Astrazeneca renovis cerovive.
Spin traps for skin care.
Peter H. Proctor, PhD, MD
The spin trap homepage covers the biological and therapeutic aspects of nitrone and nitroxide spin labels and spin traps.
Nitroxides and nitrones are stabilized forms of the biological messenger nitric oxide. Unlike other antioxidants, they generally neither act as proxidants, nor do they propagate free radical chain reactions.
Similarly, these agents inhibit the reaction of superoxide and nitric oxide to produce peroxinitrite. Recent evidence suggests that this reaction may play a crucial role in a wide range of degenerative diseases. These include Parkinsonism, stroke, ischaemic injury, heart attack, and age-related dementias.
Similarly, free radicals are also important, often extracellular, "redox" signaling messengers and this is likely responsible for much "cellular dysfunction" . Thus, many of the actions of the archetype spin trap, PBN or its disulfonic acid derivative ( AstraZeneca's "Cerovive" ), are likely explicable in terms of redox-signaling-mediated processes. One example is the effect of such compounds on cytokines such as TNF alpha. This may acount for the effect of REN-1654, Renovis' drug for neuropathic pain. Similarly, the redox-modulated ion channel TRPM7 may play a key role in neuronal death in stroke.
Because they inhibit fundamental pathogenic mechanisms, these spin traps and spin labels are extremely promising for the treatment of inflammatory and degenerative diseases such as the senile dementias, parkinsonism, cancer, stroke, etc. The archetype nitrone drug, PBN, uniquely extends maximum lifespan in experimental animals. For a summary of such diseases and pathogenic processes, read my review article " Free Radicals and Human Disease ",
Patent Dispute with Centaur
Look here for my patents, etc. on nitrone and nitroxide drugs. While nominally for topical use, these patents also grant general utility for "ameliorating a cellular dysfunction of a tissue". This includes "parenteral" use. Thus, the patents incorporate claims for the treatment of diseases which I had previously listed in review articles.
E.g., US patent 5,732,502 (covering use of PBN and other nitrones as drugs) claims " other free radical diseases as outlined in Proctor et al., "Free Radicals and Disease in Man," Physiological Chemistry and Physics and Medical NMR, volume 16, pp. 175-195 (1984) which is hereby incorporated herein by reference; and the like." Click Free radicals and Human Disease for a copy of this review article.
Similarly, the '502 patent claims treatment of "ischemic reperfusion injury secondary to myocardial infarction, stroke (emphasis-added) and surgical procedures". Because of their early priority date these are the primary patents for the use of such compounds as drugs. But their late date of issue means they still have many years to run.
However, while my patents were pending, reseachers with Centaur Pharmaceuticals applied for similar ones. These applications were years after the European publication of my claims, which they did not cite, as well as other "prior art". Go to Centaur for their statement concerning this patent dispute.
Infringement only begins when a drug company applies for FDA approval--- here, not before 2006. Thus, Centaur temporized on this patent issue. Unfortunately, VC investors are a nervous lot who read the patent literature. My IP aside, this did not exactly correspond to what Centaur said.
Patent problems can kill a company. By 2002, Centaur had a potential blockbuster drug (Cerovive) going into phase-3 trials. Moreover, at this point all further costs were assumed by AstraZeneca, along with a $4,500,000 milestone payment to Centaur. Not to mention other promising nitrone drugs were in the pipeline.
However, Centaur could not raise a last round of funding and liquidated. Apparently findng few other bidders, Centaur then sold its assets at a fraction of their former book value to Renovis , another drug development firm. This was a good deal for Renovis stockholders, if Renovis can resolve the multiple patent problems that apparently caused Centaur to fail. This is not certain.
Renovis then did an IPO primarily based upon Centaur's intellectual property. See Renovis IPO for their prospectus. Renovis' statement on my part of this patent issue.**
Stroke--- Decades ago, Demopoulos et al reported a role for free radicals etc. in stroke and and ischaemic injury. For a good general review, see " Mechanisms of Action of Neuroprotectants in Stroke ". The disulfonyl derivative of PBN ( phenybutylnitrone ), NXY059 or "Cerovive" (TM) is now in phase-3 clinical trials for stroke at Astrazeneca. For a review (needs signup for full access), see Cerovive.
Now, we introduce a line of topical facial skin care products based upon our patented spin trap and spin label technology. The first of these, "SpinTrap-C" , combines a spin trap, topical vitamin-C, and the spin label TEMPO.
Although our patents have previously prevented their marketing for skin antiaging, topical spin traps have generated much excitement as age-defying cosmeceuticals and skin care products. For example, in The Wrinkle Cure, Dr. Nicholas Perricone notes that spin traps are capable of "Stopping Free-Radical Damage Before it Begins .." and that such agents 'create a barrier - a trap - that holds free radicals in place' so that they can be "stopped before they scar the cells that make up your skin." Dr Perricone also notes that researchers "found that the traps actually prevented the free radicals from moving from place to place and damaging cells."
Similarly, in a press release from the American Academy of Dermatology, dermatologist Patricia Farris, MD, Clinical Assistant Professor at Tulane University School of Medicine states, "From all indications, I suspect that spin traps will be emerging as a new technology in the war on aging".
Spin traps and spin labels also suppliment current antiaging skin treatment. For example, free radical production limits the usefulness of both alpha-hydroxyacids and Vitamin-C as topical antiaging treatments. Spin traps and spin labels trap the free radicals produced by alpha-hydroxyacids such as lactic or glycolic acids as well as by topical vitamin-C.
Further, vitamin-C is unstable in topical formulations. For this reason, most formulations use some derivative such as ascorbyl phosphate. However, only vitamin-C itself raises skin vitamin-C levels. "Derivatives of ascorbic acid including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid did not increase skin levels of L-ascorbic acid. "
Our advanced formula markedly stabilizes vitamin-C. So SpinTrap-C not gives you the benefits of spintraps and spin labels, it also provides you with the antiaging benefits of high-concentration Vitamin-C.
Peter H. Proctor, PhD, MD
4126 SW Freeway, Suite 1616
Houston, TX 77027
Phone: +1 713 960 1616
FAX: +1 713 960 1616
stroke astrazeneca renovis cerovive.
Cerovive, is the registered trademark of AstraZeneca for NXY-059, the disulfo derivative of the spin trap phenylbutylnitrone (PBN).
nxy-059 aka disufenton is the generic name of a trademark of the group of companies of due to Here is a patent for spin traps and spin labels are often nitroxide, nitrones and nitroso compounds
index antioxidant free radical organic semiconductors trpm7 cerovive alzheimers multiinfarct dementia superoxide ros reperfusion injury reperfusion injury peroxide catalase sod dismutase uric acid ascorbic acid signaling redox vascular skin disufenton nxy-059 astrazeneca stroke musculoskeletal disorder arthritis inflammation skin wrinkles wrinkle treatment facial skin care products endothelium no inos cnos signaling messenger active pbn skin care oxygen deafness nkbeta inner ear cis platinum stria wrinkle topical treatment lipoic acid cure nxy-059 astrazenica topical vitamin c ascorbate urate electron transfer hydroxyl radical catalase peroxidase topical ischaemic injury anticancer phenothiazine cerovive is a trademark of the astrazeneca group of companies dopa uric acid radioprotection radiation treatment melanin hemochromatosis iron copper disufenton nxy-059 stroke porphyria cancer radiotherapy nkbeta apoptosis.