Traditional Chinese medicine composition for drug rehabilitation as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to a traditional Chinese medicine composition for drug rehabilitation as well as a preparation method and application of the traditional Chinese medicine composition, and relates to the technical field of traditional Chinese medicine pharmacy. The traditional Chinese medicine composition for drug rehabilitation comprises the following components: 4-5 parts of ginseng, 7-8 parts of angelica sinensis, 9-11 parts of hypericum perforatum, 10-12 parts of corydalis amabilis, 4-5 parts of rheum officinale, 2-3 parts of clove, 3-4 parts of spina date seed, 6.5-7.5 parts of albizia flower and 3.5-4.5 parts of liquorice. The traditional Chinese medicine composition for drug rehabilitation provided by the invention can be completely independently used as a drug for drug rehabilitation, and does not need any western medicine; meanwhile, the medicine has a good drug rehabilitation effect, can achieve the purpose of detoxification through treatment, is high in safety and suitable for industrial batch production, and has a practical application value.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine pharmaceutical manufacturing, and in particular to a traditional Chinese medicine composition for drug addiction treatment, and a preparation method and application thereof. Background Art

[0002] Drug addiction treatment is a recognized medical challenge worldwide. Western medications, represented by methadone, have become the mainstream treatment for drug addiction. Methadone, in essence, is a "replacement therapy" drug. While relatively low in toxicity, it is still addictive. Due to the limitations of Western medicine, drug addiction research has seemingly stagnated since the introduction of methadone. Consequently, many researchers have turned their attention to Traditional Chinese Medicine (TCM). Unlike Western medicine, which focuses solely on alleviating symptoms, modern TCM preparations not only eliminate toxins but also effectively replenish the body's qi and blood, restoring organ function, and regulating physiological systems, thereby achieving a comprehensive treatment of both the symptoms and the root cause. Furthermore, TCM detoxification treatment offers advantages such as non-addictiveness, low side effects, ease of administration, and compatibility with family-based detoxification programs. Currently, TCM is superior to Western medicine in both detoxification and recovery. Certain TCM formulations are even more effective than Western medicine in restoring organ function and regulating physiological systems. Combined with its lack of addictive potential, TCM detoxification treatment has already surpassed Western medicine in overall effectiveness.

[0003] Because of this, there are more than 90 patents for drug inventions for drug addiction treatment published in China, but there are not many varieties that can be used for clinical treatment. Currently, the Chinese medicines for drug addiction treatment that have been marketed in China include Kangling Tablets, Fukang Tablets, Yian Huisheng Oral Liquid, Lingyi Capsules, etc., but most of these Chinese medicines cannot be used independently and require sedatives, hypnotics and drugs for auxiliary treatment. They still have certain damage to the patient's brain nerves. Therefore, developing a Chinese medicine that does not require auxiliary drugs and can well control symptoms is a problem that many medical developers have to solve. Summary of the Invention

[0004] To solve the above problems, the present invention provides a traditional Chinese medicine composition for drug addiction treatment, a preparation method thereof, and an application thereof. The traditional Chinese medicine composition for drug addiction treatment is convenient and simple to take, safe to use, and has good effects, is easily accepted by patients, and has been clinically tested to be rapid in effect and significant in efficacy.

[0005] In a first aspect, the present invention provides a traditional Chinese medicine composition for drug addiction treatment, wherein the traditional Chinese medicine composition for drug addiction treatment comprises the following components in parts by weight:

[0006] 4-5 parts of ginseng, 7-8 parts of angelica, 9-11 parts of St. John's wort, 10-12 parts of summer dwarf, 4-5 parts of rhubarb, 2-3 parts of cloves, 3-4 parts of sour jujube kernel, 6.5-7.5 parts of julibrissin, and 3.5-4.5 parts of liquorice.

[0007] Furthermore, the Chinese medicine composition for drug addiction treatment comprises the following components in parts by weight:

[0008] 4.4 parts of ginseng, 7.2 parts of angelica, 10 parts of St. John's wort, 11 parts of summer nectarine, 4.4 parts of rhubarb, 2.2 parts of cloves, 3.4 parts of spinach seeds, 6.8 parts of jujube flowers and 3.8 parts of liquorice.

[0009] In a second aspect, the present invention provides a method for preparing the Chinese medicine composition for drug addiction treatment according to any one of the first aspects, the preparation method comprising the following steps:

[0010] Step (1): adding angelica and cloves to water for steam distillation extraction to separate and obtain volatile oil, first medicinal residue and steam distillate;

[0011] Step (2): adding rhubarb to ethanol for a first reflux extraction, followed by filtering, concentrating, drying, and crushing and sieving to obtain dry paste powder A;

[0012] Step (3): adding the summer ginseng and 3.3 to 4.2 parts by weight of ginseng to ethanol for a second reflux extraction, followed by filtering to obtain a first filtrate and a second medicinal residue; crushing and grinding the remaining ginseng and sieving to obtain ginseng powder;

[0013] Step (4): adding the first medicinal residue, the second medicinal residue, liquorice, spinach seeds, and jujube flowers into water for decoction, combining the resulting decoction with the steam distillate, filtering and concentrating to obtain a mixture with a relative density of 1.15-1.20; adding ethanol to the mixture to adjust the alcohol content to 55%-65% (V / V), allowing the mixture to stand, combining the supernatant with the first filtrate, filtering, concentrating, drying, and pulverizing and sieving to obtain a dry paste powder B;

[0014] Step (5): St. John's wort extract, the dry paste powder A, the dry paste powder B and the ginseng powder are mixed to obtain a mixed powder, and then ethanol is added to granulate the mixed powder, dried, sprayed with the volatile oil, sealed, and stored to obtain the Chinese medicine composition.

[0015] Furthermore, the working parameters of the steam distillation extraction include: the weight of water added is 8 to 12 times the total weight of the angelica and cloves, and the extraction time is 4 to 6 hours; the working parameters of the decoction include: the decoction time is 1 to 3 hours, the weight of water added is 8 to 14 times the total weight of the added Chinese medicinal materials, and the number of decoctions is 1 to 3 times.

[0016] Furthermore, the working parameters of the first reflux extraction include: the volume fraction of ethanol is 80%-90%, the number of extractions is 1 to 3 times, the extraction time for each time is 0.4-1.5 hours, and the reflux extraction temperature for each time is 60 to 70°C; the working parameters of the second reflux extraction include: the volume fraction of ethanol is 75%-85%, the added weight of ethanol is 7-12 times the total weight of the summer melon and the ginseng, the number of extractions is 1 to 3 times, the extraction time for each time is 1-4 hours, and the reflux extraction temperature for each time is 60 to 70°C.

[0017] Furthermore, the preparation method of the St. John's wort extract comprises the following steps: adding St. John's wort to ethanol for alcohol extraction 1 to 3 times, then concentrating, drying, crushing and screening to obtain the St. John's wort extract. The extraction process of St. John's wort is as follows: adding ten times the amount of 70% ethanol to a decoction, soaking for half an hour, and then decocting for one hour. After filtering, adding eight times the amount of ethanol and decocting for one hour, combining the two decoctions, recovering the ethanol, and mixing with the above materials and drying.

[0018] In a third aspect, the present invention provides a Chinese medicine composition for drug addiction treatment as described in any one of the first aspects, and / or the use of a Chinese medicine composition prepared by the preparation method as described in any one of the second aspects in the preparation of drug addiction treatment drugs.

[0019] In a fourth aspect, the present invention provides a Chinese medicine capsule preparation for drug addiction treatment, wherein the Chinese medicine capsule preparation for drug addiction treatment comprises the Chinese medicine composition for drug addiction treatment described in any one of the first aspects, and / or the Chinese medicine composition prepared by the preparation method described in any one of the second aspects.

[0020] Furthermore, the Chinese medicine capsule preparation also includes pharmaceutical excipients.

[0021] Furthermore, the pharmaceutical excipient includes magnesium stearate.

[0022] The above technical solution provided by the present invention has at least the following advantages compared with the prior art:

[0023] The present invention provides a Chinese medicine composition for drug addiction treatment. Based on the overall symptoms of drug addiction treatment, the researchers of the present invention fully considered the characteristics of Chinese angelica, julibrissin, rhubarb, cloves, liquorice and other medicines, and based on the theory of syndrome differentiation and treatment in traditional Chinese medicine, re-established the formula of Chinese medicine ginseng, Chinese angelica, summer clover, St. John's wort, julibrissin, rhubarb, cloves, spinach seeds, and liquorice; after long-term research, a better preparation process was determined, which is suitable for the industrial production of the capsule preparation of the present application; the preparation can be used as a drug for drug addiction treatment completely independently, without the need for any Western medicine; pharmacological experiments show that the capsule preparation prepared by the Chinese medicine composition of the present invention has a good drug addiction treatment effect, and the purpose of detoxification can be achieved through treatment; toxicological experiments show that the capsule preparation of the present application has a very high safety. Specifically:

[0024] In the new formula, ginseng is used to replenish vital energy, nourish the spleen and lungs, replenish qi and generate blood, calm the mind and improve intelligence, and strengthen the body; angelica is used to replenish blood and relieve stagnation, warm the meridians and relieve pain. The two herbs are used together to replenish qi and blood, unblock the meridians and relieve pain, and calm the mind. They are used to treat qi and blood deficiency, pain, anxiety, and insomnia during detoxification.

[0025] In summer, there is no blood circulation and qi activating, meridians relieving pain, focusing on calming wind and stopping spasms, opening the orifices and refreshing the mind; the above medicines can enhance the effects of the main medicine in relieving pain, calming wind and stopping spasms, calming the mind and improving intelligence, and treat pain, restlessness, spasms and convulsions during detoxification, and are collectively referred to as the minister medicine;

[0026] Albizia julibrissin flowers soothe the liver and relieve depression, calm the mind and stabilize the spirit; Ziziphus jujuba seeds soothe the mind and promote sleep, nourish yin and restrain sweating; Rhubarb clears heat and promotes bowel movements, detoxifies and lowers turbidity, resolves blood stasis and relieves pain; Clove soothes the stomach and stops vomiting. The above herbs, when used together, have the effects of awakening the mind, relieving pain and vomiting, and expelling nicotine toxins, and are used as adjuvants to treat insomnia, anxiety, pain, sweating, vomiting, and nicotine retention during detoxification.

[0027] Licorice can nourish, relieve, and detoxify. It can increase the effect of ginseng in replenishing qi and strengthening the spleen, and help rhubarb to eliminate tobacco toxins. At the same time, it can strengthen the analgesic and anti-vomiting effects of the above-mentioned medicines, and can harmonize the medicinal properties, so that the whole prescription has appropriate attack and nourishment, and balances cold and heat. It has multiple uses and is an adjuvant. DETAILED DESCRIPTION

[0028] To make the objectives, technical solutions, and advantages of the present invention more clear, the technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the embodiments described are part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts shall fall within the scope of protection of the present invention.

[0029] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0030] In a first aspect, the present invention provides a traditional Chinese medicine composition for drug addiction treatment, wherein the traditional Chinese medicine composition for drug addiction treatment comprises the following components in parts by weight:

[0031] 4-5 parts of ginseng, 7-8 parts of angelica, 9-11 parts of St. John's wort, 10-12 parts of summer dwarf, 4-5 parts of rhubarb, 2-3 parts of cloves, 3-4 parts of sour jujube kernel, 6.5-7.5 parts of julibrissin, and 3.5-4.5 parts of liquorice.

[0032] The present invention provides a Chinese medicine composition for drug addiction treatment. Based on the overall symptoms of drug addiction treatment, the researchers of the present invention fully considered the characteristics of Chinese angelica, julibrissin, rhubarb, cloves, liquorice and other medicines, and based on the theory of syndrome differentiation and treatment in traditional Chinese medicine, re-established the formula of Chinese medicine ginseng, Chinese angelica, summer clover, St. John's wort, julibrissin, rhubarb, cloves, spinach seeds, and liquorice; after long-term research, a better preparation process was determined, which is suitable for the industrial production of the capsule preparation of the present application; the preparation can be used as a drug for drug addiction treatment completely independently, without the need for any Western medicine; pharmacological experiments show that the capsule preparation prepared by the Chinese medicine composition of the present invention has a good drug addiction treatment effect, and the purpose of detoxification can be achieved through treatment; toxicological experiments show that the capsule preparation of the present application has a very high safety. Specifically:

[0033] In the new formula, ginseng is used to replenish vital energy, nourish the spleen and lungs, replenish qi and generate blood, calm the mind and improve intelligence, and strengthen the body; angelica is used to replenish blood and relieve stagnation, warm the meridians and relieve pain. The two herbs are used together to replenish qi and blood, unblock the meridians and relieve pain, and calm the mind. They are used to treat qi and blood deficiency, pain, anxiety, and insomnia during detoxification.

[0034] In summer, there is no blood circulation and qi activating, meridians relieving pain, focusing on calming wind and stopping spasms, opening the orifices and refreshing the mind; the above medicines can enhance the effects of the main medicine in relieving pain, calming wind and stopping spasms, calming the mind and improving intelligence, and treat pain, restlessness, spasms and convulsions during detoxification, and are collectively referred to as the minister medicine;

[0035] Albizia julibrissin flowers soothe the liver and relieve depression, calm the mind and stabilize the spirit; Ziziphus jujuba seeds soothe the mind and promote sleep, nourish yin and restrain sweating; Rhubarb clears heat and promotes bowel movements, detoxifies and lowers turbidity, resolves blood stasis and relieves pain; Clove soothes the stomach and stops vomiting. The above herbs, when used together, have the effects of awakening the mind, relieving pain and vomiting, and expelling nicotine toxins, and are used as adjuvants to treat insomnia, anxiety, pain, sweating, vomiting, and nicotine retention during detoxification.

[0036] Licorice can nourish, relieve, and detoxify. It can increase the effect of ginseng in replenishing qi and strengthening the spleen, and help rhubarb to eliminate tobacco toxins. At the same time, it can strengthen the analgesic and anti-vomiting effects of the above-mentioned medicines, and can harmonize the medicinal properties, so that the whole prescription has appropriate attack and nourishment, and balances cold and heat. It has multiple uses and is an adjuvant.

[0037] In some specific embodiments, the Chinese medicine composition for drug addiction treatment comprises the following components in parts by weight:

[0038] 4.4 parts of ginseng, 7.2 parts of angelica, 10 parts of St. John's wort, 11 parts of summer nectarine, 4.4 parts of rhubarb, 2.2 parts of cloves, 3.4 parts of spinach seeds, 6.8 parts of jujube flowers and 3.8 parts of liquorice.

[0039] In a second aspect, based on the same inventive concept, the present invention provides a method for preparing the Chinese medicine composition for drug addiction treatment according to any one of the first aspects, the preparation method comprising the following steps:

[0040] Step (1): adding angelica and cloves to water for steam distillation extraction to separate and obtain volatile oil, first medicinal residue and steam distillate;

[0041] Step (2): adding rhubarb to ethanol for a first reflux extraction, followed by filtering, concentrating, drying, and crushing and sieving to obtain dry paste powder A;

[0042] Step (3): adding the summer ginseng and 3.3 to 4.2 parts by weight of ginseng to ethanol for a second reflux extraction, followed by filtering to obtain a first filtrate and a second medicinal residue; crushing and grinding the remaining ginseng and sieving to obtain ginseng powder;

[0043] Step (4): adding the first medicinal residue, the second medicinal residue, liquorice, spinach seeds, and jujube flowers into water for decoction, combining the resulting decoction with the steam distillate, filtering and concentrating to obtain a mixture with a relative density of 1.15-1.20; adding ethanol to the mixture to adjust the alcohol content to 55%-65% (V / V), allowing the mixture to stand, combining the supernatant with the first filtrate, filtering, concentrating, drying, and pulverizing and sieving to obtain a dry paste powder B;

[0044] Step (5): St. John's wort extract, the dry paste powder A, the dry paste powder B and the ginseng powder are mixed to obtain a mixed powder, and then ethanol is added to granulate the mixed powder, dried, sprayed with the volatile oil, sealed, and stored to obtain the Chinese medicine composition.

[0045] The preparation method of the traditional Chinese medicine composition for drug addiction treatment provided by the present invention is simple to operate, does not require additional special equipment, and is suitable for industrial batch production.

[0046] In some specific embodiments, the working parameters of the steam distillation extraction include: the weight of the added water is 8 to 12 times the total weight of the angelica and cloves, and the extraction time is 4 to 6 hours; the working parameters of the decoction include: the decoction time is 1 to 3 hours, the weight of the added water is 8 to 14 times the total weight of the added Chinese medicinal materials, and the number of decoctions is 1 to 3 times.

[0047] In some specific embodiments, the working parameters of the first reflux extraction include: the volume fraction of ethanol is 80%-90%, the number of extractions is 1 to 3 times, the extraction time is 0.4-1.5 hours each time, and the reflux extraction temperature is 60-70°C each time; the working parameters of the second reflux extraction include: the volume fraction of ethanol is 75%-85%, the added weight of ethanol is 7-12 times the total weight of the summer melon and the ginseng, the number of extractions is 1 to 3 times, the extraction time is 1-4 hours each time, and the reflux extraction temperature is 60-70°C each time.

[0048] In some specific embodiments, the preparation method of the St. John's wort extract comprises the following process: adding St. John's wort to ethanol for alcohol extraction 1 to 3 times, then concentrating, drying, crushing and screening to obtain the St. John's wort extract. The extraction process of St. John's wort is as follows: adding ten times the amount of 70% ethanol to a decoction, soaking for half an hour, and then boiling for one hour. After filtering, adding 8 times the amount of ethanol and boiling for one hour, combining the two decoctions, recovering the ethanol, and mixing with the above materials and drying.

[0049] In some specific embodiments, the preparation method of the traditional Chinese medicine composition for drug addiction treatment comprises the following steps:

[0050] (1) Take angelica and cloves and add 10 times the amount of water, and extract the oil by steam distillation for 4-6 hours. Separate the volatile oil, medicinal residue and steam distillate for later use;

[0051] (2) extracting rhubarb by adding 80%-90% ethanol and refluxing twice, first adding 8-12 times the amount of ethanol and refluxing at 60°C for 0.5-1.5 hours, and second adding 6-9 times the amount of ethanol and refluxing at 60°C for 0.4-0.6 hours, combining the two extracts and filtering; recovering ethanol below 60°C, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain dry paste powder A for later use;

[0052] (3) Take two herbs, Xiatianwu and 5 / 6 ginseng, and extract them 2-3 times with 75%-85% ethanol. For the first extraction, add 8-12 times the amount of ethanol and reflux for 2-4 hours. For the second and third extractions, add 7-9 times the amount of ethanol and reflux for 1-3 hours. Combine the ethanol extracts, filter, and set aside the filtrate and the residue for later use.

[0053] (4) taking the dregs of the medicinal material from step (1) and step (3), decocting them with liquorice, jujube seeds, and jujube flowers twice with water, adding 10-14 times the amount of water for the first time, extracting for 1-3 hours, and adding 8-12 times the amount of water for the second time, extracting for 1-2 hours, combining the two decoctions and the steam distillate from step (1), filtering, and concentrating the filtrate under reduced pressure to a relative density of 1.15-1.20 at 60°C, adding ethanol to make the alcohol content reach 55%-65%, and standing for 24 hours, taking the supernatant and combining it with the alcohol extract from step (3), recovering ethanol, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain a dry paste powder B for standby use;

[0054] (5) St. John's wort extract, raw materials are selected, extracted twice with alcohol, concentrated, spray-dried, mixed, sieved, and tested for later use;

[0055] (6) Grind the remaining ginseng into powder, pass it through a 100-mesh sieve, and mix it with the dry paste powder A, dry paste powder B, and St. John's wort extract to obtain a mixed powder. Then, add ethanol to granulate the powder, dry it, spray it with the volatile oil, seal it, and let it sit for 2-4 hours to obtain the Chinese medicine composition.

[0056] It should be noted that, unless otherwise specified or specified, the raw materials of each component in the above-mentioned traditional Chinese medicine composition for drug addiction treatment provided by the present invention can be directly commercially available products; unless there are special steps in the traditional Chinese medicine composition for drug addiction treatment, the preparation techniques disclosed in the prior art, such as pill making and tablet making, or existing equipment can be used, and the present invention document will not go into details.

[0057] In a third aspect, the present invention provides a Chinese medicine composition for drug addiction treatment as described in any one of the first aspects, and / or the use of a Chinese medicine composition prepared by the preparation method as described in any one of the second aspects in the preparation of drug addiction treatment drugs.

[0058] In a fourth aspect, the present invention provides a Chinese medicine capsule preparation for drug addiction treatment, wherein the Chinese medicine capsule preparation for drug addiction treatment comprises the Chinese medicine composition for drug addiction treatment described in any one of the first aspects, and / or the Chinese medicine composition prepared by the preparation method described in any one of the second aspects.

[0059] In some specific embodiments, the traditional Chinese medicine capsule preparation further includes pharmaceutical excipients.

[0060] In some specific embodiments, the pharmaceutical excipient includes magnesium stearate.

[0061] In some specific embodiments, the preparation method of the Chinese medicine capsule preparation includes: based on the preparation method of the Chinese medicine composition for drug addiction treatment, adding 0.5wt% of magnesium stearate to the prepared Chinese medicine composition, mixing, and filling into capsules to obtain the finished product.

[0062] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. The experimental methods in the following examples where specific conditions are not specified are generally measured in accordance with national standards. If there are no corresponding national standards, then the methods are carried out in accordance with general international standards, conventional conditions, or the conditions recommended by the manufacturer.

[0063] Example 1

[0064] This example provides a Chinese medicine capsule preparation for drug addiction treatment, the preparation method of which includes the following steps:

[0065] (1) Prescription: 400g ginseng, 700g angelica, 1000g St. John's wort, 1000g summer jasmine, 400g rhubarb, 200g cloves, 300g jujube kernel, 650g jujube flower, 350g liquorice root;

[0066] (2) Take angelica and cloves and add 10 times the amount of water, and extract the oil by steam distillation for 4 hours. Separate the volatile oil, medicinal residue and steam distillate for later use;

[0067] (3) Extracting rhubarb with 80% ethanol (v / v) and refluxing twice, first extracting with 8 times the amount of ethanol at 60°C for 1 hour, and second extracting with 6 times the amount of ethanol at 60°C for 0.5 hour, combining the two extracts and filtering; recovering ethanol below 60°C, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain dry paste powder A for later use;

[0068] (4) Take two herbs, Xiatianwu and 5 / 6 ginseng, and extract them three times with 75%-80% ethanol. For the first extraction, add 8 times the amount of ethanol and reflux for 2 hours. For the second and third extractions, add 7 times the amount of ethanol and reflux for 1 hour respectively. Combine the ethanol extracts, filter, and set aside the filtrate and the medicinal residue for later use.

[0069] (5) taking the dregs of the medicinal material from step (1) and step (3), decocting them with liquorice, jujube seeds, and jujube flowers twice with water, adding 10 times the amount of water for the first time and extracting for 2 hours, adding 8 times the amount of water for the second time and extracting for 1 hour, combining the two decoctions and the steam distillate from step (1), filtering, and concentrating the filtrate under reduced pressure to a relative density of 1.15-1.20 at 60°C, adding ethanol to make the alcohol content reach 55%-60% (V / V), and standing for 24 hours, taking the supernatant and combining it with the alcohol extract from step (3), recovering ethanol, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain a dry paste powder B for use;

[0070] (6) Take 1 / 6 of the ginseng and grind it into fine powder, pass it through a 100-mesh sieve, and mix it with the above-mentioned dry paste powder A and B to obtain fine powder; then add an appropriate amount of 50% ethanol to granulate, dry it, spray it with volatile oil, seal it, and let it sit for 3 hours. Then add 0.5% magnesium stearate and mix it evenly. Put it into capsules to obtain 1000 capsules of the finished product.

[0071] Example 2

[0072] This example provides a Chinese medicine capsule preparation for drug addiction treatment, the preparation method of which includes the following steps:

[0073] (1) Prescription:

[0074] 500g ginseng, 800g angelica, 1000g St. John's wort, 1200g summer jasmine, 500g rhubarb, 300g cloves, 400g jujube kernel, 750g jujube flower, 450g liquorice root;

[0075] (2) Take angelica and cloves and add 10 times the amount of water, and extract the oil by steam distillation for 6 hours. Separate the volatile oil, the medicinal residue and the steam distillate for later use;

[0076] (3) Extracting rhubarb with 90% ethanol (v / v) and refluxing twice, first extracting with 12 times the amount of ethanol at 60°C for 1.5 hours, and second extracting with 9 times the amount of ethanol at 60°C for 0.6 hours, combining the two extracts and filtering; recovering ethanol below 60°C, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, pulverizing, and passing through an 80-mesh sieve to obtain dry paste powder A for later use;

[0077] (4) Take two herbs, Xiatianwu and 5 / 6 of the weight of ginseng, and extract them twice with 80%-85% ethanol. The first time, add 12 times the amount of ethanol and reflux for 3 hours. The second time, add 9 times the amount of ethanol and reflux for 2 hours. Combine the ethanol extracts, filter, and set aside the filtrate and the medicinal residue for later use.

[0078] (5) taking the dregs of the medicinal material from step (1) and step (3), decocting them with liquorice, jujube seeds, and jujube flowers twice with water, adding 14 times the amount of water for the first time, extracting for 3 hours, and adding 12 times the amount of water for the second time, extracting for 2 hours, combining the two decoctions and the steam distillate from step (1), filtering, and concentrating the filtrate under reduced pressure to a relative density of 1.15-1.20 at 60°C, adding ethanol to make the alcohol content reach 60%-65% (V / V), and standing for 24 hours, taking the supernatant and combining it with the alcohol extract from step (3), recovering ethanol, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain a dry paste powder B for standby use;

[0079] (6) Grind 1 / 6 of the weight of ginseng into powder, pass through a 100-mesh sieve, and mix with the above-mentioned dry paste powders A and B to obtain fine powder; then add an appropriate amount of 50% ethanol to granulate, dry, spray with volatile oil, seal, and let stand for 4 hours; add 0.5% magnesium stearate and mix well, and put into capsules to obtain 1000 finished capsules.

[0080] Example 3

[0081] This example provides a Chinese medicine capsule preparation for drug addiction treatment, the preparation method of which includes the following steps:

[0082] (1) Prescription:

[0083] 440g ginseng, 720g angelica, 1000g St. John's wort, 1100g summer dwarf ...

[0084] (2) Take angelica and cloves and add 10 times the amount of water, and extract the oil by steam distillation for 5 hours. Separate the volatile oil, medicinal residue and steam distillate for later use;

[0085] (3) Extracting rhubarb with 85% ethanol (v / v) and refluxing twice, first extracting with 10 times the amount of ethanol at 60°C for 1 hour, and second extracting with 8 times the amount of ethanol at 60°C for 0.5 hour, combining the two extracts and filtering; recovering ethanol below 60°C, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain dry paste powder A for later use;

[0086] (4) Take two medicinal materials, namely, Xiatianwu and 5 / 6 of the weight of ginseng, and extract them twice with 80% ethanol. The first time, add 10 times the amount of ethanol and reflux for 3 hours. The second time, add 8 times the amount of ethanol and reflux for 2 hours. Combine the ethanol extracts, filter, and set aside the filtrate and the medicinal residue for later use.

[0087] (5) Take the dregs of step (1) and step (3), add liquorice, spinach seeds, and jujube flowers and boil them in water for two times.

[0088] The mixture was added with 12 times the amount of water for the first time and extracted for 2 hours. The mixture was added with 10 times the amount of water for the second time and extracted for 1.5 hours. The decoctions from the second time and the steam distillate from step (1) were combined and filtered. The filtrate was concentrated under reduced pressure to a relative density of 1.15-1.20 at 60°C. Ethanol was added to make the alcohol content reach 60%. The mixture was allowed to stand for 24 hours. The supernatant was combined with the alcohol extract from step (3) above. The ethanol was recovered and concentrated under reduced pressure to a relative density of 1.25-1.35 at 60°C. The mixture was dried under reduced pressure, crushed, and passed through an 80-mesh sieve to obtain a dry paste powder B for later use.

[0089] (6) Grind 1 / 6 of the weight of ginseng into powder, pass through a 100-mesh sieve, and mix with the above-mentioned dry paste powders A and B to obtain fine powder; then add an appropriate amount of 50% ethanol to granulate, dry, spray with volatile oil, seal, and let stand for 3 hours, add 0.5% magnesium stearate and mix well, and put into capsules to obtain 1000 finished capsules.

[0090] Example 4

[0091] This example provides a Chinese medicine capsule preparation for drug addiction treatment, the preparation method of which includes the following steps:

[0092] (1) Prescription:

[0093] 410g ginseng, 705g angelica, 1000g St. John's wort, 1050g summer dwarf rhubarb, 415g cloves, 205g jujube kernel, 315g jujube seeds, 660g julibrissin flowers, 360g liquorice root;

[0094] (2) Take angelica and cloves and add 10 times the amount of water, and extract the hair oil by steam distillation for 4.5 hours. Separate the volatile oil, medicinal residue and steam distillate for later use;

[0095] (3) Extracting rhubarb with 85%-90% ethanol (v / v) and refluxing twice, first extracting with 9 times the amount of ethanol at 60°C for 0.7 hours, and second extracting with 7 times the amount of ethanol at 60°C for 0.4 hours, combining the two extracts and filtering; recovering ethanol below 60°C, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, pulverizing, and passing through an 80-mesh sieve to obtain dry paste powder A for later use;

[0096] (4) Take three herbs, including Xiatianwu and 5 / 6 of the weight of ginseng, and extract them twice with 80%-85% ethanol. The first time, add 9 times the amount of ethanol and reflux for 2.5 hours. The second time, add 7 times the amount of ethanol and reflux for 1.5 hours. Combine the ethanol extracts, filter, and set aside the filtrate and the medicinal residue.

[0097] (5) The dregs of the medicinal material from step (1) and step (3) were decocted with liquorice, jujube seeds, and jujube flowers with water twice, with 11 times the amount of water added for the first time and extraction for 1.5 hours, and 9 times the amount of water added for the second time and extraction for 1.5 hours. The two decoctions and the steam distillate from step (1) were combined, filtered, and the filtrate was concentrated under reduced pressure to a relative density of 1.15-1.20 at 60°C, ethanol was added to make the alcohol content reach 60%-65% (V / V), and allowed to stand for 24 hours. The supernatant was combined with the alcohol extract from step (3) above, and the ethanol was recovered. The decoction was concentrated under reduced pressure to a relative density of 1.25-1.35 at 60°C, dried under reduced pressure, crushed, and passed through an 80-mesh sieve to obtain a dry paste powder B for later use;

[0098] (6) Grind 1 / 6 of the weight of ginseng into powder, pass through a 100-mesh sieve, and mix with the above-mentioned dry paste powders A and B to obtain fine powder; then add an appropriate amount of 50% ethanol to granulate, dry, spray with volatile oil, seal, and let stand for 4 hours; add 0.5% magnesium stearate and mix well, and put into capsules to obtain 1000 finished capsules.

[0099] Example 5

[0100] This example provides a Chinese medicine capsule preparation for drug addiction treatment, the preparation method of which includes the following steps:

[0101] (1) Prescription:

[0102] 480g ginseng, 780g angelica, 1000g St. John's wort, 1150g summer dwarf rhubarb, 435g cloves, 280g cloves, 385g jujube kernel, 740g julibrissin flower, 440g liquorice root;

[0103] (2) Take angelica and cloves and add 10 times the amount of water, and extract the oil by steam distillation for 4-5 hours. Separate the volatile oil, the residue and the steam distillate for later use;

[0104] (3) Extracting rhubarb with 80%-85% ethanol (v / v) and refluxing twice, first extracting with 11 times the amount of ethanol and refluxing at 60°C for 1.5 hours, and second extracting with 9 times the amount of ethanol and refluxing at 60°C for 0.6 hours, combining the two extracts and filtering; recovering ethanol below 60°C, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, pulverizing, and passing through an 80-mesh sieve to obtain dry paste powder A for later use;

[0105] (4) Take two herbs, Xiatianwu and 5 / 6 of the weight of ginseng, and extract them twice with 80%-85% ethanol. The first time, add 11 times the amount of ethanol and reflux for 3.5 hours. The second time, add 9 times the amount of ethanol and reflux for 2.5 hours. Combine the ethanol extracts, filter, and set aside the filtrate and the medicinal residue for later use.

[0106] (5) taking the dregs of the medicinal material from step (1) and step (3), decocting them with liquorice, jujube seeds, and jujube flowers twice with water, adding 13 times the amount of water for the first time, extracting for 2.5 hours, and adding 11 times the amount of water for the second time, extracting for 2 hours, combining the two decoctions and the steam distillate from step (1), filtering, and concentrating the filtrate under reduced pressure to a relative density of 1.15-1.20 at 60° C., adding ethanol to make the alcohol content reach 65%, and standing for 24 hours, taking the supernatant and combining it with the alcohol extract from step (3), recovering ethanol, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60° C., drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain a dry paste powder B for standby use;

[0107] (6) Grind 1 / 6 of the weight of ginseng into powder, pass through a 100-mesh sieve, and mix with the above-mentioned dry paste powders A and B to obtain fine powder; then add an appropriate amount of 50% ethanol to granulate, dry, spray with volatile oil, seal, and let stand for 2-4 hours, add 0.5% magnesium stearate and mix well, and put into capsules to obtain 1000 finished capsules.

[0108] Example 6

[0109] This example provides a Chinese medicine capsule preparation for drug addiction treatment, the preparation method of which includes the following steps:

[0110] (1) Prescription:

[0111] 460g ginseng, 740g angelica, 1000g St. John's wort, 1130g summer dwarf rhubarb, 450g cloves, 350g jujube kernel, 700g jujube flower, 400g liquorice root;

[0112] (2) Take angelica and cloves and add 10 times the amount of water, and extract the oil by steam distillation for 5-6 hours. Separate the volatile oil, medicinal residue and steam distillate for later use;

[0113] (3) Extracting rhubarb with 85% ethanol (v / v) and refluxing twice, first extracting with 9 times the amount of ethanol at 60°C for 1.5 hours, and second extracting with 8 times the amount of ethanol at 60°C for 0.6 hours, combining the two extracts and filtering; recovering ethanol below 60°C, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, pulverizing, and passing through an 80-mesh sieve to obtain dry paste powder A for later use;

[0114] (4) Take two herbs, Xiatianwu and 5 / 6 of the weight of ginseng, and extract them twice with 80% ethanol. The first time, add 11 times the amount of ethanol and reflux for 3 hours. The second time, add 7 times the amount of ethanol and reflux for 2 hours. Combine the ethanol extracts, filter, and set aside the filtrate and the medicinal residue.

[0115] (5) taking the dregs of the medicinal material from step (1) and the dregs from step (3), decocting them with liquorice, jujube seeds, and jujube flowers twice with water, adding 13 times the amount of water for the first time, extracting for 2.5 hours, and adding 9 times the amount of water for the second time, extracting for 1 hour, combining the two decoctions and the steam distillate from step (1), filtering, and concentrating the filtrate under reduced pressure to a relative density of 1.15-1.20 at 60° C., adding ethanol to make the alcohol content reach 65%, and standing for 24 hours, taking the supernatant and combining it with the alcohol extract from step (3), recovering ethanol, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60° C., drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain a dry paste powder B for standby use;

[0116] (6) Grind 1 / 6 of the weight of ginseng into powder, pass through a 100-mesh sieve, and mix with the above-mentioned dry paste powders A and B to obtain fine powder; then add an appropriate amount of 50% ethanol to granulate, dry, spray with volatile oil, seal, and let stand for 2-4 hours, add 0.5% magnesium stearate and mix well, and put into capsules to obtain 1000 finished capsules.

[0117] Example 7

[0118] This example provides a Chinese medicine capsule preparation for drug addiction treatment, the preparation method of which includes the following steps:

[0119] (1) Prescription:

[0120] 4400g ginseng, 7200g angelica, 10000g St. John's wort, 11000g summer jasmine, 4400g rhubarb, 2200g cloves, 3400g jujube kernel, 6800g jujube flower, 3800g liquorice root;

[0121] (2) Take angelica and cloves and add 10 times the amount of water, and extract the oil by steam distillation for 5 hours. Separate the volatile oil, medicinal residue and steam distillate for later use;

[0122] (3) Extracting rhubarb with 85% ethanol (v / v) and refluxing twice, first extracting with 10 times the amount of ethanol at 60°C for 1 hour, and second extracting with 8 times the amount of ethanol at 60°C for 0.5 hour, combining the two extracts and filtering; recovering ethanol below 60°C, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60°C, drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain dry paste powder A for later use;

[0123] (4) Take two medicinal materials, namely, Xiatianwu and 5 / 6 of the weight of ginseng, and extract them twice with 80% ethanol. The first time, add 10 times the amount of ethanol and reflux for 3 hours. The second time, add 8 times the amount of ethanol and reflux for 2 hours. Combine the ethanol extracts, filter, and set aside the filtrate and the medicinal residue for later use.

[0124] (5) taking the dregs of the medicinal material from step (1) and step (3), decocting them with liquorice, jujube seeds, and jujube flowers twice with water, adding 12 times the amount of water for the first time, extracting for 2 hours, and adding 10 times the amount of water for the second time, extracting for 1.5 hours, combining the two decoctions and the steam distillate from step (1), filtering, and concentrating the filtrate under reduced pressure to a relative density of 1.15-1.20 at 60° C., adding ethanol to make the alcohol content reach 60%, and standing for 24 hours, taking the supernatant and combining it with the alcohol extract from step (3), recovering ethanol, concentrating under reduced pressure to a relative density of 1.25-1.35 at 60° C., drying under reduced pressure, crushing, and passing through an 80-mesh sieve to obtain a dry paste powder B for standby use;

[0125] (6) Grind 1 / 6 of the weight of ginseng into powder, pass through a 100-mesh sieve, and mix with the above-mentioned dry paste powders A and B to obtain fine powder; then add an appropriate amount of 50% ethanol to granulate, dry, spray with volatile oil, seal, and let stand for 3 hours, add 0.5% magnesium stearate and mix well, and put into capsules to obtain 10,000 finished capsules.

[0126] Test Case

[0127] The Chinese medicine capsule preparation for drug addiction treatment prepared in Example 1 was subjected to the following tests and analyses.

[0128] 1. Detection and analysis

[0129] Inspection basis: "Quality Standards for Clinical Research".

[0130] The test results (according to the test report issued by Henan Provincial Food and Drug Inspection Institute on May 19, 2006) are as follows:

[0131] The test results, test items, standard provisions, and test results of the capsule preparation of the present invention. [Properties] and [Identification]: (1) Microscopic characteristics; (2) Thin layer chromatography; (3) Thin layer chromatography; (4) Thin layer chromatography; (5) Thin layer chromatography; (6) Thin layer chromatography; (7) Thin layer chromatography; (8) Thin layer chromatography. [Inspection]: Moisture content, disintegration time, filling volume difference, microbial limit, it should be a capsule preparation, the contents are brown to brown granules or powder, fragrant, bitter, slightly spicy, and cool. It should have the microscopic characteristics of the capsule of this application; should be consistent with the main spots of ginseng control medicinal material and ginsenoside Rb1, Re, and Rg1 control substances; should be consistent with the main spots of cholic acid and deoxycholic acid control substances; should be consistent with the main spots of summer control medicinal materials; should be consistent with the main spots of rhubarb control medicinal material and rhubarb control drug; should be consistent with the main spots of eugenol and control substances; should be consistent with the main spots of glycyrrhetinic acid control substances; should not exceed 9.0%; should comply with the regulations within 30 minutes; should comply with the regulations. It is a capsule preparation with the contents being brown granules or powder, fragrant, bitter, slightly spicy, and cool. The microscopic features of the capsules of the present application are consistent with the main spots of ginseng reference medicinal materials and ginsenoside Rb1, Re, and Rg1 reference substances; consistent with the main spots of cholic acid and deoxycholic acid reference substances; consistent with the main spots of summer uncontrolled medicinal materials; consistent with the main spots of rhubarb reference medicinal materials and emodin reference medicinal materials; consistent with the main spots of eugenol reference substances; consistent with the main spots of glycyrrhetinic acid reference substances; 6.5% 23 minutes meets the requirements [content determination]; each capsule contains rhubarb with emodin (C 15 H 10 O6) and chrysophanol (C 15 H 10 O4) shall not be less than 1.20mg1.75mg.

[0132] Conclusion: This product was tested according to the quality standards for clinical research and the results were in compliance with the regulations.

[0133] 2. Pharmacological experiments

[0134] (1) Pharmacodynamic research data

[0135] 1. In the rat induced withdrawal treatment experiment, the Mor model group showed obvious withdrawal symptoms (P < 0.01) and a significant decrease in body weight (P < 0.01). The three dosage groups of the capsule of the present invention (0.4, 2.0 and 4.0 g / kg) showed a certain therapeutic effect on withdrawal symptoms and weight loss. The withdrawal symptom score and weight loss 30 minutes and 60 minutes after urging in the high-dose group were significantly lower than those in the Mor model group (P < 0.05 or P < 0.01). The weight loss in the medium-dose group was significantly lower than that in the Mor model group (P < 0.01). This shows that the capsule of the present application can significantly counteract the induced withdrawal reaction of Mor-dependent rats in this model, but its therapeutic effect on withdrawal reaction is not as good as that of clonidine.

[0136] 2. In the natural withdrawal treatment experiment on rats, the body weight of the Mor model group decreased significantly (P < 0.01). The three dosage groups of the capsule of the present application (0.3, 0.8 and 1.6 g / kg) can control the weight loss of rats to a certain extent, especially the high-dose group and the medium-dose group have a more obvious control on the weight loss of rats. The percentage of weight loss in the high-dose group on the third day after withdrawal and the low-dose group on the fourth day were significantly lower than those in the Mor model group (P < 0.01 or P < 0.05). The clonidine group did not inhibit the loss of body weight after withdrawal. This shows that in this model, the capsule of the present invention exhibits an obvious detoxification therapeutic effect.

[0137] 3. In a natural withdrawal treatment experiment in monkeys, the Mor model group exhibited significant withdrawal symptoms, with significant decreases in body weight and temperature (p < 0.05 or p < 0.01). Both dose groups of the present invention's capsule (0.36 and 0.72 g / kg) were able to control withdrawal symptoms to varying degrees, with significantly lower reductions in weight and temperature than in the Mor model group (p < 0.05 or p < 0.01), demonstrating a significant therapeutic effect on morphine withdrawal reactions. Compared with the positive control drug clonidine, the present invention's capsules were comparable to clonidine in controlling withdrawal symptoms, superior to clonidine in controlling weight loss, and inferior to clonidine in controlling temperature drop.

[0138] Based on the results of the above three experiments, the following conclusions can be drawn: the capsule of the present invention has a significant detoxification therapeutic effect on the withdrawal syndrome produced by morphine-dependent animals after withdrawal, and its effect is superior to clonidine in some aspects.

[0139] (2) Toxicology research data

[0140] Test drug: the capsule of the present invention (i.e., the Chinese medicine capsule preparation for drug addiction treatment prepared in Example 1), provided by Henan Huisenfu Biopharmaceutical Technology Co., Ltd., batch number: 001006.

[0141] 1. General toxicology studies

[0142] Effects on rats' ECG: Paired t-tests of the ECG parameters at different times after administration of 2.0, 4.0, and 8.0 g / kg Dujing Capsules showed no significant differences (P>0.05) between the pre-administration and post-administration periods. This indicates that the 2.0-8.0 g / kg Dujing Capsules administered to rats did not significantly alter their ECG.

[0143] Effect on blood pressure in rats: Rats were administered 2.0, 4.0 and 8.0 g / kg of the capsule of the present invention by gavage, and the changes in blood pressure of each animal at various time points after administration were measured. Paired data t-test results showed that at various time points after gavage of the capsule of the present invention, the systolic blood pressure, diastolic blood pressure and mean arterial blood pressure of the rats in the three dosage groups were not statistically significantly different from those before administration (P>0.05), indicating that gavage of 2.0 g / kg to 8.0 g / kg of the capsule of the present invention had no significant effect on the blood pressure of rats.

[0144] Effects on the Respiratory System of Rats: Rats were administered 2.0, 4.0, and 8.0 g / kg of the capsule of the present invention by gavage. Tidal volume (VT), respiratory rate (RE), and minute ventilation (VE) of the rats were measured before and after administration. Paired t-tests revealed no significant differences between the values ​​measured at different times after administration and before administration (P>0.05). This indicates that gavage of 2.0-8.0 g / kg of the capsule of the present invention to rats had no significant effect on any of the respiratory parameters (TV, RE, and VE).

[0145] Effects on the psychoneurological system: After mice were gavaged with the capsule of the present invention at doses of 2.8, 5.6, and 11.2 g / kg and a solvent, the various parameters of the mice's spontaneous activity were measured. Oral administration of 2.8 g / kg of the capsule of the present invention had no significant effect on the mice's spontaneous activity. However, the number of spontaneous activities of mice in the 5.6 g / kg dose group increased significantly from 45 to 60 minutes after administration (P < 0.05); the total intensity of spontaneous activities increased significantly at 45 minutes (P < 0.01) and at 60 minutes (P < 0.05). Both of the above parameters began to recover after 120 minutes. The number of spontaneous activities and the total intensity of spontaneous activities of mice in the 11.2 g / kg dose group increased significantly 45 minutes after administration (P < 0.05); at 60 minutes, the number of spontaneous activities and the total intensity of spontaneous activities increased significantly (P < 0.01). Both of the above parameters began to recover after 120 minutes.

[0146] Effects of the present invention's capsules on general animal behavior: Rats: 2.8 g / kg to 11.2 g / kg of the present invention's capsules were administered gavagely. Each rat in each dose group was observed from the time of administration until 180 minutes after administration, and no abnormal behavior was observed. Mice: 2.8 g / kg to 11.2 g / kg of the present invention's capsules were administered gavagely. Their reactions were observed after administration. Mice in the low-dose group showed no abnormalities within 180 minutes of administration. Mice in the medium- and high-dose groups showed symptoms of excitement and agitation 45-60 minutes after administration, but gradually calmed down after 120 minutes.

[0147] Summary: After gavage administration of the present invention capsule to rats at doses of 2.8g / kg to 11.2g / kg, no significant changes were observed in the measured ECG, blood pressure, and respiratory parameters within 180 minutes. After gavage administration of the present invention capsule to mice in the 2.8g / kg dose group, no significant changes were observed in the measured parameters of spontaneous activity within 180 minutes. However, in the 5.6g / kg dose group, the number of spontaneous activities increased significantly 45-60 minutes after administration (P < 0.05); the total intensity of spontaneous activities increased significantly at 45 and 60 minutes (P < 0.01, P < 0.05). Both of these parameters began to recover after 120 minutes. In the 11.2g / kg dose group, the number of spontaneous activities and the total intensity of spontaneous activities increased significantly 45 minutes after administration (P < 0.05); at 60 minutes, the number of spontaneous activities and the total intensity of spontaneous activities increased significantly (P < 0.01). Both of the above parameters began to recover after 120 minutes; in short, the capsule of the present invention had no effect on the electrocardiogram, blood pressure and respiration of rats at a dose within the range of pharmacological effect, but the medium and high dose groups had a significant effect on the spontaneous activity of mice.

[0148] 2. Acute toxicity test

[0149] The maximum dosage experiment of the capsule of the present invention in mice: mice were gavaged with Dujing capsule three times a day, with a maximum dosage of 24g / kg (equivalent to 160 times the intended clinical dosage). At this dosage, only a temporary decrease in activity and diarrhea were observed after gavage, and no animals died.

[0150] Experimental results: Mice administered the capsule of the present invention at a dose of 24.0 g / kg showed a brief decrease in activity after gavage, which fully returned to normal after half an hour. On the second day of administration, traces of dried brown liquid were found on the body hair and anus, possibly due to brown stool. No mortality was observed during the 7-day observation period.

[0151] Calculation of maximum tolerated dose and multiples: The maximum dose in this experiment was 24.0 g / kg, which did not cause the death of mice. At this dose, the tolerable dose per mouse was approximately 0.48 g. The recommended clinical dosage of the capsule in this application is 9.0 g / day / person (60 kg). Calculate the maximum tolerated dose multiple.

[0152] The proposed clinical dosage of the capsule is 9.0 g, and the maximum dosage in mice is 24.0 g / kg (equivalent to 367.2 g / kg of crude drug), which is 160 times the proposed clinical dosage. At this dosage, only a temporary decrease in activity and diarrhea were observed.

[0153] The maximum dosage experiment of the capsule of the present invention in rats: The capsule of the present invention was gavaged (ig) three times a day to rats, with a maximum dosage of 30 g / kg (equivalent to 200 times the intended clinical dosage). At this dosage, only a temporary decrease in activity and diarrhea were observed in the rats after gavage, and no animals died.

[0154] Experimental results: Rats administered the capsule of the present invention, at a cumulative dose of 30.0 g / kg, experienced a brief decrease in activity after administration, which fully returned to normal after half an hour. On the second day of administration, traces of dried brown liquid were observed on the body hair and anus, possibly due to brown stool. No mortality was observed during the 7-day observation period.

[0155] Calculation of maximum tolerated dose and multiples: In this experiment, the cumulative dose of the capsule of the present invention was 30.0 g / kg, which did not cause death in rats. At this dose, each rat tolerated 6.0 g of the drug. The recommended clinical dosage of the capsule of the present invention is 9.0 g / day / 60 kg per person. The maximum tolerated dose multiples were calculated (in the formula, mice were replaced by rats, and the average body weight was 200 g).

[0156] The proposed clinical dosage of the capsule of the present invention is 9.0 g, and the maximum dosage for rats is 30.0 g / kg (equivalent to 459 g / kg of crude drug), which is 200 times the proposed clinical dosage. Only diarrhea is observed at this dosage.

[0157] 3. Long-term poisoning experiment

[0158] (1) Long-term toxicity test of the capsule of the present invention on rats: The capsule of the present invention was orally administered to Wistar rats at doses of 1.5 g / kg, 3.75 g / kg and 10 g / kg (equivalent to 10 times, 25 times and 67 times the clinically intended daily dose) for 1.5 months. Changes in the general conditions of the animals, such as body weight and food intake, as well as hematology, blood biochemistry, and pathological changes of various organs, were detected after administration and 2 weeks after drug withdrawal. The results are as follows:

[0159] General Condition: Some rats in the high-dose group showed symptoms such as decreased activity, loose stools, lethargy, erect piloerection, hunched backs, and weight loss. Rats in the medium-dose group showed no abnormal changes within one week of dosing. After the second week, some animals showed lethargy and weight loss, but the difference was not significant. No drug effects were observed in the low-dose group. After the fifth week, symptoms in the high-dose group were alleviated.

[0160] Hematological examination: After administration and 2 weeks after drug withdrawal, the hematological test values ​​were compared with those of the blank control group, and no significant differences were found (P>0.05).

[0161] Blood biochemical indices: After administration and 2 weeks after drug withdrawal, there was no significant difference in the blood biochemical indices compared with the blank control group (P>0.05).

[0162] Examination of organ coefficients: After drug administration and 2 weeks after drug withdrawal, there was no significant difference in organ coefficients between the two groups (P>0.05).

[0163] Pathological examination: No drug-induced organic lesions were found in each dosage group.

[0164] Conclusion: The oral administration of the capsule of the present invention to rats is safe at a dose equivalent to 25 times the clinical dosage.

[0165] (2) Long-term toxicity test of the capsules of the present invention on dogs: The capsules of the present invention were administered orally to dogs at doses of 0.75 g / kg, 2.25 g / kg, and 4.5 g / kg (equivalent to 5 times, 15 times, and 30 times the intended clinical daily dose) for 1.5 months. Changes in the body weight, appetite, and other general conditions of the animals, as well as blood biochemistry, hemogram, electrocardiogram, urinalysis, and pathological changes of various organs were measured after administration and 2 weeks after drug withdrawal. The results are as follows:

[0166] General Condition: During the dosing period, dogs in the high-dose group experienced salivation (foamy), 4 / 6 animals experienced vomiting and loose stools, and 5 / 6 animals experienced anorexia and decreased activity. Vomiting and loose stools gradually subsided with prolonged dosing. Dogs in the medium-dose group showed no outward symptoms within the first three days after dosing. On the fourth day, 1 / 6 animals experienced salivation and vomiting, and another 1 / 6 animals experienced salivation and vomiting in the third week. No abnormal changes were observed in the low-dose group. During the dosing period, the weight gain of dogs in the high-dose group was slower than that of the control group, which was more pronounced in the sixth week (P < 0.01). There was no significant difference in weight change between the medium-dose and low-dose groups and the blank control group (P > 0.05).

[0167] Hematological examination: After drug administration and 2 weeks after drug withdrawal, there was no significant difference in the hematological test values ​​between the drug administration group and the blank control group (P>0.05).

[0168] Blood biochemical indices: After administration and 2 weeks after drug withdrawal, there was no significant difference in the blood biochemical indices compared with the blank control group (P>0.05).

[0169] Electrocardiogram examination: After drug administration and 2 weeks after drug withdrawal, standard lead II ECG II waves, intervals and heart rate were measured. The results showed no significant difference between the drug administration groups and the blank control group (P>0.05).

[0170] Urine examination: After administration, the pH value, protein and glucose in urine were measured using triple urine test strips. The results showed no significant difference between the drug-treated groups and the blank control group (P>0.05).

[0171] Examination of organ coefficients: After drug administration and 2 weeks after drug withdrawal, there was no significant difference in organ coefficients between the two groups (P>0.05).

[0172] Pathological examination: No drug-induced organic lesions were found in each dosage group.

[0173] Conclusion: Oral administration of the capsule of the present invention to mixed breed dogs is safe at a dose equivalent to 15 times the clinical dosage.

[0174] (3) Drug dependence experiment

[0175] 1. Accelerated Withdrawal Experiment in Mice: The number of jumps and percentage weight loss after accelerated withdrawal in the morphine group were significantly different from those in the control group (P < 0.05), indicating that the mice developed a significant physical dependence on morphine. The mice in the three dose groups of the present invention capsule (cumulative daily doses of 51.9, 103.8, and 207.6 g crude drug / kg, respectively) showed no significant differences in either the number of jumps or the weight loss compared to the control group (P > 0.05), indicating that the mice did not develop a significant physical dependence on the capsule of the present invention.

[0176] 2. Natural withdrawal experiment in rats: After drug withdrawal, rats in the morphine group showed a significant decrease in body weight (P < 0.01). Their body weight did not return to pre-drug withdrawal levels until 7 days after withdrawal, indicating that the rats had developed a significant physical dependence on morphine. Rats in the three dose groups of the present invention's capsules (cumulative daily doses of 17.4, 69.3, and 103.8 g crude drug / kg, respectively) showed no significant decrease in body weight compared to the control group after drug withdrawal (P > 0.05), indicating that the rats had not developed a significant physical dependence on the capsules of the present invention.

[0177] 3. Rat Conditioned Place Preference Experiment: The rats in the morphine group spent significantly more time in the companion drug box than the control group (P < 0.01), indicating that the rats in the morphine group developed a significant conditioned place preference effect. The rats in the low-, medium-, and high-dose groups of the present invention's capsule (doses of 5.8, 23.1, and 34.6 g crude drug / kg, respectively) spent no significant difference in the duration of their stay in the companion drug box compared to the control group (P > 0.05), indicating that the rats did not develop a significant conditioned place preference effect for the present invention's capsule. This suggests that in this model, the present invention's capsules do not exhibit the potential to produce psychological dependence.

[0178] Experimental conclusion: The capsules of the present invention have no potential to cause physical dependence and mental dependence.

[0179] In summary, the present invention provides a traditional Chinese medicine composition for drug rehabilitation, which can be used as a drug rehabilitation drug completely independently without the need for any Western medicine. At the same time, it has a good drug rehabilitation effect, can achieve the purpose of detoxification through treatment, and is highly safe, suitable for industrial mass production, and has practical application value.

[0180] Various embodiments of the present invention may be presented in the form of a range; it should be understood that the description in a range format is only for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention; therefore, the range description should be considered to have specifically disclosed all possible subranges and single numerical values ​​within the range. For example, the description of a range from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the range, such as 1, 2, 3, 4, 5, and 6, regardless of the range. In addition, whenever a numerical range is indicated herein, it is intended to include any cited numeral (fractional or integer) within the indicated range. The foregoing description is intended only to provide specific embodiments of the present invention, which will enable those skilled in the art to understand and implement the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not intended to be limited to the embodiments shown herein, but is intended to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A Chinese medicine composition for drug addiction treatment, characterized in that: The Chinese medicine composition for drug addiction treatment comprises the following components in parts by weight: 4-5 parts of ginseng, 7-8 parts of angelica, 9-11 parts of St. John's wort, 10-12 parts of summer dwarf, 4-5 parts of rhubarb, 2-3 parts of cloves, 3-4 parts of sour jujube kernel, 6.5-7.5 parts of julibrissin, and 3.5-4.5 parts of liquorice.

2. The Chinese medicine composition for drug addiction treatment according to claim 1, wherein The Chinese medicine composition for drug addiction treatment comprises the following components in parts by weight: 4.4 parts of ginseng, 7.2 parts of angelica, 10 parts of St. John's wort, 11 parts of summer nectarine, 4.4 parts of rhubarb, 2.2 parts of cloves, 3.4 parts of spinach seeds, 6.8 parts of jujube flowers and 3.8 parts of liquorice.

3. A method for preparing the Chinese medicine composition for drug addiction treatment according to any one of claims 1 to 2, characterized in that: The preparation method comprises the following steps: Step (1): adding angelica and cloves to water for steam distillation extraction to separate and obtain volatile oil, first medicinal residue and steam distillate; Step (2): adding rhubarb to ethanol for a first reflux extraction, followed by filtering, concentrating, drying, crushing and sieving to obtain dry paste powder A; Step (3): adding the summer ginseng and 3.3 to 4.2 parts by weight of ginseng to ethanol for a second reflux extraction, followed by filtering to obtain a first filtrate and a second medicinal residue; crushing and grinding the remaining ginseng and sieving to obtain ginseng powder; Step (4): adding the first medicinal residue, the second medicinal residue, liquorice, spinach seeds, and jujube flowers into water for decoction, combining the resulting decoction with the steam distillate, filtering and concentrating to obtain a mixture with a relative density of 1.15-1.20; adding ethanol to the mixture to adjust the alcohol content to 55%-65% (V / V), allowing the mixture to stand, combining the supernatant with the first filtrate, filtering, concentrating, drying, and pulverizing and sieving to obtain a dry paste powder B; Step (5): St. John's wort extract, the dry paste powder A, the dry paste powder B and the ginseng powder are mixed to obtain a mixed powder, and then ethanol is added to granulate the mixed powder, dried, sprayed with the volatile oil, sealed, and stored to obtain the Chinese medicine composition.

4. The method for preparing the Chinese medicine composition for drug addiction treatment according to claim 3, wherein: The working parameters of the steam distillation extraction include: the weight of the added water is 8 to 12 times the total weight of the angelica and cloves, and the extraction time is 4 to 6 hours; the working parameters of the decoction include: the decoction time is 1 to 3 hours, the weight of the added water is 8 to 14 times the total weight of the added Chinese medicinal materials, and the number of decoctions is 1 to 3 times.

5. The method for preparing the Chinese medicine composition for drug addiction treatment according to claim 3, wherein: The working parameters of the first reflux extraction include: the volume fraction of ethanol is 80%-90%, the number of extractions is 1 to 3 times, the extraction time is 0.4-1.5 hours each time, and the reflux extraction temperature is 60-70°C each time; the working parameters of the second reflux extraction include: the volume fraction of ethanol is 75%-85%, the added weight of ethanol is 7-12 times the total weight of the summer melon and the ginseng, the number of extractions is 1 to 3 times, the extraction time is 1-4 hours each time, and the reflux extraction temperature is 60-70°C each time.

6. The method for preparing the Chinese medicine composition for drug addiction treatment according to claim 3, wherein: Preparation method of St. John's wort extract The method comprises the following steps: adding St. John's wort to ethanol for alcohol extraction 1 to 3 times, then concentrating, drying, crushing and screening to obtain the St. John's wort extract. The extraction process of St. John's wort comprises the following steps: adding ten times the amount of 70% ethanol to a decoction, soaking for half an hour, and then decocting for one hour; filtering, adding eight times the amount of ethanol and decocting for one hour; combining the two decoctions, recovering the ethanol, and mixing with the above materials for drying.

7. Use of the traditional Chinese medicine composition for drug addiction treatment according to any one of claims 1 to 2, and / or the traditional Chinese medicine composition prepared by the preparation method according to any one of claims 3 to 6 in the preparation of drugs for drug addiction treatment.

8. A Chinese medicine capsule preparation for drug addiction treatment, characterized in that: The Chinese medicine capsule preparation for drug addiction treatment comprises the Chinese medicine composition for drug addiction treatment according to any one of claims 1 to 2, and / or the Chinese medicine composition prepared by the preparation method according to any one of claims 3 to 6.

9. The Chinese medicine capsule preparation for drug addiction treatment according to claim 8, characterized in that: The traditional Chinese medicine capsule preparation also includes pharmaceutical excipients.

10. The Chinese medicine capsule preparation for drug addiction treatment according to claim 9, characterized in that: The pharmaceutical excipients include magnesium stearate.