What Is Pentoxifylline?

Pentoxifylline (Pentoxifylline) Chemical name 3,7-dihydro-3,7-dimethyl-1- (5-oxohexyl) -1H-purine-2,6-dione, white needle-like crystals . 105 ° C melting point. Soluble in water, benzene, ethanol, chloroform, slightly soluble in ethanol. Odorless and bitter. The molecular formula is C13H18N4O3, the molecular weight is 278.30700, the density is 1.31g / cm3, the melting point is 98-100 ° C, and the boiling point is 531.3ºC at 760mmHg.

Pentoxifylline (Pentoxifylline) Chemical name 3,7-dihydro-3,7-dimethyl-1- (5-oxohexyl) -1H-purine-2,6-dione, white needle-like crystals . 105 ° C melting point. Soluble in water, benzene, ethanol, chloroform, slightly soluble in ethanol. Odorless and bitter. The molecular formula is C13H18N4O3, the molecular weight is 278.30700, the density is 1.31g / cm3, the melting point is 98-100 ° C, and the boiling point is 531.3ºC at 760mmHg.

Chinese name

Pentoxifylline

Foreign name

Pentoxifylline

Chemical formula

C13H18N4O3

Molecular weight

278.3

CAS number

6493-05-6

Brief introduction of pentoxifylline

Hexanone cocoa basebook information

Chinese name: hexanone theobromine

Chinese alias: 1- (5-oxohexyl) theobromine; PENTOXIFYLINE; hexacocoline -2,6-dione; 3,7-dimethyl-1- (5-oxohexyl) xanthine;

English name: Pentoxifylline

English alias: 3,7-dimethyl-1- (5-oxohexyl) purine-2,6-dione

CAS number: 6493-05-6

MDL number: MFCD00063379

EINECS number: 229-374-5

RTECS number: XH2475000

PubChem number: 24278190

Molecular formula: C ₁₃ H ₁₈ N ₄ O ₃

Molecular weight: 278.30700

Structural formula:

Exact mass: 278.13800

PSA: 78.89000

LogP: 0.19300 ^[1]

Properties of Pentoxifylline

Appearance and properties: white to off-white solid

Density: 1.31g / cm ³

Melting point: 98-100 ° C

Boiling point: 531.3ºC at 760mmHg

Flash point: 275.1ºC

Storage conditions: Store at RT ^[1]

Pentoxifylline molecular structure data

1. Molar refractive index: 74.28

2. Molar volume (cm3 / mol): 211.2

3. Isometric Zhang Rong (90.2K): 563.2

4. Surface tension (dyne / cm): 50.5

5. Dielectric Constant: None available

6. Polarizability (10-24cm3): 29.44

7. Mass of single isotope: 278.13789Da ^[2]

8. Nominal mass: 278Da

9. Average mass: 278.307Da

Pentoxifylline

Source (name) and content (valency) of pentoxifylline

This product is 3,7-dihydro-3,7-dimethyl-1- (5-oxohexyl) -1H-purine-2,6-dione. Calculated on dry basis, containing C13H18N4O3 shall not be less than 99.0%. ^[3]

Hexanone cocoa alkaline

White powder or granules; slightly smelly and bitter.

Soluble in chloroform, soluble in water or ethanol, slightly soluble in ether.

The melting point is 103 to 107 ° C.

Pentoxifylline

(1) Take about 10mg of this product, add 1ml of hydrochloric acid and 0.1g of potassium chlorate, evaporate to dryness in a water bath, the residue will appear purple when ammonia gas is added, and then add a few drops of sodium hydroxide test solution, the purple will disappear.

(2) Take about 10mg of this product, add 5ml of water to dissolve it, add 1ml of dilute sulfuric acid, and add a few drops of iodine test solution to form a brown precipitate.

(3) The infrared light absorption spectrum of this product should be consistent with the control spectrum ("Infrared Spectra of Drugs" 29). ^[3]

Pentoxifylline test

acidity

Take 1.0g of this product, add 50ml of water to dissolve, immediately add 1 drop of bromothymol blue indicator solution, the solution should be green or yellow, titrate with sodium hydroxide titration solution (0.01mol / L) to microscopic blue, consume Sodium hydroxide titration solution (0.01mol / L) shall not exceed 0.2ml.

Clarity and color of the solution

Take 1.0g of this product and add 50ml of water to dissolve. The solution should be clear and colorless; if it is turbid, it must not be more concentrated than the turbidity standard solution No. 1; if it is colored, it is compared with the yellow standard colorimetric solution (2010 edition Pharmacopeia The two appendixes A first method) comparison must not be deeper.

Bromide

Take 0.50g of this product, add 10ml of water to dissolve, add dilute nitric acid 0.5ml and silver nitrate test solution 1ml, heat to boiling, let cool, add water to dilute 25ml, shake well, and standard potassium bromide solution 11.0ml [per 1ml standard bromine Potassium solution is equivalent to 0.01mg of bromine (Br)], compared with the control solution made by the same method, it must not be more concentrated.

relative substance

Take this product, accurately weigh it, dissolve with solvent [methanol-0.544% potassium dihydrogen phosphate solution (1: 1) mixed solution] and quantitatively dilute it to make a solution containing about 1mg per 1ml as the test solution; Theobromine reference substance, theophylline reference substance, caffeine reference substance, and hexaketo theoline theophylline reference substance are precisely weighed, dissolved and quantitatively diluted with the above-mentioned solvent to prepare a mixed solution containing approximately 1 g per 1 ml, as a reference solution. . Tested according to high performance liquid chromatography. Use octylsilane-bonded silica gel as filler; mobile phase A is methanol-0.544% potassium dihydrogen phosphate solution (3: 7), and mobile phase B is methanol-0.544% potassium dihydrogen phosphate solution (7: 3); The detection wavelength was 272 nm. Gradient elution was performed according to the following table. Take 20l of the reference solution and inject it into the liquid chromatograph to adjust the detection sensitivity so that the peak height of the hexanothebroline chromatographic peak is about 10% of the full range; the order of the peaks of each component is theobromine, theophylline, and caffeine With pentoxifylline. The retention time of pentoxifylline is about 12 minutes, the resolution of the theophylline peak and the caffeine peak should be greater than 4, and the resolution of the peak of the caffeine peak and the pentoxifylline should be greater than 10; Peak calculation is not less than 5000. Then, 20 l of each of the test solution and the reference solution was precisely measured, injected into a liquid chromatograph, and the chromatogram was recorded. The chromatograms of the test solution should have peaks consistent with the retention times of theobromine, theophylline, or caffeine. The peak area calculated according to the external standard method should not exceed 0.1%; the peak area of other single impurities should not be larger than the reference product. Peak area of pentoxifylline in solution (0.1%); the total amount of impurities must not exceed 0.5%. ^[3]

Time (minutes)	Mobile phase A (%)	Mobile phase B (%)
0	86	14
6	86	14
13	10	90
30	10	90
38	86	14
43	86	14

Loss on drying

Take this product and dry it under reduced pressure at 60 ° C to constant weight. The weight loss shall not exceed 0.5%.

Residue on ignition

Must not exceed 0.1%.

Heavy metal

Take 1.0g of this product, add 2ml of dilute acetic acid and dissolve it into 25ml with appropriate amount of water, and check according to law that the content of heavy metals must not exceed 20 parts per million. ^[3]

Determination of pentoxifylline

Take about 0.2g of this product, accurately weigh, add 8ml of glacial acetic acid to dissolve, add 32ml of acetic anhydride, according to the potentiometric titration method (Appendix A of the second edition of the Pharmacopoeia, 2010 edition), and use perchloric acid titration solution (0.1mol / L) Titrate and correct the results of the titration with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 27.83mg of C13H18N4O3. ^[3]

Pentoxifylline drug analysis

Method name: pentoxifylline the bulk drug-determination of pentoxifylline-spectrophotometry

Scope of application: This method uses spectrophotometry to determine the content of pentoxifylline in the pentoxifylline theophylline bulk drug.

This method is suitable for pentoxifylline theophylline drug substance.

Principle of the method: A test solution is dissolved in water and quantitatively diluted to prepare a test solution. An ultraviolet-visible spectrophotometer is set, and the absorbance is measured at a wavelength of 274 nm to calculate the content.

Reagent: water

Equipment: UV-visible spectrophotometer

Sample preparation: 1. Preparation of test solution

Accurately weigh an appropriate amount of the test product, dissolve it with water, and quantitatively dilute it to make a solution containing about 10 g per microliter of each mL to obtain a test solution.

Note: "Precision weighing" means that the weighing weight should be accurate to one thousandth of the weighing weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards.

Operation steps: Take the test solution according to the ultraviolet spectrophotometry, measure the absorbance at a wavelength of 274nm, and calculate it according to the absorption coefficient (E1% 1cm) of C13H18N4O3 as 365, that is, it is obtained.

Note: The spectrophotometric method should be based on the same batch of solvent prepared as the test product, using a 1cm quartz absorption cell. The wavelength with the largest absorbance is used as the measurement wavelength. Generally, the error of the absorbance reading of the test product is between 0.3-0.7. The slit band width of the instrument should be less than half the width of the absorption band of the test product, otherwise the measured absorbance is low. The selection of the slit width should be based on reducing the absorption of the test article when the slit width is reduced. Because the absorption cell and the solvent may have blank absorption, the blank reading should be subtracted after measuring the absorbance of the test product, and the content should be calculated. ^[4]

Pentoxifylline drugs

Pentoxifylline drug name:

[General name] Pentoxifylline sustained-release tablets

[Product Name] Rui Pan Tong Pentomer ( )

[English name] Pentoxifylline Sustained-Release Tablets

[Chinese Pinyin] Ji Tong Ke Ke Jian Huan Shi Pian ^[5]

Pentoxifylline ingredients:

The main ingredients of this product are: Pentoxifylline

Its chemical name is: 3,7-dihydro-3,7-dimethyl-1- (5-oxohexyl) -1H-purine-2,6-dione

Molecular formula: C13H18N4O3

Molecular weight: 278.31 ^[5]

Pentoxifylline category:

Chemicals & Biological Products >> Nervous System Drugs >> Cerebrovascular Drugs

Chemical Medicine and Biological Products >> Circulatory System Drugs >> Vasoactive Drugs >> Vasodilators ^[5]

Ketococo alkaline :

This product is a white film-coated tablet.

Pentoxifylline indications:

This product is used to treat peripheral vascular disease (such as intermittent claudication) of degree II (based on Fontaine classification) ^[5]

Pentoxifylline usage and dosage:

The following dosage guidelines are suitable for adults or adolescents weighing more than 50 kg:

1 tablet (equivalent to 400 mg of pentoxifylline) 3 times a day. That is, the maximum daily dose is 3 tablets (equivalent to 1200 mg of pentoxifylline).

For patients with severe renal insufficiency (creatinine clearance <10ml / min), the dose of this product should be reduced to 50-70% of the normal dosage.

This product should be delivered completely after meals with an appropriate amount of water without chewing. ^[5]

Pentoxifylline adverse reactions:

Common adverse reactions are gastrointestinal symptoms (such as: nausea, vomiting, bloating, indigestion and diarrhea).

Occasionally dizziness and headache.

Rarely reduced blood pressure, angina pectoris, arrhythmia, facial flushing and allergic symptoms (such as itchy skin, flushing and urticaria).

Rare jaundice and elevated liver enzymes (transaminase, alkaline phosphatase).

There have been independent reports of severe allergic reactions within minutes of injection of this product, manifested as angioedema, bronchial smooth muscle spasm, and allergic shock. The first signs of an allergic reaction must be discontinued and the doctor notified.

Rare bleeding (eg, mucosal, skin, and gastrointestinal bleeding), thrombocytopenia, and anemia. Patients' blood routines should be monitored regularly.

If a patient notices an adverse reaction not described in this manual during treatment, please consult a doctor immediately. ^[5]

Pentoxifylline contraindications:

This product is contraindicated in the following patients:

-People who are allergic to pentoxifylline and other mesosulfurine drugs

-Acute myocardial infarction

-Active major bleeding

-Retinal bleeding. ^[5]

Pentoxifylline notes:

This product should be used with caution in patients with severe coronary and cerebral arteriosclerosis and severe arrhythmia.

Hypotension, blood pressure instability and renal dysfunction should be used with caution, and the dosage should be adjusted appropriately.

For patients with severe renal insufficiency (creatinine clearance <10ml / min), the dose of this product needs to be reduced to 50 to 70% of the normal dose. And strict monitoring after medication.

Patients who develop retinal hemorrhage, severe hypotension, and allergic reactions during medication should stop the medication immediately.

Patients who drive vehicles and perform machine operations should pay attention when using this product. ^[5]

Pentoxifylline for pregnant and lactating women:

As there is not enough medication information for pregnant and lactating women, this product is contraindicated in pregnant and lactating women.

Pentoxifylline for elderly use:

Elderly patients have a slower metabolism in the liver and a slower rate of excretion through the kidneys and feces. They should be reduced as appropriate or as directed by a doctor.

Pentoxifylline drug interactions:

This product can enhance the pharmacological effects of antihypertensive drugs, hypoglycemic drugs and anticoagulants.

Pentoxifylline overdose:

The symptoms after overdose of this product are: dizziness, nausea, decreased blood pressure, tachycardia, facial flushing, loss of consciousness, fever, agitation, loss of reflexes, tonic-clonic convulsions, coffee-like vomiting, and arrhythmia.

Symptomatic treatment should be taken. Mainly monitor blood pressure and breathing. Diazepam can be used to treat convulsions. ^[5]

First aid measures for severe allergic reactions (shock):

-First symptoms (sweating, nausea, cyanosis)

-Immediately stop the injection / infusion and leave the cannula in the blood vessel;

-If needed, establish a venous input.

Other conventional emergency measures:

-Raise lower limbs above head and body

-Keep your airways open.

Emergency measures:

-Immediate intravenous injection of epinephrine: Dilute 1ml of epinephrine solution (1: 1000) into 10ml solution, and inject intravenously 1ml (equivalent to 0.1mg of epinephrine), you need to closely observe the patient's heart rate and blood pressure (for patients with arrhythmia, there may be Danger). Repeated intravenous epinephrine treatment can be used.

-Subsequent venous expansion therapy: for example: plasma, human albumin and electrolyte balance solution.

-Subsequent intravenous glucocorticoid treatment: for example: 250-000 mg of prednisolone (or other equivalent glucocorticoid). Repeated administration of glucocorticoids.

Other treatments can be considered: for example: artificial respiration, oxygen and antihistamine therapy. ^[5]

Pentoxifylline pharmacology and toxicology:

Pentoxifylline is a dimethylxanthine derivative that can reduce blood viscosity, thereby improving blood flow, promoting microcirculation of ischemic tissue, and increasing oxygen supply to special organs.

Pentoxifylline improves the deformability of red blood cells by inhibiting phosphodiesterase and increasing intracellular adenosine triphosphate. It can also reduce fibrinogen and inhibit the aggregation of red blood cells and platelets. ^[5]

Pharmacokinetics of Pentoxifylline:

After oral administration, pentoxifylline is quickly and completely absorbed. This product has a first pass effect, and the system bioavailability is only 20-30%. Oral non-sustained release preparations, the peak time of plasma is less than 1 hour.

Almost all pentoxifylline is metabolized by the liver. In plasma, the main active metabolite 1- (5-hydroxyhexyl) -3,7-dimethylxanthine has a high level, and the content ratio to the original drug is 2: 1.

The half-life of pentoxifylline is 0.4-0.8 hours in plasma and the half-life of metabolites is 1-1.6 hours. This product is mainly cleared by the kidney, and only 4% is eliminated by feces. Only trace amounts of the prototype drug were excreted.

The pentoxifylline is released in a slow manner in this formulation. ^[5]

Pentoxifylline expert reviews

This product is an agent for improving cerebral circulation and peripheral vascular disorders. Clinically used to treat sequelae caused by cerebrovascular disorder, stroke or trauma, improve its symptoms such as attention and memory loss, and poor mental state. This product has the effect of expanding the brain and peripheral blood vessels, at the same time can reduce blood viscosity and improve blood circulation of the brain and limbs. In addition, there are still anti-fibrotic effects. This product can not only improve skin microcirculation, improve skin blood flow, but also improve the oxidizing capacity of hypoxic tissues, which has a certain effect on atrophic skin diseases. ^[6]