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LEUPRORELIN, リュープロレリン;

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Leuprorelin.svg

LEUPRORELIN

  • Molecular FormulaC59H84N16O12
  • Average mass1209.398 Da
5025
53714-56-0 [RN]
5-Oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide
pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHC2H5
pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
TAP-144
UNII:EFY6W0M8TG
リュープロレリン;
For treatment of prostate cancer, endometriosis, uterine fibroids and premature puberty
INGREDIENT UNII CAS
Leuprolide acetate 37JNS02E7V 74381-53-6

Synthesis Reference, Daniel Kadzimirzs, Gerhard Jas, Volker Autze, “Solution-Phase Synthesis of Leuprolide and Its Intermediates.” U.S. Patent US20090005535, issued January 01, 2009.US20090005535

Leuprolide
CAS Registry Number: 53714-56-0
CAS Name: 6-D-Leucine-9-(N-ethyl-L-prolinamide)-10-deglycinamideluteinizing hormone-releasing factor (pig)
Additional Names: leuprorelin; (D-Leu6)-des-Gly10-LH-RH-ethylamide
Molecular Formula: C59H84N16O12
Molecular Weight: 1209.40
Percent Composition: C 58.59%, H 7.00%, N 18.53%, O 15.88%
Literature References: Synthetic nonapeptide agonist analog of LH-RH, q.v. Prepn: M. Fujino et al., DE 2446005 (1975 to Takeda), C.A. 83, 10895y (1975); R. L. Gendrich et al., US 4005063 (1977 to Abbott). Synthesis: J. A. Vilchez-Martinez et al.,Biochem. Biophys. Res. Commun. 59, 1226 (1974); M. Fujino et al., ibid. 60, 406 (1974). Comparison of biological activity with natural LH-RH: D. H. Coy et al., ibid. 67, 576 (1975). Pharmacokinetics: L. T. Sennello et al., J. Pharm. Sci. 75, 158 (1986). Clinical efficacy in prostatic carcinoma: M. B. Garnick et al., N. Engl. J. Med. 311, 1281 (1984); in benign prostatic hypertrophy: L. M. Eri, K. J. Tveter, J. Urol. 150, 359 (1993). Clinical trial in endometriosis: J. M. Wheeler et al., Am. J. Obstet. Gynecol. 167, 1367 (1992).
Properties: Fluffy solid. [a]D25 -31.7° (c = 1 in 1% acetic acid).
Optical Rotation: [a]D25 -31.7° (c = 1 in 1% acetic acid)
Derivative Type: Monoacetate (salt)
CAS Registry Number: 74381-53-6
Additional Names: Leuprolide acetate
Manufacturers’ Codes: Abbott 43818; A-43818; TAP-144
Trademarks: Carcinil (Abbott); Eligard (Sanofi-Aventis); Enantone (Takeda); Leuplin (Takeda); Lucrin (Abbott); Lupron (TAP); Prostap (Wyeth); Viadur (Alza)
Molecular Formula: C59H84N16O12.C2H4O2
Molecular Weight: 1269.45
Percent Composition: C 57.71%, H 6.99%, N 17.65%, O 17.64%
Therap-Cat: Antineoplastic (hormonal); LH-RH agonist.
Keywords: Antineoplastic (Hormonal); LH-RH Analogs; LH-RH Agonist.
Leuprolide belongs to the general class of drugs known as hormones or hormone antagonists. It is a synthetic 9 residue peptide analog of gonadotropin releasing hormone. Leuprolide is used to treat advanced prostate cancer. It is also used to treat uterine fibroids and endometriosis. Leuprolide is also under investigation for possible use in the treatment of mild to moderate Alzheimer’s disease.

Jitsubo , a subsidiary of  Sosei , was investigating JIT-1007 , presumed to be a biosimilar version of an undisclosed peptide therapeutic, generated using its proprietary Molecular Hiving, for the treatment of an unidentified indication, however no development has been reported for some time, this program is assumed to be discontinued.

Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancerbreast cancerendometriosisuterine fibroids, and early puberty.[1][2] It is given by injection into a muscle or under the skin.[1]

Common side effects include hot flashes, unstable mood, trouble sleepingheadaches, and pain at the site of injection.[1] Other side effects may include high blood sugarallergic reactions, and problems with the pituitary gland.[1] Use during pregnancy may harm the baby.[1] Leuprorelin is in the gonadotropin-releasing hormone (GnRH) analogue family of medications.[1] It works by decreasing gonadotropin and therefore decreasing testosterone and estradiol.[1]

Leuprorelin was patented in 1973 and approved for medical use in the United States in 1985.[1][3] It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] In the United Kingdom a monthly dose costs the NHS about GB£75.24.[5] In the United States the equivalent dose has a wholesale cost of US$1,011.93.[6] It is sold under the brand name Lupron among others.[1]

Medical use

Leuprorelin may be used in the treatment of hormone-responsive cancers such as prostate cancer and breast cancer. It may also be used for estrogen-dependent conditions such as endometriosis[7] or uterine fibroids.

It may be used for precocious puberty in both males and females,[8] and to prevent premature ovulation in cycles of controlled ovarian stimulation for in vitro fertilization (IVF).

It may be used to reduce the risk of premature ovarian failure in women receiving cyclophosphamide for chemotherapy.[9]

Along with triptorelin and goserelin, it is has been used to delay puberty in transgender youth until they are old enough to begin hormone replacement therapy.[10] Researchers have recommended puberty blockers after age 12, when the person has developed to Tanner stages 2-3, and then cross-sex hormones treatment at age 16. This use of the drug is off-label, however, not having been approved by the Food and Drug Administration and without data on long-term effects of this use.[11]

They are also sometimes used as alternatives to antiandrogens like spironolactone and cyproterone acetate for suppressing testosterone production in transgender women.[citation needed]

It is considered a possible treatment for paraphilias.[12] Leuprorelin has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia.[13][14]

Side effects

Common side effects of Lupron Injection include redness/burning/stinging/pain/bruising at the injection site, hot flashes (flushing), increased sweating, night sweats, tiredness, headache, upset stomach, nausea, diarrhea, constipation, stomach pain, breast swelling or tenderness, acne, joint/muscle aches or pain, trouble sleeping (insomnia), reduced sexual interest, vaginal discomfort/dryness/itching/discharge, vaginal bleeding, swelling of the ankles/feet, increased urination at night, dizziness, breakthrough bleeding in a female child during the first 2 months of leuprorelin treatment, weakness, chills, clammy skin, skin redness, itching, or scaling, testicle pain, impotence, depression, or memory problems.[15] The rates of gynecomastia with leuprorelin have been found to range from 3 to 16%.[16]

Mechanism of action

Leuprorelin is a gonadotropin-releasing hormone (GnRH) analogue acting as an agonist at pituitary GnRH receptors. Agonism of GnRH receptors initially results in the stimulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion by the anterior pituitary ultimately leading to increased serum estradiol and testosterone levels via the normal physiology of the hypothalamic–pituitary–gonadal axis (HPG axis); however, because propagation of the HPG axis is incumbent upon pulsatile hypothalamic GnRH secretion, pituitary GnRH receptors become desensitised after several weeks of continuous leuprorelin therapy. This protracted downregulation of GnRH receptor activity is the targeted objective of leuprorelin therapy and ultimately results in decreased LH and FSH secretion, leading to hypogonadism and thus a dramatic reduction in estradiol and testosterone levels regardless of sex.[17][18]

In the treatment of prostate cancer, the initial increase in testosterone levels associated with the initiation of leuprorelin therapy is counterproductive to treatment goals. This effect is avoided with concurrent utilisation of 5α-reductase inhibitors, such as finasteride, which function to block the downstream effects of testosterone.

Chemistry

The peptide sequence is Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt (Pyr = LPyroglutamyl).

History

Leuprorelin was discovered and first patented in 1973 and was introduced for medical use in 1985.[19][20] It was initially marketed only for daily injection, but a depot injectionformulation was introduced in 1989.[20]

Society and culture

Names

Leuprorelin is the generic name of the drug and its INN and BAN, while leuprorelin acetate is its BANM and JANleuprolide acetate is its USAN and USPleuprorelina is its DCIT, and leuproréline is its DCF.[21][22][23][24] It is also known by its developmental code names A-43818Abbott-43818DC-2-269, and TAP-144.[21][22][23][24]

Leuprorelin is marketed by Bayer AG under the brand name Viadur, by Tolmar under the brand name Eligard, and by TAP Pharmaceuticals (1985–2008), by Varian Darou Pajooh under the brand name Leupromer and Abbott Laboratories (2008–present) under the brand name Lupron. It is available as a slow-release implant or subcutaneous/intramuscular injection.

In the UK and Ireland, leuprorelin is marketed by Takeda UK as Prostap SR (one-month injection) and Prostap 3 (three-month injection).

Approvals

Available formsLupron injection was first approved by the FDA for treatment of advanced prostate cancer on April 9, 1985.

  • Lupron depot for monthly intramuscular injection was first approved by the FDA for palliative treatment of advanced prostate cancer on January 26, 1989, and subsequently in 22.5 mg/vial and 30 mg/vial for intramuscular depot injection every 3 and 4 months, respectively. 3.75 mg/vial and 11.25 mg/vial dosage forms were subsequently approved for subcutaneous depot injection every month and every 3 months, respectively for treatment of endometriosis or fibroids. 7.5 mg/vial, 11.25 mg/vial, and 15 mg/vial dosage forms were subsequently approved for subcutaneous depot injection for treatment of children with central precocious puberty.
  • Viadur (72 mg yearly subcutaneous implant) was first approved by the FDA for palliative treatment of advanced prostate cancer on March 6, 2000. Bayer will fulfill orders until current supplies are depleted, expected by the end of April 2008
  • Eligard (7.5 mg for monthly subcutaneous depot injection) was first approved by the FDA for palliative treatment of advanced prostate cancer on January 24, 2002, and subsequently in 22.5 mg, 30 mg, and 45 mg doses for subcutaneous depot injection every 3, 4, and 6 months, respectively.
  • Leupromer 7.5 (7.5 mg, one month depot for subcutaneous injection) is the second in situ-forming injectable drug in the world. It is used for palliative treatment of advanced prostate cancer, endometriosis, and uterine fibroids. It was approved by The Ministry of Health and Medical Education Of Iran.

Leuprorelin is available in the following forms, among others:[25][26][27]

  • Short-acting daily intramuscular injection (Lupron): 5 mg/mL (2.8 mL) used as 1 mg every day.
  • Long-acting depot intramuscular injection (Lupron Depot): 7.5 mg once a month, 22.5 mg every 3 months, or 30 mg every 4 months.
  • Long-acting depot subcutaneous injection (Eligard): 7.5 mg once a month, 22.5 mg every 3 months, 30 mg every 4 months, or 45 mg every 6 months.
  • Long-acting subcutaneous implant (Viadur): 65 mg pellet once every 12 months.

“Lupron protocol”

A 2005 paper in the controversial and non-peer reviewed journal Medical Hypotheses suggested leuprorelin as a possible treatment for autism,[28] the hypothetical method of action being the now defunct hypothesis that autism is caused by mercury, with the additional unfounded assumption that mercury binds irreversibly to testosterone and therefore leuprorelin can help cure autism by lowering the testosterone levels and thereby mercury levels.[29] However, there is no scientifically valid or reliable research to show its effectiveness in treating autism.[30] This use has been termed the “Lupron protocol”[31] and Mark Geier, the proponent of the hypothesis, has frequently been barred from testifying in vaccine-autism related cases on the grounds of not being sufficiently expert in that particular issue[32][33][34] and has had his medical license revoked.[31] Medical experts have referred to Geier’s claims as “junk science”.[35]

Veterinary use

Leuprorelin is frequently used in ferrets for the treatment of adrenal disease. Its use has been reported in a ferret with concurrent primary hyperaldosteronism,[36] and one with concurrent diabetes mellitus.[37]

Research

As of 2006 leuprorelin was under investigation for possible use in the treatment of mild to moderate Alzheimer’s disease.[38]

by mouth formulation of leuprorelin is under development for the treatment of endometriosis.[39] It was also under development for the treatment of precocious pubertyprostate cancer, and uterine fibroids, but development for these uses was discontinued.[39] The formulation has the tentative brand name Ovarest.[39] As of July 2018, it is in phase II clinical trials for endometriosis.[39]

Patent

WO-2019198834

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019198834&tab=FULLTEXT&_cid=P11-K25LCW-03723-1

Process for producing leuprorelin as LH-RH (GnRH) agonist useful for treating endometriosis, uterine fibroids, premenopausal breast cancer and prostate cancer.

PATENT

WO2019198833

WO2016140232

References

  1. Jump up to:a b c d e f g h i “Leuprolide Acetate”. The American Society of Health-System Pharmacists. Archived from the original on 23 December 2016. Retrieved 8 December2016.
  2. ^ “19th WHO Model List of Essential Medicines (April 2015)” (PDF). WHO. April 2015. Archived (PDF) from the original on May 13, 2015. Retrieved May 10, 2015.
  3. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 514. ISBN 9783527607495.
  4. ^ “WHO Model List of Essential Medicines (19th List)” (PDF)World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
  5. ^ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 655. ISBN 9780857111562.
  6. ^ “NADAC as of 2016-12-07 | Data.Medicaid.gov”Centers for Medicare and Medicaid ServicesArchived from the original on 21 December 2016. Retrieved 23 December 2016.
  7. ^ Crosignani PG, Luciano A, Ray A, Bergqvist A (January 2006). “Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain”. Human Reproduction21 (1): 248–56. doi:10.1093/humrep/dei290PMID 16176939.
  8. ^ Badaru A, Wilson DM, Bachrach LK, et al. (May 2006). “Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty”. The Journal of Clinical Endocrinology and Metabolism91 (5): 1862–7. doi:10.1210/jc.2005-1500PMID 16449344.
  9. ^ Clowse ME, Behera MA, Anders CK, Copland S, Coffman CJ, Leppert PC, Bastian LA (March 2009). “Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis”Journal of Women’s Health18 (3): 311–9. doi:10.1089/jwh.2008.0857PMC 2858300PMID 19281314.
  10. ^ David A. Wolfe; Eric J. Mash (9 October 2008). Behavioral and Emotional Disorders in Adolescents: Nature, Assessment, and Treatment. Guilford Press. pp. 556–. ISBN 978-1-60623-115-9Archived from the original on 2 July 2014. Retrieved 24 March 2012.
  11. ^ Dreger, A. (2009, Jan.-Feb.). Gender Identity Disorder in childhood: Inconclusive advice to parents. Hastings Center Report, pp. 26-29.
  12. ^ Saleh FM, Niel T, Fishman MJ (2004). “Treatment of paraphilia in young adults with leuprolide acetate: a preliminary case report series”. Journal of Forensic Sciences49 (6): 1343–8. doi:10.1520/JFS2003035PMID 15568711.
  13. ^ Schober JM, Byrne PM, Kuhn PJ (2006). “Leuprolide acetate is a familiar drug that may modify sex-offender behaviour: the urologist’s role”. BJU International97 (4): 684–6. doi:10.1111/j.1464-410X.2006.05975.xPMID 16536753.
  14. ^ Schober JM, Kuhn PJ, Kovacs PG, Earle JH, Byrne PM, Fries RA (2005). “Leuprolide acetate suppresses pedophilic urges and arousability”. Archives of Sexual Behavior34 (6): 691–705. doi:10.1007/s10508-005-7929-2PMID 16362253.
  15. ^ “Common Side Effects of Lupron (Leuprolide Acetate Injection) Drug Center”Archived from the original on 2015-07-29. Retrieved 2015-07-26.[full citation needed]
  16. ^ Di Lorenzo G, Autorino R, Perdonà S, De Placido S (December 2005). “Management of gynaecomastia in patients with prostate cancer: a systematic review”. Lancet Oncol6 (12): 972–9. doi:10.1016/S1470-2045(05)70464-2PMID 16321765.
  17. ^ Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 372–3. ISBN 978-3-8047-1763-3.
  18. ^ Wuttke W, Jarry H, Feleder C, Moguilevsky J, Leonhardt S, Seong JY, Kim K (1996). “The neurochemistry of the GnRH pulse generator”Acta Neurobiologiae Experimentalis56(3): 707–13. PMID 8917899Archived from the original on 2015-12-08.
  19. ^ Jamil, George Leal (30 September 2013). Rethinking the Conceptual Base for New Practical Applications in Information Value and Quality. IGI Global. pp. 111–. ISBN 978-1-4666-4563-9.
  20. Jump up to:a b Hara T (1 January 2003). Innovation in the Pharmaceutical Industry: The Process of Drug Discovery and Development. Edward Elgar Publishing. pp. 106–107. ISBN 978-1-84376-566-0.
  21. Jump up to:a b J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 730–. ISBN 978-1-4757-2085-3.
  22. Jump up to:a b Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 599–. ISBN 978-3-88763-075-1.
  23. Jump up to:a b I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 164–. ISBN 978-94-011-4439-1.
  24. Jump up to:a b “Leuprorelin”.
  25. ^ Sara K. Butler; Ramaswamy Govindan (25 October 2010). Essential Cancer Pharmacology: The Prescriber’s Guide. Lippincott Williams & Wilkins. pp. 262–. ISBN 978-1-60913-704-5.
  26. ^ Richard A. Lehne; Laura Rosenthal (25 June 2014). Pharmacology for Nursing Care – E-Book. Elsevier Health Sciences. pp. 1296–. ISBN 978-0-323-29354-9.
  27. ^ Prostate Cancer. Demos Medical Publishing. 20 December 2011. pp. 503–. ISBN 978-1-935281-91-7.
  28. ^ Geier M, Geier D (2005). “The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity”. Med Hypotheses64 (5): 946–54. doi:10.1016/j.mehy.2004.11.018PMID 15780490.
  29. ^ Allen A (2007-05-28). “Thiomersal on trial: the theory that vaccines cause autism goes to court”SlateArchived from the original on 2008-02-03. Retrieved 2008-01-30.
  30. ^ “Testosterone regulation”. Research Autism. 2007-05-07. Archived from the original on 2015-04-18. Retrieved 2015-04-09.
  31. Jump up to:a b “Maryland medical board upholds autism doctor’s suspension”Chicago Tribune. May 11, 2011. Archived from the original on October 21, 2011.
  32. ^ John and Jane Doe v. Ortho-Clinical Diagnostics, Inc Archived 2008-03-06 at the Wayback Machine“, US District Court for the Middle District of North Carolina, July 6, 2006
  33. ^ Dr. Mark Geier Severely Criticized Archived 2016-12-02 at the Wayback Machine“, Stephen Barrett, M.D., Casewatch.org
  34. ^ Mills S, Jones T (2009-05-21). “Physician team’s crusade shows cracks”Chicago TribuneArchived from the original on 2009-05-25. Retrieved 2009-05-21.
  35. ^ ‘Miracle drug’ called junk science: Powerful castration drug pushed for autistic children, but medical experts denounce unproven claims Archived 2013-12-03 at the Wayback MachineChicago Tribune, May 21, 2009
  36. ^ Desmarchelier M, Lair S, Dunn M, Langlois I (2008). “Primary hyperaldosteronism in a domestic ferret with an adrenocortical adenoma”. Journal of the American Veterinary Medical Association233 (8): 1297–301. doi:10.2460/javma.233.8.1297PMID 19180717.
  37. ^ Boari A, Papa V, Di Silverio F, Aste G, Olivero D, Rocconi F (2010). “Type 1 diabetes mellitus and hyperadrenocorticism in a ferret”. Veterinary Research Communications34(Suppl 1): S107–10. doi:10.1007/s11259-010-9369-2PMID 20446034.
  38. ^ Doraiswamy PM, Xiong GL (2006). “Pharmacological strategies for the prevention of Alzheimer’s disease”. Expert Opinion on Pharmacotherapy7 (1): 1–10. doi:10.1517/14656566.7.1.S1PMID 16370917.
  39. Jump up to:a b c d “Leuprorelin oral – Enteris BioPharma – AdisInsight”adisinsight.springer.com. Retrieved 16 July 2018.

External links

Leuprorelin
Leuprorelin.svg
Leuprorelin ball-and-stick.png
Clinical data
Trade names Lupron, Eligard, Lucrin, others
Synonyms Leuprolide; Leuprolidine; A-43818; Abbott-43818; DC-2-269; TAP-144
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a685040
Pregnancy
category
  • X
Routes of
administration
implantinjection
Drug class GnRH analogueGnRH agonistAntigonadotropin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life 3 hours
Excretion Kidney
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.161.466 Edit this at Wikidata
Chemical and physical data
Formula C59H84N16O12
Molar mass 1209.421 g·mol−1
3D model (JSmol)

//////////LEUPRORELIN, リュープロレリン ,


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DR ANTHONY CRASTO

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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