CN1314408C - Compound traditional Chinese medicine prepn. for treating symptom of delayed giving-up of opium, and its application - Google Patents

Abstract

The invention mainly relates to a traditional Chinese medicine compound preparation clinically used for treating protracted withdrawal symptoms of opioids, comprising: ginseng, rhubarb root, angelica, astragalus, radix radix and other components. The traditional Chinese medicine compound preparation can be made into dosage forms such as tablets, oral liquids, etc., can effectively treat protracted withdrawal symptoms of opioids, and has good social and economic benefits.

Description

Traditional Chinese medicine compound preparation and its application for treating opioid protracted withdrawal symptoms

technical field

The invention relates to a traditional Chinese medicine compound preparation and its application for treating protracted withdrawal symptoms of opioids

Background technique

Opioid drug addiction is a chronic recurrent encephalopathy characterized by compulsive drug-seeking and drug use behaviors, and reasonable and effective drug treatment is the first step to help addicts get rid of drug troubles. At present, drug treatment is generally divided into two stages at home and abroad: the detoxification period and the rehabilitation period. The detoxification period is mainly to help addicts get rid of physical dependence on drugs. There are two types of commonly used drugs: ① opioid receptor agonists with decreasing substitution, such as methadone, buprenorphine, etc.; ② non-opioid receptor agonists for symptomatic Treatment; such as α ₂ receptor agonist clonidine or lofexidine, M cholinergic receptor antagonist scopolamine, 654-2 symptomatic treatment, generally 7-10 days can basically control the acute withdrawal symptoms. The goal of the recovery period is to get rid of mental dependence and strive to reduce the relapse rate. ①Methadone maintenance treatment is used abroad to replace drug addiction with drug addiction, but it is impossible to implement it generally in our country at this stage. ②Establish a rehabilitation treatment group (Therapeutic Community, TC), let the patients live a collective life for about two years in an environment isolated from drugs, so as to gradually reduce their psychological desire for drugs, and up to 30 people can complete the whole process of treatment and return to society %. But this is a very costly and labor-intensive work, and it is difficult to promote it in our country at present. ③Naltrexone prevents relapse. Naltrexone is an opioid receptor antagonist, so that patients will not feel euphoric when they use opioid drugs again; in this way, the positive reinforcement effect of drugs will be gradually eliminated, which will help improve the rate of behavior after drug withdrawal . However, the maintenance cost of naltrexone is high, the actual acceptance rate is low, and fewer people can insist on taking it according to the doctor's advice, which does not help to improve the overall drug abuse situation.

To sum up, detoxification is not difficult, but it is difficult to completely detoxify. Statistics at home and abroad show that the relapse rate within six months is 95% without special treatment after early detoxification. There are many reasons for the high relapse rate, the long-term existence of psychological craving (spiritual dependence) and the protracted withdrawal symptoms are the main reasons. The existing domestic and foreign drug treatment drugs are unsatisfactory in this respect, such as methadone, clonidine, etc., which can only partially control acute withdrawal symptoms, but are ineffective for protracted withdrawal symptoms. There is no improvement effect on the imbalance of the environment. At present, traditional Chinese medicine has been used to control acute withdrawal symptoms, but there is no report of further research on traditional Chinese medicine that is in line with my country's national conditions and can effectively control protracted withdrawal symptoms

Contents of the invention

In order to provide a traditional Chinese medicine capable of effectively controlling protracted withdrawal symptoms, the present invention prepares a traditional Chinese medicine compound (Guiyuan Tablet), which comprises the following components: 5 parts of ginseng, 16 parts of Yuanhu, 25 parts of astragalus, 5 parts of angelica, and 6 parts of Radix Radix share.

The present invention is based on the experience of clinical detoxification and drug treatment, and is formed by adding and subtracting the famous ancient prescriptions "Danggui Buxue Decoction" and "Shaoyao Gancao Decoction".

Ginseng has the effects of invigorating qi, strengthening yang, calming the nerves, and improving intelligence. It is a good medicine for treating palpitations caused by qi deficiency and blood deficiency, insomnia, and forgetfulness. Happy Puzzle", ranks first in the prescription. Yuanhu enters both the qi and the blood. It can move the qi in the blood and the blood in the qi. It can only treat all kinds of pains in the whole body. It is a good medicine for invigorating blood, regulating qi, calming the nerves and relieving pain. It is a king medicine in total. A total of famous prescription Danggui Buxue Decoction. The above 2 herbs are used to help the king’s medicine, and they are ministerial medicines. They are supplemented by Ophiopogon japonicus to nourish liver and kidney yin and blood, nourish the lungs and nourish yin, benefit the stomach and promote body fluid, clear the heart and eliminate troubles, replenish qi and nutrition, and moisturize the skin. All medicines are used in combination to treat both symptoms and root causes, and play the functions of nourishing yin and strengthening yang, invigorating qi and nourishing blood, and calming pain and nerves.

From the perspective of modern medicine, the extract of Angelica sinensis has the effect of promoting cerebral blood circulation and protecting neurons, while the main component of Yuanhu, tetrahydroprotocylinoid, has an inhibitory effect on the central nervous system and can prevent the development of morphine addiction. Formation, has an inhibitory effect on morphine-induced sensitization. Formulations based on these two drugs can improve the symptoms of protracted opioid withdrawal and reverse the damage of related neurons.

The medicine of the present invention can be prepared by conventional techniques for preparing traditional Chinese medicine preparations, and can be made into dosage forms such as tablets and oral liquids.

See embodiment one for relevant prescription and preparation method.

The medicine (Guiyuan tablet) provided by the present invention proves in relevant animal model experiments: Guiyuan tablet can reduce the autonomic activity of mice in a dose-dependent manner, shows that Guiyuan tablet has non-specific inhibitory effect on the central nervous system; Dose-dependently inhibits the acquisition of morphine behavioral sensitization; dose-dependently reduces the expression of morphine behavioral sensitization; has no effect on the conversion of morphine behavioral sensitization. In the clinical curative effect research of Guiyuan preparation on procrastination symptoms, it is proved that Guiyuan tablet has a good curative effect on relieving physical fatigue, improving energy, reducing muscle and joint soreness and pain, improving sexual function and reducing yawning. There is a significant difference in the placebo group; it is stronger than doxepin in relieving soreness and pain of muscles and joints and improving energy, and there is a statistically significant difference; it has a better curative effect in relieving anxiety and depression, and Compared with the placebo, there is a significant difference; it can improve the quality of sleep, and there is a significant difference compared with the placebo, but doxepin increases dreaming; it has curative effect on the eight symptoms reflecting desire, and it has a significant difference compared with the placebo. Significant difference; For somatic symptoms, sleep symptoms, craving symptoms, etc., Guiyuan Tablet and Doxepin had no rebound phenomenon after drug withdrawal. For anxiety and depression symptoms, there was a certain rebound phenomenon after stopping doxepin, but no rebound phenomenon was found in the Guiyuan Tablet treatment group.

The traditional Chinese medicine compound preparation provided by the invention can effectively control protracted withdrawal symptoms, has broad market prospects and good social benefits.

Detailed ways

              Example 1 Preparation of Gui Yuan Tablets

prescription:

5 parts of ginseng, 16 parts of Yuanhu, 25 parts of astragalus, 5 parts of angelica, 6 parts of Ophiopogon japonicus

Preparation method:

1. Properly crush 5 parts of Angelica sinensis in the recipe, distill with water steam for 4 hours, collect about 20ml of volatile oil, absorb the volatile oil on an appropriate amount of micro-powder silica gel, evaporate to dry at room temperature, and pass through an 80-mesh sieve for later use;

2. The residue of Angelica sinensis after steam distillation and 15 parts of Astragalus (reserve 1 part for later use) and Ophiopogon japonicus (35 parts by weight) in the above prescription are properly crushed and boiled for 2 hours with four times the amount of water for the first time. Add 3 times the amount of water twice to decoct for 1.5 hours, warm filter, combine the filtrates, and evaporate to dryness to obtain 5.9 parts of Part A (yield 20.8%);

3. Properly pulverize 5 parts of ginseng, reflux and extract twice with 60% ethanol, reflux for 2 hours each time, warm filter, recover the solvent under reduced pressure until dry, and obtain 0.935 parts of Part B (yield 22.0%);

4. Combine the above parts A and B, add 10 parts of distilled water to dissolve, add 8 times the amount of 90% ethanol under stirring, make the precipitate, let it stand overnight, filter the supernatant, wash the precipitate with an appropriate amount of 90% ethanol, and mix with the supernatant Liquefied and reclaimed to small volume, will set aside 1 part through pulverizing through the astragalus powder of 60 mesh sieves, 1.8 parts of starch (15%), 0.21 part of microcrystalline cellulose (5%), 0.042 part of magnesium stearate (1% ) into the above solution, properly stirred and evaporated to dryness, dried in an oven at a temperature lower than 90°C (control the water content below 3%), crushed through a 40-mesh sieve to obtain about 3.8 parts of fine powder for later use;

5. Properly pulverize 16 parts of Rhizoma chinensis, percolate with 0.5% sulfuric acid aqueous solution (50 parts) for 3 days, collect the water, alkalinize it with 5% NaOH aqueous solution to pH 10, let it stand overnight, collect the precipitate, and obtain the crude alkaloid , Repeated recrystallization with ethanol, to obtain about 0.3 parts of tetrahydroprotophylline (yield about 1.87%). Heat 0.3 part of tetrahydroprotohormonine with absolute ethanol, add 3 times the calculated amount of concentrated sulfuric acid under warming, immediately precipitate and place it. Collect the precipitate by filtration, wash the precipitate with a small amount of water and ethanol for 2-3 times, and dry the precipitate at 60°C to obtain about 0.36 parts of tetrahydrogen protopalline, which is passed through an 80-mesh sieve for later use;

6. The above-mentioned 3.8 parts of fine powder, 0.36 parts of tetrahydrogen protohormonal base powder, mixed evenly with angelica volatile oil adsorbed on an appropriate amount of micropowder silica gel, pressed into tablets, and then added with film coating to obtain Guiyuan tablets.

Example 2 Effect of Guiyuan Tablets on Behavioral Sensitization to Morphine in Mice

1. Test drug:

Guiyuan Tablets, developed by the Institute of Basic Medical Sciences, Academy of Military Medical Sciences; Guiyuan Tablets powder for experiments, containing 12g of crude drug per g, prepared into a solution of the required concentration with distilled water; administration volume: 10ml/kg, administration route: intragastric administration .

2. Reagents:

Morphine hydrochloride, produced by Qinghai Pharmaceutical Factory.

3. Animals:

Kunming mice, grade 2, weighing 18-22 g, half male and half male, were purchased from the Experimental Animal Center of the Academy of Military Medical Sciences.

4. Experimental method

1. Determination of mouse activity

After the animals are administered, they are immediately put into a small animal autonomous activity detector to measure the activity of the mice. The small animal autonomous activity detector consists of 5 measuring boxes (25×14×14cm) connected to a controller.

2. Effect of Guiyuan Tablets on Autonomic Activity of Mice

After a single gavage (i.g.) of Guiyuan Tablets (1.25g/kg, 2.5g/kg, 5g/kg, 10g/kg), the mouse was immediately placed in a small animal autonomous activity detector to measure the autonomous activity of the mice , recording the voluntary activity of mice for 1 hour.

3. Establishment of morphine behavioral sensitization mouse model

The mice were given subcutaneous (s.c) morphine 20mg/kg for 7 days, once a day, and the administration time was fixed at 8:00-10:00 in the morning. Then, the drug was stopped for 4 days. After being challenged with a small dose of morphine (10mg/kg) on the 12th day, put it into the small animal autonomous activity detector immediately, and record the autonomous activity of the mouse 20min-40min after the excitation.

4. Effect of Guiyuan Tablets on Behavioral Sensitization to Morphine in Mice

4.1. Effect of Guiyuan Tablets on the Acquisition of Behavioral Sensitization to Morphine in Mice

Administration procedure: vehicle (vehicle, Veh) + normal saline (NS) group: i.g. Veh, after 25 min, s.c. NS, for 7 consecutive days. Then, stop the drug for 4 days. Autonomic activity of mice was measured at d12. Veh+morphine hydrochloride (Mor) group: i.g.Veh, after 25min, s.c.Mor, for 7 consecutive days. Then, stop the drug for 4 days. Autonomic activity of mice was measured at d12. Guiyuan tablet+Mor group: i.g. Guiyuan tablet (2.5g/kg, 5g/kg, 10g/kg, 20g/kg), s.c.Mor after 25min for 7 consecutive days. Then, stop the drug for 4 days. Autonomic activity of mice was measured at d12.

4.2. Effects of Guiyuan tablets on the expression of behavioral sensitization to morphine in mice

Dosing procedure: after chronic Mor treatment (the NS group was given the same volume of NS), the drug was stopped for 4 consecutive days. d12, NS+Veh group: i.g.Veh, after 25min, s.c.Mor, and then measure the autonomic activity of the mice immediately. Mor+Veh group: i.g.Veh, s.c.Mor after 25min, and then measure the autonomous activity of the mice. Mor+Guiyuan tablet group: i.g. Guiyuan tablet (2.5g/kg, 5g/kg, 10g/kg), after 25min, sc Mor, and then measure the autonomous activity of the mice.

4.3. Effect of Guiyuan Tablets on Behavioral Sensitization to Morphine in Mice

Administration procedure: after chronic morphine treatment (NS group was given the same volume of NS), d8-d11, NS+Veh group: i.g.Veh. Mor+Veh group: i.g. Veh. Mor+ Guiyuan tablet group: i.g. Guiyuan tablet (5g/kg, 10g/kg, 20g/kg). On d12, after each group of s.c.Mor, immediately put them into the small animal autonomous activity detector to measure the autonomous activity of the mice.

5. Experimental results

1. Effect of Guiyuan Tablets on Autonomic Activity of Mice

After i.g. different doses of Guiyuan Tablets, the mice were immediately put into the small animal autonomic activity detector to measure autonomic activities. The number of autonomic activities decreased significantly, and the maximum effect was reached 25 minutes after administration. 2.5g/kg, 5g/kg, 10g/kg Guiyuan Tablets can dose-dependently reduce the autonomic activity of mice [F(4,45)=12.349, p<0.001). It shows that Guiyuan Tablet has a non-specific inhibitory effect on the central nervous system.

Guiyuan Tablets (2.5g/kg, 5g/kg, 10g/kg) group had a significant difference in voluntary activity count at 20-40min compared with Veh group (Table 1). In order to exclude the impact of the experimental animals' exploration behavior on the results in the new environment, the following experiments choose to observe the autonomous activities of the animals 20min-40min after being stimulated.

Table 1. Inhibitory effect of Guiyuan Tablets on autonomic activity in mice Guiyuan tablets (g/kg) Independent activities (times) 01.252.55.010.0 1019.90±606.591022.10±550.37426.90±181.09**227.00±207.12***140.50±105.43***

Note: X±SD, n=10, **p<0.01, ***p<0.001, vs. Veh group

2. Effect of Guiyuan Tablets on the Acquisition of Behavioral Sensitization to Morphine in Mice

As shown in Table 2, in the chronic morphine treatment stage, before sc morphine 25min i.g. Guiyuan tablet, before d12 was not given morphine challenge, the autonomous activities of experimental animals in each group were measured, and there was no significant difference in activity. After challenged with a small dose of morphine, the activity of the animals in the Veh+Mor group was significantly higher than that in the Veh+NS group, p<0.01, indicating that the experimental animals had established a stable behavioral sensitization to morphine. The activity of animals in Guiyuan Tablet+Mor group was lower than that in Veh+Mor group in a dose-dependent manner. The activity count of 10g/kg, 20g/kg Guiyuan Tablet group was significantly different from that of NS+Mor group, p<0.05. It indicated that Guiyuan tablets could inhibit the acquisition of morphine behavioral sensitization in a dose-dependent manner.

Table 2. Blocking effect of behavioral sensitization to morphine in mice with Guiyuan tablets group dose Independent activities (times) Veh+NSVeh+Mor Guiyuan slice+Mor Guiyuan slice+Mor Guiyuan slice+Mor Guiyuan slice+Mor 002.5g/kg5.0g/kg10.0g/kg20.0g/kg 3110.5±s630.704215.5±s758.20**3969.0±s1003.303658.6±s876.403517.0±s633.64#3332.0±s843.56#

Note: X±SD means, n=12-14, **p<0.01vs.Veh+NS group; #p<0.05vs.Veh+Mor group

3. Effect of Guiyuan Tablets on Expression of Behavioral Sensitization to Morphine in Mice

25min i.g.Veh before the s.c.Mor excitation in the determination of autonomous activities, the activity count of the experimental animals in the Mor+NS group was 4197.0±s950.26 times, compared with the NS+Veh group, there was a significant difference, p<0.001, indicating that the experimental animals Behavioral sensitization to morphine is well established. I.g. Guiyuan tablet 25 minutes in advance can reduce the expression of morphine behavioral sensitization in a dose-dependent manner. The activity counts of the experimental animals in different dosage groups of Guiyuan Tablets were significantly lower than those in the Mor+Veh group, with statistical significance, p<0.001.

Table 3. The blocking effect of Guiyuan tablets on the expression of morphine behavioral sensitization in mice group Dose (g/kg) Independent activities (times) NS+VehMor+VehMor+Guiyuan slice Mor+Guiyuan slice Mor+Guiyuan slice 002.55.010.0 2696.4±s729.74183.92±s907.17***2980.7±s419.32 ^## 2202.0±s1137.72 ^### 481.9±s457.81 ^###

Note: X±SD, n=12, ***p<0.001vs. NS+Veh group: ##p<0.05 ###p<0.001vs.Mor+Veh group.

4. Effect of Guiyuan Tablets on Behavioral Sensitization to Morphine

After chronic morphine treatment, at d8-d11 i.g. Veh, the activity of Mor+Veh group was significantly higher than that of NS+Veh group (Table 1), p<0.01, indicating that the behavioral sensitization of experimental animals to morphine had been established. i.g. Guiyuanpian, Guiyuanpian group and Mor+Veh group had no significant difference in autonomic activity count. It indicated that Guiyuan tablets had no effect on the conversion of morphine behavioral sensitization.

Table 4. Effect of Guiyuan Tablets on Behavioral Sensitization to Morphine in Mice group Dose (g/kg) Independent activities (times) NS+VehMor+VehMor+Guiyuan slice Mor+Guiyuan slice Mor+Guiyuan slice 005.010.020.0 3257.7±s616.104288.1±s632.5**4434.7±s855.824734.6±s878.893909.7±s976.47

Note: X±SD, n=10, **p<0.01 vs. NS+Veh group.

Example 3 Clinical curative effect study of Guiyuan Tablets on protracted symptoms

1. Research Methods

1. Inclusion criteria

(1) First explain the purpose of the experiment to the patient, and the patient agrees to participate in this research

(2) Patients who meet the DSM-IV (Diagnostic and Classification of Mental Disorders Manual, Fourth Edition) diagnostic criteria for opioid dependence after voluntary or compulsory acute detoxification, regardless of gender, aged between 18 and 55;

(3) Before entering the experiment, detailed physical examination and laboratory examination are required to exclude mental diseases and serious physical diseases, such as hepatitis, tuberculosis, etc.

(4) All are hospitalized patients

2. Exclusion criteria

(1) Severe heart, liver, kidney damage or other serious physical diseases, such as tuberculosis, severe malnutrition, etc.;

(2) Those with a history of severe mental illness;

(3) Multiple drug abusers

3. Early Termination Criteria

(1) The 15-day clinical trial was not completed because the patient refused treatment;

(2) Sneaking behavior during treatment,

4. Grouping

According to the random principle, the subjects were divided into Guiyuan preparation group, doxepin group and placebo group, 40 cases in each group.

5. Observation indicators

(1) General status of drug abuse: fill in the self-made drug abuse questionnaire, including general demographic information and understand the patient’s drug abuse reasons, time, dose, frequency, drug withdrawal status, etc.

(2) Severity of withdrawal symptoms and cravings: Use the withdrawal symptom self-assessment scale to assess the severity of withdrawal symptoms and cravings and the change of each symptom;

(3) Procrastination Symptom Scale: mainly assesses craving, anxiety, depression, sleep problems, etc.;

(4) Urine drug test: use immunochromatography to qualitatively detect urine drugs to determine whether the patient is taking drugs.

6. Research Procedures

(1) Complete the admission record and addiction behavior questionnaire before hospitalization;

(2) The hospitalization time is at least 1 month. On the 7th day after being admitted to the hospital, the group entered the experimental stage, taking medicine 2 times a day, Guiyuan preparation 2 tablets/time, doxepin 25mg/time, placebo 2 tablets/time; 12, 18, 24, 30, 45, 60 days to complete a protracted symptom assessment. A qualitative urine test was done on admission and discharge.

(3) Statistical method: All data are processed on 686 computer with SPSS8.0 statistical software package

7. Analyze the data obtained above to see whether the two traditional Chinese medicine preparations have a therapeutic effect on protracted symptoms, what are their characteristics and advantages, and which one is better in comparison.

2. Results

Protracted symptoms are divided into four categories: somatic symptoms, anxiety and depression symptoms, sleep symptoms, and craving symptoms

Therefore, the curative effect analysis of Guiyuan tablets, doxepin and placebo on protracted symptoms is also carried out from the above four categories.

The effect on physical symptoms: (1) Overall, there was no significant difference among the three groups at the time of enrollment, and there was no significant difference among the groups on the 6th day, the 12th day, the 18th day, and the 24th day after the medication. difference; on the 30th day after medication, there was a significant difference between the Guiyuan Tablet group and the placebo group, and Guiyuan Tablet could reduce physical symptoms; on the 14th day after drug withdrawal, there was no significant difference between the groups; On the 28th day after taking the medicine, there were significant differences between Guiyuan Tablets and the other two groups, but there was no significant difference between the other two groups. (2) Specifically, Guiyuan Tablets have good curative effects on relieving physical fatigue, improving energy, reducing muscle and joint soreness and pain, improving sexual function, and reducing yawning. Compared with the placebo group, there is a significant There was also a significant difference between doxepin and placebo in improving energy and reducing yawning; while Guiyuan Tablet was stronger than doxepin in relieving muscle and joint soreness and pain and improving energy. have significant difference.

The effect on anxiety and depression symptoms: (1) Overall, there was no significant difference among the three groups at the time of enrollment; There was a significant difference between the Guiyuan Tablet group and the placebo group on the first day; on the 24th day of medication and the 28th day of drug withdrawal, there was no significant difference among the three groups. It can be seen from the results that during the medication period, there has been no significant difference between the Guiyuan tablet group and the doxepin group, and between the doxepin group and the placebo group. (2) Specifically, Guiyuan Tablet has a good curative effect on the following symptoms (1. I feel that I am very laborious, 2. I am often upset, 3. I feel that my mind is very confused. 4. I am very irritable. 5. I feel that everything is not satisfactory. 6 has troubles that cannot be shaken off, 7 feels guilty, 8 has nothing to do, is empty and bored, 9 often wants to urinate), it can be seen that Guiyuan Tablet has a better curative effect on relieving anxiety and depression, and it is more effective than placebo. Significant difference; the curative effect of doxepin on anxiety and depression symptoms is not as good as that of Guiyuan tablets, only in (1 low efficiency, 2 very irritable, 3 often upset, 4 unresponsive, often in a daze, 5 nothing to do, Emptiness and boredom) Several symptoms were significantly different from placebo, which may be related to the low dose of doxepin (50 mg/day).

Effects on sleep symptoms: (1) Overall, there was no significant difference between the groups at the time of enrollment; on the 6th day of medication, there was a significant difference between the Guiyuan tablet group and the placebo group; On the 12th, 18th, 24th, 30th day of medication and the 14th and 28th day of drug withdrawal, there was no significant difference among the groups. (2) Specifically, Guiyuan Tablets have a good curative effect on several symptoms (1. Insomnia, 2. Light sleep, Easy to wake up midway, 3. Sleepy all day long, 4. Restless sleep, Frequent dreaming). Compared with the placebo, there is a significant difference, while doxepin has a better effect on (1 insomnia, 2 light sleep, easy to wake up in the middle), and there is a significant difference compared with the placebo, but it makes Dreaming increases.

The effect on craving symptoms: Overall, there was no significant difference between the groups when the group was enrolled; on the 6th, 12th, and 18th days of medication, there were significant differences between the Guiyuan tablet group and the placebo group. Significant difference; on the 24th and 30th days of medication, and on the 14th and 28th days of drug withdrawal, there were significant differences between the Guiyuan tablet group, doxepin group and the placebo group; There was always no significant difference between element slice group and doxepin group. Specifically, Guiyuan tablets have curative effects on the eight symptoms reflecting craving, and there are significant differences compared with placebo; doxepin also has curative effects on the eight symptoms reflecting craving, and there is also a significant difference compared with placebo However, there was a significant difference between Guiyuan Tablets and Doxepin in the efficacy of certain symptoms at the beginning of the medication, but as time went on, the difference gradually disappeared, and there was no significant difference in the second week of medication ; Guiyuan tablets are the same as doxepin, with the prolongation of medication time, the effect becomes more and more obvious.

For somatic symptoms, sleep symptoms, and craving symptoms, Guiyuan Tablets and Doxepin had no rebound phenomenon after drug withdrawal. For anxiety and depression symptoms, there was a certain rebound phenomenon after stopping doxepin, but no rebound phenomenon was found in the Guiyuan Tablet treatment group.

Claims (1)

1. A Chinese medicine compound preparation for the treatment of opioid protracted withdrawal symptoms, characterized in that: said Chinese medicine compound preparation is made up of the following Chinese medicines: 5 parts of Radix Ginseng, 16 parts of Rhizoma Rhizoma Radix, 25 parts of Radix Astragali, 5 parts of Chinese Angelica, Winter 6 servings.