Solid and Liquid preparations of 6-Azaindole

A method for preparing a pharmaceutically acceptable salt of 6-Azaindole according to the invention may be carried out by an appropriate combination of those methods that are conventionally used in the field of organic synthetic chemistry. A specific example thereof is a method in which a solution of the compound in its free form is subjected to neutralization titration with an alkaline solution or an acidic solution. 

Examples of the ester of 6-Azaindole(CAS NO.: 271-29-4) include methyl ester and ethyl ester. Such esters can be prepared by esterification of a free carboxyl group according to a conventional method. 

With regard to each preparation, various preparation forms can be selected, and examples thereof include oral preparations such as tablets, capsules, powders, granules or liquids, or sterilized liquid parenteral preparations such as solutions or suspensions, suppositories, ointments and the like. 

Solid preparations of 6-Azaindole can be prepared in the forms of tablet, capsule, granule and powder without any additives, or prepared using appropriate carriers (additives). Examples of such carriers (additives) may include saccharides such as lactose or glucose; starch of corn, wheat or rice; fatty acids such as stearic acid; inorganic salts such as magnesium metasilicate aluminate or anhydrous calcium phosphate; synthetic polymers such as polyvinylpyrrolidone or polyalkylene glycol; alcohols such as stearyl alcohol or benzyl alcohol; synthetic cellulose derivatives such as methylcellulose, carboxymethylcellulose, ethylcellulose or hydroxypropylmethylcellulose; and other conventionally used additives such as gelatin, talc, plant oil and gum arabic. 

These solid preparations such as tablets, capsules, granules and powders may generally contain, for example, 0.1 to 100% by weight, and preferably 5 to 98% by weight, of 6-Azaindole of the Formula I as an active ingredient, based on the total weight of the preparation. 

Liquid preparations are produced in the forms of suspension, syrup, injection and drip infusion (intravenous fluid) using appropriate additives that are conventionally used in liquid preparations, such as water, alcohol or a plant-derived oil such as soybean oil, peanut oil and sesame oil. 

In particular, when the preparation is administered parenterally in a form of intramuscular injection, intravenous injection or subcutaneous injection, appropriate solvent or diluent may be exemplified by distilled water for injection, an aqueous solution of lidocaine hydrochloride (for intramuscular injection), physiological saline, aqueous glucose solution, ethanol, polyethylene glycol, propylene glycol, liquid for intravenous injection (e.g., an aqueous solution of citric acid, sodium citrate and the like) or an electrolytic solution (for intravenous drip infusion and intravenous injection), or a mixed solution thereof. 

Such injection may be in a form of a preliminarily dissolved solution, or in a form of powder per se or powder associated with a suitable carrier (additive) which is dissolved at the time of use. The injection liquid may contain, for example, 0.1 to 10% by weight of an active ingredient based on the total weight of the preparation. 

Liquid preparations of 6-Azaindole such as suspension or syrup for oral administration may contain, for example, 0.1 to 10% by weight of an active ingredient based on the total weight of the preparation. 

Each preparation can be prepared by a person having ordinary skill in the art according to conventional methods or common techniques. For example, a preparation containing another antitumor agent that is used in combination with the compound represented by the above Formula I, can be prepared, if the preparation is an oral preparation, for example, by mixing an appropriate amount of the antitumor agent with an appropriate amount of lactose and filling this mixture into hard gelatin capsules which are suitable for oral administration. On the other hand, preparation can be carried out, if the preparation containing the antitumor agent is an injection, for example, by mixing an appropriate amount of the antitumor agent with an appropriate amount of 0.9% physiological saline and filling this mixture in vials for injection. 


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How to prepare 5-Hydroxymethylthiazole

5-Hydroxymethylthiazole is a kind of slightly yellow oil liquids, the Molecular Formula is C4H5NOS, Molecular weight is 115.15, and the CAS NO. is 38585-74-9. It is an important intermediate for Ritonavir, and a kind of anti-AIDS pharmaceuticals. But how to prepare it, now I will give you 4 examples.

Example 1:

In a reaction flask IOml 50ml of methanol, 1. 5g (IOmmol) 2_ chloro-5 - (hydroxymethyl) thiazole and 1. 7g (26mmol) of zinc powder, the above mixture was heated to 50 C, and hydrochloric acid was slowly added 30ml (IN), at a temperature of 60 C for 2 hours detected by TLC or HPLC, until the starting material disappeared, the reaction was stopped and the reaction solution was filtered, concentrated and neutralized with sodium hydroxide to PH is 9, then extracted with ethyl acetate to give crude product, the final crude solvent was removed by distillation under reduced pressure, collecting 115 ~ 122 C (24mmHg) the distillate, 1.05g 5 - (hydroxymethyl) thiazole. The determination of the purity of 94%, the yield was 85%.

Example 2:

In a reaction flask IOOml 250ml of ethanol, 15g (0. Imol) 2_ chloro-5 - (hydroxymethyl) thiazole and 13. 5g (0. 20mol) zinc powder, the above mixture was heated to 50 C , then slowly add 150ml hydrochloric acid (2N), at a temperature of 70 C for 2 hours detected by TLC or HPLC, until the starting material disappeared, the reaction was stopped and the reaction solution was filtered, concentrated and neutralized with sodium hydroxide to PH of 10, and then extracted with ethyl acetate to give crude product, the final crude solvent was removed by distillation under reduced pressure, collecting 115 ~ 122 C (24mmHg) the distillate, 8. 5g 5 - (hydroxymethyl) thiazole. The determination of the purity% 99. 3% (HPLC), the yield was 74%.

Example 3:

In a reaction flask 50ml IOml propanol, 1. 5g (IOmmol) 2_ chloro-5 - (hydroxymethyl) thiazole and 0. 95g (15mmol) of zinc powder, the above mixture was heated to 50 C , then slowly add 3ml of sulfuric acid (6N), at a temperature of 40 C for 5 hours, TLC or HPLC detection, until the starting material disappeared, the reaction was stopped and the reaction solution was filtered, concentrated and neutralized with sodium hydroxide to PH is 9, then extracted with ethyl acetate to give crude product, the final crude solvent was removed by distillation under reduced pressure, collecting 115 ~ 122 C (24mmHg) fraction, to l.lg 5 - (hydroxymethyl) thiazole. The determination of the purity of 91%, the yield was 95%.

Example 4:

In a reaction flask IOOml 250ml of ethanol, 45g (0. 3mol) 2_ chloro-5 - (hydroxymethyl) thiazole and 33g (0. 5mol) zinc powder, and then added slowly 75ml hydrochloric acid (6N), the temperature of 60 C for 2 hours, by TLC or HPLC detection, until the starting material disappeared, the reaction was stopped and the reaction solution was filtered, concentrated and neutralized with sodium hydroxide to a PH of 10, and then extracted with ethyl acetate and to give the crude product, the final crude solvent was removed by distillation under reduced pressure, collecting 115 ~ 1220C (24mmHg) the distillate, 25g 5 - (hydroxymethyl) thiazole. The purity was determined 99. 5% (HPLC), the yield was 72%.

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6-Hydroxynicotinic acid is an important chemical synthesis

6-Hydroxynicotinic acid with the CAS number of 5006-66-6, it can be called 1,6-dihydro-6-oxo-3-pyridinecarboxylicacid,2-Hydroxy-5-pyridinecarboxylicacid,2-hydroxypyridine-5-carboxylicacid,5-carboxy-2(1h)-pyridinone,6-hydroxy-3-pyridinecarboxylicacid,6-hydroxynicotinic acid. 6-Hydroxynicotinic acid is an off-white powder, it is used as building block in chemical synthesis. Here are the detail properties and safety profiles of 6-Hydroxynicotinic acid.

Chemical and physical properties

IUPAC Name: 6-oxo-1H-pyridine-3-carboxylic acid 
Empirical Formula: C6H5NO3
Molecular Weight: 139.1088
Polar Surface Area: 46.61 
Index of Refraction: 1.579
Molar Volume: 95.8 cm3
Molar Refractivity: 31.84 cm3
Surface Tension: 61 dyne/cm
Density: 1.451 g/cm3
Flash Point: 186 °C
Boiling Point: 384 °C at 760 mmHgH bond donors: 2
Melting point: >300 °C(lit.)
Vapour Pressure: 5.81E-07 mmHg at 25°C
H bond acceptors: 4
Freely Rotating Bonds: 1
Enthalpy of Vaporization: 69.45 kJ/mol
BRN: 472182
EINECS: 225-682-9
CAS NO.: 5006-66-6
Product Categories: We category 6-Hydroxynicotinic acid into Nitrogen cyclic compounds; blocks; Carboxes; Pyridines; Pyridine; Organic acids.

Safety profiles

Hazard Codes: Irritant Xi
Hazard Note: Irritant
TSCA: T
Risk Statements: 36/37/38
R36/37/38: 6-Hydroxynicotinic acid has Irritation to eyes, respiratory system and skin. 
Safety Statements: 26-36-24/25
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. 
S36:Wear suitable protective clothing when deal with the accident of 6-Hydroxynicotinic acid. 
S24/25:Avoid 6-Hydroxynicotinic acid contact with skin and eyes. 
WGK Germany: 3


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A question list of Diphenylamine for you

1.Diphenylamine test for deoxyribose?
Answer1:
When adding diphenylamine to deoxyribose you will get a dark deep purple color. If you react diphenylamine with crude DNA you will get a pink-violet color. DIphenylamine test is quantitative and the darker the color the greater the concentration of DNA in the solution

2.What is diphenylamine test for deoxyribose for?
Answer2:
It can be used to test for the presence of DNA in a substance. The test consists of diphenylamine(CAS NO.: 122-39-4) in acid, which reacts with the deoxyribose in the DNA to produce a blue color. The intensity of the blue color is in direct proportion to the concentration of DNA.

One major difference between DNA and RNA is their sugar: DNA contains deoxyribose, whereas RNA contains ribose. DNA can be identified chemically with the Dische diphenylamine test. The reaction between the Dische reagent and 2-deoxypentose results in the development of a blue color. The reaction depends on the conversion of the pentose to w-hydroxylaevulinic aldehyde which then reacts with diphenylamine to give a a blue colored complex. The intensity of the blue color is proportional to the concentration of DNA. Dische reagent does not react with the ribose sugar in RNA and does not form a blue-colored complex

3.What is responsible for the formation of the absorbed color of DNA with diphenylamine?
Answer 3:
When you heat DNA in acid the 2-deoxyribose is converted to w-hydroxylevulinyl aldehyde, which reacts with the compound, diphenylamine, to produce a blue-colored compound.

4.Why does blue colour appears in diphenylamine test?
Answer 4:
Blue color appears in diphenylamine test because of the reaction of nitrates.

5.Detection of DNA with Diphenylamine?
Answer 5:
A diphenylamine indicator is often used for the detection of DNA. Diphenylamine is an organic compound and classified as an aromatic amine due to the presence of a benzene ring in its chemical makeup. Chemical hydrolysis of DNA must take place when looking for it using diphenylamine. The DNA concentration in an organism is measured by looking for the absorbency rate of the diphenylamine. DNA molecules are the building blocks of life and contain specific genetic coding for the organism it is contained in.

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The preparation of Anthranilic acid derivative

The present invention relates to the selective preparation of anthranilic acid. Anthranilic acid is a valuable intermediate for the preparation of benzonorbornene fungicides, as described for example in WO 2007/048556.

According to WO 2007/031323, anthranilic acid (A) can be prepared according to the following scheme:

3-Nitro-phthalimide (E) is a useful starting material for the preparation of anthranilic acid(CAS NO.: 118-92-3), in particular for large scale manufacturing which requires high safety standards.

However, an efficient process for the preparation of anthranilic acid starting from 3- nitro-phthalimide has to avoid the form tion of the undesired regioisomer of formula (B) which reduces yield and quality of the product. Therefore, the process according to WO 2007/031323 is performed in two separate steps. In the scheme above, 3-nitro-phthalimide (E) is converted in a first step by reaction with an aqueous base, and by subsequent reaction with an aqueous acid, into 6-nitrophthalamic acid (D). During the precipitation of the amido acid, the desired isomer (D) is enriched. 

In a second step, 6-nitrophthalamic acid (D) is then converted to anthranilic acid (A). In that step, 6-nitrophthalamic acid may be reacted first with aqueous base, such as, for example, aqueous sodium hydroxide, and sodium hypochlorite, and then with aqueous acid, such as, for example, aqueous hydrochloric acid. The disadvantage of this prior art process is the relatively low yield in each of the two steps (70-73%). Further, isolation is required to enrich the desired isomer with additional filtration which leads to high waste generation and higher cycle time (energy inefficient). Also, a two step synthesis is undesired for large scale production.

The aim of the present invention is therefore to provide a novel process for the selective production of anthranilic acid that avoids the disadvantages of the known process and makes it possible to prepare anthranilic acid in high yields and good quality in an economically and ecologically advantageous way in a one-pot process with a high safety standard.

Thus, according to the present invention, there is provided a process for the preparation of a compound of anthranilic acid derivative

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Introduction of Vinblastine sulfate

Basic information:

English name: Vincristine Sulphate
English Synonyms: Vincristine Sulfate, Apocynaceae sp.; Vincristine Sulphate; Vincristine sulfate salt; 22-Oxovincaleukoblastine sulfate salt; Leurocristine sulfate salt 
Specification: 99%, pharmaceutical grade
Formula: 6H56N4O10.H2SO4
Purity: 99% min
Melting point: 273-281 ℃
Molecular Weight: 923.04 
CAS No. : 2068-78-2
Properties: white or white loose-like or amorphous solid, hygroscopic, easy to turn yellow when exposed to light or heat.

Characters:

Vinblastine sulfate is a white or almost white crystalline powder; odorless; hygroscopic; easy to turn yellow when exposed to light or heat. Vinblastine sulfate is soluble in water, soluble in methanol or chloroform, very slightly soluble in ethanol.

Inspection about Vinblastine sulfate:

Acidity detection: Take this product 10mg, dissolved in 10ml water, according to the determination (Appendix Ⅵ H), pH value should be 3.5 to 5.0.
Clarity of solution test: Take this chemical 10mg, dissolves into 5ml of water, the solution should be clarified.

Other alkaloids detection: Take Vinblastine sulfate, add methanol containing 10mg per 1ml of solution as the test solution; precise amount of the check amount, diluted with methanol to 0.20mg per 1ml of the solution, as a control solution. Thin layer chromatography (Appendix Ⅴ B) test, to learn the two solutions 5μl, respectively, in the same gel GF254 TLC plate with petroleum ether (boiling range 30 ~ 60 ℃) - chloroform - acetone - diethylamine (12:6:1:1) as the agent, started to dry, UV light (254nm), under review. The test solution were impurities such as spots, not more than two, the color control solution with the main spots, not deeper.

Loss on drying test: Take Vinblastine sulfate, phosphorus pentoxide as desiccant, at 80 ℃ vacuum drying to constant weight, less weight loss should not exceed 12.0% (Appendix Ⅷ L).

Identification about Vinblastine sulfate:

(1) Take this product 0.1mg, plus 1% sulfuric acid solution of ammonium cerium 1 to 2 drops, that was purple to dark purple.
(2) Take the determination of the solution, according to spectrophotometry (Appendix Ⅳ A) measured at 215 and 264nm wavelength of maximum absorption.
(3) The Vinblastine sulfate of the aqueous solution of sulphate of differential response (Appendix Ⅲ).

Classes and storage:

Vinblastine sulfate is an important antineoplastic agents. Preservation should pay attention to shading, sealed and refrigerated.


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Medicine name: Dexamethasone Sodium Phosphate for Injection

Specification: 5mg (by dexamethasone sodium phosphate meter)

Whether prescription drugs: prescription drugs

Main components: Dexamethasone sodium phosphate(CAS NO:2392-39-4 )

Indications

Dexamethasone Sodium Phosphate for Injection for the treatment of lymphoma, acute leukemia, ulcerative colitis, dermatitis, bronchial asthma, rheumatoid arthritis, rheumatoid arthritis, it also has a good effect on hematology, gastroenterology, dermatology, respiratory medicine, Division of Rheumatology class diseases.

Usage and dosage

General dose intravenous injection every 2-20mg; intravenous infusion should be diluted with 5% glucose injection. Dexamethasone sodium phosphate can be repeated dose 2-6 hours until a stable condition, but the high-dose administration is generally not more than 72 consecutive hours.

Dexamethasone Sodium Phosphate for Injection can also be used to relieve cerebral edema caused by malignant tumors, the first dose of intravenous injection of 10mg, followed by intramuscular injection every 6 hours 4mg, generally 12-24 hours patients can be improved gradually reduced for 2-4 days amount,5-7 days withdrawal. Inoperable brain tumor, the first dose of intravenous bolus injection 50mg, repeated after every two hours to give 8mg, every few days and then reduced to 2mg, 2-3 times given intravenously.

Dexamethasone Sodium Phosphate for intrathecal injection every 5mg, spaced 1-3 weeks for once injection; intra-articular injection usually every 0.8-4mg, according to the joint cavity size.

Pharmacological effects

Dexamethasone Sodium Phosphate for Injection is an kind of adrenal cortex hormones drugs. It has the functions of anti-inflammatory, anti-allergic, anti-rheumatic, immunosuppressive, the mechanisms of actions are in the following list:
anti-inflammatory effect: This product is to reduce and prevent tissue response to inflammation, thereby reducing the performance of inflammation. To inhibition of inflammatory cells, including macrophages and accumulation of leukocytes in inflammatory sites, and inhibition of phagocytosis, lysosomal enzyme release and synthesis of chemical mediators of inflammation and release.

Immunosuppression: Dexamethasone Sodium Phosphate can prevent or inhibit cell-mediated immune responses, delayed hypersensitivity reactions, reduction of T lymphocytes, monocytes, macrophages acid number of cells of the immune globulin and cell surface receptor binding capacity, and inhibition of interleukin synthesis and release, thereby reducing the T lymphocytes to lymphoblastoid cell transformation, and to alleviate the situation of the primary immune response extensions.

Dexamethasone Sodium Phosphate for Injection can also reduce immune review material through the basement membrane, and it can reduce the complement components and immunoglobulin concentrations.

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Does some risks occur when combine Celecoxib and Alcohol

Celecoxib is a sulfonamide nonsteroidal anti-inflammatory Medication (NSAID) and selective COX-2 inhibitor Applied in the Remedy of osteoarthritis, rheumatoid arthritis, acute Discomfort, Discomfortful menstruation and menstrual Signs and symptoms, and to Decrease Quantities of colon and rectum polyps in Folks with familial adenomatous polyposis.

Side effects include a 30% increase in rates of heart and blood vessels disease. Much moreover the Chance of Abdomen side Results is 80% Higher. It is marketed by Pfizer. It is Identified Be Minimal the Manufacturer Identify Celebrex(CAS NO:169590-42-5) or Celebra for arthritis and Onsenal for polyps. Celecoxib is Obtainable by prescription in capsule Type.

Celecoxib is a Discomfortkiller that is in the Family members of Drugs called the non-steroidal anti-inflammatory Medications (NSAIDs). Like other NSAIDs, the Mixture of celecoxib and Booze can Confirm Hazardous. For this Cause, The two Healthcare Pros and the Medication's Suppliers warn Versus mixing it with Booze, even when Used in Minimal doses.

The Risk of mixing celecoxib and Booze Arrives Bigly from the way that Each and every of these Ingredients Operate in the System. A single Risk Arrives from Prospective Abdomen Harm, Even Although this Chance is not as Fantastic as with other Kinds of NSAIDs. Celecoxib, like other NSAIDs, suppresses inflammation in the System by inhibiting a Necessary protein called cyclooxygenase-2 (COX-2), which is Included in the immune response. This Medication, for the most Component, Particularly Focus ons COX-2, In contrast to NSAIDs like ibuprofen, but there is some residual inhibition of a Associated enzyme, COX-1.

Discovered in the Abdomen, COX-1 assists in Guarding the Abdomen from its Personal acids. Even Little Quantities of inhibition can Minimaler the defenses of the Abdomen Versus Harm. Alcohol can Straight irritate the Abdomen lining and Market the Launch of Abdomen acid, Even more damaging his Location. Combining celecoxib and Booze can Lead to Abdomen bleeding Via these mechanisms. In essence, celecoxib can Depart from the Abdomen unable to Defend By itself Versus Harm mediated by Booze.

As noted, celecoxib's Particular Focus oning of COX-2 Minimalers the Chance of Abdomen bleeding and ulcers, Although does not Eradicate it Completely. Consuming Big Quantities of Booze, Getting Big doses of the Medicine, or engaging in The two Actions for Prolonged periods of time can all increase the Chances of Unwanted Results. Taking other NSAIDs like acetaminophen or ibuprofen with celecoxib and Booze can also Appreciably increase the Odds of Damaging Functions.

One more Feasible Chance from the mixture of celecoxib and Booze Arrives from Results that Each and every substance can have on the Center. NSAIDs This kind of as celecoxib that Particularly Focus on the COX-2 enzyme Appear to have a Higher Possibility of Top to Significant cardiovascular Issues, Which include strokes and Center attacks. Consuming heavily can Direct to cardiovascular Issues as Properly, This kind of as a Problem that enBigs the Center, which also increases the Chance of Severe Unwanted Functions, which also can Consist of Center attacks and strokes. Much more Investigation Should be performed on People that have mixed celecoxib and Booze, but from the Proof Obtainable, there Seems to be a Feasible Chance of this Mixture contributing to Existence-threatening Center Issues.

What is 6-Azaindole?

Chemical and physical properties

Product Name: 6-Azaindole
English Synonyms: 1H-Pyrrolo [2,3-c] pyridine, Harmyrine, 1,6-Diazaindene
CAS Number: 271-29-4
Molecular formula: C7H6N2
Molecular Weight: 118.14
Density: 1.242 g / cm3
Melting point: 136 - 137 ° c
Boiling Point: 295.761 ° c at 760 mmhg
Flash Point: 137.4 ° c
Appearance: 6-Azaindole is a kind of white powder.

Usage 

6-Azaindole is a kind of important organic synthesis intermediates.

Safety information 

Hazard Codes: Xi
Hazard Note: Irritant
HS CODE: 29339980


Related Categories

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Indole
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Something about making 6-hydroxynicotinic acid

Product Name: 6-Hydroxynicotinic Acid

English Synonyms: 2-Hydroxy-5-pyridinecarboxylic acid
CAS No.: 5006-66-6
Molecular formula: C6H5NO3
Molecular Weight: 139.11
Appearance Description: 6-Hydroxynicotinic acid is a kind of white to brown powder.

A process for the production of 6-hydroxynicotinic acid from nicotinic acid by means of enzymatic hydroxylation in the presence of microorganisms of the genera Pseudomonas, Bacillus or Achromobacter. By maintaining a specific concentration range during the addition of nicotinic acid, the biomass formation can take place in the same process step as the product formation, without product losses occurring by further decomposition.

1. Field of the Invention
The invention relates to a process for the production of 6-hydroxynicotinic acid by enzymatic hydroxylation of nicotinic acid.

2. Prior Art
Processes are known which make possible the production of 6-hydroxynicotinic acid by means of live microorganisms of the genera Pseudomonas, Bacillus or Achromobacter (see Swiss Patent Nos. 658,866 and 658,867). Such processes use a biomass suspension of the corresponding microorganisms, which are obtained in a separate process step by multiplication of a starter culture.

The actual hydroxylation takes place either in a batch process with single addition of nicotinic acid as the sodium salt (batch process, see Swiss Patent No. 658,866), or in a continuous process in which the nicotinic acid is added as the (easily soluble) magnesium or barium salt and the 6-hydroxynicotinic acid is isolated as slightly soluble magnesium or barium salt (see Swiss Patent No. 658,867). Since the multiplication of the microorganisms is inhibited by the nicotinic acid concentrations used in such processes, it is necessary in both processes to obtain the total amount of the effective biomass in an upstream process step.

Moreover, the known processes for the enzymatic production of 6-hydroxynicotinic acid have still other drawbacks. The continuous process according to Swiss Patent No. 658,867 yields magnesium or barium salts from which the 6-hydroxynicotinic acid is released by acid addition.

In this case, the magnesium or barium salt of the added acid results, which has to be disposed of as waste. But especially soluble barium salts are highly toxic for higher organisms. With prolonged continuous operation, moreover incrustations by the crystallized salts or foreign infections easily occur.

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What is Doxycycline hyclate used for?

Doxycycline hyclate is used to treat a wide variety of bacterial infections, including those that cause acne. Doxycycline hyclate is also used to prevent malaria. It is known as a tetracycline antibiotic. It works by stopping the growth of bacteria.

Doxycycline hyclate（CAS NO: 24390-14-5） is an antibiotic which treats only bacterial infections. It will not work for viral infections (such as common cold, flu). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

Doxycycline hyclate also has other usages. This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.This drug may also be used to treat a certain skin condition (rosacea).

If you are allergic to any ingredient in doxycycline hyclate or to another tetracycline (eg, minocycline), taking acitretin, isotretinoin, or a penicillin (eg, amoxicillin), you can not use Doxycycline hyclate. If you have recently received or will be receiving a live oral typhoid vaccine, you should also not to use this medicine. Contact your doctor or health care provider right away if any of these apply to you.

Use doxycycline hyclate as directed by your doctor. Check the label on the medicine for exact dosing instructions. Here, I will show you some advices if you need to take Doxycycline hyclate.

1.Take doxycycline hyclate by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.
2.Do not take an antacid that has aluminum, calcium, or magnesium in it; bismuth-containing products; iron; urinary alkalinizers (eg, sodium bicarbonate); or multivitamins with minerals within 2 hours before or 2 hours after you take doxycycline hyclate.
3.To clear up your infection completely, take doxycycline hyclate for the full course of treatment. Keep taking it even if you feel better in a few days.
4.Drink plenty of fluids with doxycycline hyclate to wash it down and avoid the risk of throat irritation.
5.Do not use doxycycline hyclate if it is outdated or has been stored incorrectly.
6.If you are taking doxycycline hyclate to prevent malaria, you should begin to take it 1 to 2 days before you travel to the malaria-infected area. You will need to keep taking it for 4 weeks after you leave the area. Discuss any questions with your doctor.
7.If you miss a dose of doxycycline hyclate, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use doxycycline hyclate.

I hope this article can make you get a deeper understanding of Doxycycline hyclate, and give you a little help when you need to take Doxycycline hyclate. If you want to learn more information about Orthoboric acid, you can access the guidechem.com.

Hypericin extract from hypericum perforatum

Hypericin is derived from perforatum of the whole plant extract, the main ingredients of Hypericin extract is hypericin, faint scent. Hypericin has bitter taste, soluble in water. It has antidepressant, anti-viral effect. Hypericin is also used as veterinary drugs for prevention of avian influenza in chickens.

Hypericin（CAS NO: 548-04-9） is a kind of brown flowing powder, smells the unique fragrance, bitter taste, soluble in water. Hypericin may be blue-black or purple needle crystal. It is easily soluble in pyridine and other organic bases, a cherry red solution and was red fluorescence. The aqueous alkali solution of Hypericin is almost insoluble in other organic solvents. In pH11.5 less is red, pH11.5 above is green, and shows a red fluorescence. Melting point> 320 ℃ (decomposition).The main source of hypericin is  extraction from the hypericum perforatum.

According to the 2000 report of the British Medical Journal study, comparing the efficacy of Hypericum perforatum with imipramine for the treatment of depression. The findings are both similar efficacy, but more acceptable to patients taking hypericin, which 26% of the patients occur adverse reactions after taking imipramine, give up taking the drug, as Hypericum perforatum group, only 3% of patients taking hypericin to give up. Hypericum perforatum (Melaleuca F) is that many people have studied herbs, clinical experience, drug generally safe.

By the Chinese Academy of Agricultural Sciences, Lanzhou Institute of Animal Husbandry and Veterinary submitted to the National Avian Influenza Reference Laboratory "the effect of hypericin to kill the H9N2 avian influenza virus and subtype H5N1 " test completed. The results showed that hypericin on highly pathogenic avian influenza virus killing effect is good, and finally kill rate is up to 100%.

Hypericin extract of Hypericum perforatum, has strong antiviral activity. For the control of avian influenza as a national new formulations are now available across the country to obtain a good response and effects; The clinical application of hypericin proved good results in prevention and treatment of influenza virus again. Because the long-term vaccine prevention and drug treatment, leading to influenza virus gradually mutate, was atypical of clinical symptoms, concurrent bladder inflammation, E. coli and other diseases, the proposed clinical use of drugs, with the appropriate medicine use, the effect is more precise.


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The usages and bad effects of L-Carnitine fumarate

L-Carnitine fumarate is a stable form of L-carnitine, easy to absorb moisture as a white powder or crystalline powder, soluble in water. Formula is C11H19NO7, molecular weight is 277.27, CAS No. is 90471-79-7. L-carnitine fumarate may be used as a substitute for L-carnitine tartrate, and better stability than tartrate, applicable to solid preparation.

L-carnitine fumarate is a dietary supplement widely used as a weight loss aid. and supporter of cardiac, neurological and muscular function. The supplement is a combination of L-carnitine and fumaric acid, both of which purport to have several health related benefits.

L-carnitine fumarate is a well-known supplemental amino acid with antioxidant and metabolism boosting qualities. Fumaric acid is an element of the Krebs or citric acid cycle which allows cells to produce energy. In combination in L-carnitine fumarate supplements, the two elements are believed to complement and enhance their beneficial qualities.

Dietary supplements which possess claimed weight loss, energy, and performance boosting qualities have become hugely popular, and L-carnitine fumarate is no exception. Based on the beneficial characteristics of its two active ingredients, the supplement may offer a wide spectrum of value for those whose natural intake or production of carnitine and fumaric acid is lacking or compromised.

Deficiencies in both elements are not uncommon, and the often rushed and questionable nutritional quality of modern day diets does little to aid in restoring a balance. Although dietary supplements such as L-carnitine fumarate should never be viewed as a replacement for a healthy diet, they can be of great value in boosting natural levels of the essential elements they contain.

L-Carnitine fumarate side effects are rare. When symptoms do occur, however, individuals often note minor to moderate stomach and digestive discomfort, headaches and skin irritations. In some, bladder infections, sleep disturbances and an unusual body odor are experienced.

Although it is easily accessed through the consumption of dairy products and red meat, many people who avoid these food products purchase it in supplement form instead and are often curious about any known L-carnitine side effects.

Individuals suffering from hemodialysis and age-related memory loss may also benefit from L-Carnitine fumarate. Researchers are unclear, however, if supplementing this amino acid will actually prevent such losses. With sleep disturbances being one of the rarely reported L-carnitine side effects, individuals taking it to slow memory loss often find it less effective.

Sometimes referred to simply as carnitine or acetyl L-Carnitine fumarate, side effects are very rarely reported in healthy individuals. Few, if any, side effects are even noted in people with other health issues. In fact, in some HIV patients, antiviral medications used to treat HIV infections are known to actually cause a deficiency of L-Carnitine fumarate. Side effects like these are commonly treated with carnitine supplementation, which helps restore healthy levels of it to the body.

Even though most people do not experience L-Carnitine fumarate side effects, those who do experience issues usually report mild to moderate symptoms and disturbances such as skin rash, nasal congestion, nausea, diarrhea and vomiting. Several have even reported the presence of a peculiar body odor possibly resulting from chemical interactions with the supplement taking place within the body. While body odor is one of the less common L-carnitine side effects, researchers have found that it can be avoided by also taking riboflavin supplements.

Even in the absence of any apparent physical L-Carnitine fumarate side effects, doctors recommend that people taking carnitine supplements also regularly undergo clinical screenings. This is due to the fact that some L-Carnitine fumarate side effects are only discovered via medical testing. Researchers testing children with attention disorders have also found L-Carnitine fumarate supplementation to be somewhat effective, but recommend that such treatment only be administered under a doctors care so that side effects can be closely monitored and treated if they do occur.

Aggregate Risk Assessment of Chlorimuron ethyl

Chlorimuron ethyl is a sulfonylurea class herbicide that inhibits acetolactate synthase, which regulates plant growth. It is registered for use on soybeans and peanuts. Chlorimuron ethyl may be applied to soybean crops at preplant,preemergence, postemergence, or postharvest stages by band treatment, broadcast, ground spray, low volume spray, or soil incorporated treatment at the current maximum application rate of 0.08025 lbs active ingredient per acre per crop cycl. Chlorimuron ethy lmay be applied to peanut crops at the foliar stage by band treatment, broadcast, or low volume spray at the current maximum application rate of 0.0078125 lbs active ingredient per acre per crop cycl.

The preharvest intervals are 60 days for soybeans and 45 days for peanuts. Chlorimuron ethyl(CAS NO: 90982-32-4) may also be applied to non-crop land at the foliar stage by broadcast at the current maximum application rate of .03125 lbs active ingredient per acre. There are no residential uses for chlorimuron ethyl. Fifteen end-use products in water dispersible granular formulations have been identified, and one pending registration exists for a granular formulation. The percentage of active ingredient in these products ranges from 8.3 to 31.8%. A dditionally, there is a technical and an intermediate product with 97.8% and 54% active ingredient, respectively.

The uncertainty factors applied in the chlorimuron ethyl risk assessment consist of a standard uncertainty factor of 100X and an FQPA Safety Factor of 1x. The uncertainty factor of 100X includes both a 10X uncertainty factor for intraspecies variability i.e. differences among human and a 10X uncertainty factor for interspecies variability i.e. differences between humans and anim. The FQPA Safety Factor is a method of accounting for any increased susceptibility of infants and children to toxic effects. The A gency concluded that, because there are low concerns, no residual uncertainties with regard to pre- and/or postnatal toxicity, and high confidence that exposure estimates have not been underestimated, the factor could be reduced to 1x from the standard 10x.

Chlorimuron ethyl is classified as Toxicity Category III for acute dermal and Toxicity Category IV for acute oral toxicity and inhalation. It is a mild eye and skin irritant and does not cause skin sensitization. There is no evidence of potential neurotoxicity, mutagenicity, or carcinogenicity for chlorimuron ethyl provided in the available studies.

EPA is required under the FFDCA , as amended by FQPA , to develop a screening program to determine whether certain substances including all pesticide active and other ingredi "may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the A dministrator may designate." Following the recommendations of its Endocrine Disruptor Screening and Testing A dvisory Committee EDSTA C, EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system.

EPA also adopted EDSTA Cs recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. A s the science develops andresources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program EDSP.

Based on currently available data, chlorimuron ethyl does not appear to be an endocrine disruptor. However, when the appropriate screening and/or testing protocols being considered under the A gencys EDSP have been developed, chlorimuron ethyl may be subjected to additional screening and/or testing to better characterize effects related to endocrine disruption.

There are no studies identifying an acute dietary endpoint based on toxic effects observed following a single dose, therefore no acute dietary risk assessment was performed. For chronic dietary exposure, a no observed adverse effect level NOA EL of 9 mg/kg/day was identified from a chronic dog study in which mild anemia was observed at the lowest observed adverse effect level LOA EL of 51 mg/kg/day. Because chlorimuron ethyl has no residential uses, only dietary exposure was assessed.

For chlorimuron ethyl, the aggregate chronic dietary risk estimates including food and drinking wat for the general U.S. and all population subgroups are less than 1% of the cPA D and are below the A gencys level of concern.

Chronic aggregate dietary exposure to chlorimuron ethyl was calculated using a Tier 1 approach which assumes that 100% of each crop is treated with chlorimuron ethyl, that pesticide residues exist on food at the legal tolerance levels, and that levels in drinking water are at upper-bound estimates.

The Dietary Exposure Evaluation Model software was employed for the risk assessment with the Food Commodity Intake Database DEEM-FCIDtm, Version 1.3 which incorporates food consumption data from USDA s Continuing Surveys of Food Intakes by Individuals CSFII from 1994-1996 and 1998. Chronic aggregate risk was assessed by comparing chronic dietary exposure estimates to the chronic Population A djusted Dose cPA D, with risk expressed as a percent of the cPA D. Exposure estimates that are less than 100% of the cPA D indicate a determination of safety can be concluded. The degradates of chlorimuron ethyl are not expected to be more toxic nor exceed levels of the parent compound.

Information about 2-Butyl-5-chloro-1H-imidazole-4-carboxaldehyde

Physical and Chemical Properties 

Chemical product:2-Butyl-5-chloro-1H-imidazole-4-carboxaldehyde

Physical State: Crystalline powder

Color: white to light yellow 

Freezing/Melting Point: 97 - 100 deg C 

Solubility in water: Slightly soluble

Molecular Formula: C8H11ClN2O 

Molecular Weight: 186.64

CAS NO:83857-96-9

Stability and Reactivity 

Chemical Stability: Stable under normal temperatures and pressures. 

Conditions to Avoid: Incompatible materials. 

Incompatibilities with Other Materials Not available Hazardous Decomposition Products Hydrogen chloride, nitrogen oxides, carbon monoxide, carbon dioxide. Hazardous Polymerization Will not occur. 

Potential Health Effects of 2-Butyl-5-chloro-1H-imidazole-4-carboxaldehyde

Eye: May cause eye irritation. 

Skin: May be harmful if absorbed through the skin. May cause sensitization by skin contact. 

Ingestion: May cause irritation of the digestive tract. May be harmful if swallowed. 

Inhalation: May cause respiratory tract irritation. May be harmful if inhaled. 

First Aid Measures 

Eyes: 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. 

Ingestion: Get medical aid. Wash mouth out with water. 

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. 

Notes to Physician: Treat symptomatically and supportively. 

Fire Fighting Measures about 2-Butyl-5-chloro-1H-imidazole-4-carboxaldehyde

General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. 

Extinguishing Media: Use water spray, dry chemical, carbon dioxide, or chemical foam. 

Handling and Storage of 2-Butyl-5-chloro-1H-imidazole-4-carboxaldehyde

Handling: Avoid breathing dust, mist, or vapor. Avoid contact with skin and eyes. 

Storage: Store in a cool, dry place. Store in a tightly closed container. 

Exposure Controls, Personal Protection 

Engineering Controls: 

Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low. 

Exposure Limits

Personal Protective Equipment 

Eyes: Wear chemical splash goggles. 

Skin: Wear appropriate protective gloves to prevent skin exposure. 

Clothing: Wear appropriate protective clothing to prevent skin exposure. 

Respirators:Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced. 

Basic information of 1,3-Dimethoxy benzene

Chemical name:1,3-Dimethoxy benzene
Molecular formula : C8H10O2
Synonyms:Dimethyl resorcinol; m-Dimethoxybenzene; Dimethylresorcinol; Dimethylether resorcinolu；Resorcinol dimethyl ether 
MW : 138.17
CAS No. :151-10-0
Molecular Weight:138.16
Density:1.055
Boiling Point:85-87℃ (7 torr)

Melting Point:-52℃
Flash Point:87℃
Refractive index:1.523-1.525
Solubility:Slightly soluble in water
Appearance:colorless and transparent liquid. There are orange blossom aroma ether, slightly spicy taste
Stability:Stable at room temperature in closed containers under normal storage and handling conditions.
Preparation of 1,3-Dimethoxy benzene: resorcinol and dimethyl sulfate derived reaction.

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

Storage Temperature of 1,3-Dimethoxy benzene:
Keep away from heat, sparks, and flame. Keep away from sources of ignition. Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

1,3-Dimethoxy benzene hazards：
Eye: 1,3-Dimethoxy benzene may cause eye irritation. It may cause chemical conjunctivitis and corneal damage. 
Skin: If you touch 1,3-Dimethoxy benzene accidentally, it may cause skin irritation, and may lead to cyanosis of the extremities. 
Ingestion: Ingestion 1,3-Dimethoxy benzene accidentally, it may cause gastrointestinal irritation with nausea, vomiting and diarrhea. The toxicological properties of 1,3-Dimethoxy benzene have not been fully investigated. It may cause respiratory tract irritation. The toxicological properties of 1,3-Dimethoxy benzene have not been fully investigated.
Inhalation: Can produce delayed pulmonary edema. Inhalation at high concentrations may cause CNS depression and asphixiation.
Chronic: Prolonged or repeated skin contact may cause dermatitis. Effects may be delayed.

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