Introduction to levopropazine Respiratory disease has the highest incidence rate of various diseases in any age group throughout the world. According to data from the American Statistical Yearbook, among all causes of death, Respiratory-related diseases (excluding tumors) have risen to third place as a cause of death. In China, due to factors such as dense population, large number of smokers, and environmental pollution, the incidence and mortality rates have remained high in recent years. According to the survey data on the causes of injuries and deaths among residents in 19 provinces, cities and 88 counties recently released by the Ministry of Health, the top 10 causes of death for urban residents were respiratory diseases, followed by cerebrovascular diseases and malignant tumors, ranking third, while for rural residents, respiratory diseases ranked third. First place. This issue has attracted increasing attention, so the development of drugs for respiratory diseases has also become an important part of drug research. Cough is a common disease of the respiratory system. Based on the current pharmacological mechanism of clinical antitussives, antitussives are mainly divided into two categories: central and peripheral. Because central antitussives directly inhibit the cough center in the brain to exert antitussive function. It has a coughing effect, so it produces more side effects. Drugs that inhibit a certain link in the receptors, afferent nerves, and effectors in the cough reflex arc, that is, peripheral antitussives, have side effects due to central suppression. It is small and will not cause clinical drug dependence, so it is welcomed by the clinic. Levoxypropazine is a new antitussive drug developed and marketed by Dompe'Farm S.P.A. in Italy in 1988. Its effect is the same as that of racemic hydroxypropazine. It has almost no central sedative effect of original hydroxypropazine and has no effect on cardiovascular disease. It does not produce any obvious effects on the respiratory system, has no drug dependence, has a high tolerance index, lasts longer, and has good clinical application prospects. At present, there is still little research on peripheral antitussives in China. Only a few palliative antitussives (such as licorice extract) and expectorants (ammonium chloride) are used clinically, but the efficacy is not ideal. The use is limited and cannot meet the large needs of clinical patients with such frequently-occurring and common diseases. Central antitussives are mainly used. For this reason, levopropazine was developed to improve the level of domestic medication and has important social and economic benefits. . Clinically, a study on the efficacy of 174 adult patients with bronchitis showed that the antitussive effect of this product (60 mg, three times a day) was significantly stronger than placebo, the same as Keping, and greater than morpholinobenzophenone. After one day of treatment, 80% of patients are effective, and the cough frequency of effective patients is reduced by an average of 33-51%. Its antitussive effect has nothing to do with the type of disease and cough frequency. 99% of patients generally tolerated the drug very well or well after taking it, similar to placebo. Only 3% of patients experienced mild and short-lived side effects without the need to stop taking the drug, which is better than the above two drugs. The antitussive efficacy and tolerability of hydroxypropazine and its enantiomer, levopropazine, were evaluated in children with nonproductive cough. Patients were randomized to take hydroxypropazine (1 mg/kg) or levoxypropazine (2 mg/kg) orally three times a day for 3 days. Children who received hydroxypropazine and levopropazine had statistically significant reductions in the number of transient coughing episodes and nocturnal awakenings due to coughing (P<0.001). Gastrointestinal symptoms were mild in both groups. The incidence of somnolence in children taking hydroxypropazine was twice that of the levoxypropazine group (10.3% vs. 5.3%). There was a clinically relevant difference, but it was not statistically significant. Levoxypropazine has the same antitussive properties as hydroxypropazine, but is less likely to cause drowsiness. This drug has not applied for a patent in my country and does not meet the conditions for applying for administrative protection in China, so it will not involve intellectual property infringement issues. This drug is not listed in any country’s pharmacopoeia and has not been imported into our country. According to the current "Measures for the Administration of Drug Registration", this drug belongs to Category 3 (1) new drugs. At present, our company has obtained licenses for capsules, dispersible tablets, oral liquids and drops. Clinical approval documents. Levoxypropazine sustained-release tablets. The dosage forms of Levoxypropazine on the market abroad and in domestic clinical research include: oral liquid, drops, capsules, dispersible tablets, etc. The sustained-release tablet is a new dosage form developed by our company after conducting research on this dosage form. Its technical content is at a leading level at home and abroad. Our company has applied for a national invention patent for this dosage form. The patent name is: a levohydroxypropyl tablet. Piperazine extended release formulation. The preparation is a double-layer tablet, including an immediate-release layer and a sustained-release layer of levoxypropiperazine. The immediate-release layer can release the active ingredients quickly, ensuring that the drug takes effect quickly; the sustained-release layer can release the active ingredients slowly and continuously, and the drug effect lasts longer. Compared with ordinary preparations, this preparation has the following advantages: 1. The frequency of medication is reduced, which increases the patient's compliance.
Ordinary preparations need to be taken three times a day, while this preparation only needs to be taken once in the morning and once in the evening; 2. After taking the medicine, the blood-drug concentration is stable and the difference between peaks and valleys is small, which is beneficial to reducing the adverse reactions of levopropazine;
Dosage forms: double-layer sustained-release tablets, capsules, drops, oral solutions
Pharmacology and Toxicology This product is a peripheral antitussive and exerts an antitussive effect by selectively inhibiting the peripheral C-fibers of the trachea and bronchus. Cough effect. Its site of action is behind the peripheral nodes at sites associated with sensory neuropeptides. It has a strong antitussive effect and lasts for a long time. Since it has no interaction with β-adrenergic receptors, M-choline receptors and opioid receptors, it has fewer side effects of central inhibition and is an efficient and safe antitussive drug. Subacute and long-term toxicity test data on rats and dogs show that the main phenomena during the medication include salivation, food intake and weight loss in rats, central sedation, peripheral vasodilation and heart rate increase in dogs; at high doses, the two animals Hepatotoxic. The test found that the maximum tolerated oral dose of the two animals was 24mg/kg/d, which is 10 times the clinical dose. Levoxypropazine only has a slight effect when the clinical dosage is 30 times.
Functions and Indications: This product is suitable for dry cough and persistent cough caused by acute upper respiratory tract infection and acute bronchitis.
Pharmacokinetics
Tests on rats, dogs and humans have shown that the absorption, distribution and metabolism of levopropiperazine are basically the same among the three. The absolute bioavailability after oral administration is greater than 75%. The binding of this product to human plasma proteins is lower than that of rats and dogs (11-16%). Oral administration of levoxypropazine is rapidly absorbed and is mainly distributed in the bronchi and lungs. Since there is no data on the effect of food on this product, this product should be taken as far away from meal times as possible.
Usage and Dosage
Take orally, for adults, 60 mg (1 capsule) three times a day, or once every six hours or more, or as directed by your doctor. Generally, after two weeks of continuous use, it is recommended to stop taking the medicine or follow the doctor's advice. In addition, coughing is only a superficial phenomenon. The root cause of the cough should be found and then treated.
Use by pregnant and lactating women
After research, this product has not been found to be particularly toxic to embryos and childbirth. However, in drug toxicity tests, it was found that taking 24mg/kg delayed embryonic growth. Since the effects on humans are unknown, women who are about to become pregnant or are already pregnant are advised to use it with caution. Tests on rats and other animals have shown that breast milk contains this drug within 8 hours of taking this product. Therefore, it is best to avoid taking it while breastfeeding.
Adverse reactions
In clinical trials, 4 out of 100 people had adverse reactions after taking this drug, but they would disappear on their own after stopping the drug. Adverse reactions include nausea, heartburn, indigestion, diarrhea, etc. in the gastrointestinal aspect. Central nervous system fatigue, drowsiness, headache, dizziness, etc. Cardiovascular palpitations. Occasionally there is a rash.
Contraindications
Contraindicated for those who are known or may be extremely allergic to the drug or have excessive phlegm.
Precautions
Because this product may occasionally cause drowsiness, patients should use it with caution when driving or operating machinery.
Drug interactions
Pharmacological studies on experimental animals have shown that this product also affects the hypoglycemic effect of insulin and digestive system drugs.
Specifications
60mg/capsule
Storage
Shield and sealed.
Packaging
Aluminum plastic packaging, 10 capsules/plate, 1 plate/box.
Validity period
Tentatively 12 months.