CN1219513C - Application of Penhyclidine Hydrochloride in Pharmaceuticals - Google Patents

Abstract

The invention discloses the application of penehyclidine hydrochloride in pharmacy, especially the application of penehyclidine hydrochloride in the preparation of medicines for relieving colds and acute rhinitis. Through animal experiments and clinical observations, it has been confirmed that penehyclidine hydrochloride is effective for treating colds and acute rhinitis. The catarrhal symptoms such as reducing nasal mucous membrane secretion, runny nose and sneezing have obvious curative effects, thereby expanding the medical application and field of penhyclidine hydrochloride.

Description

Application of Penhyclidine Hydrochloride in Pharmaceuticals

Technical field:

The invention relates to the application of penehyclidine hydrochloride, in particular to the application of penehyclidine hydrochloride in clinical medicine for gastrointestinal diseases, eye diseases, respiratory diseases, central nervous system diseases, anesthesia, urogenital tract renal colic and bladder irritation Syndrome, anti-septic shock, anti-biliary colic, etc.

Background technique:

Penehyclidine hydrochloride, English name: Penehyclidine Hydrochloride, its chemical name is 3-(2-cyclopentyl-2-hydroxy-2-phenylethoxy)quinuclidine hydrochloride, molecular formula: C ₂₀ H ₂₉ NO ₂ ·CHl, molecular weight: 351.92. Prior to this, penehyclidine hydrochloride has been found and confirmed to have the efficacy and clinical efficacy of rescuing organophosphate poisoning, but no other medical clinical effects have been found.

Invention content:

The purpose of the present invention is to propose new indications of penehyclidine hydrochloride through animal experiments and clinical observations. , genitourinary tract renal colic and bladder irritation, anti-septic shock, anti-biliary colic and other applications.

Application of penhyclidine hydrochloride in pharmacy, the chemical name of the main component of said penhyclidine hydrochloride is 3-(2-cyclopentyl-2-hydroxyl-2-phenylethoxy)quinuclidine Hydrochloride, molecular formula: C ₂₀ H ₂₉ NO ₂ ·HCl, molecular weight: 351.92, is characterized in that: anticholinergic effect medicine is clinically used in gastrointestinal diseases, or eye diseases, or respiratory diseases, or central nervous system diseases, Or anesthesia, or the treatment and application of urogenital tract renal colic and bladder irritation, or anti-septic shock, or anti-biliary colic.

The application of penhyclidine hydrochloride of the present invention in clinical medicine for gastrointestinal diseases includes: A, the therapeutic application of peptic ulcer; C. Therapeutic application of inhibition of saliva secretion, salivation of Parkinson's disease, and dysphagia of saliva caused by esophageal mechanical obstruction.

The application of penhyclidine hydrochloride of the present invention in ophthalmic diseases in clinical medicine includes: A, pupil dilation, fundus examination and iritis, keratitis, the therapeutic application of preventing adhesion; B, the adjustment paralysis that is used for optometry application.

The application of penehyclidine hydrochloride of the present invention in clinical medicine for respiratory diseases includes: A, the application of relieving colds and acute and chronic rhinitis; B, the application of relieving asthma.

The application of the penhyclidine hydrochloride of the present invention in central nervous system diseases in clinical medicine mainly includes: the application for the treatment of Parkinson's disease.

The application of penhyclidine hydrochloride anesthesia in clinical medicine of the present invention refers to: administration before anesthesia.

The present invention is used for quantitative administration according to different diseases in clinic.

The present invention can be made into different dosage forms according to clinical needs. The administration methods include systemic administration and local administration. The dosage forms include oral administration, subcutaneous injection, intramuscular injection, intravenous injection, nasal drops, and sprays. Injections and intravenous injections contain 0.01-10 mg of penhyclidine hydrochloride per preparation unit, and the concentration of nasal drops and sprays is 0.025-3%.

Pharmacology and toxicology of the present invention: the present invention is a selective anticholinergic drug, which can enter the brain through the blood-brain barrier. It can block the stimulatory effect of acetylcholine on the haematine receptor (M receptor) and nicotinic receptor (N receptor) in the brain; therefore, it can better antagonize the symptoms of central intoxication caused by organophosphate poison (pesticide) poisoning , such as convulsions, central respiratory and circulatory failure, and restlessness. At the same time, it also has a strong ability to block the stimulatory effect of acetylcholine on M receptors in the periphery; therefore, it can better antagonize the muscarinic poisoning symptoms caused by organic squamous poison (pesticide) poisoning, such as bronchial smooth muscle spasm and increased secretions , sweating, salivation, miosis and gastrointestinal smooth muscle spasm or contraction. It can also increase respiratory rate and respiratory flow, but because this product has no obvious effect on _M2 receptors, it has no obvious effect on heart rate; it has no obvious antagonistic effect on peripheral N receptors. The toxicity of the present invention is less, mouse LD ₅₀ is 261.7mg/Kg (im), 71.2mg/Kg (iv); Rat LD ₅₀ 450.7mg/Kg (im), 71.2mg/Kg (iv); Rat and In the long-term toxicity test of dogs, except for some common anticholinergic reactions, no other abnormalities were found, and the local stimulation of intramuscular injection of salt was in compliance with the regulations. The mutagenicity test was negative; there was no obvious general reproductive toxicity within 75 times the equivalent human dose; no teratogenic effect and embryotoxicity were seen within 300 times the equivalent human dose, and no behavioral teratogenic effect was seen.

Pharmacokinetics of the present invention: after intramuscular injection of 1 mg of penehyclidine hydrochloride in healthy adults, penehyclidine hydrochloride can be detected in the blood within 2 minutes, and the blood drug concentration reaches a peak value in about 0.56 hours, and the peak concentration is 13.20 μg/L , and the elimination half-life is about 10.35 hours. Animal experiments show that: the present invention is distributed to various tissues of the whole body, and submandibular gland, lung, spleen and intestine are more common. This product is mainly excreted by urine and feces, and the total excretion in 24 hours is 94.17% of the administered dose.

Preclinical pharmacodynamic research on penehyclidine hydrochloride of the present invention, the present invention is a white powder, found after pharmacodynamic research:

(1) Antiasthmatic effect

1. Effects on the isolated trachea of guinea pigs: it has obvious anti-tracheal constriction caused by _A , with a PA ₂ value of 6.99±1.25, while that of atropine is 10.51±3.30.

2. The effect on isolated guinea pig lung strips: it can resist the contraction caused by Ach, and the ED ₅₀ is 1.21±2.58×10 ^-7 mol/L, while the ED ₅₀ of atropine is 0.20±0.27×10 ^-7 .

3. Antiasthmatic effect on guinea pigs: penehyclidine hydrochloride 1mg/ml and 0.5mg/ml spray administration have obvious antiasthmatic effect, and its 0.5mg/ml spray dose and 0.5mg/ml isoproterenol The effect is equivalent.

(2) Reduce nasal mucous secretion, runny nose and sneezing

Penehyclidine hydrochloride 1mg/ml, 0.5mg/ml nasal drops each 2 drops, after the nasal drops are given to guinea pigs, they can significantly inhibit the expansion of nasal mucosa telangiectasia caused by histamine phosphate, and make nasal secretions caused by histamine The secretion was significantly reduced, and the sneezing was significantly relieved by nasal drops at a concentration of 1mg/ml.

(3) Detoxification effect on stomach, ileum, colon, gallbladder and bladder

1. Penehyclidine hydrochloride can inhibit the spontaneous contraction of the isolated guinea pig stomach, ileum, colon, gallbladder, and bladder, and has an obvious antispasmodic effect against the spastic contraction of the isolated stomach, ileum, colon, gallbladder, and bladder caused by Ach. Its antispasmodic effect against Ach-induced bladder contraction was significantly stronger than that of atropine.

2. Intravenous injection of penehyclidine hydrochloride 0.01mg/Kg, 0.02mg/Kg, 0.05mg/Kg Oral administration of 0.1mg/Kg, 0.2mg/Kg, 0.5mg/Kg can inhibit the gastric anesthesia caused by Ach , Ileum, colon, gallbladder, bladder spasmodic contraction, with obvious antispasmodic effect.

The clinical effect of the present invention is:

a. It is effective for abdominal pain, diarrhea, biliary colic, renal colic, enuresis, urinary incontinence and bladder irritation caused by hyperactivity of visceral smooth muscle:

b. It can relieve the wheezing symptoms caused by asthma, chronic bronchitis and other chronic obstructive respiratory diseases;

c. It can relieve the symptoms of rigidity and tremor in patients with Parkinson's disease, and can inhibit salivation and excessive sweating;

d. It can relieve the initial symptoms of colds, such as nasal congestion, runny nose, etc., and acute and chronic rhinitis;

e. Administration before anesthesia is effective;

f. Effective for septic shock;

g. It is effective in dilating pupils and regulating paralysis in ophthalmology.

The invention proposes a new indication of penehyclidine hydrochloride and its application, expands the pharmaceutical use of penehyclidine hydrochloride, and has obvious curative effect on the new indication.

Detailed ways:

Example 1

The application of the present invention in the preparation of medicines for the treatment of gastrointestinal diseases includes: A, the therapeutic application of peptic ulcer; Therapeutic application of hypermotility of the small intestine, dysentery and rectal irritation; C, inhibition of saliva secretion, salivation of Parkinson's disease, and therapeutic application of saliva dysphagia caused by esophageal mechanical obstruction.

Medication can be taken orally, intramuscularly or intravenously, and the preferred dosage range is 0.01-10mg/time.

Example 2

The application of the present invention in ophthalmic diseases in clinical medicine includes: A, pupil dilation, fundus examination, and iritis, keratitis, and anti-adhesion treatment applications; B, application for regulating paralysis in optometry.

The dosage form can be selected as eye drops or eye paint, and the preferred concentration is 0.03-3%.

Example 3

The clinical application of the present invention in respiratory diseases includes: A, the application of relieving cold and acute and chronic rhinitis; B, the application of relieving asthma.

The dosage forms can be nasal drops or sprays, and the preferred concentration is 0.025-2.8.

Example 4

The clinical application of the present invention to diseases of the central nervous system mainly includes: application for the treatment of Parkinson's disease.

Medication can be taken orally, intramuscularly or intravenously, and the preferred dosage range is 0.01-8.8mg/time.

Example 5

The application of anesthesia in clinical medicine of the present invention mainly refers to pre-anesthesia medication, and the medication method can be intramuscular injection, intravenous injection or subcutaneous injection, and the preferred dosage range is 0.02-8mg/time.

Example 6

For the application of the present invention in urogenital tract renal colic and bladder irritation in clinical medicine, oral administration, intramuscular injection or intravenous injection can be selected as the medication method, and the preferred dosage range is 0.03-8.9 mg/time.

Example 7

For the application of the present invention in anti-septic shock in clinical medicine, intramuscular injection, intravenous injection or subcutaneous injection can be used for medication, and the preferred dosage range is 0.05-9.5 mg/time.

Example 8

For the treatment and application of the present invention in the aspect of anti-biliary colic in clinical medicine, oral administration, intramuscular injection or intravenous injection can be selected as the medication method, and the preferred dosage range is 0.02-8.5 mg/time.

Claims (3)

1. Use of penehyclidine hydrochloride in the preparation of medicines for treating and relieving colds and acute rhinitis. 2. The use of penehyclidine hydrochloride as claimed in claim 1 in the preparation of medicines for relieving colds and acute rhinitis, characterized in that: the administration of penehyclidine hydrochloride in the preparation of medicines for treating colds and acute rhinitis The method is systemic administration or local administration, and the dosage form includes oral administration, subcutaneous injection, intramuscular injection, intravenous injection, nasal drops, and spray. 3. The use of penehyclidine hydrochloride as claimed in claim 1 or 2 in the preparation of medicines for relieving colds and acute rhinitis, characterized in that: the oral administration of penehyclidine hydrochloride in the preparation of medicines for treating colds and acute rhinitis , subcutaneous injection, intramuscular injection, and intravenous injection contain 0.01-10 mg of penhyclidine hydrochloride per preparation unit, and the concentration of nasal drops and sprays is 0.025-3%.