CN1149456A - New medical use for cucoline - Google Patents

Abstract

This invention relates to the application of cucoline in the preparation of medicine for dropping drug-addiction with the main resolution of the draw-back that such an existing medicine may produce new addiction and large by-effect. In view of cucoline not only having the similar structural formula and effect of morphine, but also featuring no formation of addiction, this invention uses cucoline for preparing the said medicine which is prepared through pulverizing cucoline, sieving and sterilizing. The clinic result shows that this invention can obviously relieve and eliminate the abstention symptoms without drug-dependence and addiction, and a general drug-addict after treatment for 7-12 days, can have the addiction dropped, with a curative effect manifestation rate of 92.2%.

Description

The new medical use of sinomenine

The present invention relates to the application in the preparation drug-breaking medicine of a kind of medical usage of chemical compound, particularly sinomenine.

As everyone knows, drug abuse is the infringement health of human body, wrecks the bad habit of life.According to national interrelated data, China about people more than 320,000 that is being addicted to drug, serious harm social order, brokenly encircled spiritual civilization, the various crime rates of Yin Faing are still in continuous growth therefrom.So drug rehabilitation is an extremely important and urgent social problem.At present, the anti-additive medicament that each narcotic house adopts mainly contains three kinds: (1) dihydroetorphine hydrochlorate, this medicine is artificial synthetic drug, main effect is to substitute drugs, because its psychic dependence is 100 times of morphine, thereby in drug addiction treatment addiction very easily, become and behind drugs, second rely on medicine; (2) Mei Shadong, this medicine also belongs to the synthetic medicine, equally also has addiction; (3) do not have addiction drug-dropping tablet (phenylamino imidazoline) fast, the former hypertension that is used for the treatment of of this medicine does not have addiction though this medicine is used for drug addiction treatment, exists patient's blood pressure is obviously descended the deficiency that side effect is big.

The purpose of this invention is to provide a kind of do not have addiction and the little application of medicine in the preparation drug-breaking medicine of side effect.

Realize that the object of the invention technical scheme is to use the medicine of sinomenine as preparation drug rehabilitation usefulness.Sinomenine is separating obtained from menispermaceae plant Caulis Sinomenii rhizome, has pharmacological actions such as antiinflammatory, calmness, analgesia, antitussive, spasmolytic, is applied to treating rheumatoid arthritis clinically.In view of sinomenine chemical constitution and morphine approximate, but addicted characteristics of tool not, the present invention uses the application of sinomenine as the preparation drug-breaking medicine.Its preparation method is that sinomenine is pulverized, and sieves, sterilizes to make and treat the powder medicine of quitting drug abuse with 100 mesh sieves.

One of important feature of the present invention is that toxicity is little, sees Table 1 acute zoopery and sub-acute toxicity test respectively.

(1) acute toxicity test.

10 one group of mice, male and female half and half, after trial test, selected 4-5 dosage group, promptly observe after the mice administration toxicity anti-main should, dead mouse number in the continuous record 7 days, and through BLiss method mensuration LD ₅₀Dosage, it the results are shown in Table 1.

Chmice acute toxicity test table 1

Route of administration	Dosage (mg/kg)	The experiment number	Death toll	???LD 50(mg/kg) (95% fiducial limit)
					Subcutaneous	?????350 ?????400 ?????450 ?????500	????10 ????10 ????10 ????10	????1 ????2 ????6 ????8	???????439 ????(410-471)
Per os	?????600 ?????650 ?????700 ?????750 ?????800	????10 ????10 ????10 ????10 ????10	????1 ????4 ????6 ????8 ????9	???????685 ????(652-719)

(2) subacute toxicity test

With 15 body weight is rat childhood of 44～53 grams, with 5 is one group, sinomenine of lumbar injection every day, the first group is given 40 milligrams/kilogram, and the second group is given 80 milligrams/kilogram, and third group of feedwater in contrast, continuous 14 days, three treated animals are at body weight gain, food-intake, hemogram and general situation, the equal no significant difference in internal organs pathological section aspect.

Two of important feature of the present invention is that the chemical constitution of sinomenine is close with morphine, and all has analgesia, antitussive, calmness, and pharmacological actions such as excited spinal cord see Table 2.

The chemical constitution comparison sheet 2 of sinomenine and morphine

Three of important feature of the present invention is that sinomenine does not have addiction, sees following experimental result:

Four body weight 4.5-7kg of monkey, experimental group subcutaneous administration 5mg/kg/ day begins to increase to 80mg/kg/ day, no withdrawal symptom and any unusual performance in 72 hours after successive administration 39 days, 45 days, the observation drug withdrawal, matched group awards the drug withdrawal after 39 days and 45 days of morphine hydrochloride successive administration, occur remarkable dyspnea after drug withdrawal in 24 hours, the expression withdrawal symptom such as gruel that withers lasts 72 hours.

The clinical use result of the present invention shows that following advantage is arranged:

1. the present invention is from the non-spiritual narcoticness drug-breaking medicine of a kind of pure natural that forms from the menispermaceae plant extract, and human body is not had obvious toxic and side effects.

2. the present invention has obvious alleviation and removes the withdrawal symptom that junkie termination drugs contact the back appearance, can improve central nervous system's metabolism, promotes antisecosis.

3. phenomenon such as no drowsiness, disturbance of consciousness is negative through pharmacokinetics check addicted substance metabolite after the medication of the present invention, no drug dependence and addiction.

4. need not special care in the treatment, the drug abuse patient can reach the purpose of withdrawal, drug rehabilitation through behind 7-12 days the general treatment under the situation without any misery.

For showing curative effect, the present invention is qualitative about the definition and the urine morphine of drug dependence according to The World Health Organization (WHO), makes a definite diagnosis and select opioid drug dependent patient 32 examples, age 21-31 year, male's 22 examples wherein, age 21-36 year; Women's 10 examples, 22-31 year.Be and scald opium eating class drug dependence person, history of drug abuse is 2-84 month.Whole be a cup too low disease and infectious disease of cases, and get rid of other body complication, do not pass through the other medicines withdrawal and treatment yet.Its observational technique adopts: (1) CINA (the narcotic withdrawal symptom is estimated scale) physical dependence is estimated scale, and the health withdrawal symptom is observed day by day and marked before treatment and in treating; (2) range estimation scale, health check-up every day, and observe the crave for degree of patient to used medicine; (3) intend the toxic and side effects that the observation post day by day of adverse effect scoring causes with medicine certainly.

Medication: the powder of will quitting drug abuse places Xi Bo to go up heating, makes powder become liquid, and the smog continuously of pressing ascension with paper tube hard sucks rapidly, each 20-60mg, and every day three times, 10-15 days is a drug treatment, clinical test results such as table 3, table 4, table 5.

Medicine control withdrawal symptom is efficacy result (N=32) table 3 day by day

The treatment date		?????????X±S
			In the treatment	D before the treatment 1????d 2????d 3????d 4????d 5????d 6????d 7????d 8????d 9????d 10????d 11????d 12	?????24.63±2.68 ?????15.94±4.72 ?????12.41±5.13 ?????10.03±4.20 ??????8.16±3.96 ??????7.44±4.15 ??????7.75±4.31 ??????6.09±3.95 ??????4.03±3.35 ??????3.40±3.23 ??????2.06±2.03 ??????1.63±1.45 ??????1.00±1.21

Compare (N=32) table 4 in the treatment of medicine control withdrawal symptom with before the treatment

Treatment time	Equal value difference	Standard deviation	Standard error	Probability
					72 hours 12 days	??14.954 ??23.625	??2.826 ??3.976	??0.499 ??0.685	?P＜0.0001 ?P＜0.0001

32 routine patients drug rehabilitation in 12 days symptom curative effect information slip table 5

	Symptom example number appears before the treatment	Treat 12 days routine digital displays and imitate effective obvious effective rate (%)
			Perspire to have the fidgets the trembling nasal obstruction yawn belly of shedding tears of n and V goose pimples changes body temperature myalgia heart rate	??????32 ??????32 ??????32 ??????32 ??????32 ??????32 ??????32 ??????32 ??????32 ??????32 ??????32 ??????32	??30???????2???????93.8 ??29???????3???????90.6 ??30???????2???????93.8 ??26???????6???????81.3 ??32???????0???????100 ??32???????0???????100 ??32???????0???????100 ??28???????4???????87.5 ??28???????4???????87.5 ??29???????3???????90.6 ??26???????6???????81.3 ??32???????0???????100

Table 3, table 4 can obviously suppress the generation and the extent of reaction of withdrawal symptom as can be seen after the medication, 72 hours and treat not phase efficacy result and treatment before difference highly significant (P＜0.0001) relatively.

Table 5 shows that various withdrawal symptoms all have remarkable minimizing after treating 72 hours.Wherein be effectively with the remission, symptom is removed and is produce effects, and all patients are all effective through treatment.

Clinical observation result shows: (1) dosage can show the curative effect of controlling withdrawal symptom at 120mg/ in day, with the increase curative effect raising of dosage.And in used dosage, even 100mg/ time does not produce the euphoriant effect of opioid drug yet, the close medicine degree of using range estimation analogy scale to observe user is to successively decrease successively with Time of Administration, stops using to 12 days, the patient does not have tangible withdrawal symptom and exists, and it all is negative that the urine morphine is measured; (2) can alleviate or remove anxiety after patient's medication, fidgety, pain etc. are subjective uncomfortable, its therapeutic efficiency reaches 92.2% does not have obviously stomachache, the common complication of giving up such as cough, abundant expectoration, (3) administering mode adopts to scald and sucks, satisfied the psychological need of drug abstainer, the patient takes like a shot in the treatment, and not having has drug dependence.

Claims (1)

1. a chemical compound sinomenine is characterized in that can be used as the preparation drug-relief medicine.