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DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Garcinia Cambogia Kills 89% of Pancreatic Cancer Cells and Synergizes with Curcumin
Garcinia Cambogia Extract Explained
The latest in innovation in weight loss supplements is Garcinia Cambogia. It is unparalleled in its ability to help boost your body’s weight loss potential, and help you achieve your perfect weight.
There’s no wonder it’s quickly gained a huge following, with endorsements from celebrities to health experts, with scientifically proven ability to help you increase your fat burning power.
As with all supplements like this, there are questions as to how it works, and just how it can benefit you, with your health and in losing weight. This site’s goal is to hopefully answer some of these questions, and to show you just how you can benefit from this amazing supplement.
What is Garcinia Cambogia?
Garcinia Cambogia is a fruit, that is grown all over Asia, but originating in Indonesia and grows particularly well grows best with tropical conditions. It rose to prominence after appearance on the massively lauded American health show, Doctor Oz. It had recently been subject to a medical trial where the study scientifically proved it was highly effective in increasing burning up fat and aiding in overall weight loss.
Can Garcinia Cambogia Extract Help Me Lose Weight?
Well Garcinia Cambogia contains a useful compound called Hydroxycitric Acid, which I’ll refer to as HCA for ease of reference. Garcinia Cambogia contains one of the highest known concentrations of HCA, and this was why it was noticed as a potential weight loss supplement. HCA has two main mechanisms in which it works to boost your fat burning potential:
Firstly it will reduce the ability for the body to convert carbohydrates into fat cells, meaning that even without a calorific controlled diet; you will be able to aid your body’s ability to burn of existing fat, while not gaining additional fat.
Secondly it will also suppress your appetite, meaning that it will not only help reduce the weight you can put on by stopping putting on additional fat, it will also massively reduce the cravings and hunger that usually lead to breaking a diet and weight loss routine. This means that your body will just be burning off the existing fat, helping you to achieve that perfect weight!
What About Side Effects form Garcinia Cambogia?
The most amazing thing about Garcinia Cambogia is that the side effects of the product are almost non-existent in the all-natural extract. By this I mean an extract that contains purely Garcinia Cambogia extract without any additional additives that some unrepeatable sellers will try to pass off as the quality product. Those extracts that contain additives can cause side effect in users of Garcinia Cambogia, which are related to the different additives and binding agents added.
The cost of Garcinia Cambogia from a supplier, whom ensures a high quality and natural product, will range from $40-50 a bottle. There is however introductory offers from some suppliers, such as Miracle Garcinia Cambogia currently offering a free bottle of Garcinia Cambogia with every order.
This means the overall cost per bottle of this amazing product can drop as low as $28.99. Most of these offers unfortunately do have a limited stock and therefore won’t be around forever.
Garcinia gummi-gutta is a tropical[2] species of Garcinia native to Indonesia. Common names include garcinia cambogia (a former scientific name), as well as gambooge, brindleberry,[3] brindall berry, Malabar tamarind,[2] assam fruit, vadakkan puli (northern tamarind) and kudam puli (pot tamarind).[4] This fruit looks like a small pumpkin and is green to pale yellow in color. It has recently received considerable media attention because of its purported effects on weight loss, although there is no clinical evidence to support this claim.
Cultivation
Ripe fruit
Garcinia gummi-gutta is grown for its fruit in southeast Asia, coastal Karnataka/Kerala, India, and west and central Africa. It thrives in most moist forests.
Garcinia gummi-gutta is one of several closely related Garcinia species from the plant family Guttiferae.[5] With thin skin and deep vertical lobes, the fruit of G. gummi-gutta and related species range from about the size of an orange to that of a grapefruit; G. gummi-gutta looks more like a small yellowish, greenish or sometimes reddish pumpkin.[6] The color can vary considerably. When the rinds are dried and cured in preparation for storage and extraction, they are dark brown or black in color.
Along the west coast of South India, G. gummi-gutta is popularly termed “Malabar tamarind,” and shares culinary uses with the tamarind (Tamarindus indica). The latter is a small and the former a quite large evergreen tree. G. gummi-gutta is also called “goraka” or, in some areas, simply “kattcha puli” (souring fruit).
Uses
Cooking
Garcinia gummi-gutta is used in cooking, including in the preparation of curries. The fruit rind and extracts of Garcinia species are called for in many traditional recipes,[7] and various species of Garcinia are used similarly in food preparation in Assam (India), Thailand, Malaysia, Burma and other Southeast Asian countries. In the Indian Ayurvedic medicine, “sour” flavors are said to activate digestion. The extract and rind of Garcinia gummi-gutta is a curry condiment in India. It is an essential souring ingredient in the Southern Thai variant of kaeng som, a sour curry.
Garcinia gummi-gutta is employed commercially in fish curing, especially in Sri Lanka (Colombo curing) and South India, which makes use of the antibacterial qualities of the fruit.
The trees can be found in forested areas and also are protected in plantations otherwise given over to pepper, spice, and coffee production.
Traditional medicine
Aside from its use in food preparation and preservation, extracts of G. gummi-gutta are sometimes used in traditional medicine aspurgatives. The fruit rind is also used to make medicine.
Weight loss
In late 2012, a United States television personality, Dr. Oz, promoted Garcinia cambogia extract as a “magic” weight-loss aid. Dr. Oz’s previous endorsements have often led to a substantial increase in consumer interest in the promoted products. However, a dearth of scientific evidence and clinical trials do not support claims that Garcinia cambogia is an effective weight-loss aid.[8][9] A meta-analysis found a possible small, short-term weight loss effect (under 1 kilogram).[10] However, side effects—namely hepatotoxicity (chemical-driven liver damage)—led to one preparation being withdrawn from the market.[11][12]
A 1998 randomized controlled trial looked at the effects of hydroxycitric acid, the purported active component in Garcinia gummi-gutta, as a potential antiobesity agent in 135 people. The conclusion from this trial was that “Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo”.[13]
When the fruit is sun dried for several days, it becomes black with a shrivelled body
References
- “Garcinia gummi-gutta (L.) Roxb.”. The Plant List. Royal Botanic Gardens, Kew and Missouri Botanical Garden. Retrieved 1 June 2013.
- “USDA GRIN Taxonomy”.
- “Potential treatments for insulin resistance in the horse: A comparative multi-species review”. Science Direct. Retrieved 6 October 2013.
- “Meals that heal – Soul curry”. The Hindu. Retrieved 3 October 2013.
- Publications & Information Directorate, Council of Scientific & Industrial Research (1986). G. cambogia Desr. The Useful Plants of India. (New Delhi: Publications & Information Directorate, 1986) 229.
- “Fruit yellowish or reddish, size of an orange having six or eight deep longitudinal grooves in its fleshy pericarp. Pulp acid of a pleasant flavor. It is dried among the Singalese who use it in curries.” Uphof, J.C. Th. (1968).
- “The acid rinds of the ripe fruit are eaten, and in Ceylon are dried, and eaten as a condiment in curries.” Drury, Heber (1873). “Garcinia gambogia(Desrous) N. 0. Clusiaceae”. The Useful Plants of India, second edition. London: William H. Allen & Co. p. 220.
- Belluz, Julia; Hoffman, Steven J. (1 January 2013). “Dr. Oz’s Miraculous Medical Advice; Pay no attention to that man behind the curtain”. Slate. The Slate Group. Retrieved 31 May 2013.
- Márquez F1, Babio N, Bulló M, Salas-Salvadó J (2012). “Evaluation of the safety and efficacy of hydroxycitric acid or Garcinia cambogia extracts in humans”. Crit Rev Food Sci Nutr 52 (7): 585–94. doi:10.1080/10408398.2010.500551. PMID 22530711.
- Hepatotoxicity (from hepatic toxicity) implies driven liver damage.
- Lobb, A. (2009). “Hepatoxicity associated with weight-loss supplements: A case for better post-marketing surveillance”. World Journal of Gastroenterology 15 (14): 1786–1787. doi:10.3748/wjg.15.1786. PMC 2668789. PMID 19360927.
- Kim YJ1, Choi MS, Park YB, Kim SR, Lee MK, Jung UJ (2013). “Garcinia Cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation”. World J Gastroenterol 19 (29): 4689–701. doi:10.3748/wjg.v19.i29.4689. PMID 23922466.
- Heymsfield, S. B.; Allison, D. B.; Vasselli, J. R.; Pietrobelli, A.; Greenfield, D.; Nunez, C. (1998). “Garcinia cambogia (Hydroxycitric Acid) as a Potential Antiobesity Agent: A Randomized Controlled Trial”. JAMA: the Journal of the American Medical Association 280 (18): 1596–1600.doi:10.1001/jama.280.18.1596. PMID 9820262.
When Antibiotics Fail, Are Herbs the Answer?
Complex Compounds in Natural Herbs:
Now looking at the rate of adaptation and mutability of bacteria, it is inevitable that they will form resistance to most forms of simplistic human made antibiotic compounds. And when everything fails we will fall back to the old biblical medicinal herbs such as Ginger, Garlic, Black Pepper, Ashwagandha, etc. These herbs not only contain dozens of mild antibiotic compounds, they are also widely available in abundance.
Brisbane scientists make cancer treatment breakthrough
BERAPROST….Stable prostacyclin analog.
BERAPROST
https://www.ama-assn.org/resources/doc/usan/beraprost.pdf
2,3,3a,8b-tetrahydro-2-hydroxy-1-(3-hydroxy-4-methyl-1-octen-6-ynyl)-1H-cyclopenta(b)benzofuran-5-butanoic acid
(±)-(IR*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octene-6-inyl]-1H-cyclopenta[b]benzofuran-5-butyric acid
rac-4-{(1R,2R,3aS,8bS)-2-hydroxy-1-[(1E,3S,4RS)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2,3,3a,8b-tetrahydro-1H-cyclopenta[b][1]benzofuran-5-yl}butanoic acid
- Beraprost
- Beraprostum
- Beraprostum [INN-Latin]
- MDL 201229
- MDL-201229
- ML 1229
- ML-1229
- UNII-35E3NJJ4O6
Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. It is also being studied for use in avoiding reperfusion injury.
As an analogue of prostacyclin PGI2, beraprost effects vasodilation, which in turn lowers the blood pressure. Beraprost also inhibits plateletaggregation, though the role this phenomenon may play in relation to pulmonary hypertension has yet to be determined.
Beraprost …sodium salt
ML 1129; Procyclin; TRK 100 (CAS 88475-69-8)
| Synonyms |
|
|---|---|
| Formal Name | 2,3,3a,8b-tetrahydro-2-hydroxy-1-(3-hydroxy-4-methyl-1-octen-6-ynyl)-1H-cyclopenta[b]benzofuran-5-butanoic acid, monosodium salt |
| CAS Number | 88475-69-8 |
| Molecular Formula | C24H29O5 · Na |
| Formula Weight | 420.5 |
- Beraprost sodium is a prostacyclin analog and an NOS3 expression enhancer that was first launched in 1992 in Japan pursuant to a collaboration between Astellas Pharma and Toray for the oral treatment of peripheral vascular disease (PVD), including Raynaud’s syndrome and Buerger’s disease. In 2000, the drug was commercialized for the treatment of pulmonary hypertension. Development for the oral treatment of intermittent claudication associated with arteriosclerosis obliterans (ASO) was discontinued at Kaken and United Therapeutics after the product failed to demonstrate statistically significant results in a phase III efficacy trial.
- In terms of clinical development, beraprost sodium is currently in phase II clinical trials at Kaken for the treatment of lumbar spinal canal stenosis and at Astellas Pharma for the oral treatment of primary chronic renal failure. The company is also conducting phase III trials for the treatment of nephrosclerosis. The drug has also been studied through phase II clinical trials at Kaken for the oral treatment of diabetic neuropathy, but recent progress reports for this indication have not been made available.
- Beraprost is an oral form of prostacyclin, a member of the family of lipid molecules known as eicosanoids. Prostacyclin is produced in the endothelial cells from prostaglandin H2 by the action of the enzyme prostacyclin synthase. It has been shown to keep blood vessels dilated and free of platelet aggregation.
- Beraprost sodium was originally developed at Toray in Japan, and rights to the drug were subsequently acquired by Astellas Pharma. A 1972 alliance between Toray and Kaken Pharmaceutical to develop and commercialize prostaglandin led to a later collaboration agreement for the development of beraprost. In 1990, Toray granted the right to market the drug to Sanofi (formerly known as sanofi-aventis), a licensing agreement that was later expanded to include Canada, the U.S., South America, Africa, Southeast Asia, South Asia, Korea and China. In September 1996, Bristol-Myers Squibb entered into separate agreements with Sanofi and Toray to acquire all development and marketing rights to beraprost in the U.S. and Canada. In January 1999, United Therapeutics and Toray agreed to cooperatively test the drug in North America, and in July 2000, a new agreement was signed pursuant to which United Therapeutics gained exclusive North American rights to develop and commercialize sustained-release formulations of beraprost for all vascular and cardiovascular diseases. In 1999, orphan drug designation was received in the U.S. for the treatment of pulmonary arterial hypertension associated with any New York Heart Association classification (Class I, II, III, or IV). In 2011, orphan drug designation was assigned in the U.S. for the treatment of pulmonary arterial hypertension.
-
The compound name of beraprost which is used as an antimetastasis agent of malignant tumors according to the present invention is (±)-(IR*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octene-6-inyl]-1H-cyclopenta[b]benzofuran-5-butyric acid. This compound has the following structure.
Beraprost is described in Japanese Laid-open Patent Application (Kokai) Nos. 58-32277, 57-144276 and 58-124778 and the like as a PGI₂ derivative having a structure in which the exoenol moiety characteristic to beraprost is converted to inter-m-phenylene structure. However, it is not known that beraprost has an activity to inhibit metastasis of malignant tumors.
-
The beraprost which is an effective ingredient of the agent of the present invention includes not only racemic body, but also d-body and l-body. Beraprost can be produced by, for example, the method described in the above-mentioned Japanese Laid-open Patent Application (Kokai) No. 58-124778. The salts of beraprost include any pharmaceutically acceptable salts including alkaline metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt and calcium salt; ammonium salt; primary, secondary and tertiary amine salts; and basic amino acid salts.
…………………..
EXAMPLE 6 Beraprost of the Formula (I)
0.246 g (0.6 mmol) of compound of the general formula (II) obtained in Example 5 is dissolved in 1 ml of methanol and 1 ml of 1 M aqueous sodium hydroxide solution is added dropwise slowly thereto. After stirring for an hour the methanol is distilled off from the reaction mixture in vacuum. The aqueous residue is diluted with 10 ml of water extracted with methyl-tert.butyl-ether and the combined organic phase is washed with saturated NaCl solution, dried on Na2SO4 and evaporated. The residue of evaporation is crystallized from ethylacetate-hexane mixture and the pure above mentioned title compound is obtained as colourless crystals.
Yield: 0.21 g (87%)
TLC-Rf (toluene-dioxan-acetic acid 20:10:1)=0.41
Melting point: 98–112° C.
1H NMR (400 MHz, CDCl3), δH (ppm): 1.00d, 1.03d [3H; J=6.8 Hz; 21-H3]; 1.79m [1H; 16-H]; 1.80t, 1.81t [3H, J=2.5,2.4 Hz; 20-H3]; 2.3–1.9m [5H, 3-H2, 10Hb, 17-H2]; 2.34t [1H; J=7.4 Hz; 2-H2]; 2.43m [1H; 12-H]; 2.64m [3H; 10-Ha, 4-H2]; 3.43t, 3.44t [1H, J=8.7,8.5 Hz; 8-H]; 3.92m [1H; 11-H]; 4.07t, 4.17t [1H, J=7.3,5.6 Hz; 15-H]; 4.3b [2H; OH]; 5.09m [1H, 9-H]; 5.58dd, 5.61dd [1H; J=15.3,6.5 Hz; 14-H]; 5.67dd, 5.68dd [1H; J=15.3,8.0 Hz; 13-H]; 6.77m [1H; 2′-H]; 6.95m [2H; 1′-H,3′-H]13C NMR (100 MHz, CDCl3), δC (ppm): 3.5, 3.6 [C-20]; 14.7, 15.8 [C-21]; 22.3, 22.6 [C-17]; 24.6 [C-2]; 29.1 [C-4]; 33.1 [C-3]; 38.2, 38.3 [C-16]; 41.2 [C-10]; 50.4 [C-8]; 58.8 [C-12]; 75.8, 76.3, 76.4 [C-11, C-15]; 77.2, 77.4 [C-18, C-19]; 84.5, 84.6 [C-9]; 120.6 [C-2′]; 121.9 [C-3′]; 123.2 [C-5]; 129.0 [C-1′]; 129.7 [C-7]; 132.3, 133.0, 133.8, 134.0 [C-13, C-14]; 157.2 [C-6]; 178.3 [C-1].
EXAMPLE 7 Beraprost Sodium Salt (The Sodium Salt of the Compound of Formula (I)
0.199 g of beraprost is dissolved in 2 ml of methanol, 0.5 ml of 1 M aqueous solution of sodium hydroxide is added thereto and after their mixing the solvent is evaporated in vacuum and thus the above title salt is obtained as colourless crystals.
Yield: 0.21 g (100%)
Melting point: >205° C.
1H NMR (400 MHz, DMSO-d6), δH (ppm): 0.90d, 0.92d [3H; J=6.7 Hz; 21-H3]; 1.75–1.55m [7H; 10Hb, 16-H, 3-H2, 20-H3]; 1.89t [2H, J=7.6 Hz; 2-H2]; 1.94m [1H; 17-Hb]; 2.16q [1H, J=8.5 Hz; 12-H]; 2.25m [1H; 17-Ha]; 2.44t [2H; J=7.5 Hz; 4-H2]; 2.50o [1H; 10-Ha]; 3.39t [1H, J=8.5 Hz; 8-H]; 3.72td [1H; J=8.5,6.1 Hz; 11-H]; 3.84t 3.96t [1H, J=6.5,6.0 Hz; 15-H]; 4.85b [2H, OH]; 5.01dt [1H, J=8.5,6.6 Hz; 9-H]; 5.46dd, 5.47dd [1H; J=15.4,6.5 Hz, J=15.4,6.0 Hz; 14-H]; 5.65dd, 5.66dd [1H; J=15.4,8.5 Hz; 13-H]; 6.71m [1H; 2′-H]; 6.92m [2H; 1′-H, 3′-H] During the above thin layer chromatography (TLC) procedures we used plates MERCK Kieselgel 60 F254, thickness of layer is 0.2 mm, length of plates is 5 cm.
…………….
-
Reaction Scheme A.
-
The starting material of bromocarboxylic acid, Compound 1, and the process for the preparation thereof are disclosed in Japanese Patent Application No. 29637/81.
-
Scheme B.
REACTION SCHEME B
-
- REACTION SCHEME C
-
Org Lett 2012, 14(1): 299
EP0024943A1 Sep 2, 1980 Mar 11, 1981 Toray Industries, Inc. 5,6,7-Trinor-4,8-inter-m-phenylene PGI2 derivatives and pharmaceutical compositions containing them EP0084856A1 Jan 19, 1983 Aug 3, 1983 Toray Industries, Inc. 5,6,7-Trinor-4, 8-inter-m-phenylene prostaglandin I2 derivatives JP3069909B Title not available
-
Sulfoaildenafil …. An analog of Sildenafil which has been used as an illegal adulterant in some dietary supplements
Sulfoaildenafil
An analog of Sildenafil which has been used as an illegal adulterant in some dietary supplements.
856190-47-1 cas no
5-(5-(((3R,5S)-3,5-Dimethylpiperazin-1-yl)sulfonyl)-2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-7(4H)-thione
-
7H-Pyrazolo(4,3-d)pyrimidine-7-thione, 5-(5-(((3R,5S)-3,5-dimethyl-1-piperazinyl)sulfonyl)-2-ethoxyphenyl)-1,6-dihydro-1-methyl-3-propyl-, rel-
- Sildenafil thione
- Thioaildenafil
- UNII-33DX49E09G
-
-
C23-H32-N6-O3-S2
- 504.6768
-
Sulfoaildenafil (thioaildenafil) is a synthetic chemical compound that is a structural analog of sildenafil (Viagra).[1] It was first reported in 2005,[2] and it is not approved by any health regulation agency. Like sildenafil, sulfoaildenafil is a phosphodiesterase type 5 inhibitor.
Sulfoaildenafil has been found as an adulterant in a variety of supplements which are sold as “natural” or “herbal” sexual enhancement products.[3][4][5][6] A range of designer analogues of USA FDA-approved inhibitors of type-5 cGMP-specific phosphodiesterase (PDE5), such as sildenafil and vardenafil, have been detected in recent years as adulturants in over-the-counter herbal aphrodisiac products and dietary supplements,[7][8][9] in an apparent attempt to circumvent both the legal restrictions on sale of erectile dysfunction drugs, which are prescription-onlymedicines in most Western countries, and the patent protection which prevents sale of these drugs by competitors except under license to their inventors.
Figure 1. Biological pathway of penile erection
These compounds have been demonstrated to display PDE5 inhibitory activity in vitro and presumably have similar effects when consumed, but have undergone no formal testing in either humans or animals, and as such represent a significant health risk to consumers of these products due to their unknown safety profile.[10] Some attempts have been made to ban these drugs as unlicensed medicines, but progress has been slow so far, as even in those jurisdictions which have laws targeting designer drugs, the laws are drafted to ban analogues of illegal drugs of abuse, rather than analogues of prescription medicines. However at least one court case has resulted in a product being taken off the market.[11]
Figure 2. PDE5 domains
In December 2010, the United States Food and Drug Administration (FDA) issued a warning to consumers about such products stating, “The FDA has found many products marketed as dietary supplements for sexual enhancement during the past several years that can be harmful because they contain active ingredients in FDA-approved drugs or variations of these ingredients.”[12]
Figure 3. PDE5 Domains
Volume 50, Issue 2, 8 September 2009, Pages 228–231
Phosphodiesterase type 5 (PDE-5) inhibitors represent a class of drugs used primarily in the treatment of erectile dysfunction. Currently, three PDE-5 inhibitors have been approved by the U.S. Food and Drug Administration (FDA) for use in the United States: sildenafil citrate, tadalafil, and vardenafil hydrochloride trihydrate. A bulk material, labeled as an ingredient for a dietary supplement, was analyzed for the presence of PDE-5 inhibitors. The compound that was detected displayed structural similarities to sildenafil, and was characterized further using LC–MSn, FTICRMS, X-ray crystallography and NMR. The compound was given the name sulfoaildenafil. When compared to sildenafil, sulfoaildenafil contains a sulfur atom substitution for the oxygen atom in the pyrazolopyrimidine portion of the molecule, and a 3,5-dimethyl substitution on the piperazine ring, rather than the 4-methyl moiety. The X-ray crystallographic data indicate that the material in this sample is comprised of two polymorphs, which may affect the chemical and/or biological properties of any product formulated with this compound.
……………..
http://www.theresonance.com/2012/categories/pharmaceutical/adulterated-natural-products
……………….
Herbal Supplement for Erectile Dysfunction Found to Contain Thio Structural Analog of Sildenafil (Viagra)
A herbal supplement marketed to alleviate erectile dysfunction was recently submitted for testing in our laboratory because it was surprisingly effective considering it should only contain the traditional herbals utilized for this problem such as Oyster, 2-Deoxy-D Glucose, Barberry, Snow Lotus, Bombyx Mori L., Ginger Root, Salfron Crocus.
http://process-nmr.com/WordPress/?cat=5
References
- Gratz, SR; Zeller, M; Mincey, DW; Flurer, CL (2009). “Structural characterization of sulfoaildenafil, an analog of sildenafil”. Journal of pharmaceutical and biomedical analysis 50 (2): 228–31. doi:10.1016/j.jpba.2009.04.003. PMID 19427155.
- Li, Shuxin; Ren, Jianping; Zhao, Yanjin; Lv, Qiujun; Guo, Jinhua. Pyrazolopyrimidinethione Derivatives, Salts and Solvates thereof, Preparation Methods and Use thereof. WO 2005058899
- Gryniewicz, CM; Reepmeyer, JC; Kauffman, JF; Buhse, LF (2009). “Detection of undeclared erectile dysfunction drugs and analogues in dietary supplements by ion mobility spectrometry”. Journal of pharmaceutical and biomedical analysis 49 (3): 601–6. doi:10.1016/j.jpba.2008.12.002. PMID 19150190.
- FDA warns consumers to avoid sexual enhancement pills, Sanjay Gupta, CNN, December 13th, 2010
- Reepmeyer JC, d’Avignon DA (January 2009). “Structure elucidation of thioketone analogues of sildenafil detected as adulterants in herbal aphrodisiacs”. Journal of Pharmaceutical and Biomedical Analysis 49 (1): 145–50. doi:10.1016/j.jpba.2008.10.007. PMID 19042103.
- Balayssac S, Trefi S, Gilard V, Malet-Martino M, Martino R, Delsuc MA (November 2008). “2D and 3D DOSY (1)H NMR, a useful tool for analysis of complex mixtures: Application to herbal drugs or dietary supplements for erectile dysfunction”. Journal of Pharmaceutical and Biomedical Analysis 50 (4): 602–12. doi:10.1016/j.jpba.2008.10.034. PMID 19108978.
- Zou P, Oh SS, Hou P, Low MY, Koh HL (February 2006). “Simultaneous determination of synthetic phosphodiesterase-5 inhibitors found in a dietary supplement and pre-mixed bulk powders for dietary supplements using high-performance liquid chromatography with diode array detection and liquid chromatography-electrospray ionization tandem mass spectrometry”. J Chromatogr A 1104 (1-2): 113–22. doi:10.1016/j.chroma.2005.11.103. PMID 16364350.
- Gratz SR, Gamble BM, Flurer RA (2006). “Accurate mass measurement using Fourier transform ion cyclotron resonance mass spectrometry for structure elucidation of designer drug analogs of tadalafil, vardenafil and sildenafil in herbal and pharmaceutical matrices”. Rapid Commun. Mass Spectrom. 20 (15): 2317–27. doi:10.1002/rcm.2594. PMID 16817245.
- Hou P, Zou P, Low MY, Chan E, Koh HL (September 2006). “Structural identification of a new acetildenafil analogue from pre-mixed bulk powder intended as a dietary supplement”. Food Addit Contam 23 (9): 870–5. doi:10.1080/02652030600803856. PMID 16901855.
- Oh, SS; Zou, P; Low, MY; Koh, HL (2006). “Detection of sildenafil analogues in herbal products for erectile dysfunction.”. Journal of toxicology and environmental health. Part A 69 (21): 1951–8.doi:10.1080/15287390600751355. PMID 16982533.
- Venhuis, BJ; Blok-Tip, L; De Kaste, D (2008). “Designer drugs in herbal aphrodisiacs.”. Forensic Science International 177 (2–3): e25–7. doi:10.1016/j.forsciint.2007.11.007. PMID 18178354.
- FDA warns consumers to avoid Man Up Now capsules, United States Food and Drug Administration, Dec. 15, 2010
Vinorelbine …For the treatment of non-small-cell lung carcinoma.
4-(acetyloxy)- 6,7-didehydro- 15-((2R,6R,8S)-4-ethyl- 1,3,6,7,8,9-hexahydro- 8-(methoxycarbonyl)- 2,6-methano- 2H-azecino(4,3-b)indol-8-yl)- 3-hydroxy- 16-methoxy- 1-methyl- methyl ester,
3′,4′-Didehydro-4′-deoxy-8′-norvincaleukoblastine
71486-22-1 cas
(2R,3R)-2,3-Dihydroxysuccinic acid – methyl (2ξ,3β,4β,5α,12β,19α)-4-acetoxy-15-[(12S,14R)-16-ethyl-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.03,11.04,9]octadeca-3(11),4,6, 8,15-pentaen-12-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate (2:1)
Vinorelbine (trade name Navelbine) is an anti-mitotic chemotherapy drug that is given as a treatment for some types of cancer, including breast cancer and non-small cell lung cancer.
Vinorelbine i.v. is a semi-synthetic derivative of a vinca alkaloid launched in 1989 by Pierre Fabre for the treatment of non-metastatic breast cancer and non-small cell lung cancer (NSCLC). In 2011, a complete response letter was assigned by the FDA for an NDA filed by Adventrx Pharmaceuticals seeking approval for the treatment of non-small cell lung cancer (NSCLC). Pierre Fabre and licensee GlaxoSmithKline had been evaluating the potential of the drug for the treatment of breast cancer, prostate cancer and NSCLC with an oral formulation, but no recent developments have been reported. The evaluation of an injectable emulsion formulation developed by Adventrx Pharmaceuticals is in phase I clinical development for the potential treatment of these indications. Several trials are ongoing to evaluate vinorelbine in combination with other chemotherapy for the treatment of metastatic breast cancer. The University of California, Davis is evaluating vinorelbine in combination with lapatinib for the treatment of solid tumors.
Clinicians sometimes use the abbreviation “NVB” for vinorelbine, although (like many medical abbreviations) it is not a unique identifier.
The antitumor activity is due to inhibition of mitosis through interaction with tubulin.[2] Vinorelbine is the first 5´NOR semi-synthetic vinca alkaloid. It is obtained by semi-synthesis from alkaloids extracted from the rosy periwinkle, Catharanthus roseus. It is marketed in India by Abbott Healthcare under the brand name Navelbine.
History
Vinorelbine was invented by the pharmacist Pierre Potier and his team from the CNRS in France in the 1980s and was licensed to the oncology department of the Pierre Fabre Group. The drug was approved in France in 1989 under the brand name Navelbine for the treatment of non-small celllung cancer. It gained approval to treat metastatic breast cancer in 1991. Vinorelbine received approval by the United States Food and Drug Administration (FDA) in December 1994 sponsored by Burroughs Wellcome Company. Pierre Fabre Group now markets Navelbine in the U.S., where the drug went generic in February 2003.
Vinorelbine interferes with microtubule assembly, particularly that of mitotic microtubules. Like other vinca alkaloids, vinorelbine may also interfere with the metabolism of amino acid, cyclic AMP, and glutathione, the activity of calmodulin-dependent Ca+2 transport ATPase, cellular respiration, and the biosynthesis of lipids and nucleic acid.
Originally developed at Pierre Fabre, vinorelbine i.v. was first licensed to GlaxoSmithKline in the U.S., Canada and Europe and to Kyowa Hakko in Japan. In July 2005, Pierre Fabre licensed the U.S. and Canadian rights to an oral formulation of vinorelbine to Novacea (acquired by Transcept Pharmaceuticals in 2009), while Pierre Fabre will continue to develop and commercialize this formulation in Europe and other countries. In October 2005, SD Pharmaceuticals granted Adventrx an exclusive license to certain rights to the emulsion formulation of the drug. In 2009, the company filed a regulatory application seeking approval for an injectable emulsion for the treatment of patients with stage III or IV NSCLC. Vinorelbine i.v. is currently registered in over 80 countries worldwide. In 2010, this application was withdrawn upon receipt of a refuse to file (FTF) decision from the FDA. The product is available for outlicensing.
In most European countries, vinorelbine is approved to treat non-small cell lung cancer and breast cancer. In the United States it is approved only for non-small cell lung cancer.
NAVELBINE (vinorelbine tartrate) Injection is for intravenous administration. Each vial contains vinorelbine tartrate equivalent to 10 mg (1-mL vial) or 50 mg (5-mL vial) vinorelbine in Water for Injection. No preservatives or other additives are present. The aqueous solution is sterile and nonpyrogenic. Vinorelbine tartrate is a semi-synthetic vinca alkaloid with antitumor activity. The chemical name is 3′,4′-didehydro-4′-deoxy-C’-norvincaleukoblastine [R-(R*,R*)-2, 3-dihydroxybutanedioate (1:2)(salt)]. Vinorelbine tartrate has the following structure:
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vinorelbine tartrate is a white to yellow or light brown amorphous powder with the molecular formula C45H54N4O8•2C4H6O6 and molecular weight of 1079.12. The aqueous solubility is > 1,000 mg/mL in distilled water. The pH of NAVELBINE (vinorelbine tartrate) Injection is approximately 3.5.
Uses
As stated above, Vinorelbine is approved for the treatment of non small cell lung cancer and metastatic breast cancer. It is also active inrhabdomyosarcoma.[3]
Oral formulation
An oral formulation has been marketed and registered in most European countries for the same settings. It has similar efficacy as the intravenous formulation, avoids venous toxicities of an infusion and is easier to take.
Side effects
Vinorelbine has a number of side-effects that can limit its use:
Chemotherapy-induced peripheral neuropathy (a progressive, enduring and often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs[4]), lowered resistance to infection, bruising or bleeding, anaemia,constipation, diarrhea, nausea, tiredness and a general feeling of weakness (asthenia), inflammation of the vein into which it was injected (phlebitis). Seldom severe hyponatremia is seen.
Less common effects are hair loss and allergic reaction.
vinorelbine (trade name: Navelbine (Navelbing)) is a novel semi-synthetic vinca alkaloids anticancer drugs, chemical name 3 ‘, 4’ – didehydro-4 ‘- deoxy _8 ‘- vinorelbine, developed by the French PieerFabre company and was listed first in France in 1989, it is mainly through inhibition of centromere tubulin polymerization, to stop cell division in mitotic metaphase, is a cell cycle-specific antineoplastic agents. A change in the structure, it has a strong and specific anti-mitotic properties, and exhibit antineoplastic vinca alkaloids than other low neurotoxicity, characteristics of strong anti-tumor activity.
vinorelbine complex chemical structure, synthesis is difficult, and the difficulty of separating large, making the synthesis of low yield and high cost.Published patent, if the application Patent CN101037446A, CN101284842A, CN1552715A, which are made of boron tetrafluoride shrink ring silver as reagents, but boron tetrafluoride is the price of silver more expensive chemical reagents, increased production costs.
http://www.google.com/patents/EP2135872A1?cl=en
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(1) or a salt thereof to dehydration vinblastine (I) as starting material, the reaction of bromo-condensed ring integrated crude vinorelbine (III):
Example 1
(a) by the dehydration hydrochloride ⑴ vinblastine vinorelbine crude preparation (III)
In a dry round bottom flask, dehydrated hydrochloric vinblastine 20g (laboratory preparation, HPLC purity 92.5%), in the dark and under nitrogen was added IOOOml dry dichloromethane, stirred and dissolved, add 20ml of pyridine , cooled in a dry ice-acetone bath to _50 ° C below bromosuccinimide was added dropwise 6g, trifluoroacetic acid and 13ml of dry methylene IOOOml mixed solution after the addition was complete, stirring below -50 ° C maintaining the reaction 2 hours.After completion of the reaction, adding silver nitrate 12g, 12g and IOOOml ammonium acetate and 800ml of deionized water mixed solution of tetrahydrofuran, stirred rapidly, and gradually heated to 20 ~ 30 ° C, maintaining this temperature, the reaction was stirred for 16 hours. After completion of the reaction, stirring was added dropwise 10% aqueous sodium carbonate aqueous phase PH8 ~ 9, filtered through celite after phase separation, the aqueous phase discarded, and the organic phase was dried, filtered and concentrated to dryness to give crude 14 vinorelbine. 3g (HPLC purity San 85%), 75% yield.
(2) Purification
The above crude product was 14.3g vinorelbine the column of basic alumina with 300 mesh, and with an eluent of 4% methanol – methylene chloride, collecting rich eluate was concentrated to dryness to give product vinorelbine First pure Bin 10. 7g (HPLC purity ^ 97%); then pure product obtained in the beginning of a C18 reversed phase column packing 50μπι, and with an eluent of 40% water – ethanol solution eluted, collected and washed pure deliquored product was extracted with dichloromethane and concentrated to dryness to give 8. lg, and then recrystallized from methanol to obtain pure vinorelbine 6. lg (HPLC purity San 99.5%). Relative to the total dewatering vinblastine hydrochloride 32% yield.
Example 2
(a) by the dehydration hydrochloride ⑴ vinblastine vinorelbine crude preparation (III)
In a dry round bottom flask, dehydrated hydrochloric vinblastine 20g (laboratory preparation, HPLC purity 92.5%), in the dark and under nitrogen was added IOOOml dry dichloromethane, stirred to dissolve, add 2,6 – lutidine 20ml, cooled in a dry ice-acetone bath to _50 ° C or less, is added dropwise bromosuccinimide and 5. 5g, 15ml of trifluoroacetic acid and a mixed solution of dry methylene IOOOml, dropping After stirring below -50 ° C maintaining the reaction 1.5 hours. After completion of the reaction, adding silver nitrate 12g, 12g and IOOOml ammonium acetate and 800ml of deionized water mixed solution of tetrahydrofuran, stirred rapidly, and gradually heated to 20 ~ 30 ° C, maintaining this temperature, the reaction was stirred M hours. After completion of the reaction, stirring was added dropwise 10% aqueous sodium carbonate aqueous phase PH8 ~ 9, filtered through celite and phase separation, the aqueous phase discarded, and the organic phase was dried, filtered and concentrated to dryness to give crude 14 vinorelbine. 7g (HPLC purity> 85%), yield 77.8%.
(2) Purification
The above crude vinorelbine 14. 7g on a column of basic alumina column with 300 mesh, and with an eluent of 4% methanol – methylene chloride, collecting rich eluate was concentrated to dryness to give product vinorelbine early pure llg (HPLC purity ^ 97%); Then get in early on 50 μ m pure product of C18 reverse phase column packing, and then with an eluent of 40% water – ethanol elution fractions containing pure product eluate product is extracted with dichloromethane and concentrated to dryness to give 8. 4g, and then recrystallized from methanol to obtain pure vinorelbine 6. 3g (HPLC purity> 99.5%) relative to the dewatering 0 Vinblastine Hydrochloride total yield of 33.3%.
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Bioorganic and Medicinal Chemistry, 2008 , vol. 16, 11 p. 6269 – 6285
http://www.sciencedirect.com/science/article/pii/S0968089608003532?via=ihub
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Journal of Heterocyclic Chemistry, 1995 , vol. 32, 4 p. 1255 – 1260
http://onlinelibrary.wiley.com/doi/10.1002/jhet.5570320427/abstract
During the development of the bis-indole alkaloid anticancer drug Navelbine® (vinorelbine), several chemical degradants of the drug were isolated and identified. These included 7′-nor-6′,9′-secovinorelbine (7′,8′-bisnor-6′,9′-secoanhydrovinblastine) and 4-deacetyl-8′-vinorelbine (4-deacetyl-8′-noranhydrovinblastine). The elucidation of the structure of 7′-nor-6′,9′-secovinorelbine is described; the assignment of the proton and carbon spectra of both compounds is contrasted to the shift assignments of Navelbine.
References
- Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I, Puozzo C (2001). “Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors”. Ann Oncol 12 (11): 1643–9. doi:10.1023/A:1013180903805. PMID 11822766.
- Jordan, M.A.; Wilson, L. (2004). “Microtubules as a target for anticancer drugs.”. Nature Reviews. Cancer 4 (4): 253–65. doi:10.1038/nrc1317.PMID 15057285.
- Casanova, M; Ferrari, A; Spreafico, F; Terenziani, M; Massimino, M; Luksch, R; Cefalo, G; Polastri, D et al. (2002). “Vinorelbine in previously treated advanced childhood sarcomas: Evidence of activity in rhabdomyosarcoma”. Cancer 94 (12): 3263–8. doi:10.1002/cncr.10600. PMID 12115359.
- del Pino BM. Chemotherapy-induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010;7(4):6.
Advanced Nanoparticle System Kills Cancer Cells From Within
The latest cancer targeting nanoparticles being developed in labs around the world are getting ever more complex and are utilizing multiple mechanisms to find and strike their targets. Researchers at North Carolina State University and the University of North Carolina at Chapel Hill just published an article in Nature Communications describing a nanoparticle that delivers its killer payload only when inside cells by homing in on ATP (adenosine triphosphate).
ATP is the famous energy molecule that powers the activity inside of cells, and the new nanoparticle carries DNA strands bound to doxorubicin, an anti-cancer drug, than unfold when high levels of ATP are present. The nanoparticles themselves have a layer of hyaluronic acid (HA) that attracts some types of cancer cells, allowing the nanoparticles to enter and open up, releasing the folded DNA strands.
From study abstract in Nature Communications:
The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells…
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Chemists devise a new way to manufacture peptide drugs, which hold promise for treating many diseases
MIT chemists have devised a way to rapidly combine amino acids into protein fragments known as peptides. Credit: Alexander Vinogradov
Small protein fragments, also called peptides, are promising as drugs because they can be designed for very specific functions inside living cells. Insulin and the HIV drug Fuzeon are some of the earliest successful examples, and peptide drugs are expected to become a $25 billion market by 2018.
However, a major bottleneck has prevented peptide drugs from reaching their full potential: Manufacturing the peptides takes several weeks, making it difficult to obtain large quantities, and to rapidly test their effectiveness.
That bottleneck may soon disappear: A team of MIT chemists and chemical engineers has designed a way to manufacture peptides in mere hours. The new system, described in the March 21st issue of journal ChemBioChem, could have a major impact on peptide drug development, says Bradley Pentelute, an assistant…
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100th approval … Pradaxa® (dabigatran etexilate) now approved in more than 100 countries for stroke prevention in atrial fibrillation
More than 100 countries have now approved Boehringer Ingelheim’s Pradaxa® for the prevention of stroke and systemic embolism for adult patients with the most common sustained heart rhythm condition (non-valvular atrial fibrillation, nvAF).
The 100th approvalwas announced by the Jordan Food and Drug Administration. Further regulatory approvals for Pradaxa® are expected to be received in the near future. The continuous flow of regulatory approvals from health authorities all over the world reaffirms the overarching benefits delivered to patients by the treatment and supports previous announcements by the U.S. Food and Drugs Administation (FDA) and the European Medicines Agency (EMA).Pradaxa®, in addition, offers the most robust clinical data set and the longest real-world experience for stroke prevention in atrial fibrillation (SPAF) compared to any of the novel oral anticoagulants, providing ongoing support for physician use of the novel treatment
Effective Natural Remedies For Kidney Stones
Effective Natural Remedies For Kidney Stones
==> http://www.rapidhomeremedies.com/remedies-to-cure-kidney-stones.html
Facts & Remedies You Should Know to Prevent and Cure Kidney Stones
If you have been diagnosed with kidney stones, you know how painful it is to live with these stones- big or small- in your kidneys. The acute pain in your left or right flanks going towards the lower abdomen and groin area and even towards your back is something that makes you shudder even if thought about. The feeling of nausea and vomiting along with the burning sensation while you pass urine and also the urgency and frequency of urinating, all these has led you to wish that you get rid of kidney stones as soon as possible.
While most kidney stones are small, it doesn’t mean they are harmless bunnies. One little stone in the urinary tract can make you suffer more than you can imagine.http://www.rapidhomeremedies.com/remedies-to-cure-kidney-stones.html
New Drug Approvals 