Dihydroxypropyltheophylline is an organic compound with the chemical formula CtenHfourteenNfourOfour, a white crystalline powder, easily soluble in water, is mainly used as a smooth muscle relaxant. It has the function of dilating bronchi and coronary arteries, and has diuretic effect. It is stable in gastric juice. Its antiasthmatic effect is similar to aminophylline, especially suitable for patients with tachycardia.
Reference value for drainage parameter calculation (XlogP): None
Number of hydrogen bond donors: 2
Number of hydrogen bond receptors: 5
Number of rotatable chemical bonds: 3
Number of tautomers: 0
Topological molecular polar surface area: 98.9
Number of heavy atoms: 18
Surface charge: 0
Complexity: 364
Number of isotope atoms: 0
Determine the number of atomic structure centers: 0
Number of uncertain atomic structure centers: 1
Determine the number of chemical bond structure centers: 0
Number of uncertain chemical bond structure centers: 0
Number of covalent bond units: 1[2]
purpose
Dihydroxypropyltheophylline smooth muscle relaxant has the function of dilating bronchi and coronary arteries, and has diuretic effect. It is stable in gastric juice. Its antiasthmatic effect is similar to that of aminophylline, especially suitable for patients with tachycardia.
Pharmacopoeia information
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essential information
This product is 1,3-dimethyl-7 - (2,3-dihydroxypropyl) - 3,7-dihydro-1H-Purine-2,6-dione, calculated as dry product, containing CtenHfourteenNfourOfourNot less than 98.00%.
character
This product is white powder or granule, odorless.
This product is easily soluble in water, slightly soluble in ethanol, and very slightly soluble in chloroform or ether.
melting point
The melting point of this product (general rule 0612) is 160~164 ℃.
absorption coefficient
Take this product, precisely weigh it, add water to dissolve and quantitatively dilute it to make a solution containing about 10 μ g per 1mL, and measure the absorbance and absorption coefficient (E1%1cm）354~376.
identify
1. Take about 0.1g of this product, add 1mL of hydrochloric acid and 0.1g of potassium chlorate, steam it dry on a water bath, the residue will appear purple when encountering ammonia, add a few drops of sodium hydroxide test solution, and the purple will disappear.
2. The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 12 figure).
inspect
PH
Take 0.50g of this product, add 10mL of water to dissolve it, add 5 drops of bromothymol blue indicator solution, which should be yellow or green, and add 0.20mL of sodium hydroxide titrant (0.02mol/L), which should be blue.
Clarity and color of solution
Take 1.0g of this product, add 10mL of water, shake to dissolve it, the solution should be clear and colorless, if it develops color, it should not be deeper than the yellow or yellow green No. 1 standard colorimetric solution (General Rule 0901 Method 1).
chloride
Take 0.25g of this product, add 5mL of water and 1.0mL of sodium hydroxide test solution, boil for 30 seconds, let it cool, and check according to the law (general rule 0801). Compared with 7.0mL of standard sodium chloride solution prepared by the same method, it should not be more concentrated (0.028%).
Related substances
Determine according to the method of high performance liquid chromatography (general rule 0512).
Test solution: Take an appropriate amount of this product, weigh it accurately, add water to dissolve it and dilute it quantitatively to make a solution containing about 1.0mg per 1mL.
Control solution: Take 10mg of theophylline reference substance, weigh it precisely, put it into a 100mL measuring flask, add water to dissolve it and dilute it to the scale, shake it up, precisely measure 10mL and 1mL of test solution, put it into a 200mL measuring flask, dilute it with water to the scale, shake it up.
Chromatographic conditions: octadecyl silane bonded silica gel is used as the filler, potassium dihydrogen phosphate solution (1.0g of potassium dihydrogen phosphate, dissolved with water and diluted to 1000mL) - methanol (72:28) is used as the mobile phase, the detection wavelength is 254nm, and the injection volume is 10 μ L.
System adaptability requirements: in the chromatogram of the reference solution, the number of theoretical plates shall not be less than 2000 based on the peak of dihydroxypropyltheophylline, and the resolution between the peak of dihydroxypropyltheophylline and theophylline shall be greater than 3.5.
Determination method: Precisely measure the test solution and the reference solution, respectively inject them into the liquid chromatograph, and record the retention time of the chromatogram to three times of the main component peak.
Limit: if there is a chromatographic peak in the chromatogram of the test solution that is consistent with the retention time of theophylline, the peak area shall not exceed 0.5% according to the external standard method, and the peak area of other impurities shall not exceed 0.5% of the peak area of dihydroxypropyltheophylline in the control solution.
Loss on drying
Take this product, dry it at 105 ℃ to constant weight, and the weight loss shall not exceed 0.5% (general rule 0831).
Ignition residue
It shall not exceed 0.15% (general rule 0841).
heavy metal
Take 1.0g of this product, add 2mL of acetate buffer solution (pH3.5) and appropriate amount of water to dissolve it into 25mL, and check according to the law (General Rule 0821, Method 1). The content of heavy metals should not exceed 20 parts per million.
Assay
Take about 0.2g of this product, precisely weigh it, add 2mL of anhydrous formic acid to dissolve it, slowly add 50ml of acetic anhydride, shake it for 3 minutes, add 4-5 drops of Sudan IV indicator solution, titrate with perchloric acid titrant (0.1mol/L) until the solution turns purple, and correct the titration result with blank test.Every 1mL perchloric acid titrant (0.1mol/L) is equivalent to 25.42mg CtenHfourteenNfourOfour。
category
Smooth muscle relaxants.
Storage
Seal and store in a dry place.
preparation
1. Dihydroxypropyltheophylline tablets.
2. Dihydroxypropyltheophylline injection.[1]
Brief Introduction to Drugs
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category
This product is an over-the-counter antiasthmatic drug.
pharmacological action
The antiasthmatic effect of this product is similar to theophylline.The cardiac excitatory effect is only 1/20-1/10 of that of aminophylline. It has little effect on the heart and nervous system.It is especially suitable for asthma patients with tachycardia.This product has a direct relaxation effect on the smooth muscle of the respiratory tract, and its mechanism is complex. In the past, it was thought that the increase of CAMP content in cells was caused by inhibiting phosphodiesterase.Recent experiments suggest that theophylline's bronchiectasis is partly due to the release of endogenous adrenaline and norepinephrine. In addition, theophylline is a purine receptor blocker, which can resist the contraction of the respiratory tract caused by adenine.Theophylline can enhance the contractility of the diaphragm, especially when the diaphragm is weak, so it is helpful to improve the respiratory function.
indication
It is suitable for people with asthma, asthmatic bronchitis and other asthmatic symptoms.
Usage and dosage
Oral administration: 0.1-0.2g (0.5-1 tablet) once for adults, three times a day.
Adverse reactions
Gastrointestinal symptoms such as headache, insomnia, palpitation, nausea and vomiting may occur after taking it, but it is less irritating than aminophylline.In case of excess, there are central excitation, arrhythmia, muscle fibrillation or epilepsy.
taboo
It is forbidden for those allergic to other theophylline drugs.
matters needing attention
1. This product can pass through the placental barrier and can also be discharged with milk. Pregnant women and lactating women should use it with caution.
2. Patients with heart, liver and kidney dysfunction, hyperthyroidism, active gastrointestinal ulcer, diabetes, prostatic hyperplasia and dysuria should be cautious.
3. It is forbidden for people with allergies to this product. People with allergies should use it with caution.
4. It is forbidden to use this product when its properties change.
5. Please keep this product away from children.
6. Children must be used under adult supervision.
7. If you are using other drugs, please consult a doctor or pharmacist before using this product.
Drug interaction
1. When used together with erythromycin, lincomycin, clindamycin and some fluoroquinolones, the clearance of the product can be reduced, and the blood concentration of the drug increases, which may lead to poisoning.
2. Lithium carbonate can accelerate the removal of this product, reducing the efficacy of this product.
3. If it is used together with other drugs, drug interaction may occur. For details, please consult a doctor or pharmacist.
Internal process
It is easy to be absorbed after oral administration. After oral administration: 19-28mg/kg, the plasma drug concentration is 19.3-36.4 μ g/ml.The highest effect can be achieved after 15-30 minutes of injection.Partial metabolism in the body, metabolites and prototype drugs are excreted with urine.
