Thursday, 30 January 2014

EMA panel issues positive opinion for DSP and Takeda's schizophrenia drug lurasidone

Japanese firms Dainippon Sumitomo Pharma (DSP) and Takeda Pharmaceutical (Takeda) have received positive opinion from the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) for the use of lurasidone in the treatment of adults with schizophrenia.


EMA panel issues positive opinion for DSP and Takeda's schizophrenia drug lurasidone 


Saturday, 18 January 2014

Neostigmine methylsulfate

Flamel Technologies today announced that the U.S. Food and Drug Administration (FDA) has approved the company’s New Drug Application (NDA) for Bloxiverz (neostigmine methylsulfate)

Flamel Technologies Announces FDA Approval of Bloxiverz 
06/03/2013 — Flamel Technologies today announced that the U.S. Food and Drug Administration (FDA) has approved the company’s New Drug Application (NDA) for Bloxiverz (neostigmine methylsulfate), a drug used intravenously in the operating room for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery. Flamel expects to launch Bloxiverz in July 2013 in 0.5 and 1.0 mg/mL strengths


Neostigmine, N,N,N-trimethyl-meta-(dimethylcarbomoyloxy)-phenylammonium methylsulfonate, which can be viewed as a simplified analog of physostigmine, is made by reacting 3-dimethylaminophenol with N-dimethylcarbamoyl chloride, which forms the dimethylcarbamate, and its subsequent alkylation using dimethylsulfate forming the desired compound. Neostigmine synthesis.png
Neostigmine shows notable UV/VIS absorption at 261nm, 267nm, and 225nm.
Neostigmine’s 1H NMR Spectroscopy reveals shifts at: 7.8, 7.7, 7.4, 7.4, 3.8, and 3.1 parts per million. The higher shifts are due to the aromatic hydrogens. The lower shifts at 3.8ppm and 3.1ppm are due to the electronic withdrawing nature of the tertiary and quarterary nitrogen, respectively.

Krill oil is being studied as a natural remedy for high cholesterol

Krill oil is being studied as a natural remedy for high cholesterol

Krill Oil

Krill are shrimp-like crustaceans that are approximately 1 to 6 centimeters long. They live is the ocean, where they feed mainly on phytoplankton. They’re near the bottom of the food chain and are eaten by whales, seals, penguins, squid and fish.
Commercial fishing of krill occurs primarily in the Southern Ocean and the northern Pacific Ocean along the coasts of Canada and Japan. Krill that are caught are used for aquaculture and aquarium feeds, sport fishing bait or they are eaten as food. In Japan, krill that’s caught for food is called okiami.
Krill oil, the oil that’s found naturally in krill, is extracted and sold as a nutritional supplement. It’s sold in some health food stores and online in capsule form.
Krill oil contains omega-3 fatty acids, which is the main reason it’s becoming popular as a nutritional supplement.
Another reason krill oil is becoming popular is because it contains an antioxidant called astaxanthin. The algae that krill eat produces the bright red pigment astaxanthin that gives krill and other crustaceans such as lobster and shrimp their reddish-pink color.
Antioxidants protect our body cells from damage from free radicals, unstable substances that are thought to contribute to certain chronic diseases. Unlike many other antioxidants, astaxanthin crosses the blood-brain barrier, where it could theoretically protect the eye, brain and central nervous system from free radical damage.
The recent popularity of krill oil supplements has raised concerns that it could threaten the population of its predators, including penguins, seals and whales. people use krill oil for the same reasons they use fish oil, flax oil or other omega-3 fatty acids. Unlike fish oil, krill oil doesn’t cause fishy burps or an aftertaste, a common side effect of fish oil. Also, krill oil contains higher amounts of astaxanthin than fish oil. Here are some specific conditions for which it’s used.

1) High Cholesterol

Krill oil is being studied as a natural remedy for high cholesterol. In one study, 120 people were given krill oil, fish oil or a placebo. Krill oil reduced LDL (commonly referred to as “bad”) cholesterol by 34% and increased HDL (“good”) cholesterol by 43.5% compared to the placebo. In comparison, fish oil reduced LDL cholesterol by 4.6% and increased HDL cholesterol by 4.2%. Krill also lowered triglycerides.

2) Premenstrual Syndrome

Preliminary research suggests krill oil may help reduce symptoms of premenstrual syndrome (PMS), however, more research is needed.


A study in the Journal of the American College of Nutrition examined krill oil (300 mg daily) compared to a placebo and found that krill oil was effective at reducing arthritis symptoms and inflammation.
People with allergies to seafood shouldn’t use krill oil. People with bleeding disorders shouldn’t use krill oil unless under the supervision of a qualified health professional.
Side effects of krill oil may include loose stools, diarrhea or indigestion.

people taking blood thinners (anticoagulant or anti-platelet medication), such as aspirin, warfarin (Coumadin), heparin, clopidogrel (Plavix), non-steroidal anti-inflammatory medications (NSAIDS) such as ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve) should only use krill oil under a physician’s supervision.

Krill oil should also be used with caution by people taking herbs and supplements that are thought to increase the risk of bleeding, such as ginkgo biloba and garlic.
Bunea R, El Farrah K, Deutsch L.Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia. Altern Med Rev. (2004) 9.4: 420-428.
Deutsch L. Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptoms. J Am Coll Nutr. (2007) 26.1: 39-48.
Krill oil is a nutrient from a tiny crustacean (similar to a shrimp) that lives in the icy waters around the Antarctic. It is a rich source of the omega-3 essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
The main selling points for krill oil are that its omega-3s are packaged differently from fish oils, in the form of a phospholipid that is easier for the body to absorb. This better absorption rate – up to 60 per cent, according to some manufacturers – means less capsules need to be taken to achieve the desired health benefits.
It is also said to have the added bonus of containing another essential nutrient, choline, as well as an antioxidant, astaxanthin. Astaxanthin is found in sea algae and it’s what gives shrimp, lobster, salmon, krill and other sea-life that feed on algae their rosy color.
Krill oil supplements are also more expensive than fish oils because of the extensive processes undertaken to ensure quality and eco-sustainability. However, many argue that it is better value for money, as you have to take less capsules than if you were taking fish oil.

Omecamtiv mecarbil

Amgen, Cytokinetics expand collaboration on Omecamtiv mecarbil , CK-1827452, is a cardiac specific myosin activator

File:Omecamtiv mecarbil.svg
Omecamtiv mecarbil
Omecamtiv mecarbil
Omecamtiv mecarbil
Omecamtiv mecarbil

Omecamtiv Mecarbil provides new hope for heart failure patients

Omecamtiv mecarbil provides new hope for heart failure patientsA new drug which helps the heart pump more easily could improve the lives of thousands of people afflicted by debilitating heart failure, research suggests. Omecamtiv mecarbil is the first of a new class of drugs, called myosin activators, targeting proteins that make the heart contract. Rather than forcing the heart to beat more often, the drug causes heart muscles to contract for longer, increasing the volume of blood pumped out with each stroke. A British trial reported in The Lancet medical journal showed that omecamtiv mecarbil significantly improved the heart function of 45 heart failure patients.
Amgen, Cytokinetics expand collaboration
Thursday, June 13, 2013
Amgen and Cytokinetics, a clinical-stage biopharmaceutical company, have expanded their strategic collaboration to include Japan. In 2006, Cytokinetics and Amgen entered into a collaboration to discover, develop and commercialize novel small-molecule therapeutics that activate cardiac muscle contractility for potential applications in the treatment of heart failure. Omecamtiv mecarbil is the most advanced drug candidate in this collaboration.
- See more at:
Omecamtiv mecarbil , previously codenamed CK-1827452, is a cardiac specific myosin activator. It is clinically tested for its role in the treatment of left ventricular systolic heart failure. Systolic heart failure is characterised as a decreased cardiac output (<40% ejection fraction), due to decreased stroke volume, resulting in the inability to meet the metabolic demands of the body. The loss of contraction is caused by a reduced number of effective actin-myosin cross bridges in the left ventricular myocytes.
One possible underlying mechanism is altered signal transduction that interferes with excitation-contraction coupling. A decreased cardiac output causes peripheral hypotension and activation of the sympathetic nervous system. This in turn stimulates the cardiac myocytes excessively, eventually leading to left ventricular hypertrophy, characteristic of chronic heart failure. Some symptoms of systolic heart failure are fatigue, peripheral oedemadyspnoea, exercise intolerance and breathlessness. Current inotropic drugtherapies such as dobutamine, are palliative and not a cure. They also cause many adverse effects including arrhythmias related to increased myocardical oxygen consumption, desensitization of adrenergic receptors and altering intracellular calcium levels. Thus systolic heart failure is considered malignant, however the novel mechanism of Omecamtiv Mecarbil is a hopeful long-term resolution.
Heart failure is often caused after the heart has suffered significant damage, this is something that can occur during a heart attack. A failing heart cannot provide sufficient blood flow to the body. Natasha Steward works for the British Heart Foundation (BHF) as a senior cardiac nurse. She has stated that, “it does seem that using certain doses of Omecamtiv Mercabil can offer some improvement to a damaged heart.”
Stewart also commented that, “This is a very early stage for the drug, the study we have seen here only took place for a very short time and with a small number of patients. Before we can say this drug is safe for use and will be effective, clinical trials of a much greater scale will need to be conducted.”
The BHF runs the Mending Broken Hearts campaign which raises money in the hope of finding a cure for heart failure. The campaign hopes to raise over £50m to spend on research to help the quarter of a million people who suffer from heart failure in the UK.



The theories and principles of homeopathy have their origins in medicinal traditions established thousands of years ago in Ancient Greece and Rome.
In the 5th century BCE the Greek physician Hippocrates (460–377 BCE) clearly established the idea that disease was the result of natural forces rather than divine intervention, and that patients’ own powers of healing should be encouraged (see page 19). Contemporary medical theories were based upon the Law of Contraries, which advocated treating an illness by prescribing a substance that produced opposite or contrary symptoms. Diarrhea, for example, could be treated by a substance that caused constipation, such as aluminum hydroxide.
In contrast, Hippocrates developed the use of the Law of Similars, based on the principle that “like cures like” (see page 18). This theory proposed that substances capable of causing symptoms of illness in healthy people could also be used to treat similar symptoms during illness. For example, Veratrum album (white hellebore), which was considered effective against cholera, caused violent purging that led to severe dehydration if administered in large doses—symptoms exactly like those of cholera itself. Between the 1st and 5th centuries CE the Romans made further developments in medicine. They introduced more herbs into the pharmacopeias, improved public hygiene, and observed the structure and function of the human body, although this was limited by social taboo, which prevented the dissection of bodies. Existing medical knowledge was codified and rationalized by Galen (130–200 CE), a Roman physician, anatomist, and physiologist.
He adopted many ancient Greek principles, including the Aristotelian theory o the “four humors,” which claimed that the human body was made up of four humors—blood, choler (yellow bile), melancholy (black bile), and phlegm— that must be kept in balance to ensure vitality and health.
After the decline of the Roman empire, little progress was made for centuries in the field of European medicine. A combination of herbal folklore, religious influences, and Galenic theory provided the basis for understanding and treating illness right through to the 17th century. Only when the Swiss physician and alchemist Paracelsus (1493–1541) began to develop his theories did the study of medicine start to evolve again. Paracelsus revived the ancient Greek theory of the Doctrine of Signatures, which was based on the premise that the external appearance of a plant—God’s “signature”—indicated the nature of its healing properties. For example,Chelidonium majus (greater celandine) was used to treat conditions affecting the liver and gallbladder because the yellow juice of the plant resembled bile.
Paracelsus argued that disease was linked to external factors such as contaminated food and water rather than to mystical forces, and he challenged his contemporaries to recognize the body’s natural ability to heal itself, claiming that the practice of medicine should be based on detailed observation and “profound knowledge of nature and her works.” According to his theories, all plants and metals contained active ingredients that could be prescribed to match specific illnesses. Concentrating on practical experiments rather than on alchemy, he laid the foundations for the early stages of chemistry and subsequent development of pharmaceutical medicine, introducing new medicines, such as opium, sulfur, iron, and arsenic, into the contemporary repertory. His exploration of the chemical and medicinal properties of many substances, and his advocacy of the Hippocratic concept of “like cures like,” also made Paracelsus a key figure in the development of homeopathy.
According to the British homeopath James Compton Bunett (1840–1901), the author of several important works on homeopathy that are still in use today, “Paracelsus planted the acorn from which the mighty oak of homeopathy has grown.” intellectual climate encouraged important developments in the study of medicine, including the isolation of active ingredients from herbs, such as the extraction of morphine from the opium poppy in 1803. It was in 1790, while translating A Treatise on Materia Medica by a Scottish teacher, physician, and chemist, Dr. William Cullen, that Hahnemann began an investigation which was to prove paramount to the subsequent development of homeopathy. In his treatise Cullen argued that quinine, when isolated from Cinchona officinalis (see page 49), was a good treatment for malaria because it was an stringent. Hahnemann knew that other, more powerful, astringents had no such effect on malaria.
He dosed himself with quinine, recording the results and effectively beginning the first “proving”  see page 22). Although he did not have malaria, he found that he began to develop symptoms of the disease one after the other. With each dose of quinine, the symptoms recurred and lasted for several hours, but if he stopped taking quinine his symptoms began to disappear. Hahnemann went on to test quinine on other people, noting their reactions in great detail. The test subjects were not allowed to eat or drink strong foods such as spices, alcohol, or coffee, which he felt might distort the results. He repeated the proving process on other substances that were in use as medicines, such as arsenic and belladonna, and used the results to build up a “symptom picture” of each remedy’s effects (see page 23).
After conducting provings for six years, Hahnemann extended his research to the sick. Prior to prescription, he gave his patients a thorough physical examination and noted any existing symptoms. He questioned them closely regarding their lifestyles, general health, outlook on life, and other factors that made them feel better or worse. Following the principle of like cures like, Hahnemann then matched individual symptoms as closely as possible to the symptom picture of a remedy, and prescribed accordingly.
Development & definition
Hahnemann’s work gradually brought about the establishment of new type of medicine. In 1796 he published his first book on the subject, entitled A New Principle for Ascertaining the Curative Powers of Drugs and Some Examinations of Previous Principles. He called his new system “homeopathy,” from the Greek homeo meaning “similar” and pathos meaning “suffering.” In 1810 he set out its principles in The Organon of Rationale Medicine, and two years later he began teaching homeopathy at the University of Leipzig. During the course of his lifetime, Hahnemann proved about 100 remedies, and also continued to develop and refine the theory and practice of the system (see page 18).
The medical establishment remained generally very sceptical of Hahnemann’s theories, and he in turn continued to be intensely critical of conventional medical practice. He became known as the “raging hurricane” due to his furious tirades and sarcastic critiques during lectures at Leipzig. He also antagonized contemporary pharmacists by giving only one medicine at a time, which was contrary to their (highly lucrative) practice of generally prescribing expensive mixtures of several remedies. During the 19th century, homeopathy spread rapidly across Europe to Asia and the Americas. In the US, Dr. Constantine Hering (1800–80) and Dr. James Tyler Kent (1849–1916) were responsible for popularizing the therapy and introducing new ideas and practices (see page 19). By the time of Hahnemann’s death in 1843, homeopathy was firmly established in many parts of the world, although there remained antagonism and distrust between the advocates of conventional medicine and those of homeopathy.
Between 1860 and 1890 homeopathy flourished, as many homeopathic hospitals and schools were opened, and many new remedies were proved, considerably enlarging the materia medica. Hahnemann’s followers were often doctors who defected from conventional medicine after personally experiencing treatment, including an English doctor, Frederick Quin (1799–1878), who was cured of cholera by the Camphora remedy. Quin first visited Hahnemann in Germany in 1826, and went on to introduce homeopathy in the UK, founding the first homeopathic hospital in London in 1849. During a cholera outbreak in 1854, the mortality rate at his hospital was less than half that of conventional hospitals. This information was suppressed by the national Board of Health on the grounds that “the figures would give sanction to a practice opposed to the maintenance of truth and the progress of science,” illustrating the close stranglehold the medical establishment had achieved within social institutions.
Decline & resurrection

The predominance of conventional medicine was echoed in the US. By the late 19th century, homeopathy had become a significant part of US medical practice, with about 15 percent of doctors being practicing  homeopathy. During the early 20th century, however, homeopathy became largely overshadowed by conventional medicine, principally due to the rise of the American Medical Association.
The British Medical Association played a similar role in the UK, and divisions within homeopathy began to weaken the force of its message still further. Strict followers of Hahnemann and Kent’s original theories followed “classical” or “Kentian” constitutional prescribing, believing that a person’s emotional characteristics and physical symptoms should be taken into account and favoring high potencies (see page 19). Led by the British homeopath Dr. Richard Hughes (1836–1902), one strand of practitioners had, however, begun to prescribe on pathological symptoms alone, favoring low doses. This unfortunate division in homeopathic practice enabled the conventional medical establishment to gain the upper hand, and by the 1920s homeopathy had been largely suppressed in the UK.
During the late 20th century there has been a resurgence in the popularity of homeopathy, possibly due to disenchantment with aspects of conventional medicine. In many countries, particularly in central Europe, its popularity never waned to the same extent as in the UK and US, although differences in practice have evolved. Single-remedy classical prescribing is prevalent worldwide, although in Germany and France complex homeopathy or polypharmacy (the use of combination remedies or several remedies) is also popular (see page 21). In Australia there is a strong link with naturopathy, with homeopathic remedies often incorporated into naturopathic practice. In India, homeopaths have long worked successfully alongside traditional Ayurvedic medicine and conventional medicine. In the 1990s, courses in Eastern Europe pioneered by British teachers revitalized interest in homeopathy, and in Russia it continues to be implemented and developed. In South America, homeopathy is widely taught in medical schools, while in the US it is undergoing a major resurgence of popularity. According to a 1998 survey of Americans and their health, over
6 million Americans had used homeopathy in the preceding 12 months. Noting that it had been integrated into the national healthcare systems of numerous countries, including Germany, the United Kingdom, India, Pakistan, Sri Lanka, and Mexico, the World Health Organization is publishing a position paper in 2006.


Forest Announces U.S. Availability of New Once-Daily NAMENDA XR

Forest Announces U.S. Availability of New Once-Daily NAMENDA XR
– Treatment for moderate to severe Alzheimer’s Disease is now available to patients in a convenient extended release formulation –
NYSE:FRX.NEW YORK–(BUSINESS WIRE)–Forest Laboratories, Inc. announced today that NAMENDA XR(TM) (memantine hydrochloride) once-daily formulation is now available in pharmacies throughout the United States. NAMENDA XR is approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe dementia of the Alzheimer’s type.
Memantine is the first in a novel class of Alzheimer’s disease medications acting on theglutamatergic system by blocking NMDA-type glutamate receptors. It was first synthesized by Eli Lilly and Company in 1968. Memantine is marketed under the brandsAxura and Akatinol by MerzNamenda by ForestEbixa and Abixa by Lundbeck andMemox by Unipharm. Memantine has been shown to have a modest effect in moderate-to-severe Alzheimer’s disease  and in dementia with Lewy bodies. Despite years of research, there is little evidence of effect in mild Alzheimer’s disease.

Friday, 17 January 2014

CHINESE HERBS Ginkgo biloba for antidepressant induced sexual dysfunction.

Ginkgo biloba L.

Ginkgo biloba extract

Ginkgo (Ginkgo biloba; in Chinese and Japanese 銀杏, pinyin romanization:yín xìng, Hepburn romanization: ichō or ginnan), also spelled gingko and known as the maidenhair tree, is a unique species of tree with no close living relatives. The ginkgo is a living fossil, recognisably similar to fossils dating back 270 million years. Native to China,the tree is widely cultivated and was introduced early to human history. It has various uses in traditional medicine and as a food.
Ginkgo biloba extract (GBE, species Ginkgo biloba) has been used for centuries as part of the ancient Chinese pharmacopoeia in the treatment of respiratory ailments, cognitive impairment, and circulatory disorders. In recent years, Ginkgo has gained great worldwide acceptance for treatment of a number of medical conditions including tinnitus, cognitive decline in dementia, intermittent claudication, asthma, macular degeneration and, most recently, antidepressant induced sexual dysfunction.
The oldest tree species in the world, dating from the time of the dinosaurs, Ginkgo biloba (bi-loba, two sided leaf) is the last remaining species of theGinkgoales order. Fossil records show the species was once widespread in Asia and North America, and it is speculated that it was saved from extinction by monks in the far east who cultivated it secretly as a sacred tree. Each tree can live for more than a thousand years, immune to bugs, disease and pollution. The tree grows to 100 feet tall and has fan-like leaves and yellow-green fetid smelling fruits. If you are lucky enough to have access to a mature tree, take advantage of the fresh leaves, which contain the broadest spectrum of medicinal properties.
Case reports have confirmed GBE’s beneficial effect on ASD. An open clinical trial of Ginkgo biloba extract with 63 patients was found to be effective in 84% of patients with ASD. All phases of the sexual response cycle were improved (desire, excitement, orgasm and resolution). Minimal side effects were reported which included gastrointestinal upset, headache, CNS stimulation and easy bruisability. There were no serious adverse events. A double blind placebo-controlled trial of a GBE compound has just been completed and the results are currently under review.
Possible mechanisms of action may include improved circulation and prostaglandin agonist effects, as well as neurotransmitter and nitric oxide second messenger modulation. Although Ginkgo biloba is relatively safe, it also works as a potent inhibitor of platelet activating factor. Therefore, patients taking aspirin, nonsteroidal anti-inflammatory agents, and anti-coagulants, or patients with a coagulopathy should consult a physician and exercise caution when considering adding GBE to their existing regimen. Dose ranges of GBE 50:1 extract are 60 milligram tablets twice a day; this can be advanced to 120 mg twice a day after two weeks.
The use of the ginkgo leaf is recent, and has been studied for its cardiovascular benefits. Today ginkgo biloba is one of the most commonly prescribed herbs and is a great example of a tonic herb – one that balances whatever is going on in your system; if you are tired it can energize you, if you are stressed it will relax you.
The bilobalides, ginkgolides, flavonoids, and other substances unique to the tree restore better blood flow to all parts of the body but particularly to the brain, allowing improved use of oxygen. Ginkgo’s antioxidant actions also stabilize the structure of brain and nerve cells and protect them from oxidative attacks from free radicals. Research indicates ginkgo action of supporting healthier circulation in the eyes, make it an herb of choice for natural treatment eye health and macular degeneration.
There is an significant body of scientific and clinical evidence supporting the safety and efficacy of ginkgo extract for both cognitive function and improved circulation, said Mark Blumenthal, the founder and executive director of ABC
. Ginkgo’s hallmark effect is increased circulation, which is important in maintaining our energy level and one of the factors in stopping early hair loss. Increasing genital blood flow heightens responsiveness, making for higher libido in both men and women. Good circulation means getting the full benefit from the foods we eat and the vitamins and herbal supplements we take.
Allergies and asthma also improve with ginkgo. The herb contains a dozen different anti-inflammatory chemicals and seven natural antihistamines. 1
  • Medicinal Uses: * Allergies * Alopecia * Asthma * Bronchitis * Circulation * Eyes/Vision * Libido * Longevity Tonics * Memory/Focus * Varicose Veins
  • Properties: * Anti-inflammatory * AntiCancer * Antioxidant * Antitussive * Astringent * Cardiac tonic Cordial * Tonic * Vasodilator * Vermifuge
  • Parts Used: Leaves and Nuts
  • Constituents: gibberellin, cytokinin-like substances, ginkgolic acid, bilobol, ginnol, aspartine, calcium
EGb 761 [Ginkgo biloba extract EGb 761, Rökan, Tanakan, Tebonin] is a standardised extract of Ginkgo biloba leaves and has antioxidant properties as a free radical scavenger. A standardised extract of Ginkgo biloba leaves is a well defined product and contains approximately 24% flavone glycosides (primarily quercetin, kaempferol and isorhamnetin) and 6% terpene lactones (2.8-3.4% ginkgolides A, B and C, and 2.6-3.2% bilobalide). Ginkgolide B and bilobalide account for about 0.8% and 3% of the total extract, respectively. Other constituents include proanthocyanadins, glucose, rhamnose, organic acids, D-glucaric and ginkgolic acids. EGb 761 promotes vasodilation and improves blood flow through arteries, veins and capillaries. It inhibits platelet aggregation and prolongs bleeding time. EGb 761, which was originated by Dr Willmar Schwabe Pharmaceuticals (Dr Willmar Schwabe Group), has been available in Europe as a herbal extract since the early 1990s. However, products containing EGb 761 are not approved for use by the US FDA. As a dietary supplement, Nature’s Way in the US distributes and markets a standardised extract of Ginkgo biloba leaves (the EGb 761 Formula) under the name Gingold Nature’s Way. The French company Beaufour-Ipsen and its German subsidiary Ipsen Pharma are co-developing EGb 761 with Dr Willmar Schwabe Group. Beaufour-Ipsen (France) is developing EGb 761 as Tanakan, Dr Willmar Schwabe Pharmaceuticals (Germany) as Tebonin and Ipsen Pharma (Germany) as Rökan. Intersan was formerly developing EGb 761 in Germany, but Intersan appears to have been merged into Ipsen Pharma. However, there has been no recent development for these indications. In the UK and other European countries, the cardioprotective effects of EGb 761 in myocardial ischaemia and reperfusion are being investigated in preclinical studies. The psychological and physiological benefits of ginkgo are said to be based on its primary action of regulating neurotransmitters and exerting neuroprotective effects in the brain, protecting against or retarding nerve cell degeneration. Ginkgo also benefits vascular microcirculation by improving blood flow in small vessels and has antioxidant activity. There has been conflicting evidence about the benefits of ginkgo, e.g. the ginkgo clinical trial published in August 2002 in JAMA concluded that a leading ginkgo supplement did not produce measurable benefits for memory in healthy adults over 60, although a month earlier, another study concluded that the same ginkgo extract is effective in helping normal healthy older adults in memory and concentration. However, in December 2002, the Cochrane Collaboration, the world’s most respected scientific reviewer of clinical trials in medicine, concluded that the published literature strongly supports the safety and potential benefits of ginkgo in treating memory loss and cognitive disorders associated with age- related dementia. A phase II study of EGb 761 in combination with fluorouracil is in progress in Germany in patients with pancreatic cancer. German researchers are investigating the potential of EGb 761 for the treatment of sudden deafness and tinnitus in clinical studies. EGb 761 was undergoing preclinical development for the potential treatment of diabetes in France, diabetic neuropathies in Russia, and cancer in Brazil. However, there has been no recent development for these indications. Beaufour-Ipsen has expressed the intention to license out its diabetes projects that may include EGb 761.
The first mentioned  use of Ginkgo biloba appears in China. Ginkgo leaf is first mentioned in Lan Mao’s Dian Nan Ben Cao, published in 1436 during the Ming dynasty. Lan Mao notes external use to treat skin and head sores as well as freckles. Internal use of the leaves is first noted in Liu Wen-Tai’s Ben Cao Pin Hui Jing Yao , an imperial commissioned work recorded in 1505. Liu Wen Tai notes use of the leaves in the treatment of diarrhea. The leaves of ginkgo are known in Chinese medicine as bai-guo-ye. Recent clinical reports in modern China suggest that the leaves lower serum cholesterol levels and have some clinical value in angina pectoris.
In Traditional Chinese pharmacopeia the seeds (with fleshy rind removed) are considered more important than the leaves. The nut, called Pak Ko, is recommended to expel phlegm, stop wheezing and coughing, urinary incontinence and spermatorrhea. The raw seed is said to help bladder ailments, menorrhea, uterine fluxes, and cardiovascular ailments. The powdered leaf is inhaled for ear, nose, and throat disorders like bronchitis and chronic rhinitis. Locally applied boiled leaves are used for chilblains.. The seeds are used as an astringent for the lung, to stop asthma and enuresis.
Ginkgo leaves are a Chinese herb that has been used much more in the West than in its homeland. Over five hundred scientific studies on the chemistry, pharmacology and clinical effects of gingko leaves have been conducted by European researchers over the last 20 to 30 years. The majority of studies on ginkgo leaf extract have involved a product produced by a German/French consortium, referred to in the scientific literature as EGb761.
The extract utilized in medicine is standardized in a multi-step procedure designed to concentrate the desired active principles from the plant. These extracts contain approximately 24% flavone glycosides (primarily composed of quercetin, kaempferol, and isorhamnetin) and 6% terpene lactones (2.8-3.4% ginkgolides A, B, and C, and 2.6-3.2% bilobalide). Other constituents include proanthocyanadins, glucose, rhamnose, organic acids, D-glucaric acid and ginkgolic acid (at most 5 ppm ginkgolic acids). Biochemical studies have concentrated on the flavonoids: much of the curative properties of the ginkgo tree are due to the activities of these flavonoids. The complex extract itself, rather than a single isolated component, is believed to be responsible for Ginkgo’s biological activity.
Ginkgo leaf extracts have been shown to have a wide range of biological activities. The most well-known use is the ability to improve short term memory. Other important effects include a protective effect on the blood-brain barrier and an anti-radical (antioxidant) effect. The leaf extracts has also been shown to increase vasodilation and peripheral blood flow rate in capillary vessels and end-arteries in various circulatory disorders. Ginkgo leaf helps to maintain integrity and permeability of cell walls by inhibiting lipid peroxidation of membranes. Other studies have shown vascular-tone regulating effects, and help in modulating cerebral energy metabolism.

Ginkgo biloba extract (Gbe) and two ingredients, bilobalide and ginkgolide B, are presented to the CSWG as part of a review of botanicals being used as dietary supplements in the United States. ( 1 of 3 adults in the United States are now taking dietary supplements ). Sweeping deregulation of botanicals now permits GBE to be sold as a dietary supplement to a willing public eager to “improve brain functioning” or “promote radical scavenging activity.”. In the U.S, there are four primary distribution channels: drug stores, supermarkets, mass merchandisers, and specialty vitamin shops and nutrition centers. The Internet is also becoming an increasingly important distribution channel.
Gbe is a well defined product, and it or its active ingredients, the ginkgolides, especially ginkgolide B, and bilobalide, have clearly demonstrated biological activity. It can be consumed in rather large doses for an extended period of time. Under the Dietary Supplement Health and Education Act of 1994, Gbe can be sold legally if it is not labeled or accompanied by any therapeutic or health claims. Herbal remedies can be labeled with descriptions of their role in affecting physiological structure or function, but must be labeled with a disclaimer that the product has not been evaluated by the FDA for cure, prevention, or treatment of a disease.
 GINKGO Biloba Extract (Gbe)Trade Names: Egb 761, Ginkgold, Tebonin, LI 1370, rökan, Tanakan
Standardized ingredients of Gbe
    The extract utilized in medicine is standardized in a multi-step procedure designed to concentrate the desired active principles from the plant. These extracts contain approximately 24% flavone glycosides (primarily composed of quercetin, kaempferol, and isorhamnetin) and 6% terpene lactones (2.8-3.4% ginkgolides A, B, and C, and 2.6-3.2% bilobalide). Ginkgolide B accounts for about 0.8% of the total extract, and bilobalide accounts for about 3% of the extract. Other constituents include proanthocyanadins, glucose, rhamnose, organic acids, D-glucaric acid and ginkgolic acid (at most 5 ppm ginkgolic acids).Much of the curative properties of Gbe are due to the activities of these flavonoids.

CAS Registry Number: 117-39-5
Molecular Formula: C15 H10 OMol. wt.: 338.3
Chemical Abstracts Service Name: 4H-1-Benzopyran-4-one, 2-(3,4-dihydroxyphenyl)- 3,5,7-trihydroxy- (9CI)
CAS Registry Number: 520-18-3
Molecular Formula: C15 H10 OMol. wt.: 286.2
Chemical Abstracts Service Name: 4H-1-Benzopyran-4-one, 3,5,7-trihydroxy-2-(4- hydroxyphenyl)- (9CI)
CAS Registry Number: 480-19-3
Chemical Abstracts Service Name: 4H-1-Benzopyran-4-one, 3,5,7-trihydroxy-2-(4- hydroxy-3-methoxyphenyl)- (9CI)
Molecular Formulat: C15 H12 O6 Mol. wt.: ~314
Ginkgolide AOHHH
Ginkgolide BOHOHH
Ginkgolide COHOHOH
CAS Registry Number: 33570-04-6
Chemical Abstracts Service Name: 4H,5aH,9H- Furo(2,3-b)furo(3′,2′:2,3)cyclopenta (1,2-c)furan-2,4,7 (3H,8H) -trione,9-(1,1-dimethylethyl)-10,10a-dihydro-8,9-dihydroxy-, (5aR-(3aS*,5aa,8b,8aS*,9a,10aa))- (9CI)
Molecular Formula: C15H18O8 Mol. wt.: 326.3
Modern pharmacological research into the active constituents of ginkgo leaves began in the late 1950s. Spearheaded by the phytopharmaceutical company Dr. Willmar Schwabe GmbH, twenty years of research resulted in a standardized, concentrated extract of ginkgo leaves. The 27 step extraction process requires fifty pounds of leaves to yield one pound of extract and takes up to two weeks to complete. Most critical to the extraction process and final product is the standardization of ginkgo flavone glycosides and terpene lactones. The 24% ginkgo flavone glycosides content of GBE constitutes a carefully measured balance of quercetin, kaempferol, and isorhamnetin. The group of constituents unique to GBE, however, are the terpene lactones which constitute 6% of the final extract.
Human Exposure: There is potential for ingestion of Gbe to a widespread consumer population, since this product is readily available without prescription at a cost highly competitive with prescription medications. The recommended dose of Gbe is 120 to 160 mg daily for persons with intermittent claudication and 240 mg daily for cerebrovascular insufficiency, early stage Alzheimer’s disease, resistant depression, and impotence.

TetraLogic’s BIRINAPANT for treatment of acute myeloid leukemia, pancreatic cancer, or ovarian cancer

ChemSpider 2D Image | Birinapant | C42H56F2N8O6
BIRINAPANT, Apoptosis inhibitor
1260251-31-7 cas no
US20110003877,WO 2013049350 A1
Molecular Weight:806.94
Birinapant Formula:C42H56F2N8O6
Birinapant, also known as TL32711,  is a synthetic small molecule and peptido mimetic of second mitochondrial-derived activator of caspases (SMAC) and inhibitor of IAP (Inhibitor of Apoptosis Protein) family proteins, with potential antineoplastic activity. As a SMAC mimetic and IAP antagonist, TL32711 binds to and inhibits the activity of IAPs, such as X chromosome-linked IAP (XIAP) and cellular IAPs 1 and 2. Since IAPs shield cancer cells from the apoptosis process, this agent may restore and promote the induction of apoptosis through apoptotic signaling pathways in cancer cells. IAPs are overexpressed by many cancer cell types and suppress apoptosis by binding and inhibiting active caspases-3, -7 and -9 via their baculoviral lAP repeat (BIR) domains
Birinapant is currently in Phase II clinical trials in patients with acute myeloid leukemia, pancreatic cancer, or ovarian cancer. Although these trials don’t have a control group, the emerging data are promising, TetraLogic chief executive officer John M. Gill told C&EN. (Early-stage cancer clinical trials are commonly run without placebo groups.) The birinapant trials show preliminary evidence both that the drug is having the desired effect and that this effect is associated with signs of clinical activity. Given these results, the company plans to launch randomized Phase II studies early in 2014
(From left) Guangyao Yu, Yijun Deng, Gurpreet Singh Kapoor, Condon, Susan Rippin, Martin Graham, Angeline Mufalli, Jennifer Burns, Martin Seipel, Eric Neiman, Thomas Haimowitz, Christopher Benetatos, Yasuhiro Mitsuuchi, Srinivas Chunduru Not pictured: Divya Goel
(From left) Guangyao Yu, Yijun Deng, Gurpreet Singh Kapoor, Condon, Susan Rippin, Martin Graham, Angeline Mufalli, Jennifer Burns, Martin Seipel, Eric Neiman, Thomas Haimowitz, Christopher Benetatos, Yasuhiro Mitsuuchi, Srinivas Chunduru. Not pictured: Divya Goel
Credit: Courtesy of TetraLogic
It’s often said that two heads are better than one. For Malvern, Pa.-basedTetraLogic Pharmaceuticals, it was combining two copies of a molecule into one drug candidate that did the trick. Stephen M. Condon, vice president for chemistry at TetraLogic, told the story of that candidate, birinapant, in New Orleans.
Birinapant was designed to reinstate cancer cells’ ability to die. Many cancers that are resistant to conventional chemotherapy drugs have defects in the cell death pathway known as apoptosis. The human body uses apoptosis every day to clear away abnormal or unwanted cells.
Apoptosis is a tightly regulated process, Condon explains, with a network of proteins that activate or block the process. TetraLogic’s target is a family of proteins called the Inhibitor of Apoptosis proteins. As their name suggests, these proteins block apoptosis. They interfere with protease enzymes that carry out cellular dismantling.
TetraLogic’s aim is to lift that blockade to restart apoptosis in tumors. Many tumors have excesses of the apoptosis inhibitor proteins relative to normal cells, so targeting this process has the potential to be less toxic to normal cells compared with conventional chemotherapy.
It turns out nature has a way of negating the inhibitor proteins’ actions—a protein known as Smac. TetraLogic’s founders demonstrated that only a tiny portion of Smac is necessary to keep the inhibitor proteins at bay—the four amino acids at the protein’s N-terminus. “Once you can get a protein down to a tetrapeptide,” about the size of a small-molecule drug, “you start getting a lot of interest from the pharma community,” Condon told C&EN.
Peptides fall apart in the body too quickly to be drugs, so Condon’s team worked with molecular mimics of the Smac tetrapeptide. Their biggest advance was realizing that combining two copies of their tetrapeptide mimics into one molecule made their compounds highly effective at reinstating apoptosis in cancer cell lines. Many proteins in the apoptosis pathway function as dimers, so using these so-called bivalent mimics against them makes sense, Condon said.
However, several of the bivalent compounds were associated with pronounced body weight loss in mice. Condon’s team eventually learned that replacing a branched side chain on their peptide mimics and adding a hydroxyl group to a proline residue improved the tolerability for the animals without impacting the antitumor effect. With that, birinapant was born.
In mice, birinapant shrank tumors. The compound has been in clinical trials since 2009, both on its own and in combination with other chemotherapy drugs such as irinotecan and gemcitabine. On the basis of other biochemical work on the apoptosis pathway, TetraLogic thinks these drugs could act in synergy with birinapant to treat cancer, Condon said.
Birinapant is currently in Phase II clinical trials in patients with acute myeloid leukemia, pancreatic cancer, or ovarian cancer. Although these trials don’t have a control group, the emerging data are promising, TetraLogic chief executive officer John M. Gill told C&EN. (Early-stage cancer clinical trials are commonly run without placebo groups.) The birinapant trials show preliminary evidence both that the drug is having the desired effect and that this effect is associated with signs of clinical activity. Given these results, the company plans to launch randomized Phase II studies early in 2014.
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spectral data
1H NMR (300 MHz, CDC13): 511.74 (s, 2H), 8.27 (d, J= 8.7 Hz, 2H), 7.71 (dd, J= 5.4, 8.4 Hz, 2H), 7.55 (dd, J =2.4, 9.6 Hz, 2H), 6.88 (ddd, J= 2.4, 9.3, 9.3 Hz, 2H), 4.62-4.78 (m, 4H), 4.43 (dd, J= 9.3, 9.9 Hz, 2H), 4.03 (dd, J= 4.8, 11.4 Hz, 2H), 3.80 (d, J = 11.4 Hz, 2H), 3.66 (dd, J= 2.7, 14.4 Hz, 2H), 3.53 (dd, J = 11.4, 14.4 Hz, 2H), 3.11 (q, J = 6.9 Hz, 2H), 2.56 (s, 6H), 2.45 (m, 2H), 2.19 (d, J= 14.4 Hz, 2H), 1.76-2.10 (m, 6H), 1.59 (br s, 2H), 1.39 (d, J= 6.9 Hz, 6H), 1.22-1.38 (m, 2H), 1.07 (t, J = 7.2 Hz, 6H) ppm;
13C NMR (75 MHz, d6- DMSO): 5175.2, 172.8, 161.6, 158.5, 137.3, 137.2, 128.4, 128.3, 126.4, 120.8, 120.6, 109.4, 108.7, 108.4, 98.4, 98.0, 70.8, 60.2, 59.9, 56.6, 51.8, 36.4, 35.3, 28.3, 25.6, 20.0, 10.6 ppm.
Mass spectrum (ESI), m/z 807.5 [(M)+; calcd for C42H56F2N806: 806.9].