FLAGS AND HITS
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
FACEBOOK
...................................................................Join me on twitter
..................................................................Join me on google plus
GoogleplusMYSELF
The challenges facing the pharmaceutical industry through to 2020
The challenges facing the pharmaceutical industry through to 2020
link on slideshare is
by Irish Pharmaceutical Healthcare Association (IPHA) on Nov 12, 2009
- 22,073 views on slideshare
Presentation delivered by Mr Sandy Johnston, PriceWaterhouseCoopers at the Irish Pharmaceutical Healthcare Association Annual Meeting 2009.
US green light for Warner Chilcott’s new contraceptive
May 10, 2013
US regulators have issued a green light for Warner Chilcott’s new oestrogen/progestin-based oral contraceptive, which is yet to be given an official trade name.
The product is a chewable combination of norethindrone acetate and ethinyl estradiol and ferrous fumarate tablets, approved by the US Food and Drug Administration for the prevention of pregnancy.
The oral contraceptive regimen consists of 24 white active chewable tablets that contain the active ingredients, followed by four brown non-hormonal placebo tablets containing ferrous fumarate.
Approval was based on data from a six-month clinical trial involving 743 women aged 18-45 years, which showed the risk of getting pregnant to be about one-four in 100 women during the first year of use.
second nod, may10 2013–The US Food and Drug Administration has given the green light to Novartis’ Ilaris as a treatment for a serious form of childhood arthritis.
my old post for first nod
Novartis’ Ilaris canakizumab has become the first biologic drug to be approved in the EU to treat the symptoms of gouty arthritis
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | IL-1β |
Novartis’ Ilaris has become the first biologic drug to be approved in the EU to treat the symptoms of gouty arthritis in another gain for the interleukin-1 beta inhibitor.
march01,2013
First biologic drug approved for condition in Europe
The European Commission (EC) cleared llaris (canakizumab) for the treatment of adult patients who have suffered at least three gouty arthritis attacks in the previous 12 months, but who are unsuitable for treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine or repeated courses of corticosteroids.
Gouty arthritis – commonly known as gout – is an “excruciating condition”, according to Novartis division head David Epstein, who noted that Ilaris offers new hope to patients who do not currently have treatment options.
Data from two phase III trials of Ilaris in acute gouty arthritis attacks showed that patients treated with the drug experienced significantly greater pain relief compared to the injectable steroid triamcinolone acetonide, while most adverse events were mild to moderate in severity.
The most frequent side effects were infections, and particularly upper respiratory tract infections and nasopharyngitis.
Ilaris was launched in the US and EU in 2009 as a treatment for an auto-inflammatory condition called cryopyrin-associated periodic syndrome (CAPS). The rarity of that condition has meant sales have been relatively small, coming in at $72m last year, albeit a 56 per cent gain over 2011.
Gouty arthritis is a much bigger market for the drug and, along with a juvenile arthritis indication Novartis is pursuing, could push Ilaris towards blockbuster status with sales in excess of $1bn a year.
“Our vision is to realise the potential of Ilaris wherever IL-1 beta plays a key role and available treatment options don’t give patients the help they need,” said Epstein.
EU approval comes after the US FDA knocked back Ilaris for gouty arthritis, saying in 2011 that Novartis needed to provide more data on the drug’s risk-benefit profile, specifically its potential to leave patients vulnerable to infections.
Gout has been a tricky indication for drug developers to crack, with the FDA turning down another CAPS treatment – Regeneron’s IL-1 inhibitor Arcalyst (rilonacept) – in 2012 on the grounds of inadequate safety data and concern about a risk of malignancy.
One success came in 2010 when Savient secured approval for its Krystexxa (pegloticase) drug as a second-line treatment after oral xanthine oxidase inhibitors in patients with severe debilitating chronic tophaceous gout.
However, the drug has failed to make significant inroads because of a high price and tendency to stimulate neutralising antibodies that limit its therapeutic effect, according to Decision Resources.
There is still a great demand for safer and more effective therapies with the phase III pipeline featuring another potential blockbuster in the form of AstraZeneca/Ardea Biosciences URAT1 inhibitor lesinurad.
Canakinumab (INN, trade name Ilaris, previously ACZ885)[1] is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha.[2]
Canakinumab was approved for the treatment of cryopyrin-associated periodic syndromes (CAPS) by the US FDA on June 2009[3] and by the European Medicines Agency in October 2009.[4] CAPS is a spectrum of autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle–Wells syndrome, and neonatal-onset multisystem inflammatory disease.
Canakinumab was being developed by Novartis for the treatment of rheumatoid arthritis but this trial has been discontinued.[5] Canakinumab is also in phase I clinical trials as a possible treatment for chronic obstructive pulmonary disease.[6]
References
- Dhimolea, Eugen (2010). “Canakinumab”. MAbs 2 (1): 3–13. doi:10.4161/mabs.2.1.10328. PMC 2828573. PMID 20065636.
- Lachmann, HJ; Kone-Paut I, Kuemmerle-Deschner JB et al. (4 June 2009). “Use of canakinumab in the cryopyrin-associated periodic syndrome”. New Engl J Med 360 (23): 2416–25. doi:10.1056/NEJMoa0810787. PMID 19494217.
- “New biological therapy Ilaris approved in US to treat children and adults with CAPS, a serious life-long auto-inflammatory disease” (Press release). Novartis. 18 June 2009. Retrieved 28 July 2009.
- Wan, Yuet (29 October 2009). “Canakinumab (Ilaris) and rilonacept (Arcalyst) approved in EU for treatment of cryopyrin-associated periodic syndrome”. National electronic Library for Medicines. Retrieved 14 April 2010.
- “clinicaltrials.gov, Identifier NCT00784628: Safety, Tolerability and Efficacy of ACZ885 (Canakinumab) in Patients With Active Rheumatoid Arthritis”. Retrieved 2010-08-21.
- Yasothan U, Kar S (2008). “Therapies for COPD”. Nat Rev Drug Discov 7 (4): 285. doi:10.1038/nrd2533.
Monoclonal Antibody Therapeutic Uses
AtheroNova Receives Russia’s Approval for Phase I Clinical Trials
May 09, 2013
InSite Vision Initiates Confirmatory Phase 3 Clinical Study of BromSite™ for the Reduction of Inflammation and Pain after Cataract Surgery
bromfenac
may9, 2013
InSite Vision Incorporated today announced that patient enrollment has begun in the confirmatory Phase 3 clinical trial of BromSite™ (ISV-303) for the reduction of inflammation and pain after cataract surgery. This study will seek to enroll approximately 240 patients undergoing cataract surgery in a two-arm trial designed to evaluate the efficacy and safety of BromSite against the DuraSite vehicle alone. BromSite combines a low dose (0.075%) of the non-steroidal anti-inflammatory drug (NSAID) bromfenac with InSite Vision’s DuraSite drug delivery technology.
Bromfenac is a non-steroidal anti-inflammatory drug (NSAID) marketed in the US as anophthalmic solution (current brand name Bromday, prior formulation brand name Xibrom, which has since been discontinued.) by ISTA Pharmaceuticals for short-term, local use. Bromday® is the once-daily formulation of bromfenac, while Xibrom®, which has since been discontinued, was the twice-daily formulation. Bromfenac is indicated for the treatment of ocular inflammation and pain after cataract surgery, though it may be prescribed in an off-label manner by the physician.
For ophthalmic use, bromfenac has been prescribed more than 20,000,000 times across the world. As an eye drop, it has been available since 2000, starting in Japan where it was sold as Bronuck®. It was first FDA approved for use in the United States in 2005 and it was marketed as Xibrom®, twice-daily. October 2010 was the FDA approval of the new once-daily formulation of bromfenac called Bromday®. The bromfenac molecule will be marketed in Europe and other worldwide markets with agreements from Bausch & Lomb, Croma Pharma, and other companies.
Bromfenac was formerly marketed in the United States by Wyeth-Ayerst in an oral formulation called Duract® for short-term relief of pain (less than 10 days at a time). It was brought to market in July, 1997, and was withdrawn June 22, 1998 following numerous reports of hepatotoxicity in patients who had taken the medication for longer than the recommended 10-day period. The dose was one 25 mg capsule every 6 to 8 hours, or two capsules if taken with a high-fat meal, up to a maximum of 150 mg per day.
Array Announces Global Phase 3 Trial Evaluating MEK162 In Patients With Low-Grade Serous Ovarian Cancer
MEK-162:
5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide.
May 6, 2013
Array BioPharma Inc. today announced that it will initiate a global Phase 3 clinical trial in patients with recurrent low-grade serous ovarian cancer (LGSOC) during the summer of 2013. The study, called MILO (MEK Inhibitor in Low Grade Serous Ovarian Cancer), will evaluate the efficacy and safety of MEK162 compared to standard chemotherapy treatments and is designed for worldwide regulatory submissions, including with the U.S. Food and Drug Administration and the European Medicines Agency. Array invented MEK162 and licensed worldwide rights to develop and commercialize the drug to Novartis in April 2010. The MILO study follows a recent announcement by Novartis detailing plans to initiate Phase 3 trials of MEK162 in both NRAS- and BRAF-mutant melanoma and will be covered as part of the Novartis/Array co-development agreement under which costs are capped annually and in total for Array.
MEK162 (ARRY-162) is an oral, highly selective MEK inhibitor. In preclinical studies, MEK162 showed significant antitumor activities in cell lines and animal models. MEK162 is now being investigated in trials in advanced solid tumors. Recent research confirms that the MEK pathway acts as a central axis in the proliferation of different tumors including melanoma, non-small cell lung, head/neck and pancreatic cancers. And MEK inhibition, either alone or in combination with other agents, is an important therapeutic strategy in treating cancer. ARRY-162 is a novel, orally active, potent, selective, non-ATP-competitive inhibitor of MEK 1 / 2 that has the potential to treat a range of malignant diseases. (source:http://www.arraybiopharma.com/ProductPipeline/Cancer/MEK.asp).
1. Combinations comprising methotrexate and DHODH inhibitors By Godessart Marina, Nuria; Pizcueta Lalanza, Maria Pilar From PCT Int. Appl. (2010), WO 2010083975 A1 20100729.
2. Combinations comprising methotrexate and DHODH inhibitors By Godessart Marina, Nuria; Pizcueta Lalanza, Maria Pilar From Eur. Pat. Appl. (2010), EP 2210615 A1 20100728.
3. Combination of (a) a phosphoinositide 3-kinase inhibitor and (b) a modulator of Ras/Raf/Mek pathway By Garcia-Echeverria, Carlos; Maira, Sauveur-Michel; Stuart, Darrin; Wee, Susan; Fritsch, Christine; Nagel, Tobi From PCT Int. Appl. (2010), WO 2010006225 A1 20100114.
4. Combination comprising DHODH inhibitors and methotrexate for treatment of autoimmune, inflammatory and proliferative disorders By Godessart Marina, Nuria; Pizcueta Lalanza, Maria Pilar From PCT Int. Appl. (2009), WO 2009153043 A1 20091223.
5. Combination comprising DHODH inhibitors and methotrexate for treatment of autoimmune, inflammatory and proliferative disorders By Godessart Marina, Nuria; Pizcueta Lalanza, Maria Pilar From Eur. Pat. Appl. (2009), EP 2135610 A1 20091223
The quinine-containing bark of the Cinchona tree is probably the most valuable drug the Americas gave the world
The quinine-containing bark of the Cinchona tree is probably the most valuable drug the Americas gave the world
Read more at chemistryviews
http://www.chemistryviews.org/details/ezine/4701281/From_Pharmacy_to_the_Pub_
_A_Bark_Conquers_the_World_Part_1.html
Cinchona or Quina is a genus of about 38 species in the family Rubiaceae, native to the tropical Andes forests of western South America. They are medicinal plants, known as sources for quinine and other compounds.
The name of the genus is due to Carolus “Carl” Linnaeus, who named the tree in 1742 after a Countess of Chinchón, the wife of a viceroy of Peru, who, in 1638, was introduced by native Quechua healers to the medicinal properties of cinchona bark. Stories of the medicinal properties of this bark, however, are perhaps noted in journals as far back as the 1560s–1570s.
It is the national tree of Ecuador and Peru.
Peru offers a branch of cinchona toScience (from a 17th-century engraving):Cinchona, the source of Peruvian bark, is an early remedy against malaria.
The medicinal properties of the cinchona tree were originally discovered by the Quechua peoples of Peru and Bolivia, and long cultivated by them as a muscle relaxant to halt shivering due to low temperatures. The Jesuit Brother Agostino Salumbrino (1561–1642), an apothecary by training and who lived in Lima, observed the Quechua using the quinine-containing bark of the cinchona tree for that purpose. While its effect in treating malaria (and hence malaria-induced shivering) was entirely unrelated to its effect in controlling shivering from cold, it was nevertheless the correct medicine for malaria. The use of the “fever tree” bark was introduced into European medicine by Jesuit missionaries (Jesuit’s bark). Jesuit Barnabé de Cobo (1582–1657), who explored Mexico and Peru, is credited with taking cinchona bark to Europe. He brought the bark from Lima to Spain, and afterwards to Rome and other parts of Italy, in 1632. AfterSpanish colonization of the Americas, the Jesuit missionaries were the first to bring the Jesuit’s bark cinchona compound to Europe in 1632. To maintain their monopoly on cinchona bark, Peru and surrounding countries began outlawing the export of cinchona seeds and saplings beginning in the early 19th century.
Meanwhile, also in the 19th century, the plant’s seeds and cuttings were smuggled out for new cultivation at cinchona plantations in colonial regions of tropical Asia, notably by the British to the British Raj and Ceylon (present day India and Sri Lanka), and by theDutch to Java in the Dutch East Indies (present day Indonesia).
As a medicinal herb, cinchona bark is also known as Jesuit’s bark or Peruvian bark. The bark is stripped from the tree, dried, and powdered for medicinal uses. The bark is medicinally active, containing a variety of alkaloids including the antimalarial compoundquinine and the antiarrhythmic quinidine. Currently, their use is largely superseded by more effective modern medicines.
quinine
cinchonine
CHINESE HERBS Ginkgo biloba for antidepressant induced sexual dysfunction.
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 the Ginkgoales 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.
|
|
Quercetin
CAS Registry Number: 117-39-5 Molecular Formula: C15 H10 O7 Mol. wt.: 338.3 Chemical Abstracts Service Name: 4H-1-Benzopyran-4-one, 2-(3,4-dihydroxyphenyl)- 3,5,7-trihydroxy- (9CI) |
|||
|
|
Kaempferol
CAS Registry Number: 520-18-3 Molecular Formula: C15 H10 O6 Mol. wt.: 286.2 Chemical Abstracts Service Name: 4H-1-Benzopyran-4-one, 3,5,7-trihydroxy-2-(4- hydroxyphenyl)- (9CI) |
|||
|
|
Isorhamnetin
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 |
|||
|
|
Ginkgolides |
|||
| GB | R1 | R2 | R3 | |
| Ginkgolide A | OH | H | H | |
| Ginkgolide B | OH | OH | H | |
| Ginkgolide C | OH | OH | OH | |
| GB | ||||
|
|
Bilobalide
CAS Registry Number: 33570-04-6 |
|||
.
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.
CHINESE HERBS Panax ginseng
Panax ginseng
The extract of the Chinese root Panax ginseng and the North American Panax quinquefolius contains as its putative active constituents a large group of ginsenosides, four-ring glycosides. Anecdotal reports in the scientific literature suggest that Ginseng can improve sexual dysfunction such as anorgasmia and decreased libido in patients taking antidepressants. Ginsenosides facilitate the release of nitric oxide in endothelial tissue of rabbit corpus cavernosum, a step in the events leading to erection. This property may have promise for women, as the biochemical process of erection is the same in the clitoris. Multiple orgasmic response has also been described with this Chinese herbal.
Ginseng is one the best known and widely prescribed herbs in Chinese medicine as a general adaptogenic and restorative tonic. Adaptogenic herbs such as ginseng are especially useful in debilitated persons suffering from exhaustion, fatigue, liver disease, stress and wasting from chronic disease. Unfortunately, the fame of ginseng has led to misconceptions about its use and to low grade or adulterated products being sold as ginseng in the West.
Panax, the generic name is derived from the Greek Panakos (a panacea), in reference to the miraculous virtue ascribed to it by the Chinese, who consider it a sovereign remedy in almost all diseases. The word Ginseng is said to mean wonder of the world,however, it is not universally applicable in every illness. It should not be taken during acute inflammatory disease or bronchitis since it can drive the disease deeper and make it worse. Moreover, in China, ginseng is rarely used on its own, but is usually combined with other herbs, such as licorice or Chinese dates, which temper its powerful nature.
- Medicinal Uses: * Alcoholism * Fatigue * Immune * Libido * Longevity Tonics * Memory/Focus * Stress
- Properties: * Adaptogens * Anodyne * Circulation * Immunostimulant * Stimulant * Tonic
- Parts Used: root
- Constituents: hormone-like saponins,(ginsenosides), volatile oil, sterols, starch, sugars, pectin, vitamins bl, b2 and b12, choline, fats, minerals
Ginseng is known to possess phytoestrogen activity. The herb is believed to function as an adaptogen—helping the body adapt to stressful conditions, possibly by augmenting production of the body’s own stress hormones (ACTH, Cortisol).
Adverse effects may include hypertension, insomnia, vomiting, headache and epistaxis. Isolated case reports have noted post-menopausal vaginal bleeding and breast nodularity with prolonged usage, suggesting a modest estrogen-like effect. A two-year study of 133 people using ginseng noted a central nervous system stimulant effect.(17) Nervousness and insomnia were noted in 11% of subjects; therefore, ginseng would not be recommended for use in patients with bipolar disorder (manic syndrome) or psychosis. However, this study used doses (15 g/day) on the high end of those recommended, used no placebo, and did not describe the quality or form of the extract used.
The dosage is dependent on the ginsenoside content. With a saponin content of at least 5 mg of ginsenosides with a ratio of Rb1 to Rg1 of 2:1, a typical dose would be to take this 1 to 3 times a day. It is best to begin with a lower dose and to gradually increase this if needed.
Panax ginseng appears to be effective in the treatment of erectile dysfunction, suggests a 2002 study from the Journal of Urology. In tests on 45 men with erectile dysfunction, those who took Panax ginseng for eight weeks showed greater improvements than those given a placebo for the same time period.
In an earlier study of 90 men with erectile dysfunction, 60 percent of the participants reported improvement in their symptoms compared with 30 percent of those using the placebo. The study was published in the International Journal of Impotence Research.
Unlike prescription drugs for erectile dysfunction (which are usually taken when needed), ginseng only appears to be useful for erectile dysfunction if taken on a continuous basis.
DR ANTHONY MELVIN CRASTO
ORGANIC SPECTROSCOPY
New Drug Approvals 