VITAMINS, COMMON INFORMATION

A vitamin (US /ˈvaɪtəmɪn/ or UK /ˈvɪtəmɪn/) is an organic compound required by an organism as a vital nutrient in limited amounts. An organic chemical compound (or related set of compounds) is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on the circumstances and on the particular organism. For example, ascorbic acid (vitamin C) is a vitamin for humans, but not for most other animals, and biotin (vitamin H) and vitamin D are required in the human diet only in certain circumstances.

Thiamin What it does: helps convert the food we eat to the energy we need Foods that have thiamin: spinach, tomato juice, watermelon, sunflower seeds, ham Deficiency problems: weakness, tingling in feet and hands, poor coordination
Riboflavin - named for its yellow color (flavus means yellow in Latin) What it does: helps convert the food we eat to the energy we need Foods that have riboflavin: milk, cheese, liver, broccoli, asparagus, spinach Deficiency problems: eye disorders, cracks at corners of mouth, swollen tongue
Niacin What it does: helps our body use the fat and sugar we eat for energy helps keep our skin healthy Foods that have niacin: mushrooms, tuna, green beans, broccoli, spinach, breakfast cereals Deficiency problems: diarrhea, skin problems, mental disorientation
Vitamin B6 What it does: helps make red blood cells helps our body use the fat and protein we eat for energy Foods that have vitamin B6: spinach, broccoli, tomato juice, banana, watermelon, chicken breast Deficiency problems: headache, convulsions, vomiting, flaky skin, sore tongue
Folate What it does: helps to make new cells helps prevent heart disease Foods that have folate: asparagus, broccoli, corn flakes, green beans, tomato juice, beans Deficiency problems: diarrhea, mental disorders, poor growth
Vitamin B12 What it does: helps to make new cells Foods that have vitamin B12: meat, fish, poultry, milk, cheese, eggs Deficiency problems: anemia, poor nerve function
Vitamin C- almost all animals make vitamin C in their bodies (only humans, guinea pigs, some bats, and some fish don't) What it does: protects cells from damage helps keep bones and skin healthy may help prevent cancer and heart disease Foods that have vitamin C: oranges, strawberries, peppers, kiwi, brussel sprouts, broccoli, spinach Deficiency problems: bleeding gums, tiredness, weakness, sore muscle

Vitamin A - discovered in 1913 What it does: helps with eyesight keeps skin healthy helps with growth of body organs (like bones) Foods that have vitamin A: liver, fish, milk, butter, eggs, carrots Deficiency problems: night blindness, poor growth, dry skin
Vitamin D - made in the skin by the sun What it does: helps bones grow strong Foods that have vitamin D: egg yolks, liver, butter, milk Deficiency problems: rickets (deformed bones), weak bones
Vitamin E - called the antiaging vitamin What it does: protects lungs against pollution damage helps keep heart healthy may help protect against cancer Foods that have vitamin E: sweet potatoes, peanut butter, sunflower seeds, spinach, nuts Deficiency problems: nerve destruction, red blood cell destruction
Vitamin K - made by bacteria in our intestines What it does: helps make blood clot helps keep bones healthy Foods that have vitamin K: liver, cabbage, lettuce, spinach, milk, meat, eggs Deficiency problems: hemorrhage

..........

By convention, the term vitamin includes neither other essential nutrients, such as dietary minerals, essential fatty acids, or essential amino acids (which are needed in larger amounts than vitamins) nor the large number of other nutrients that promote health but are otherwise required less often. Thirteen vitamins are universally recognized at present.

Vitamins are classified by their biological and chemical activity, not their structure. Thus, each "vitamin" refers to a number of vitamer compounds that all show the biological activity associated with a particular vitamin. Such a set of chemicals is grouped under an alphabetized vitamin "generic descriptor" title, such as "vitamin A", which includes the compounds retinal, retinol, and four known carotenoids. Vitamers by definition are convertible to the active form of the vitamin in the body, and are sometimes inter-convertible to one another, as well.

itamins have diverse biochemical functions. Some, such as vitamin D, have hormone-like functions as regulators of mineral metabolism, or regulators of cell and tissue growth and differentiation (such as some forms of vitamin A). Others function as antioxidants (e.g., vitamin E and sometimesvitamin C). The largest number of vitamins, the B complex vitamins, function as precursors for enzyme cofactors, that help enzymes in their work as catalysts in metabolism. In this role, vitamins may be tightly bound to enzymes as part of prosthetic groups: For example, biotin is part of enzymes involved in making fatty acids. They may also be less tightly bound to enzyme catalysts as coenzymes, detachable molecules that function to carry chemical groups or electrons between molecules. For example, folic acid may carry methyl, formyl, and methylene groups in the cell. Although these roles in assisting enzyme-substrate reactions are vitamins' best-known function, the other vitamin functions are equally important.

Until the mid-1930s, when the first commercial yeast-extract vitamin B complex and semi-synthetic vitamin C supplement tablets were sold, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) usually greatly altered the types and amounts of vitamins ingested. However, vitamins have been produced as commodity chemicals and made widely available as inexpensive semisynthetic and synthetic-source multivitamin dietary and food supplements and additives, since the middle of the 20th century.,,,,,,,

List of vitamins

Each vitamin is typically used in multiple reactions, and, therefore, most have multiple functions.

Vitamin generic descriptor name	Vitamerchemical name(s) (list not complete)	Solubility	Recommended dietary allowances (male, age 19–70)[6]	Deficiency disease	Upper Intake Level (UL/day)[6]	Overdose disease	Food sources
Vitamin A	Retinol, retinal, and four carotenoids including beta carotene	Fat	900 µg	Night-blindness,Hyperkeratosis, andKeratomalacia[7]	3,000 µg	Hypervitaminosis A	Orange, ripe yellow fruits, leafy vegetables, carrots, pumpkin, squash, spinach, liver, soy milk, milk
Vitamin B1	Thiamine	Water	1.2 mg	Beriberi, Wernicke-Korsakoff syndrome	N/D[8]	Drowsiness or muscle relaxation with large doses.[9]	Pork, oatmeal, brown rice, vegetables, potatoes, liver, eggs
Vitamin B2	Riboflavin	Water	1.3 mg	Ariboflavinosis	N/D		Dairy products, bananas, popcorn, green beans, asparagus
Vitamin B3	Niacin, niacinamide	Water	16.0 mg	Pellagra	35.0 mg	Liver damage (doses > 2g/day)[10] and other problems	Meat, fish, eggs, many vegetables, mushrooms, tree nuts
Vitamin B5	Pantothenic acid	Water	5.0 mg[11]	Paresthesia	N/D	Diarrhea; possibly nausea and heartburn.[12]	Meat, broccoli, avocados
Vitamin B6	Pyridoxine,pyridoxamine,pyridoxal	Water	1.3–1.7 mg	Anemia[13] peripheral neuropathy.	100 mg	Impairment ofproprioception, nerve damage (doses > 100 mg/day)	Meat, vegetables, tree nuts, bananas
Vitamin B7	Biotin	Water	30.0 µg	Dermatitis, enteritis	N/D		Raw egg yolk, liver, peanuts, certain vegetables
Vitamin B9	Folic acid, folinic acid	Water	400 µg	Megaloblastic anemiaand Deficiency during pregnancy is associated with birth defects, such as neural tube defects	1,000 µg	May mask symptoms of vitamin B12 deficiency;other effects.	Leafy vegetables, pasta, bread, cereal, liver
Vitamin B12	Cyanocobalamin,hydroxycobalamin,methylcobalamin	Water	2.4 µg	Megaloblastic anemia[14]	N/D	Acne-like rash [causality is not conclusively established].	Meat and other animal products
Vitamin C	Ascorbic acid	Water	90.0 mg	Scurvy	2,000 mg	Vitamin C megadosage	Many fruits and vegetables, liver
Vitamin D	Cholecalciferol	Fat	10 µg[15]	Rickets andOsteomalacia	50 µg	Hypervitaminosis D	Fish, eggs, liver, mushrooms
Vitamin E	Tocopherols,tocotrienols	Fat	15.0 mg	Deficiency is very rare; mild hemolytic anemiain newborn infants.[16]	1,000 mg	Increased congestive heart failure seen in one large randomized study.[17]	Many fruits and vegetables, nuts and seeds
Vitamin K	phylloquinone,menaquinones	Fat	120 µg	Bleeding diathesis	N/D	Increases coagulation in patients taking warfarin.[18]	Leafy green vegetables such as spinach, egg yolks, liver

US FDA grants breakthrough therapy designation to Boehringer Ingelheim’s volasertib to treat patients with AML « New Drug Approvals

US FDA grants breakthrough therapy designation to Boehringer Ingelheim’s volasertib to treat patients with AML « New Drug Approvals:

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Indian Medicinal Plants An Illustrated Dictionary

Indian Medicinal Plants An Illustrated Dictionary

Drug therapy: Solamargine and other solasodine rhamnosyl glycosides as anticancer agents

Modern ChemotherapyVol.2 No.2(2013), Article ID:30489,17 pagesDOI:10.4236/mc.2013.22005

http://file.scirp.org/Html/3-2510007_30489.htm

Drug therapy: Solamargine and other solasodine rhamnosyl glycosides as anticancer agents

Bill E. Cham

Australasian Institute of Medical Research, Brisbane, Australia; bill.cham@gmail.com

Copyright © 2013 Bill E. Cham. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received 24 February 2013; revised 26 March 2013; accepted 5 April 2013

Keywords: Cancer; Skin Cancer; Solamargine; Solasonine; BEC; Solasodine Rhamnosyl Glycosides; Curaderm^BEC5; Apoptosis; Antineoplastic; Targeted Therapy

ABSTRACT

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................

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http://file.scirp.org/Html/3-2510007_30489.htm

Generic versions of high cholesterol drug Lovaza can be developed, rules judge « New Drug Approvals

Generic versions of high cholesterol drug Lovaza can be developed, rules judge « New Drug Approvals:

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Scripps Research Institute Scientists Create Extremely Potent and Improved New Derivatives of Successful Anticancer Drug

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.

http://www.scripps.edu/news/press/2013/20130916boger.html

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

vincristine



http://www.scripps.edu/news/press/2013/20130916boger.html


vincristine

LEVOCETRIZINE

LEVOCETRIZINE

Levocetirizine (as levocetirizine dihydrochloride) is a third-generation non-sedative antihistamine, developed from the second-generation antihistamine cetirizine. Chemically, levocetirizine is the active enantiomer of cetirizine. It is the R-enantiomer of the cetirizine racemate. Levocetirizine works by blocking histamine receptors. It does not prevent the actual release of histamine from mast cells, but prevents it binding to its receptors. This in turn prevents the release of other allergy chemicals and increased blood supply to the area, and provides relief from the typical symptoms of hay fever.

The manufacturers claim it to be more effective with fewer side effects than the second-generation drugs; however, there have been no published studies supporting this assertion, although other studies have concluded it may be more effective.^[1]

History and formulations

Levocetirizine was first launched in 2001 by Belgian pharmaceutical company UCB. It is sold under the brand name Xyzal/ˈzaɪzæl/ in Australia, Czech Republic, Austria, Finland, France, Ireland, Netherlands, Portugal, Romania, Taiwan, Turkey, United States, South Africa and UK; Xuzal in Mexico; Xusal in Germany; and Xozal in Greece. In Hungary it is marketed by Richter Gedeon under the Zilola brand name.

In India, levocetirizine is marketed by GlaxoSmithKline under the brand name Vozet and Xyzal. On May 25, 2007, theUnited States Food and Drug Administration approved Xyzal, where it is co-marketed by Sanofi-Aventis. Torrent Pharma launched UVNIL in rural market of India. It is also available as LEZYNCET 5 mg tablets through Unichem in India. In India, generic name of Lev-Cit 5 mg is manufactured by VIP Pharmaceuticals. Also marketed in India by Croslands (Ranbaxy Laboratories Ltd.) under the brand name Teczine. In Brazil it is marketed under the brand name 'Zyxem' by Farmalab. It is marketed in Egypt by BORG Pharma under the brand name 'Xaltec', Allear by western pharmaceuticals and levcet by marcryl.

In Pakistan levocetirizine was first launched in liquid formulation by Novartis Consumer Health Division by the name of T-Day Syrup. It is available as 5 mg-strength tablets and a 0.5 mg/mL oral solution. In Pakistan levocetirizine is available in liquid formulation as well with the name of OCITRA and T-Day 2.5 mg/5 mL. In Bangladesh levocetirizine is available in 5 mg tablet & 2.5 mg/5 mL oral liquid formulation with the brand name of Alcet marketed by Healthcare Pharmaceuticals and Seasonix marketed by Incepta Pharmaceuticals. In Nepal levocetirizine is available in 5 mg tablet with brand name ofCurin manufactured by Beximco Pharma.^[2]

Side effectsl

levocetirizine is called a non-sedating antihistamine as it does not enter the brain in significant amounts, and is therefore unlikely to cause drowsiness. However, some people may experience some slight sleepiness, headache, mouth dryness,lightheadedness, vision problems (mainly blurred vision), palpitations and fatigue.^[3]

Research

latest research shows levocetirizine reduces asthma attacks by 70% in children.^[4]

Availability]

The drug is currently available by prescription in the United States. Although the drug was only authorized by the FDA on 25 May 2007, it was already available in most European countries. Like many new drugs it entered the market at a higher price than currently available third and second generation antihistamines. In India, one form of the drug is available as Crohist MK tablets and syrup, a formulation of levocetirizine hydrochloride and montelukast. In India, Crohist MK is a Schedule 'H' drug and may only be prescribed by a registered medical practitioner. In Finland, the drug is sold over-the-counter.

Different brands (Actavis, Glenmark, UCB) Levocetirizine tablets and oral solution.

1. ^ Grant, JA; Riethuisen, JM; Moulaert, B; DeVos, C; Gamalero, C.; Descalzi, D.; Folli, C.; Passalacqua, G. et al. (2002-02). "A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects.". Ann Allergy Asthma Immunol 88 (2): 190–197. doi:10.1016/S1081-1206(10)61995-3. PMID 11868924.
2. ^ http://www.beximco-pharma.com/allergic-disorders/147-curin.html
3. ^ XOZAL technical specifications booklet.
4. ^ Pasquali, M; Baiardini, I; Rogkakou, A; Riccio, AM; Gamalero, C; Descalzi, D; Folli, C; Passalacqua, G et al. (2006-09)."Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters.".Clinical & Experimental Allergy 36 (9): 1161–7. doi:10.1111/j.1365-2222.2006.02548.x. PMID 16961716.

Figure 1-The chemical structure of Xyzal

BACKGROUND

Cetirizine, chemically [2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid is an antihistamine non-sedating type histamine H₁-receptor antagonist, indicated for relief of symptoms associated with seasonal allergic rhinitis, perennial allergic rhinitis and related diseases.

U.S. Pat. No. 4,525,358 and its equivalent EP 58146 disclose cetirizine and its pharmaceutically acceptable salts. The process for the synthesis of cetirizine comprises condensation of 1-[(4-chlorophenyl)-phenylmethyl]piperazine with 2-chloroethoxy acetamide to obtain 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]-ethoxy acetamide which on hydrolysis gives cetirizine.

It was found later that the pharmacological activity resides primarily in (R)-isomer or (−) form known as levocetirizine. GB 2225321 describes a process for the preparation of the dextro and levorotatory isomers of cetirizine comprising hydrolysis of 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazynyl]-ethoxy acetonitrile.

(−)-1-[(4-chlorophenyl)-phenylmethyl]piperazine is a very important intermediate in the synthesis of levocetirizine. U.S. Pat. No. 5,478,941 discloses a process for the synthesis of (−)-1-[(4-chlorophenyl)-phenylmethyl]piperazine involving hydrolyzing 1-[(4-chlorophenyl)-phenylmethyl]-4-(4-methylphenyl)sulfonyl piperazine with hydrobromic acid in the presence of 4-hydroxybenzoic acid.

The alternative routes of synthesis of (−)-1-[(4-chlorophenyl)-phenylmethyl]piperazine disclosed in the prior art involve the use of bis chloro ethylamine which is carcinogenic in nature.

Levocetirizine is a highly-potent non-sedating anti-allergic agent. Hence, there are continuous attempts to develop new processes for the synthesis of levocetirizine and its intermediates. The present invention describes a new process for the preparation of the key intermediate (−)-1-[(4-chlorophenyl)-phenylmethyl]piperazine.

Levorotatory [2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid, also known by the generic name of levocetirizine, has proven useful as a therapeutic agent for the treatment of allergic disease.

Levocetirizine and its salts including its dihydrochloride are known and are effective in the treatment of allergies, including but not limited to, chronic and acute allergic rhinitis, allergic conjunctivitis, pruritus, urticaria and the like. Levocetirizine belongs to the second generation of H1 histamine receptor antagonists, which are believed to offer significant advantages over first generation compounds. Studies have shown that levocetirizine provides safe and effective symptomatic relief of seasonal allergies. Levocetirizine is used also for treating chronic idiopathic urticaria.

GB 2,225,321 describes a process for the preparation of cetirizine in the levorotatory form, dextrorotatory form or a mixture thereof comprising the hydrolysis of enantiomerically pure [2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetonitrile. Hydrolysis takes place in aqueous, alcoholic or aqueous-alcoholic medium by a base or by an acid; the acid thus obtained is converted to its dihydrochloride. Optically active starting material 1-[(4-chlorophenyl)phenylmethyl]piperazine is obtained by resolution of the corresponding racemic compound, preferably by conversion to its diastereoisomeric salt with tartaric acid. The yield of resolution is rather low, namely only 12.7%. The obtained optically active intermediate is further converted with chloroethoxyacetonitrile in 69% yield.

EP 0 617 028 and EP 0 955 295 disclose a process for the preparation of optically active 1-[(4-chlorophenyl)phenylmethyl]piperazine and its conversion to cetirizine in the levorotatory form or dextrorotatory form or to derivative thereof. The process for the preparation is shown in the following scheme:

The drawback of the disclosed reaction is that it requires protection of N,N-bis(2-haloethyl)amine, and consequently deprotection of the intermediate obtained.

Preparation of Cetirizine in its Levorotatory Form Proceeds in most known syntheses from enantiomerically pure 1-[(4-chlorophenyl)phenylmethyl]piperazine. Consequently it appears to be very desirable to provide new routes to prepare the enantiomers thereof with improved optical purity and good yields.

Polymorphic form I of crystalline levorotatory dihydrochloride salt of cetirizine and amorphous form thereof are disclosed in WO 2004/050647 and WO 2004/065360. Crystalline form is prepared by crystallization from ketone-containing solvent, such as acetone, methyl ethyl ketone, dimethylketone, 2-pentanone and mixtures thereof. Amorphous form was prepared by solvent evaporation.

There still exists a need for an efficient synthesis of levocetirizine, new intermediates used in the process, suitable for large-scale production.

Synthesis of Xyzal:
Figure 2 displays the synthesis of Cetirizine (Zyrtec). Levocetirizine, the R-enantiomer of cetirizine, is then formed from pyroglutamate salts in a synthesis that does not have attainable details.

(Figure 2)

The synthesis of Cetrizine begins by reducing molecule 33 with a catecholborane. This reaction yields molecule 34, which is then treated with tetraflouroboric acid and reacted with an amine, compound 35. In order to remove the chromium group, the compound is refluxed in pyridine and undergoes an acid hydrolysis. This results in a yield of cetrizine.



Identification of all chirality centers:
Stereogenic centers are carbon atoms that are bonded to 4 groups. Tetrahedral stereogenic centers are stereogenic centers that are not only bonded to 4 groups but are more importantly bonded to 4 different groups. If a molecule contains 1 tetrahedral stereogenic center it is said to be chiral (nonsuperimposable on its mirror image).If a given compound contains more than 1 stereogenic center it must be further analyzed to determine if it is chiral or achiral(superimosable on its mirror image). The carbon atom bonded to the phenyl groups was found to be a tetrahedral stereogenic center. Therefore,xyzal,which was found to contain only 1 tetrahedral stereogenic center is generally considered a chiral compound because it meets the requirements of chirality and does not have a plane of symmetry that superimposes one half of the molecule on the other and is not super imposable on its mirror image.

Spectral data for Xyzal (IR and NMR):

• Full US prescribing information Xyzal® (levocetirizine dihydrochloride) tablets and oral solution (provided by UCB, December 2010, pdf file)