Benzenesulfonamide,4-amino- and Elixir sulfanilamide

Benzenesulfonamide,4-amino- (also called sulphanilamide) is a sulfonamide antibacterial. It is a kind of white granular or crystalline powder, odorless, slightly bitter taste. It is slightly soluble in cool water, ethanol, methanol, acetone, soluble in boiling water, glycerol, hydrochloric acid, potassium hydroxide and sodium hydroxide solution, insoluble in benzene, chloroform, ether and petroleum ether. Drug use in medicine can do for bacterial growth and proliferation inhibition.CAS NO is 63-74-1, Formula is C6H8N2O2S, and the Molecular Weight is 172.22.

Chemically, Benzenesulfonamide,4-amino- is a molecule containing the sulfonamide functional group attached to an aniline. As a sulfonamide antibiotic, it functions by competitively inhibiting (i.e., by acting as a substrate analogue) enzymatic reactions involving para-aminobenzoic acid (PABA). PABA is needed in enzymatic reactions that produce folic acid which acts as a coenzyme in the synthesis of purine, pyrimidine and other amino acids.

Elixir sulfanilamide was an improperly prepared Chemically, Benzenesulfonamide,4-amino- medicine that caused mass poisoning in the United States in 1937. It caused the deaths of more than 100 people. The public outcry caused by this incident and other similar disasters led to the passing of the 1938 Federal Food, Drug, and Cosmetic Act.

Aside from the Pure Food and Drug Act of 1906 and the Harrison Act of 1914 banning the sale of some narcotic drugs, there was no federal regulatory control insuring the safety of new drugs until Congress enacted the 1938 Food, Drug, and Cosmetic Act in response to a drug poisoning crisis.

In 1937, S. E. Massengill Co., a pharmaceutical manufacturer, created a preparation of sulfanilamide using diethylene glycol (DEG) as a solvent, and called the preparation "Elixir Sulfanilamide". DEG is poisonous to humans, but Harold Watkins, the company's chief pharmacist and chemist, was not aware of this (although it was known at the time). The company chemist merely added raspberry flavoring to the sulfa drug which he had dissolved in DEG and the company marketed the product. Although animal testing should have been routine in most drug company operations, Massengill performed none and there were no regulations requiring premarket safety testing of new drugs.

The company started selling and distributing the medication in September 1937. By October 11, the American Medical Association received a report of several deaths caused by the medication. The Food and Drug Administration was notified, and an extensive search was conducted to recover the distributed medicine. Frances Oldham Kelsey assisted on a research project, which verified that the excipient DEG was responsible for the fatal adverse effects. At least 100 deaths were blamed on the medication.

The owner of the company, when pressed to admit some measure of culpability, famously answered, "We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results. I do not feel that there was any responsibility on our part." Massengill's chief chemist, Harold Watkins, committed suicide while awaiting trial.2

Congress responded to public outrage by passing the 1938 Food, Drug, and Cosmetic Act which required that companies perform safety tests on their proposed new drugs and submit the data to the FDA before being allowed to market their product. The Massengill Company paid a minimum fine under provisions of the 1906 Pure Food and Drugs Act which prohibited labeling the preparation an "elixir" if it had no alcohol in it.

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1,3-Dimethoxy benzene information

1,3-Dimethoxy benzene, which is also known as Dimethyl resorcinol, m-Dimethoxybenzene, Resorcinol dimethyl ether, Dimethylresorcinol, 3–Methoxyanisole, Dimethylether resorcinolu(Czech), 1,3-Dimethoxybenzeen, 1,3-Dimethoxybenzene and Dimethylether resorcinolu. The CAS NO of 1,3-Dimethoxy benzene is 151-10-0, MF is C8H10O2, MW is 138.1638.

The density of 1,3-Dimethoxy benzene is 1.055. Boiling point is 85-87 degree. Refractive index is 1.523-1.525, flash point is 87 degree, and relative density is 1.005g/cm3. It is a kind of colorless and transparent liquid. There are orange blossom aroma ether, slightly spicy taste

1,3-Dimethoxy benzene is used for organic synthesis intermediates, and benzoyl chloride in three aluminum chloride catalyst for mandrax-Crafts reaction, to be 2,4-dimethoxy benzophenone. It is the UV absorber UV-9 intermediates. 

A Typical Iodination Procedure Using Micromixing. 

A solution of 1,3-dimethoxybenzene (112 mg, 0.811 m mol) in CH3CN and an I+ solution (8 mL, cooled at 0 ℃), generated from I2 (127 mg, 0.500 m mol) using the electrochemical method described above, were simultaneously introduced to an IMM single mixer (version 2) having a Si inlet (channel width = 50 μm), which was dipped in a coolant at 0 ℃, using syringe pumps (flow rate is 3.0 mL/min each). Then, the reaction mixture coming out from the outlet of the micromixer was collected with a 100 mL round bottom flask, containing sat. NaHCO3 (30 mL), sat. NaS2O3 (1 mL), and Et2O (30 mL), with magnetic stirring. 

The organic layer was separated and the solvent was removed under reduced pressure. The residue 
was quickly filtered through a short column (10 cm) of silica gel to remove Bu4NBF4. The silica gel was washed with Et2O (100 mL). The solvent was removed under reduced pressure and the residue was dissolved in hexane (50 mL). The organic phase was washed with sat. NaHCO3 (30 mL) and then was separated. The solvent was removed to give a crude product (204 mg). Yields of 4-iodo-1,3-dimethoxybenzene (monoiodo product) and 4,6-diiodo-1,3- dimethoxybenzene (diiodo product) were determined by GC analysis: 4-iodo-1,3-dimethoxybenzene 78% (167 mg, 0.632 m mol): 4,6-diiodo-1,3- dimethoxybenzene 4% (13 mg, 0.033 m mol).

First Aid Measures

Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid. 

Skin: Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse. 

Ingestion: Do not induce vomiting. If victim is conscious and alert, give 2-4 cupfuls of milk or water. Never give anything by mouth to an unconscious person. Get medical aid. 

Inhalation: Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid. 


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Our body need L-Glutamine,N-ethyl-

L-Glutamine,N-ethyl- was discovered as a constituent of green tea in 1949 and was approved in Japan in 1964 for unlimited use in all foods, including chocolates, soft drinks, and herb teas, except infant foods. It also provides a unique umami (brothy or savory) taste and flavor to green tea infusion.

In 1950, the tea laboratory of Kyoto successfully separated L-Glutamine,N-ethyl- from gyokuro leaf, which has high L-Glutamine,N-ethyl- content. It is an analog to glutamine and glutamate, and can cross the blood–brain barrier. It is sold in the US as a dietary supplement, and is classified by the Food and Drug Administration (FDA) as a generally recognized as safe (GRAS) ingredient. However, the German Federal Institute for Risk Assessment (Bundesinstitut für Risikobewertung, BfR) has objected to the addition of isolated L-Glutamine,N-ethyl- to beverages.

L-Glutamine,N-ethyl-(CAS NO:3081-61-6) is an amino acid derived from another amino acid, glutamic acid. Glutamine plays a role in the health of the immune system, digestive tract, and muscle cells, as well as other bodily functions. It appears to serve as a fuel for the cells that line the intestines. Heavy exercise, infection, surgery, and trauma can deplete the body's L-Glutamine,N-ethyl- reserves, particularly in muscle cells.

The fact that L-Glutamine,N-ethyl- does so many good things in the body has led people to try L-Glutamine,N-ethyl- supplements as a treatment for various conditions, including preventing the infections that often follow endurance exercise, reducing symptoms of overtraining syndrome, improving nutrition in critical illness, alleviating allergies, and treating digestive problems.

Early studies of this chemical involved much larger doses than are found in an everyday cup of tea. Researchers wonder whether drinking tea might have the same effects found in those studies.However, one recent study by Unilever found that smaller doses typical of those found in a cup of tea did induce changes in alpha waves as shown by EEG. Alpha waves occur in the brain and are associated with relaxation.

As a naturally occurring amino acid, L-Glutamine,N-ethyl- is thought to be a safe supplement when taken at recommended dosages. There is strong evidence that this medicine is safe at levels up to 14 g per day, although higher dosages have been tested without apparent adverse effects. 

Nevertheless, those who are hypersensitive to monosodium glutamate (MSG) should use L-Glutamine,N-ethyl- with caution, as the body metabolizes it into glutamate. Also, because many anti-epilepsy drugs work by blocking glutamate stimulation in the brain, high dosages of L-Glutamine,N-ethyl- might conceivably overwhelm these drugs and pose a risk to people with epilepsy . 

In one case report, high doses of the supplement L-Glutamine,N-ethyl- (more than 2 g per day) may have triggered episodes of mania in two people not previously known to have bipolar disorder. In a small randomized trial including 30 older people,L-Glutamine,N-ethyl- did not cause any clinically significant changes in lab tests. The researchers did urge caution, though, since there were some statistically significant changes for certain kidney levels. 

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The details of Topiramate

Topiramate is a white crystalline powder with a bitter taste. It is most soluble in alkaline solutions containing sodium hydroxide or sodium phosphate and having a pH of 9 to 10. It is freely soluble in acetone, chloroform, dimethylsulfoxide, and ethanol. The solubility in water is 9.8 mg/mL. Its saturated solution has a pH of 6.3. It has the molecular formula C12H21NO8S and a molecular weight of 339.36. 

Topiramate(CAS NO:97240-79-4) is an oral drug that is used to prevent the seizures of epilepsy. It is an anti-epileptic or anti-seizure drug. It is used primarily among patients who are not controlled by other anti-epileptic drugs. About 1 in 4 Americans diagnosed with epilepsy has seizures that resist treatment with other anti-epileptic drugs. It also prevents migraine headaches.

Before taking topiramate, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: a certain eye problem (narrow angle glaucoma), kidney problems (such as kidney stones), liver problems, mental/mood problems (such as depression, thoughts of suicide), lung/breathing problems, a certain metabolic imbalance (metabolic acidosis), long-term diarrhea, a diet high in fat and low in carbohydrates (ketogenic diet), brittle bones (osteoporosis).

Most commonly, topiramate is started in low doses, 25 or 50 mg per day, and then increased slowly by 25 to 50 mg per week until an effective daily dose is reached. For children 10 years or older and adults the dose may be increased by 100 mg in week 5 and 6 when it is used alone. This slow approach to treatment reduces side effects. The recommended final adult dose is 200-400 mg administered as two divided doses daily.

In children, the starting dose is up to 25 mg (1 to 3 mg/kg/day), taken nightly for the first week. The dose is then increased at 1 or 2 week intervals by 1 to 3 mg/kg/day administered in two divided doses. The target dose is 5 to 9 mg/kg per day in two divided doses.

Migraine is treated 25 mg nightly for the first week then increased by 25 mg weekly up to a maximum dose of 100 mg administered in two divided doses. Patients should maintain an adequate fluid intake in order to minimize the risk of kidney stones.

Topiramate is absorbed quickly by the body soon after you swallow it. The drug works by interacting with the neurotransmitter GABA which controls communication between brain cells. It helps GABA to reduce certain types of excitory neural impulses to prevent seizures and stabilize mood. Around 70 percent of the drug is excreted in the urine.

The half-life of a medication denotes how long it takes for the concentration of the drug in your plasma to reach half of its original concentration, in other words, how long it takes for half of the original dose to be eliminated from your blood stream. The half-life of topiramate is 19-23 hours.

You should seek medical advice immediately if you are using topiramate and experience any of the following side effects: depression, suicidal thoughts, hyperactivity, irritability, hostility or anxiety. Other possible side-effects include impaired vision. You should also avoid drinking alcohol as this can in crease the risk of seizures.

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How to take Orlistat

Orlistat (also known as tetrahydrolipstatin) is a drug designed to treat obesity. It is marketed as a prescription under the trade name Xenical by Roche in most countries, and is sold over-the-counter as Alli by GlaxoSmithKline in the United Kingdom and the United States. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It is intended for use in conjunction with a healthcare provider-supervised reduced-calorie diet.

Orlistat (prescription and nonprescription) is used with an individualized low-calorie, low-fat diet and exercise program to help people lose weight. Prescription Orlistat(CAS NO:96829-58-2) is used in overweight people who may also have high blood pressure, diabetes, high cholesterol, or heart disease. It is also used after weight-loss to help people keep from gaining back that weight. It is in a class of medications called lipase inhibitors. It works by preventing some of the fat in foods eaten from being absorbed in the intestines. This unabsorbed fat is then removed from the body in the stool.

Orlistat comes as a capsule and a nonprescription capsule to take by mouth. It is usually taken three times a day with each main meal that contains fat. Take this medicine during a meal or up to 1 hour after a meal. If a meal is missed or does not have fat, you may skip your dose. Follow the directions on your prescription label or the package label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take this medicine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor or stated on the package.

Orlistat works by inhibiting gastric and pancreatic lipases, the enzymes that break down triglycerides in the intestine. When lipase activity is blocked, triglycerides from the diet are not hydrolyzed into absorbable free fatty acids, and are excreted undigested instead. Only trace amounts of this medicine are absorbed systemically; the primary effect is local lipase inhibition within the GI tract after an oral dose. The primary route of elimination is through the feces.

Orlistat was also recently found to inhibit the thioesterase domain of fatty acid synthase (FAS), an enzyme involved in the proliferation of cancer cells but not normal cells. However, potential side effects of this medicine, such as inhibition of other cellular off-targets or poor bioavailability, might hamper its application as an effective antitumor agent. 

One profiling study undertook a chemical proteomics approach to look for new cellular targets of Orlistat, including its off-targets. Orlistat also show potential activities mycobacteria and Trypanosoma brucei parasite (See further reading).

At the standard prescription dose of 120 mg three times daily before meals, orlistat prevents approximately 30% of dietary fat from being absorbed, and about 25% at the standard over-the-counter dose of 60 mg. Higher doses do not produce more potent effects.

Keep Orlistat in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat, moisture (not in the bathroom), and light. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

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The manufacture of veratraldehyde

This invention relates to the manufacture of veratraldehyde and is more particularly directed to processes in which veratraldehyde is produced by the addition to vanillin of caustic :and dimethyl sulfate at a pH from about 8.5 to 9.5.

Veratraldehyde(CAS NO.:120-14-9) has heretofore been produced by processes in which vanillin is treated with dimethyl sulfate and caustic has been used to reduce the acidity of the reaction,'but in such prior art processes relatively poor yields are obtained, say 80%, and the products produced are of relatively poor quality.It is an object of this invention to provide simple and economical processes by means of which it may be made from vanillin.It is a further object to provide processes for the production of this chemical from vanillin in good yield and to obtain products of high quality.

Further objects will become apparent hereinafter.

The foregoing and other objects of the invention are attained by simultaneously adding caustic and dimethyl sulfate to vanillin and by maintaining a pH within the range of 8.5 to 9.5.The reaction may be represented as follows: Sulfuric acid may be used or there may be used any other acid by means of which a pH of 4 to 5 can be obtained. There may be used, for instance, hydrochloric acid, sulfamic acid, and the like.After acidiflcation the system separates into an aqueous phase and a veratraldehyde phase and the aqueous phase may be drawn off from the bottom of the reactor to leave the this chemical. It may then be treated further or may be discharged to suitable containers.

It is to be observed that the temperatures used throughout should be maintained around 80 to 90° C. When the vanillin is first put in water the temperature must be raised up to about 80' C. and heat must be supplied. During the addition of caustic and dimethyl sulfate some cooling is required to keep the temperature between about 80 and 90* C. During acidification the temperature should be maintained by supplying heat as needed to hold the temperature to about 70 to 80' C.

As has been indicated above, it is generally desirable to maintain the pH between about 8.5 In conducting a process of the present invention, vanillin is added to water and melted by heating. Caustic is added to dissolve the vanillin and the pH is then adjusted.The caustic is preferably sodium hydroxide but 35 another caustic may be used which will neutralize the acidity and maintain the indicated pH range. There may, for instance, be used potassium hydroxide, calcium hydroxide, sodium carbonate, and the like. 40 To the vanillin, which is in the desired pH range, there is then added simultaneously caustic and dimethyl sulfate. Another methylating agent such as NaCH3SO4 may be used. The addition of caustic and dimethyl sulfate is made 45 with each of the materials present in such amount as to maintain the pH within the desired range.The methylation is continued to produce the desired methylation. Usually a small excess of 50 dimethyl sulfate, say 25 per cent, will be used.

After the addition of caustic and dimethyl sulfate is complete the reaction is allowed to continue for a short time, say-fifteen minutes or so, and then/the system is acidified to pH 4.0 to 5.0. 55 and 9.5 throughout the methylation. To this end the caustic is added to the vanillin to adjust the pH within the range indicated and then caustic is supplied simultaneously with dimethyl sulfate. It is still more specifically preferred to operate within a pH range from 9.0 to 9.5. Within this narrow range the best results of the invention are obtained.

While it is quite important to hold the pH within the ranges stated, particularly during the addition of dimethyl sulfate, it will be understood that in a commercial operation this pH control may be achieved by the stepwise addition of predetermined amounts of material. A laboratory, for instance, can determine under specific conditions of operation just what increments must be added and the plant may follow a predetermined schedule of additions. It is, however, ordinarily to be preferred to check the pH of the system to be sure that the pH at no time goes outside of the ranges above indicated.

In order that the invention may be better understood reference should be had to the following illustrative example: Example A water heel from a preceding operation was charged into a reaction kettle in the amount of 442 pounds. To the water was added 362 pounds of vanillin and heat was applied to melt the vanillin. The temperature reached was about 80 to 85* C. Sodium hydroxide in the amount of 143 pounds of a 50% solution was then added and a small amount of cooling was supplied to hold the temperature within the range of 80 to 90° C. The amount of caustic was that required to adjust the pH to about 9.2.

A 50% solution of sodium hydroxide and dimethyl sulfate were then simultaneously added to the kettle over a period of about four hours. The pH was maintained within the range pH 9.0 to 9.5 during the reaction. The temperature was held by cooling within the range of 80 to 90* C. During the simultaneous reaction of caustic and dimethyl sulfate there was added 143 pounds of a 50% solution of sodium, hydroxide and 376 pounds of dimethyl sulfate..

After the addition of caustic and dimethyl sulfate was complete the reaction was held for about 15 minutes and then the reaction mixture was acidified to a pH of 4.0 to 5.0 by the addition of 58 pounds of sulfuric acid (50% HzS04). During the acidification temperature was maintained between about 70 and 80° C. using steam.

The reaction mass was allowed to settle for one hour and the aqueous phase was drawn off from the bottom of the kettle and discharged to waste except for the fraction returned to the first step of a similar reaction.i. The veratraldehyde was recovered as the product of the process.

Usages and effects of Mifepristone

Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. Mifepristone is also a powerful glucocorticoid receptor antagonist, and has occasionally been used in refractory Cushing's Syndrome (due to ectopic/neoplastic ACTH/Cortisol secretion).

During early trials, it was known as RU-38486 or simply RU-486, its designation at the Roussel Uclaf company, which designed the drug. The drug was initially made available in France, and other countries then followed—often amid controversy. It is marketed under tradenames Korlym and Mifeprex, according to FDA Orange Book. Some examples of such drugs include ibuprofen, aspirin, and naproxen. This medication is often used for people that are at an especially high risk of experiencing ulcers.

The Primary Use
Misoprostol(CAS NO.:84371-65-3) is a medication that works to stop stomach ulcers from happening when individuals take NSAIDs. It reduces the chances of severe complications of ulcers, like bleeding. It functions by defending the lining of the stomach by reducing the levels of acid that come into contact with the lining.

Used as Abortion
A secondary use for this medication is for the termination of pregnancy, which is also known as abortion.An abortion is the termination of a pregnancy. Whenever possible, abortions should be performed by the ninth week of pregnancy in order to limit complications. There are risks involved at any time---during the procedure and afterward. Choosing abortion requires careful consideration. It is used alongside another drug, which is known as mifepristone, in order to end a pregnancy. Mifeprostone obstructs progesterone, which is a hormone that is necessary to keep a pregnancy going. This results in the shedding of the uterine lining, and the softening of the cervix, which could lead to bleeding. Then, misoprostol is administered, which causes the uterus to contract and causes the pregnancy to terminate itself within approximately 6 to 8 hours.

Help with Childbirth
Mifeprostone is also sometimes used in helping with childbirth, when the baby is being delivered. It can assist in inducing labor as well as cervical ripening. It also can help treat and manage serious bleeding that sometimes happens right about delivery. It is administered vaginally in those situations, and functions by enabling the muscles of the womb to contract.

Common Side Effects
In using Mifeprostone, it is possible to experience several common side effects. These common side effects include stomach cramps, diarrhea, and nausea. These side effects are considered to be minor, because they usually rapidly subside (as the body adapts to the medicine). However, if you experience any of these side effects, and they intensify with time (as opposed to decreasing), talk with your doctor about them as soon as possible.

Severe Side Effects
Using Mifeprostone also could lead to some very uncommon, but simultaneously very severe side effects as well. If you have any of these side effects, you need to seek emergency medical attention (as they could result in potentially harmful consequences). These side effects are heavy or abnormal vaginal bleeding, and menstrual irregularities or problems.

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What is L-Glutamine,N-ethyl- ?

L-Glutamine,N-ethyl- is an amino acid commonly found in tea products. Usually found in dietary supplements, it has shown promise in relieving anxiety disorders, lowers your risks of high blood pressure and helps prevent Alzheimer's disease.

L-Glutamine,N-ethyl-(CAS NO.:3081-61-6) is a water-soluble amino acid. Amino acids are the building blocks of proteins. it has been studied for its possible health benefits, ranging from cancer and stroke prevention to weight loss . However, most research on the amino acid has been conducted to assess its stress-relieving effects. It is found mainly in tea (green tea and black tea), and to a less extent in mushrooms. it is also available in its purified form as an oral dietary supplement. 

How does L-Glutamine,N-ethyl- work in our body? One of the main ways that L-Glutamine,N-ethyl- works is in how it affects gamma-aminobutyric acid (GABA). GABA is a chemical found in the brain that when released naturally creates a calm feeling in the body. It  increases the amount of GABA the body creates and distributes to the brain. The calming effect can be a great natural way to relieve some of the symptoms associated with anxiety.

L-Glutamine,N-ethyl- also works by increasing the amount of serotonin that is made and distributed into the bloodstream. Serotonin works as a neurotransmitter for controlling emotions such as anger and happiness. The greater amount of serotonin in the body, the better ability you have to control your mood. This has helped in treatment of disorders such as depression and anxiety disorder.

L-Glutamine,N-ethyl- also works by decreasing the amount of norepinephrine released in the body. Norepinephrine is a chemical that is produced when the body enters a "fight-or-flight" status. This also dramatically increases your blood pressure. Lowering the amount of the chemical in your blood can both help relieve anxiety, as well as hypertension.

What side effects may L-Glutamine,N-ethyl- have? Although there have been a handful of studies evaluating this medicine for several conditions, 13 most research has been centered on its effects on mental status. L-Glutamine,N-ethyl- is sometimes used as an herbal sedative. However, it should not be taken in conjunction with other sedatives to avoid potentially dangerous increased sedative effects, according to Sloan-Kettering.

L-Glutamine,N-ethyl- should not be taken with stimulant drugs such as diethylpropion, epinephrine, phentermine and pseudoephedrine, according to WebMD. Stimulant drugs speed up the nervous system. It's relaxant effects counter the effects of stimulant medications.

L-Glutamine,N-ethyl- lowers overall cholesterol, meaning it lowers both low-density lipoprotein (bad cholesterol) and high-density lipoprotein (good cholesterol), according to Sloan-Kettering. Although lowering low-density lipoprotein is beneficial, some high-density lipoprotein is needed to carry cholesterol away from the arteries to the liver where it is passed through body, according to the American Heart Association.

L-Glutamine,N-ethyl- is shown to lower blood pressure and should not be taken with antihypertensive drugs, according to WebMD. Taking this medicine with drugs that decrease blood pressure can result in dangerously low blood pressure.Although the risk to infants is unknown, WebMD suggests that pregnant and breast feeding women avoid it. It is one of the few dietary supplements that crosses the blood-brain barrier, according to Life Extension Magazine. This factor may increase potential risks to fetuses, infants and small children.


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Questions about Cyclohexane

Cyclohexane is a cycloalkane with the molecular formula C6H12. Cyclohexane is used as a nonpolar solvent for the chemical industry, and also as a raw material for the industrial production of adipic acid and caprolactam, both of which being intermediates used in the production of nylon. 

On an industrial scale, cyclohexane is produced by reacting benzene with hydrogen. Producers of cyclohexane account for approximately 11.4% of global demand for benzene. Because of its unique chemical and conformational properties, it is also used in labs in analysis and as a standard. It has a distinctive detergent-like odor, reminiscent of cleaning product (in which it is sometimes used). Although Cyclohexane(CAS NO. :110-82-7) is used widely in our life, there are many questions about Cyclohexane in our mind. This article will list some questions about this chemical, I hope it will give you a little help.

First question from a chemistry student about how to make the molecular model of Cyclohexane?

If the model in your syllabus is a planar model:
1. Get 6 completely straight metal wires of equal length. The thinner the better. They represent the C-C bonds in the molecule.
2. Get some modelling clay (the soft and moldable kind) and make 6 small marble-sized balls out of it. these marbles represent carbon atoms. 
3. with the help of a protractor, measure 120 degrees and fasten the six wires using the clay-marbles to form a sort of hexagonal ring. 
4. You could attatch two small beads to each marble to represent hydrogen atoms. 

If the model is to be in accordance with the sasche-mohr theory wherin Cyclohexane has a puckered configuration, here's how you should do it: 
1. Get 6 completely straight metal wires of equal length. The thinner the better. They represent the C-C bonds in the molecule. 
2. Get some modelling clay (the soft and moldable kind) and make 6 small marble-sized balls out of it. these marbles represent carbon atoms. 
3. with the help of a protractor, measure 109.5 degrees and fasten the six wires using the clay-marbles to form a sort of ring which is not planar but resembles a chair or boat. 
4. You could attatch two small beads to each marble to represent hydrogen atoms.

Second about what are the difference between cyclohexane and benzene anybody?

Cyclohexane has no double bonds, it is just hexane joined up in a circle with two less hydrogens. Wheras benzene has a ring of dislocated electrons shown as three double bonds and so it is like cyclohexane but with only one hydrogen per carbon. In the other words, Cyclohexane is a ring of carbons single-bonded to each other with 2 hydrogens bonded to each carbon. Benzene is a ring of carbons with a double bond between every other carbon and one hydrogen bonded to each carbon. Benzene also has resonance between its bonds and is a flat molecule.
Can acetone have dipole-dipole interactions with cyclohexane?

Cyclohexane has no polar functional groups. Acetone has a polar carbonyl functional group. There would be no dipole-dipole interaction between the two because cyclohexane has no dipole moment. However, the dipole moment in the acetone (because the electron charge density favors the oxygen) will induce a momentary dipole in the cyclohexane (like a London dispersion force, but stronger because this is induced, whereas the London disperson force is due to chance). This dipole-induced dipole characterizes the intermolecular interaction between cyclohexane and acetone.

Is cyclohexane and cyclohexene soluble in water?

Cyclohexane is not soluble in, or miscible with water. Given the general rule of "like dissolves like", a quick check of the chemical structure of cyclohexane suggests that it is extremely low in polarity. It is a completely symmetrical saturated 6 membered ring containing carbon and hydrogen only. Nothing with sufficient electronegativity to cause significant polarity, and no asymmetry to cause any uneven electron distribution. Water on the other hand, not only contains highly electronegative oxygen, but also two hydrogen atoms, whose electron cloud is being pulled by the oxygen, so it is a dipole. 

I would disagree with some of the other contributors in terms of cyclohexene though. I wouldn't say it was "insoluble" in water, I would say it is "very sparingly soluble" in water. You can dissolve about 200 mg of cylcohexene into a litre of water at ambient temperature. The presence of the double bond in cyclohexene makes it (very very) slightly more polar than cyclohexane, which enables a tiny proportion to be solvated.

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Risk of Topiramate

Topiramate is a white crystalline powder with a bitter taste. It is most soluble in alkaline solutions containing sodium hydroxide or sodium phosphate and having a pH of 9 to 10. It is freely soluble in acetone, chloroform, dimethylsulfoxide, and ethanol. The solubility in water is 9.8 mg/mL. Its saturated solution has a pH of 6.3.

Topiramate has the molecular formula C12H21NO8S and a molecular weight of 339.36, the CAS NO. is 97240-79-4. It is designated chemically as 2,3:4,5Di-O-isopropyliden-β-D-fructopyranose sulfamate.

Topiramate is an oral drug that is used to prevent the seizures of epilepsy. It is an anti-epileptic or anti-seizure drug. It is used primarily among patients who are not controlled by other anti-epileptic drugs. About 1 in 4 Americans diagnosed with epilepsy has seizures that resist treatment with other anti-epileptic drugs. It also prevents migraine headaches.

A GlaxoSmithKline-sponsored Phase IV study suggested that cognitive side effects may be more common with topiramate than with lamotrigine. In studies of healthy volunteers, therapeutic doses of topiramate for bipolar disorder produced greater cognitive deficits than lamotrigine, including short term memory loss and word-finding difficulty.

Side-effects reported by > 10% of subjects in at least one clinical study (listed by prevalence):

paresthesia (numbness & tingling) (23.7%)
upper respiratory tract infection (17.5%)
diarrhea (16.8%)
nausea (15.4%)
anorexia (loss of appetite) (13.3%)
memory problems (11.2%)

Side-effects most frequently leading to discontinuation of therapy with topiramate:

psychomotor slowing (4.1%)
memory problems (3.3%)
fatigue (3.3%)
confusion (3.2%)
somnolence (3.2%)

That same study also reported that in adult patients with Bipolar 1 disorder who were already receiving either lithium or valproate, the addition of topiramate did not produce a statistically significant improvement versus placebo, while adding the above adverse reactions.

Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.

The U.S. Food and Drug Administration (FDA) has notified prescribers that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take this medicine regularly. The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of this medicine may halt the progression of the ocular damage, and may reverse the visual impairment.

Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations. This might be particularly important for women who take this medicine to prevent migraine attacks. In March 2011 the FDA notified healthcare professionals and patients of an increased risk of development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with topiramate during pregnancy and placed it in Pregnancy Category D.

Topiramate has been associated with a statistically significant increase in suicidality, and "suicidal thoughts or actions" is now listed as one of the possible side effects of the drug "in a very small number of people, about 1 in 500."

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Is Diosmin safe?

Diosmin is a supplement that is used to treat varicose veins and other vein related issues. It is basically a natural blood thinner. It not only thins the blood but also helps protect the veins from being damaged. 

Since Diosmin is a blood thinner it is important to consult a physician before talking Diosmin and also before any medical procedures. It is important to inform your physician of any thing you take whether it is through prescription or through over the counter treatments and supplements. It is a perfect example of this, as a patient would have to be off this product for a period of time before any procedure due to possible blood loss. 

The United States has allowed Diosmin(CAS NO.:520-27-4) to be sold without a prescription as an herbal supplement. The safety of this product has not been confirmed, but there is not sufficient scientific evidence to have this product banned from the United States market or labeled as a prescription drug. This supplement should not be taken in combination with other blood thinners or SSRI’s and other forms of anti-depressants. Dangerous reactions may occur.

Diosmin is a natural ingredient found in plants. The active ingredient in this medicine is known as Flavanoid. Flavanoids are blood thinner so it should be with caution and doctor’s approval that you take this supplement. In many countries Diosmin is only available through prescription, but the FDA has only allowed it to be sold as an herbal supplement. It also has not put any restrictions on this supplement as there has not been solid evidence to show it to be grossly harmful to ones health.

Diosmin prolongs the vasoconstrictor effect of norepinephrine on the vein wall, increasing venous tone, and therefore reducing venous capacitance, distensibility, and stasis. This increases the venous return and reduces venous hyperpressure present in patients suffering from CVI.

Diosmin improves lymphatic drainage by increasing the frequency and intensity of lymphatic contractions, and by increasing the total number of functional lymphatic capillaries. Furthermore, diosmin with hesperidine decreases the diameter of lymphatic capillaries and the intralymphatic pressure.

At the microcirculation level, diosmin reduces capillary hyperpermeability and increases capillary resistance by protecting the microcirculation from damaging processes.

Diosmin reduces the expression of endothelial adhesion molecules (ICAM1, VCAM1), and inhibits the adhesion, migration, and activation of leukocytes at the capillary level. This leads to a reduction in the release of inflammatory mediators, principally oxygen free radicals and prostaglandins (PGE2, PGF2a).

Diosmin is distributed in the U.S. as a dietary supplement. The FDA concluded that there was inadequate evidence on which to base an expectation of safety. One company that markets diosmin supplements, Nutratech, has responded that diosmin can reasonably be expected to be safe on the basis of clinical trials, and has a long history of use in Europe. In the U.S., dietary supplements are regulated under Dietary Supplement Health and Education Act of 1994, which does not require proof of efficacy so long as no specific health claims are made.


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What does Oxandrolone give us？

Oxandrolone, also known as oxandrin, is a drug first synthesized by Raphael Pappo while at Searle Laboratories, now Pfizer Inc., under the trademark Oxandrolone, and introduced into the United States in 1964. It is a synthetic anabolic steroid derivative of dihydrotestosterone with an oxygen atom replacing the 2 carbon and methylation in the 17 position.

Oxandrolone(CAS NO.: 53-39-4) was developed to treat conditions of muscle wasting and rapid weight loss, as is a common reason for inception with any anabolic steroid. Developed in 1964, by Searle Laboratories to treat such conditions, Searle is no longer in existence as it was bought and absorbed into Pfizer in 2003. 

However, it was Searle’s development of Oxandrolone that is of importance because this is a pharmacy that has brought us some of the most well-known medications and other items we still use today, most notably, Celebrex, Ambien, Dramamine and NutraSweet. As you can see Searle developed some very important products over the years and its development of Oxandrolone is no exception because with its inception one of the safest anabolic steroids for both men and women would hit the shelves.

As a very mild anabolic steroid Oxandrolone is not well-suited for bulking cycles or gaining phases; you will not produce a vast amount of lean muscle tissue through its use when speaking of performance enhancing purposes; however, what is produced will be solid muscle tissue. The greatest benefits associated with this particular steroid lie within muscle preservation and metabolic activity.

 This simply means Oxandrolone has the ability to not only aid in reducing body-fat but preserving muscle tissue while on a calorie restricted diet; further, the more muscle tissue we have the greater our metabolic activity will be thereby increasing the rate in-which body-fat is utilized for energy. Because Oxandrolone is apt for fat reduction and muscle preservation it is commonly used by physique athletes during their competition preparation, as well as by common gym rats who simply want to look leaner and tighter at the beach.

Most anabolic steroids carry with them the possibility of many adverse side-effects. It is important to keep in mind these side-effects are only possible, they are by no means guaranteed or assured and are largely avoidable when used responsibly. 

However, negative side-effects can occur when steroids are abused and even in some who are sensitive even though they use responsibly they may fall prey to negative outcomes; the same can be said of Aspirin. 

While many anabolic steroids carry vast possible negative side-effects such as estrogenic related due to aromatization, Oxandrolone does not possess these traits. Oxandrolone does not aromatize making common side-effects such as Gynecomastia little to no concern; Further, as most steroids are very suppressive to natural testosterone production Oxandrolone is very mild in this regard, so mild that one could take Oxandrolone and still produce some natural testosterone. However, some suppression will still exist and the extent will largely be dose dependent.

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Something important before taking Alendronate sodium

Alendronate sodium is a bisphosphonate drug used for osteoporosis and several other bone diseases. It is marketed alone as well as in combination with vitamin D. Alendronate sodium is a white Crystalline Solid, the Molecular Formula is C4H12NNaO7P2.3(H2O), Molecular Weight is 249.096042, and the CAS Registry Number is 121268-17-5.

Available by prescription only, alendronate sodium is an oral medication used for treating osteoporosis and Paget's disease of the bone. In postmenopausal women, the medication is also approved to prevent osteoporosis. The tablets come in five strengths and belong to a class of drugs known as bisphosphonates.

The medication works by slowing down the rate at which bone is broken down and encouraging normal reformation. Depending on your dose, the tablets can be taken daily or weekly. For people who are unable to take tablets, a liquid form of alendronate sodium is available.

Alendronate sodium is a medicine that can help to strengthen the bones in a body. It has Vitamin D that absorbs calcium, which is needed to make bones strong. It is most commonly taken by men and women who suffer from osteoporosis. This medicine is sometimes used to fight Paget's disease, which is a bone disease.

But there are something important you should know, while you are taking Alendronate sodium

1.Things you must do

If you develop difficulty or pain upon swallowing, chest pain, or new or worsening heartburn, stop taking Alendronate sodium and call your doctor. If you become pregnant while taking this medicine, stop taking the tablets and tell your doctor. If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking this medicine.If you require a dental procedure, tell your dentist that you are taking this medicine. If you develop new or unusual pain in your hip or thigh, tell your doctor.

Rarely, patients have experienced fracture in a specific part of the thigh bone.If you break a bone (have a fracture), tell your doctor that you are taking  Alendronate sodium. Make sure you have an adequate intake of calcium in your diet. Your doctor, dietician or pharmacist can tell you what foods you should eat.

2.Things you must not do

Do not give your medicine to anyone else, even if they have the same condition as you. Do not take Alendronate sodium to treat any other complaint unless your doctor tells you to.

3.Things that would be helpful for your osteoporosis

Some self help measures suggested below may help your osteoporosis, while you need to take Alendronate sodium. Talk to your doctor or pharmacist about these measures and for more information. Exercise can be helpful in building and maintaining strong bones. Regular exercise such as a brisk walk is a good idea. Talk to your doctor before you begin any exercise program.

Eat a balanced diet. You may need to increase the amount of calcium in your diet by eating calcium-rich foods or taking a calcium supplement. Your doctor will advise you.

Smoking appears to increase the rate at which you lose bone, therefore, may increase your risk of fracture. Your doctor may ask you to stop smoking or at least cut down, while you need to take Alendronate sodium.

Your doctor may advise you to cut down the amount of alcohol you drink, while you need to take Alendronate sodium. If you drink excessively on a regular basis, you may increase your risk of developing osteoporosis.

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What is Mifepristone?

Mifepristone (formerly known as RU-486) is a medication that blocks the action of the hormone progesterone. Progesterone is needed to sustain a pregnancy. Mifepristone has been used, in combination with other medications called prostaglandins, for medical abortion since 1988 in France and China, and since the early 1990's in the United Kingdom and Sweden. It has been licensed for use in 37 countries including the United States where it was approved in September 2000. Millions of women worldwide have safely used mifepristone regimens to end their pregnancies.

Mifepristone(CAS NO.: 84371-65-3) is used alone or in combination with misoprostol (Cytotec) to end an early pregnancy. Early pregnancy means it has been 49 days or less since your last menstrual period began. Mifepristone is in a class of medications called antiprogestational steroids. It works by blocking the activity of progesterone, a substance your body makes to help continue pregnancy.

Mifepristone comes as a tablet to take by mouth. It should be taken only in a clinic, medical office, or hospital under the supervision of a qualified doctor. You will take three tablets of mifepristone at one time on the first day. Two days later you must go back to your doctor. If your doctor is not certain that your pregnancy has ended, you will take two tablets of another medication called misoprostol. You may have vaginal bleeding for 9 to 30 days or longer. Fourteen days after taking mifepristone, you must go back to your doctor for an exam or ultrasound to make sure that the pregnancy has ended. Take mifepristone exactly as directed.

Mifepristone is also sometimes used to end pregnancies when more than 49 days have passed since the woman's last menstrual period; as an emergency contraceptive after unprotected sexual intercourse ('morning-after pill'); to treat tumors of the brain, endometriosis (growth of uterus tissue outside the uterus), or fibroids (noncancerous tumors in the uterus); or to induce labor (to help start the birth process in a pregnant woman). Talk to your doctor about the possible risks of using this drug for your condition.

Mifepristone also has some side effects on our health. Side effects, such as pain, cramping and vaginal bleeding, result from the abortion process itself, and are therefore expected with a medical abortion. Other side effects may include nausea, vomiting, diarrhea, chills, or fever. Complications are rare, but may include infection, excessive vaginal bleeding requiring transfusion (occurs in approximately 1 in 500 cases), incomplete abortion or ongoing pregnancy which requires a suction abortion (see above). In exceedingly rare instances, as with miscarriage, suction abortion and childbirth, death may occur. Reports of death after medical abortion are very rare - less than 1 in 100,000 cases - a rate comparable to that for early surgical abortion and for miscarriage.

Mifepristone is available only from your doctor. It is stored at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Keep all medicines away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

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How to treat the risk of Cyclohexane

Cyclohexane is a cycloalkane with the molecular formula C6H12. Cyclohexane is used as a nonpolar solvent for the chemical industry, and also as a raw material for the industrial production of adipic acid and caprolactam, both of which being intermediates used in the production of nylon. 

On an industrial scale, cyclohexane(CAS NO.: 110-82-7) is produced by reacting benzene with hydrogen. Producers of cyclohexane account for approximately 11.4% of global demand for benzene. Because of its unique chemical and conformational properties, cyclohexane is also used in labs in analysis and as a standard. Cyclohexane has a distinctive detergent-like odor, reminiscent of cleaning product .

Cyclohexane is extremely flammable liquid and vapor. Vapor may cause flash fire. Breathing vapors may cause drowsiness and dizziness. Aspiration hazard if swallowed. It can enter lungs and cause damage. It may cause eye and skin irritation. 

Potential Health Effects and first measure

Eye: Cyclohexane may cause mild eye irritation. Vapors may cause eye irritation. In case of contact, immediately flush eyes with plenty of water for a t least 15 minutes. Get medical aid. 

Skin: it may cause irritation with burning pain, itching and redness. Not expected to cause an allergic skin reaction. A single prolonged skin exposure is not likely to result in the material being absorbed in harmful amounts. In case of contact Cyclohexane, flush skin with plenty of water. Remove contaminated clothing and shoes. Get medical aid if irritation develops and persists. Wash clothing 
before reuse.

Ingestion: Aspiration of material into the lungs may cause chemical pneumonitis, which may be fatal. It may cause central nervous system depression. Potential for aspiration if swallowed. Get medical aid immediately. Do not induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. 

Inhalation: it may cause respiratory tract irritation. Inhalation of vapors may cause drowsiness and dizziness. If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid. 

Chronic: Prolonged or repeated skin contact may cause defatting and dermatitis.Treat symptomatically and supportively. 

Fire Fighting Measures

General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Use water spray to keep fire-exposed containers cool. Liquid will float and may reignite on the surface of water. Extremely flammable liquid and vapor. Vapor may cause flash fire. Vapors are heavier than air and may travel to a source of ignition and flash back. Vapors can spread along the ground and collect in low or confined areas. 

Extinguishing Media: Water may be ineffective. Cyclohexane is lighter than water and insoluble in water. The fire could easily be spread by the use of water in an area where the water cannot be contained. Do NOT use straight streams of water. For large fires, use water spray, fog or regular foam. For small fires, use dry chemical, carbon dioxide, water spray or regular foam. Cool containers with flooding quantities of water until well after fire is out. 

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How to evaluate Diosmin?

Diosmin is a semisynthetic drug (modified hesperidin), a member of the flavonoid family. It is an oral phlebotropic drug used in the treatment of venous disease, i.e., chronic venous insufficiency (CVI) and hemorrhoidal disease (HD), in acute or chronic hemorrhoids, in place of rubber-band ligation, in combination with fiber supplement, or as an adjuvant therapy to hemorrhoidectomy, in order to reduce secondary bleeding. 

To control internal symptoms of hemorrhoids (piles), Diosmin(CAS NO.: 520-27-4) is used with hesperidin.This medication is a semisynthetic phlebotropic, prescribed for hemorrhoids along with hesperidin. It is also used as an adjuvant therapy to hemorrhoidectomy, in order to reduce secondary bleeding.

Clinical studies have been inconclusive and no review articles on its use in vascular disease have been published. Diosmin is currently a prescription medication in some European countries, and is sold as a nutritional supplement in the United States and the rest of Europe.

Diosmin has been found to be effective in mitigating hyperglycemia in diabetic rats. It is also speculated that diosmin might have potential in the treatment of neurodegenerative diseases, such as Alzheimer's disease, and its anti-inflammatory and anti-apoptotic activity has been demonstrated in neuronal cells, in vitro.

Diosmin is a natural ingredient found in plants. The active ingredient in Diosmin is known as Flavanoid. Flavanoids are blood thinner so it should be with caution and doctor’s approval that you take this supplement. In many countries it is only available through prescription, but the FDA has only allowed it to be sold as an herbal supplement. It also has not put any restrictions on this supplement as there has not been solid evidence to show it to be grossly harmful to ones health.

Diosmin is available as a nutritional supplement and does not require a prescription in the United States. It has been also used as an effective treatment for vein issues in Europe for more than 30 years.

But Diosmin may have very serious side effects when taken with other medications and supplements. It does not assist in weight loss, which is an underlining condition to many vein issues. It has not been proven safe , but also has not been taken off the market in the United States as it is not considered extremely dangerous.

Diosmin is a flavanoid that can help reverse and heal veins. This is a blood thinner that has been used in the treatment of various vein disorders for years in Europe. It is only available through prescription in some countries but in the United States it can be found sold in nutritional and health food stores.

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What is Alendronate sodium used for?

Alendronate sodium is chemically described as (4-amino-1-hydroxybutylidene) bisphosphonic acid monosodium salt trihydrate. The empirical formula of alendronate sodium is C4H12NNaO7P2•3H2O, its formula weight is 325.12 and CAS NO. is121268-17-5. 

Alendronate sodium is a white, crystalline, nonhygroscopic powder. It is soluble in water, very slightly soluble in alcohol, and practically insoluble in chloroform. Alendronate sodium is an important medicine, it is used widely in medical community, so let talk about what Alendronate sodium treats for?

1. Treatment and prevention of osteoporosis in postmenopausal women. 

For the treatment of osteoporosis, alendronate sodium increases bone mass and reduces the incidence of fractures, including those of the hip and spine (vertebral compression fractures). Osteoporosis may be confirmed by the finding of low bone mass (for example, at least 2 standard deviations below the premenopausal mean) or by the presence or history of osteoporotic fracture. (See CLINICAL PHARMACOLOGY, Pharmacodynamics.) 

For the prevention of osteoporosis, alendronate sodium may be considered in postmenopausal women who are at risk of developing osteoporosis and for whom the desired clinical outcome is to maintain bone mass and to reduce the risk of future fracture. Bone loss is particularly rapid in postmenopausal women younger than age 60. Risk factors often associated with the development of postmenopausal osteoporosis include early menopause; moderately low bone mass (for example, at least 1 standard deviation below the mean for healthy young adult women); thin body build; Caucasian or Asian race; and family history of osteoporosis. The presence of such risk factors may be important when considering the use of alendronate sodium for prevention of osteoporosis. 

2. Treatment to increase bone mass in men with osteoporosis. 

Treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low bone mineral density (see PRECAUTIONS, Glucocorticoid-Induced Osteoporosis ). Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D. 

3. Treatment of Paget's disease of bone in men and women. 

Treatment of Alendronate sodium is indicated in patients with Paget's disease of bone having alkaline phosphatase at least 2 times the upper limit of normal, or those who are symptomatic, or those at risk for future complications from their disease. 


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Different between Doebner condensation of dimethyl acetonedicarboxylate and cyanoacetic acid

How to make Malonic Acid in laboratory？

There are a number of methods you could follow to make malonic acid, however they all depend on you having other reactants available. 

The first method requires acetaldehyde (acetic acid may also work), acetone, hydrogen peroxide, a hydroxide base, borane and permanganate/dichromate. This would involve a reaction known as aldol condensation in which the carbonyl oxygen of the acetone would be replaced by the alpha carbon on the acetaldehyde, forming a CC double bond. This is then reacted with H2O2, BH3 and OH- to perform an 'anti-markovnikov' hydration reaction, adding the OH group the the gamme carbon. This is then oxidised by the ox. agent to form malonic acid. 

An alternative method (proposed on wikipedia) requires chloro-acetic acid, sodium carbonate, sodium cyanide and sodium hydroxide. In this reaction, the initial acid is deprotonated by the carbonate before being reacted with the cyanide anion, to form cyanoacetic acid(CAS NO.:372-09-8). This is oxidised by hydroxide or one of the ox. agents used above before finally being reprotonated to form malonic acid. 

It would perhaps be easier to try to substitute the malonic acid in the experiment for something you do have access to. This would depend on what you need the malonic acid for though since sometimes it may not be able to be substituted.

What is the different between Doebner condensation of dimethyl acetonedicarboxylate and cyanoacetic acid?

The Doebner condensation is a variation of the Knoevangel condensation when there is a carboxylic acid group that can be oxidized to CO2. The hydrogens that are vicinal to two carbonyl groups are fairly acidic, because the resulting anion is stabilized both by two electronegative oxygens and by resonance between the carbanion and its adjacent carbonyl carbons. In both Knoevangel and the Doebner variation, a base B: abstracts an acidic hydrogen to create a resonance-stabilized carbanion and the conjugate acid H:B. The carbanion attacks the electrophilic carbonyl carbon of an aldehyde, creating an alkoxide that then abstracts a proton from H:B to form the alcohol and recreate the base :B. 

Now, in Knoevangel the base abstracts the other acidic proton, the twin of the proton that was abstracted to form the carbanion, to eliminate HOH and form a double bond between the carbanion carbon and the electrophilic carbonyl carbon that the carbanion attacked. In the Doebner variation, that proton stays put. Instead, the adjacent carboxylate is oxidized to CO2, and the pair of electrons in the bond between the carbanion and carboxylate carbons becomes a pi bond between the carbanion carbon and the electrophilic carbonyl carbon, kicking out -OH. 

Although it's conceivable that you might cleave one of the esters to form a carboxylate for Doebner, you'd end up with -CH2-CN replacing -O-CH3, which is not the product you want. Instead perhaps the nitrile and carboxylate of cyanoacetate, both electron withdrawing groups and both capable of resonance-stabilizing a beta anion, serve in place of the two carbonyl groups in Knoevangel as described above. (Any base will abstract the carboxylic proton of acetic acid before it grabs the beta proton, so let's assume you're either starting with the carboxylate, or else have plenty of base in the pot.) Now base :B abstracts the beta proton from cyanoacetate, the carbanion attacks the central carbonyl of dimethyl-1,3-acetonedicarboxylate, creating a symmetric alkoxide. The alkoxide abstracts a proton from H:B, then a pair of non-bonding electrons on the carboxylate hydroxy O forms a bond to its carbon, oxidizing the carboxylate to CO2, while the bond from the carboxylate to the beta carbon breaks and reforms as a pi bond to the original acetone carbonyl in a concerted reaction step. Now you have =C-CN replacing the original acetone =O, double bonded to the original central carbonyl carbon. 


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