths in the Asia-Pacific region accounting for about half of cancer deaths worldwide.
The growth in incidence of cancer has occurred despite some advances in treatment beyond the use of harsh chemicals, surgery and ionizing radiation.
One of these advances, toward the end of the twentieth century, is photodynamic therapy, especially with the introduction of the hematoporphyrin Photofrin™. See Pandey R. K; Smith K. M; Dougherty T. J: Porphyrin Dimers as Photosensitizers in Photodynamic Therapy. J. Med. Chem., 1990, 33, 2032-2038 and Byrne C. J; Morris I. K. Ward A. D: The Synthesis of the Dimer and Trimer Ether-Linked Components of Hematoporphyrin Derivative. Aust. J. Chem., 1990, 43, 1889-1907.
Photodynamic therapy is accomplished by systemic introduction of a photosensitizer, e.g. Photofrin™ that selectively accumulates into hyperproliferative tissues, such as cancer, followed by treatment with an activating wavelength of light that causes development of singlet oxygen that kills the cancer cells. Photodynamic therapy is thus much less invasive than traditional treatments and is highly selective for cancer cells thus greatly reducing side effects such as death or injury to normal cells or interference with normal physiological activities.
Photodynamic therapy, nevertheless has limitations of its own. Among such limitations are the possibility of serious subsequent light sensitivity, at least until the photosensitizer clears the system or is metabolized. An even more significant problem is the fact that photodynamic therapy only works in areas close to a surface, e.g. the skin, from which light can penetrate and penetration depth is extremely limited.
Porfimer sodium (Photofrin™), previously discussed, is in fact a mixture of a large number related compounds. The compound Bis[1-[6,7-bis[2-(sodium carbonate)ethyl]1,3,5,8,-tetra-ethyl-2-vinyl-porphin-4-yl]-ethyl]ether (DVDMS) has recently been purified from that mixture and has been found to be superior to porfimer sodium both in efficacy and with respect to reduction of the side effect of subsequent light sensitivity. The structural formula of DVDMS is believed to be represented in FIG. 1 and a cold spray spectrum of DVDMS is shown in FIG. 2.
It has recently been discovered that some compounds might be used as treatment aids that are activated by ultrasound rather than or in addition to light. This has become known as sonodynamic therapy. Unfortunately, up to now, compounds tested have not been as effective as desired and in any case have often required high dosages to have effect.
The concept is similar to the more established photodynamic therapy (PDT) except light, instead of ultrasound, is used to activate the sensitizer. Sonodynamic therapy (SDT) offers significant advantages over PDT because ultrasound is widely accepted as a cost-effective and safe clinical imaging modality and, unlike light, can be tightly focused with penetration in soft tissue up to several tens of centimeters depending on the frequency used. This therefore enables the potential of treating deeper-rooted tumors than is currently possible with PDT.
USPTO Backgrounds
USPTO Backgrounds