Tracks information on drugs on worldwide basis by Dr Anthony Melvin Crasto, helping millions with websites, 9 million hits on google, 2.5 lakh connections worldwide, P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
End to end solutions Big Data push to research In Green / shutterstock.com
The pharma sector needs to embrace emerging technologies like Big Data analytics and cloud computing
What is the secret sauce of accelerating innovation when it comes to critical areas such as drug discovery, personalised medicines or simulated healthcare? Embracing continual innovation was always an imperative for the life sciences companies to stay relevant, and stay alive. This is not just confined to the new drug discovery team within the company, it spans the entire value chain of the innovation ecosystem. The question is whether enough is being done to drive R&D innovation in the pharmaceutical industry.
Side
effects are a major reason that drugs are taken off the market and a
major reason why patients stop taking their medications, but scientists
are now reporting the development of a new way to predict those adverse
reactions ahead of time. The report on the method, which could save
patients from severe side effects and save drug companies time and
money, appears in ACS' Journal of Chemical Information and Modeling.
Yoshihiro
Yamanishi and colleagues explain that drug side effects are a major
health problem -- the fourth-leading cause of death in the U.S. -- which
by some estimates claim 100,000 lives every year. Serious side effects
are the main reason why existing drugs must be removed from the market
and why pharmaceutical companies halt development of new drugs after
investing millions of dollars. Current methods of testing for side
effects are costly and inaccurate. That's why the scientists sought to
develop a new computer-based approach to predicting possible side
effects.
Green Chem., 2013, Advance Article DOI: 10.1039/C3GC41629A, Perspective
Hans-Jurgen Federsel Focus on the outlook for a green future in the pharmaceutical industry - close-up of historical drivers, blockers, challenges, and changes.
What is the relationship between the Green Chemistry initiative and the pharmaceutical industry? The intention is to shed some light on this issue by providing an historical overview spanning a period of about 20 years – from the start of the movement towards greener processes and manufacture in the early 1990s until today where greenness and sustainability are widely embraced throughout society. To understand and appreciate the approach to the green paradigm from a pharmaceutical business point of view, it is essential to paint the broader picture explaining the landscape in which this industry operates and its particular challenges. Looking at the special features that apply to chemical production of drug molecules for commercial use – in relative terms a low volume undertaking (from kg scale through to 10s or sometimes 100s of tons per annum) – the situation is vastly different compared to conventional bulk manufacture (for instance of commodity chemicals). After an initial lag phase, the drug industry has now caught up and is very eager to fully adopt green principles and to gather evidence on how it is performing. As an example, it is a well documented fact that more than half the mass constituting a process stream in the chemical manufacture of active pharmaceutical ingredients (APIs) stems from the solvent(s) utilized; 80–90% if water is included. In a multi-step synthesis on an average composed of 8–10 discrete chemical transformations which typically runs at a process mass intensity (PMI) factor of 100–200 kg kg−1API, about 50–100 kg can be referred purely to the contribution from solvents; hence, the potential for improvements is huge. Thus, leaving the historic priorities behind in favor of drivers for change such as external pressure, goodwill, legislation, and company policies is a good strategy to ensure a rapid movement into a greener future, albeit without ignoring the existence of blockers that mainly relate to insufficient scientific and technological capabilities. From a chemical process point of view, there are several reasons to have an optimistic view about the prospects of a flourishing green agenda going forward as shown in a number of recent case studies.
In the last century, the discovery of cytotoxic agents was revolutionary for anticancer therapy. These therapies have resulted in better understanding of cancer in general. However, the development of agents that combine efficacy, safety and convenience remains a great challenge. The narrow, if not adverse, therapeutic index of most drugs, the damage not only to cancer cells, but also to normal and healthy tissue and the occurrence of resistance have limited anticancer efficacy. This review presents the development of promising novel cytotoxic solasodine rhamnosyl glycoside drugs that offer not only gains in specificity and efficacy, but also in safety, tolerability, non-resistance and convenience in the treatment of patients with cancer.
1. INTRODUCTION
In the past 100 years our understanding of the biology of cancer has come a long way. We now have a reasonable working knowledge of how tumors initially form, grow and spread. Importantly, substantial information about features distinguishing tumor from normal cells is being accumulated, resulting in major new insights into cancer biology................
Dale Boger, PhD, is chair of the Department of Chemistry at The Scripps Research Institute.
LA JOLLA, CA—September 16, 2013—Scientists at The Scripps Research Institute (TSRI) have found a way to make dramatic improvements to the cancer cell-killing power of vinblastine, one of the most successful chemotherapy drugs of the past few decades. The team’s modified versions of vinblastine showed 10 to 200 times greater potency than the clinical drug. Even more significantly, these new compounds overcome the drug resistance that emerges upon treatment relapse, which renders continued or subsequent vinblastine treatment ineffective in some patients.
The TSRI researchers expect that similar modifications will boost the effectiveness of vincristine, a closely related drug that is commonly used against childhood leukemias and Hodgkin’s disease. http://www.scripps.edu/news/press/2013/20130916boger.html
The cephalosporins structurally related to the penicillin's consist of a –beta lactam ring attached to a dihydrothiazoline ring. Substitutions of chemical groups result in varying pharmacologic properties and antimicrobial activities . What are cephalosporins Dr.T.V.Rao MD 2
History of cephalosporins :
History of cephalosporins Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu He noticed that these cultures produced substances that were effective against Salmonella typhi , the cause of typhoid fever, which had beta-lactamase. Guy Newton and Edward Abraham at the Sir William Dunn School of Pathology at the University of Oxford isolated cephalosporin C. The cephalosporin nucleus, 7-aminocephalosporanic acid (7-ACA), was derived from cephalosporin C and proved to be analogous to the penicillin nucleus 6-aminopenicillanic acid, but it was not sufficiently potent for clinical use. Modification of the 7-ACA side-chains resulted in the development of useful antibiotic agents, and the first agent cephalothin ( cefalotin ) was launched by Eli Lilly in 1964. Dr.T.V.Rao MD 3
Cephalosporins:
Cephalosporins are B-Lactam antibiotics isolated from Cephalosporium spp. inhibit wide variety of gram(+) and gram(-) bacteria Abraham and Newton, the suppliers of fungi cultures isolated three principal antibiotic components: Cephalosporin PI Cephalosporin N Cephalosporin C - a steroid with minimal antibacterial property - Identical with synnematin N ( also called penicillin N Resistant to S. aureus B-lactamase; antibacterial property is inferior to penicillin N. Dr.T.V.Rao MD 4
Slide 5:
Cephalosporins Cephalosporin N or Penicillin N - the amino acid in the chain confers more activity against gram(-) bacteria particularly Salmonella spp . - less active against gram(+) organism - contains thiazolidine ring S NH H H N HO NH 2 O O O CH 3 CH 3 OH O Dr.T.V.Rao MD 5
Slide 6:
Cephalosporins Cephalosporin C - congener of Penicillin N - contains dihydrothiazide ring NH H H N HO NH 2 O O O CH 3 OH O O O S Dr.T.V.Rao MD 6
Nomenclature of Cephalosporins:
Nomenclature of Cephalosporins Chemical Abstracts > fused ring is named 5-thia, 1-azabicyclo[4.2.0]oct-2-ene > CEPHALOTHIN ( is an antibiotic of the cephalosporin class. It is related to the penicillin drugs in how it kills bacteria, but cephalosporins have a much broader range of activity against bacteria than penicillins. is 3-(acetoxymethyl)-7-[2-(thienylacetyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. > saturated bicyclic ring system is named as cepham > all cephalosporins and cefamycins are named as 3-cephems, to designate the position of the double bond in the structure. Dr.T.V.Rao MD 7
Spectrum of Activity:
Spectrum of Activity > are considered broad-spectrum antibiotics with similar activities to that of ampicillin. > more resistant to the inactivation by the beta-lactamases, particularly those produced by gram(+) bacteria. > exhibit potent activity against most species of Klebsiella CEPHALOSPORINS Different potencies are due to: 1. Different bacterial strains 2. Characteristics of individual bacterial species 3. Resistance to the inactivation of the beta-lactamases 4. Permeability of the bacterial cell 5. Intrinsic activity against bacterial enzymes involved in cell wall synthesis and cross linking. Dr.T.V.Rao MD 8
Generation of Cephalosporins:
Cephalosporin drugs fall into five classes or generations . Each subsequent generation of these drugs demonstrates greater efficacy against gram-negative bacteria. Generation of Cephalosporins Dr.T.V.Rao MD 9
What are 5th generation Cephalosporins :
Fifth generation cephalosporins were developed in the lab to specifically target against resistant strains of bacteria . In particular, ceftobiprole is effective against methicillin-resistant Staphylococcus aureus (MRSA ). What are 5 th generation Cephalosporins Dr.T.V.Rao MD 10
Ceftraroline, a 5th. generation cephalosporin :
Ceftaroline is a beta-lactam of the cephalosporin class of antimicrobials with activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria associated with skin and respiratory infections. It also has activity against methicillin-resistant Staphylococcus aureus and Streptococcus pneumonia . Ceftraroline, a 5th. generation cephalosporin Dr.T.V.Rao MD 11
Fda approves ceftaroline fosamil:
Fda approves ceftaroline fosamil On October 29th, FDA has approved Ceftaroline Fosamil under the trade name Teflaro. Ceftaroline Fosamil (previously known by the research code TAK-599, the parent drug, Ceftaroline is also known as T-91,825) is an antibiotic indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive and Gram-negative microorganisms, such as Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes Streptococcus agalactiae , Escherichia coli , Klebsiella pneumoniae , and Klebsiella oxytoca , and also for the treatment of community-acquied bacterial pneumonia (CABP) caused by susceptible Gram-positive and Gram-negative bacteria, such as Streptococcus pneumoniae (including cases with concurrent bacteremia ), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae , Klebsiella pneumoniae , Klebsiella oxytoca , and Escherichia coli . Dr.T.V.Rao MD 12
The structure of ceftaroline fosamil resembles other Cephalosporins :
(6R,7R )-7-{(2Z)-2-(ethoxyimino)-2-[5-(phosphonoamino)-1,2,4thiadiazol-3-yl]acetamido}-3-{[4-(1-methylpyridin-1-ium-4-yl)-1,3-thiazol-2-yl]sulfanyl}-8-oxo-5-thia-1azabicyclo[4.2.0]oct-2-ene-2-carboxylate contains a cyclic amide (the beta-lactam ring) fused with a six member ring (the cephem ring). Another notable feature of Ceftaroline Fosamil is the thiazolylthio group, which is thought to be crucial for the activity against MRSA. The structure of ceftaroline fosamil resembles other Cephalosporins Dr.T.V.Rao MD 13
How ceftaroline works:
Ceftaroline is a broad-spectrum cephalosporin. Ceftaroline has the ability to bind to penicillin-binding protein (PBP) 2a , an MRSA-specific PBP that has low affinity for most other β-lactam antibacterial. The high binding affinity of ceftaroline to PBP 2a (median inhibitory concentration 0.90 μg/mL) correlates well with its low minimum inhibitory concentration for MRSA. How ceftaroline works Dr.T.V.Rao MD 14
Ceftaroline is modified from cefozopran:
Ceftaroline was developed by modifying the structure of the fourth-generation cephalosporin cefozopran The prodrug, ceftaroline fosamil , which contains a phosphono group to increase water solubility, is rapidly converted in plasma into the bioactive agent , ceftaroline The 1,3-thiazole ring attached to the 3-position of the cephalosporin nucleus and the oxime group in the C7 acyl moiety are responsible for the enhanced anti-MRSA activity observed with ceftaroline. Ceftaroline is modified from cefozopran Dr.T.V.Rao MD 15
Advantages of ceftaroline:
Advantages of ceftaroline The high affinity of ceftaroline for penicillin-binding proteins is responsible for the potent activity observed against clinically relevant pathogens. With respect to the treatment of CABP, the activity of ceftaroline against pathogens such as S. pneumoniae , S. aureus , Haemophilus influenzae and Moraxella catarrhalis demonstrates coverage across a broad range of pathogens typically encountered in clinical practice. Ceftaroline is also very active against common pathogens seen in ABSSSIs such as S. aureus (methicillin-susceptible S. aureus and methicillin-resistant S. aureus ) and Streptococcus pyogenes . Dr.T.V.Rao MD 16
Mechanism of action of Ceftaroline:
Ceftaroline was developed by modifying the structure of the fourth-generation cephalosporin cefozopran. The prodrug, ceftaroline fosamil, which contains a phosphono group to increase water solubility, is rapidly converted in plasma into the bioactive agent, ceftaroline The 1,3-thiazole ring attached to the 3-position of the cephalosporin nucleus and the oxime group in the C7 acyl moiety are responsible for the enhanced anti-MRSA activity observed with ceftaroline. Mechanism of action of Ceftaroline Dr.T.V.Rao MD 17
Ceftaroline is active on:
Ceftaroline is active on Ceftaroline is active in vitro against Gram-positive cocci, including MRSA, methicillin-resistant Staphylococcus epidermidis , penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant Enterococcus faecalis (not E. faecium ) . The broad- spectrum activity of ceftaroline includes many Gram-negative pathogens but does not extend to extended-spectrum β-lactamase-producing or AmpC-derepressed Enterobacteriaceae or most nonfermentative Gram-negative bacilli . Dr.T.V.Rao MD 18
Ceftaroline has synergistic action :
Ceftaroline has been shown to have synergistic activity against Gram-negative species in combination with an aminoglycoside. In an in vitro study, ceftaroline plus amikacin was synergistic against 90% of isolates tested, including Pseudomonas aeruginosa , extended-spectrum β- lactamase (ESBL)-producing Escherichia coli , ESBL-producing Klebsiella pneumoniae and AmpC-derepressed Enterobacter cloacae . Synergy was also demonstrated for ceftaroline in combination with meropenem against all E. coli isolates tested Ceftaroline has synergistic action Dr.T.V.Rao MD 19
Ceftaroline has limited activity …….:
Ceftaroline demonstrates limited activity against anaerobes such as Bacteroides fragilis and non-fragilis Bacteroides spp. Limited data show that ceftaroline has a low propensity to select for resistant subpopulations. Ceftaroline has limited activity ……. Dr.T.V.Rao MD 20
Advantage of ceftaroline:
Ceftaroline is an injectable cephalosporin active against MRSA & MSSA [ & RTI pathogens] It is approved for use in cSSSI & CABP Its use may be extended when combined with NXL 104 to include ESBL +ve GNB strains It is inactive against Non fermentors GNB & Carbapenemase producers. Advantage of ceftaroline
Slide 22:
Dr.T.V.Rao MD 22
Fifth generation Ceftobiprole :
Fifth generation Ceftobiprole has been described as "fifth generation ", ] though acceptance for this terminology is not universal. Ceftobiprole (and the soluble prodrug medocaril) are on the FDA fast-track. Ceftobiprole has powerful antipseudomonal characteristics and appears to be less susceptible to development of resistance. Fifth generation Ceftobiprole Dr.T.V.Rao MD 23
Ceftobiprole (Zeftera/Zevtera) is a :
Ceftobiprole ( Zeftera / Zevtera ) is a Ceftobiprole (Zeftera/Zevtera) is a 5th generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus , penicillin-resistant Streptococcus pneumoniae , Pseudomonas aeruginosa , and Enterococci It was discovered by Basilea Pharmaceutica and was developed by Johnson & Johnson Pharmaceutical Research and Development . It has been shown to be statistically non-inferior to the combination of vancomycin and ceftazidime for the treatment of skin and soft tissue infections . Dr.T.V.Rao MD 24
Pharmacology of ceftobiprole:
Ceftobiprole inhibits the 2a penicillin-binding protein (pbp ) of Methicillin-resistant Staphylococcus aureus and the 2x pbp of Streptococcus pneumoniae as well as the classic PBP-2 of MSSA. Ceftobiprole is resistant to staphylococcal β- lactamase Pharmacology of ceftobiprole Dr.T.V.Rao MD 25
How ceftobiprole differs from other beta lactams :
How ceftobiprole differs from other beta lactams Ceftobiprole can be distinguished from other beta-lactams by its increased binding to penicillin-binding protein 2a. Penicillin-binding proteins, the targets of beta-lactam antibiotics, are enzymes found in the membrane that are the last step of peptidoglycan biosynthesis. Penicillin-binding protein 2a is the enzyme most directly related to methicillin-resistant staphylococci. Activity of ceftobiprole has been studied against both the community-acquired MRSA strains and hospital-acquired MRSA Dr.T.V.Rao MD 26
Clsi puts on the list of unnamed class:
Currently, ceftaroline and ceftobiprole are on an unnamed subclass of cephalosporins by the Clinical and Laboratory Standards Institute (CLSI). Clsi puts on the list of unnamed class Dr.T.V.Rao MD 27
5th generation cephalosporins are not ultimate solutions for antibiotic resistance :
5 th generation cephalosporins are not ultimate solutions for antibiotic resistance Antimicrobial stewardship programmes can be implemented to reduce inappropriate use of antimicrobials, thereby controlling the development of resistance. These programmes are also useful in limiting toxicity and overgrowth of pathogenic organisms such as C. difficile . Typical stewardship programmes target antimicrobials that pose a risk of development of resistance, are associated with significant toxicity, require therapeutic drug monitoring, have the potential to select for pathogenic organisms or have a high cost. Dr.T.V.Rao MD 28
Slide 29:
Created by Dr.T.V.Rao MD for “ e ‘ learning resources for Medical Microbiologists in Developing World Email d octortvrao@gmail.com Dr.T.V.Rao MD 29
There is much more than meets the eye with the banana. A household favorite, a lost-leader at the grocery store, a metaphor for psychiatric problems, a mainstay of comic slap stick, the banana has woven itself deeply into human affairs, on both gut and mental levels. And this relationship is at least 10,000 years old, as far as conscious human cultivation of the species goes.
read all at http://www.greenmedinfo.com/blog/7-amazing-medicinal-properties-banana-plant
(NaturalNews) Vitamin C is one of the most important antioxidants on Earth, and its ability to aid tissue growth and repair is well-known. However, British researchers at the Imperial College of London have found another good reason to eat more oranges and lemons - vitamin C can also guard us against the negative effects of air pollutants such as car exhaust and power plants.
Pumpkin seeds, like all edible
seeds, pack an immense nutritional and medicinal punch. After all,
they contain future worlds within their compact structure. As Emerson said, "the
creation of a thousand forests is within one acorn."
Cdiffense trial to evaluate vaccine against a leading cause of life-threatening, healthcare-associated infections worldwide
SWIFTWATER, Pa., Aug. 5, 2013 /PRNewswire/ -- Sanofi Pasteur, the vaccines division of Sanofi (EURONEXT: SAN and NYSE: SNY), announced today the initiation of its Phase III clinical program called Cdiffense to evaluate the safety, immunogenicity and efficacy of an investigational vaccine for the prevention of primary symptomatic Clostridium difficile infection (CDI). Clostridium difficile (C. diff) is a potentially life-threatening, spore-forming bacterium that causes intestinal disease. The risk of C. diff increases with age, antibiotic treatment and time spent in hospitals or nursing homes, where multiple cases can lead to outbreaks. The investigational vaccine is designed to help protect at-risk individuals from C. diff, which is emerging as a leading cause of life-threatening, healthcare-associated infections (HAIs) worldwidehttp://www.pharmalive.com/sanofi-starts-phase-iii-trial-for-clostridium-difficile-vaccine
The search for a wonder drug that burns body fat and cholesterol leads to the Korean cuisine! Kochujang (KCJ), a fermented soybean-based red pepper paste, has been found to reduce body fat and improve blood lipid profile in overweight adults.
Negligence of traditional dietary lifestyle can easily be linked to the prevalence of obesity and obesity-related chronic diseases. Kochujang (KCJ) has long been a part of seasonings in Korean cuisine as a sauce, dressi
Negligence of traditional dietary lifestyle can easily be linked to the prevalence of obesity and obesity-related chronic diseases. Kochujang (KCJ) has long been a part of seasonings in Korean cuisine as a sauce, dressing or seasoning for meat, vegetable dishes, stew and soup. KCJ is a fermentation product of powdered red peppers combined with powdered meju (fermented soybean powder), salt, malt-digested rice syrup, and rice flour. It takes about six months for producing fermented KCJ.
LOXAPINE MOUNTAIN VIEW, Calif., July 30, 2013 /PRNewswire/ -- Alexza Pharmaceuticals, Inc. (ALXA) today announced that the company's commercial partner Grupo Ferrer Internacional, S.A. has initiated sales of ADASUVE® inhalation powder, pre-dispensed (Staccato® Loxapine) in the European Union ("EU"). ADASUVE is now available in Germany. The first sale and shipment of product by Ferrer triggers a $1.25 million milestone payment to Alexza, pursuant to the Company's collaboration agreement with Ferrer.
