What Is Praziquantel?
Praziquantel (Praziquantel, or Biltricide) is an insect repellent used in humans and animals to treat roundworms and trematodes. It is especially effective for schistosomiasis, liver fluke, and Diphyllobothrium latum. Praziquantel is a drug on the World Health Organization's standard list of essential drugs, and it is one of the most important drugs for basic public health in the world [1] .
- common name
- Praziquantel tablets
- English name
- PRAZIQUANTEL TABLETS
- Pinyin name
- BIKUITONG PIAN
- Drug category
- Anti-trematodes
- Character
- This product is a white tablet
- Praziquantel (Praziquantel, or Biltricide) is an insect repellent used in humans and animals to treat roundworms and trematodes. It is especially effective for schistosomiasis, liver fluke, and Diphyllobothrium latum. Praziquantel is a drug on the World Health Organization's standard list of essential drugs, and it is one of the most important drugs for basic public health in the world [1] .
Brief introduction of praziquantel compounds
- Chinese name: Praziquantel
- Chinese alias: Cyclopisoquinone; Artichoke ussin extract; 2-cyclohexylcarbonyl-1,3,4,6,7,11-hexahydro-2-pyrazino (2,1-) isoquine Quinolin-4-one;
- English name: Praziquantel
- English alias: embay8440; biltricide; Prazinon; Azinox; Cysticide;
- CAS number: 55268-74-1
- Molecular formula: C 19 H 24 N 2 O 2
- Molecular weight: 312.40600
- Exact mass: 312.18400
- PSA: 40.62000
- LogP: 2.41070
- Physical and chemical properties
- Appearance and properties: white or almost white crystalline powder
- Density: 1.22 g / cm 3
- Melting point: 136-142ºC
- Boiling point: 544.1ºCat 760 mmHg
- Flash point: 254.6ºC
- Stability: stable under normal temperature and pressure
- Storage conditions: ventilated, low temperature and dry
- Security Information
- Customs code: 2933790090
- WGK Germany: 1
- Danger category code: R11
- Safety instructions: S16; S26; S36 / 37/39; S45
- RTECS number: UQ4150000
- Dangerous goods mark: F; C [1]
- production method
- Using phenylethylamine as raw material, acylation with chloroacetyl chloride, and then amination reaction with potassium phthalamide, amino group was introduced, and 3,4-dihydroisoquinoline was cyclized under the action of phosphorus oxychloride. The derivative is hydrogenated and hydrolyzed to obtain 1-aminomethyltetrahydroquinoline, which is acylated with cyclohexanyl chloride and chloroacetyl chloride, and finally dehydrochlorinated to give praziquantel. Isoquinoline can also be used as a raw material.After the Reissert reaction, cyano and nitrogen are introduced at the l-position to be benzoylated and then hydrogenated.At the same time, benzoyl is transferred to the amino group on the side chain, and then chlorine is introduced to the amino group on the ring. Acetyl is then cyclized, hydrolyzed, and cyclohexyl acylated to give praziquantel [1] .
- use
- Broad-spectrum antiparasitic drugs. It is used for the treatment and prevention of schistosomiasis, cysticercosis, lung fluke disease, hydatid disease, ginger pieceworm disease, echinococcus disease, and helminth infection [1] .
Praziquantel Pharmacopoeia Standard
Praziquantel source (name), content (potency)
- This product is 2- (cyclohexylcarbonyl) -1,2,3,6,7,11b-hexahydro-4H-pyrazino [2,1-a] isoquinolin-4-one. Calculated on dry basis, containing C19H24N2O2 should be 98.0% to 102.0%.
Praziquantel traits
- This product is white or off-white crystalline powder; bitter.
- This product is soluble in chloroform, soluble in ethanol, and insoluble in ether or water.
- Melting point
- The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 136 to 141 ° C.
Praziquantel identification
- (1) Take this product, add ethanol to make a solution containing 0.5mg per 1ml, and measure it by ultraviolet-visible spectrophotometry (Appendix IVA of Pharmacopoeia Part II of the 2010 edition). It has maximum absorption at the wavelengths of 264nm and 272nm.
- (2) The infrared light absorption spectrum of this product should be consistent with the control spectrum ("Infrared Spectra of Drugs" 190).
Praziquantel test
- acidity
- Take 0.50g of this product, add 15ml of neutral ethanol (neutral to methyl red indicator solution), and add 1 drop of methyl red indicator solution and 0.10ml of 0.01mol / L sodium hydroxide solution, it should be yellow.
Praziquantel test
- relative substance
- Take 20mg of this product, place it in a 100ml measuring flask, add mobile phase to dissolve and dilute to the mark, shake well, and use it as a test solution; take a precise amount, and quantitatively dilute with mobile phase to make a solution containing 2g per 1ml, as Control solution. According to the chromatographic conditions under the content determination item, take 10 l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full range, and then accurately measure the test solution and the control solution. Each 20 l was injected into a liquid chromatograph, and the chromatogram was recorded to 4 times the peak retention time of the main component. If there is an impurity peak in the chromatogram of the test solution, the sum of the area of each impurity peak must not be greater than the area of the main peak of the control solution (1.0%).
- Loss on drying
- Take this product and dry it at 105 to constant weight, and the weight loss shall not exceed 0.5% (Appendix L of Part Two of the Pharmacopoeia of 2010 Edition).
- Residue on ignition
- Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.1%.
- Heavy metal
- Take the residue left under the item of burning residue and check it according to law (Appendix H of the second edition of the Pharmacopoeia of 2010 Edition, the second method H), the content of heavy metals must not exceed 20 parts per million.
Determination of praziquantel
- It was determined by high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 Edition).
- 1 Chromatographic conditions and system suitability tests
- Octadecylsilane-bonded silica gel was used as the filler; acetonitrile-water (60:40) was used as the mobile phase; the detection wavelength was 210 nm. The theoretical number of plates calculated from praziquantel peak is not less than 3000.
- 2 Assay
- Take about 50mg of this product, weigh it accurately, place it in a 100ml measuring bottle, add the appropriate amount of mobile phase, shake to dissolve, dilute to the mark with mobile phase, and shake well. 5ml was accurately measured, placed in a 50ml volumetric flask, diluted to the mark with mobile phase, shaken, 20l was accurately measured and injected into the liquid chromatograph, and the chromatogram was recorded; another praziquantel reference substance was measured by the same method. Calculate the peak area according to the external standard method to get [2] .
Praziquantel category
- Intestinal repellent.
Praziquantel storage
- Shaded and sealed.
Praziquantel preparation
- Praziquantel tablets
Praziquantel National Essential Medicines
- National retail price guide for essential medicines related to praziquantel
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- Note:
- 1. Representatives marked with "*" in the remarks column of the table.
- 2. The representative dosage form specifications in the table are marked with "" in the remarks column, and the prices of the representative dosage form specifications and related specifications with a clear price comparison relationship are temporary prices.
Praziquantel laboratory determination
- Method name: Praziquantel Tablets-Praziquantel-High Performance Liquid Chromatography
- Application: This method uses high performance liquid chromatography to determine the content of praziquantel in praziquantel tablets.
- This method is applicable to praziquantel tablets.
- Principle of the method: The test product is studied in detail, and the internal standard solution is added to dissolve it, and then diluted with methanol, and then entered into a high-performance liquid chromatography for chromatographic separation. The peak area of praziquantel is measured at a wavelength of 263 nm using a UV absorption detector, and calculated Its content.
- Reagent: 1. Methanol
- -Asarone
- Equipment: 1. Instrument
- 1.1 HPLC
- 1.2 Column
- Octadecylsilane bonded silica as filler
- 1.3 UV absorption detector
- Chromatographic conditions
- 2.1 Mobile phase: methanol water = 100 40
- 2.2 Detection wavelength: 263nm
- 2.3 Column temperature: room temperature
- Sample preparation: 1. Preparation of internal standard solution
- Accurately weigh the appropriate amount of -asarcin, add methanol to dissolve and dilute to a solution containing 0.4mg per 1mL, which is the internal standard solution.
- 2. Preparation of reference solution
- About 100 mg of praziquantel reference was accurately weighed, placed in a 10 mL volumetric flask, 5 mL of an internal standard solution was precisely added, shaken to dissolve, diluted with methanol to the mark, and shaken to obtain the reference solution.
- 3. Preparation of test solution
- Take 20 test samples, accurately weigh, grind carefully, accurately weigh an appropriate amount (approximately 100 mg of praziquantel), place it in a 10 mL volumetric flask, add 5 mL of an internal standard solution, shake to dissolve, and dilute with methanol to Scale, shake well, that is the test solution.
- Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed 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: Precisely draw 10 mL of each of the reference solution and the test solution, and inject them into a high-performance liquid chromatograph. Measure the peak area of praziquantel (C19H24N2O2) with a UV absorption detector at a wavelength of 263 nm, and calculate its content [3 ] .
Praziquantel Drug Description
Praziquantel Pharmacology and Toxicology
- This product is effective against schistosomiasis, tapeworm, cysticercosis, clonorchiasis, lung fluke, and ginger leafworm. There are two main pharmacological effects on the worm body: (1) Ankylosal contraction of the worm body muscles results in spastic paralysis. After the schistosomiasis was exposed to low-concentration praziquantel, the body tension increased within 20 seconds. When the drug concentration reached 1 mg / L or more, the body contracted rapidly. The body muscle contraction may be related to praziquantel increasing the permeability of the body cell membrane and causing intracellular calcium loss. (2) Insect cortical damage and host immune function involvement: pyridine
- Praziquantel
Praziquantel Pharmacokinetics
- It is absorbed quickly after oral administration, and more than 80% of the drug can be absorbed from the intestine. The peak of the blood drug arrives in about 1 hour. After the drug enters the liver, it metabolizes quickly, mainly forming hydroxyl metabolites, and only a small amount of unmetabolized original drug enters the systemic circulation. The portal vein blood concentration can be more than 10 times higher than the peripheral venous blood drug concentration. Cerebrospinal fluid concentration is about 15% to 20% of blood drug concentration. After breastfeeding patients take the drug, the drug concentration in milk is equivalent to 25% in serum. After oral administration of 10 to 15 mg / kg, the peak plasma level is about 1 mg / L. Drugs are mainly distributed in the liver, followed by kidneys, lungs, pancreas, adrenal glands, pituitary gland, salivary glands, etc. They rarely pass through the placenta and have no organ-specific accumulation. T1 / 2 is 0.8 to 1.5 hours, and T1 / 2 of its metabolites is 4 to 5 hours. It is mainly excreted by the kidneys in the form of metabolites, with 72% excreted within 24 hours and 80% excreted within 4 days.
Praziquantel indications
- It is a broad-spectrum anti fluke and tapeworm medicine. It is suitable for various schistosomiasis, clonorchiasis, lung fluke disease, ginger leafworm disease, ascariasis and cysticercosis.
Pharmacological effects of praziquantel
- This product mainly causes schistosomiasis and tapeworms in the host to produce spastic paralysis by 5-HT-like action, which has a good effect on most tapeworm adults and immature worms, and can affect the permeability of calcium in the muscle cells of the worms. The calcium influx is increased, the reuptake of the calcium pump of the sarcoplasmic reticulum is inhibited, and the calcium ion content in the muscle cells of the worm body is greatly increased, so that the worm body is paralyzed.
Praziquantel dosage
- Treatment of trematodes
- Schistosomiasis: Various chronic schistosomiasis are treated with a total dose of 60 mg / kg for 1 to 2 days, and the daily dose is divided into 2 to 3 times between meals. The total dose of acute schistosomiasis is 120mg / kg, taken 2 to 3 times daily for 4 days. Those who weigh more than 60kg are calculated as 60kg. Clonorchiasis sinensis: The total dose is 210mg / kg, 3 times a day, even for 3 days. Pneumochiasis: 25mg / kg, 3 times a day for 3 days. Ginger filariasis: 15mg / kg.
- Treatment of ascariasis
- Beef and pork ascariasis: 10mg / kg, taken in the morning, and then taken magnesium sulfate 1 hour later. Ascaris lumbricoides and Aspergillus laticidum: 25mg / kg, stunned. (3) The total dose for treatment of cysticercosis is 120 ~ 180mg / kg, divided into 3 ~ 5 days, and divided into 2 ~ 3 times daily.
Praziquantel adverse reactions
- Common side effects include dizziness, headache, nausea, abdominal pain, diarrhea, fatigue, sore limbs, etc., which are generally mild, have a short duration, do not affect treatment, and do not require treatment. A few cases showed palpitations, chest tightness and other symptoms. The electrocardiogram showed T wave changes and extra-constrictions. Occasionally, supraventricular tachycardia and atrial fibrillation were seen. Transient aminotransferase elevation may occur in a few cases. occasionally induce mental disorders or gastrointestinal bleeding.
Contraindications to praziquantel
- Eye cysticercosis is disabled.
Praziquantel precautions
- Treatment of parasites parasites such as schistosomiasis, lung fluke, cysticercosis, etc., due to the large amount of antigen released after the parasite is killed, it can cause fever, eosinophils, rashes, etc., and occasionally cause allergies Sexual shock must be observed. Patients with cerebral cysticercosis need to be hospitalized, and supplemented with treatment measures to prevent cerebral edema and reduce high intracranial pressure (using dexamethasone and dehydrating agents) or prevent persistent epilepsy to prevent accidents. When combined with cysticercosis, the worms must be surgically removed and then treated with drugs. Use with caution in patients with severe heart, liver, and kidney disease and those with a history of mental illness. Those who have obvious dizziness, drowsiness and other nervous system reactions, do not perform driving or mechanical operations during the treatment and within 24 hours after stopping the drug. When cysticercosis drives out tapeworms, it is necessary to exclude recessive cerebral cysticercosis to avoid accidents.
Praziquantel for pregnant and lactating women
- Breastfeeding women should not breastfeed during the medication until 72 hours after stopping the medication.
Praziquantel storage
- Shaded and sealed.
Praziquantel drug interactions
- still uncertain.
Preparation of Praziquantel
- Praziquantel has been widely used in clinical medicine as a broad-spectrum antiparasitic drug. In order to increase its efficacy and use, reduce toxic and side effects, overcome the shortcomings of large first-pass effects, low bioavailability, and short half-life, it is made into lipids. New preparations such as plastids and microcapsules are summarized as follows.
Praziquantel liposomes
- The reverse evaporation method was used to co-dissolve praziquantel, cholesterol, stearylamine and egg yolk lecithin (1: 2: 1: 8) in absolute ethanol. The ethanol was removed by rotary evaporation under reduced pressure in a water bath to obtain a praziquantel lipid membrane. Phosphate buffer was added, the membrane was shaken to remove the membrane, sonicated for 20 min, and ultracentrifuged at 15,000 r / min to remove the unencapsulated praziquantel. A liposome suspension was prepared. The average diameter of the prepared liposomes was 4.6 nm, the average number of layers was 8.2, the encapsulation efficiency was above 60%, and the leakage rate was less than 10%. After being left for 60 days at 4 , the encapsulation efficiency remained basically stable [4] . After praziquantel is made into liposomes, it can not only be administered by injection, improve bioavailability, but also increase its selectivity to target tissues such as the liver, maintain effective blood concentration, reduce dosage, and have obvious advantages over ordinary preparations.
Praziquantel capsules
- 1g of micronized praziquantel was suspended in a 3% gelatin solution, placed on a constant temperature water bath at 50 ° C, and a 4% sulfuric acid solution was slowly added dropwise. After microscopic monitoring showed that the capsule had formed, add The dilute solution of sodium sulfate was solidified with formaldehyde, and the formaldehyde was washed and dried under reduced pressure to obtain off-white powdery microcapsules. The average body diameter of the microcapsules under the microscope was 82.66 m, the average encapsulation rate was 81.1%, and it was stable to heat [5] . Praziquantel microcapsules can be injected intramuscularly to slow release, improve efficacy, and reduce toxic and side effects.
Praziquantel gel
- Carbopol 940 was used as the gel matrix, 40% of propylene glycol (w / w), 45% of ethanol (w / w), and 5% of water (w / w) were mixed solvents. After ultrasonic treatment for 2 minutes, the system was prepared. 1% praziquantel gel was obtained. Adding laurazide to the gel can effectively promote the percutaneous penetration of praziquantel. In vitro 1% praziquantel gel release experiments show that the release of praziquantel from the gel conforms to the 3.68 Higuchi equation [6 ] .
- Praziquantel gel is a transparent semi-solid with fast drug release rate. It can be formed on the skin to form a transparent film, which can be washed with water. It is easy to use for scum-type skin diseases such as Demodex mite infection.
Praziquantel coated tissue
- Weigh 2.0 g of praziquantel and put it into a 100 ml measuring bottle, add 8.0 ml of dimethyl sulfoxide to the above measuring bottle, add 95% ethanol to the mark, shake to completely dissolve praziquantel, and make 2% praziquantel. Ketone coating agent. 20cm × 20cm soft non-woven paper was stacked into a suitable size, packed into a polyethylene aluminum plastic package, and 20 ml of praziquantel coating agent was injected into the bag to make a paper towel. It has been determined that the preparation can withstand high temperature of 60 and constant temperature accelerated test in an oven at 40 for 120 days, and the content has not changed significantly [7] .
- As a skin care drug that works in schistosomiasis-affected areas and needs to prevent cercariae from entering for a long time, praziquantel coated paper towels overcome the shortcomings of past application of ointments and sprays, which have short protection time and poor practicality.