Extract with pharmaceutical detoxification effect and manufacturing process for it

Abstract

A method for producing an extract with pharmaceutical detoxification properties, characterized in that the manufacturing process comprises the following steps: S1: Remove impurities from Agrigremax agrestis, break down to 20 mesh and keep as a reserve; S2: Feeding Agrigremax agrestis processed in step S1 into an extractor for supercritical CO2 extraction and extraction, wherein the extraction pressure is 25 kPa, the temperature is 65 °C, the flow rate is 400 to 500 PV, and the extraction time is 4 hours to produce and hold the extract; S3: Adding potassium hydroxide and deionized water to the extract obtained in step S2, stirring to a uniform state with a weight ratio of extract, potassium hydroxide and deionized water of 1 : 1 : 1.5; heating and stirring so that a saponification reaction occurs, the heating temperature being 85 to 100°C and the reaction time being 2 hours to obtain the reaction liquid A, which is stored, cooled and kept ready; S4: Four additions of ethyl acetate to the reaction liquid A prepared in step S3 and extraction, the amount of ethyl acetate added each time being three times the amount of reaction liquid A, washing the ethyl acetate solution layer formed six to seven times with deionized water until the washing liquid is neutral (pH = 7), separation of the ethyl acetate solution, recovery of ethyl acetate under reduced pressure, concentration to a thick paste A and storage of the thick paste A obtained; S5: Adding the thick paste A obtained in step 4 to methanol, wherein the amount of methanol is five times the amount of thick paste A; heating, dissolving and filtering, cooling and storing for 48 hours, crystallizing and precipitating to obtain crystals A, drying the crystals A under reduced pressure, wherein the drying temperature is not more than 60°C to produce the extract with pharmaceutical detoxifying effect.

Description

TECHNICAL AREA

[0001] The present invention relates to biomedicine, in particular an extract with pharmaceutical detoxification effect and a manufacturing process for it. STATE OF THE ART

[0002] Drugs include anesthetics and psychotropic medications, which can cause addiction and seriously damage human bodily functions, health, and social environments. Currently, the number of drug users is increasing, and they are getting younger and younger; in China alone, there are more than 14 million drug users, and worldwide, the figure is between 200 and 400 million. The types of drugs are becoming increasingly diverse, ranging from opium and cannabis to heroin, potassium powder, and nitroglycerin, among others.

[0003] Detoxification and drug prohibition have always been a global problem, and so far there has been no good solution. Global detoxification methods are either mandatory detoxification or detoxification through alternative treatments involving intoxication. Mandatory detoxification is both painful and strenuous, and lengthy. In alternative treatments, such as with methadone and naltrexone, one drug replaces another, or the opioid receptors are temporarily blocked. However, people cannot be completely freed from drugs, both physically and psychologically. Rebound and relapse can easily occur, just as in the treatment of alcohol addiction with low-alcohol alcohol, a highly addictive drug is simply replaced by drugs that are only mildly addictive.

[0004] For centuries, people have searched for a safe and non-addictive detoxification medication, but so far without success. Therefore, it is of great importance to research a drug that has a detoxifying effect while preventing drug users from experiencing a rebound effect and relapse.

[0005] In the field of natural product extraction and pharmaceutical application, various biologically active components and their processing technologies have been investigated in the past. For example, CN103610699 A and CN102631371 A disclose extraction methods of active components from land snails and their application in drugs against lung cancer using membrane separation and column chromatography technologies. CN 103450310 A deals with stigmasterol derivatives for the development of cancer drugs and demonstrates the efficacy of modifications of plant sterols. CN 102697814 A relates to a drug for the treatment of hepatitis B extracted from natural sources using ultrafiltration and deproteinization processes.WO01 / 32031A2 describes cholesterol-lowering compositions based on phytosterols and surfactants and illustrates the application of plant sterols in functional formulations. Rice Bran Processing Technology (authored by He Dongping and Xiang Hai, published by China Light Industry Press in 2014) discusses extraction technologies for oryzanol, calcium phytate, and rice bran sterols, highlighting the use of natural components in rice bran. SUBJECT OF THE PRESENT INVENTION

[0006] The present invention is based on the objective of providing an extract with pharmaceutical detoxification effect and a manufacturing process for it in order to solve the problem of currently existing detoxification methods that the detoxification effect is not good and a rebound and a relapse can easily occur.

[0007] This problem is solved by a method having the features of claim 1 or 2 and an extract having the features of claim 5.

[0008] The dependent claims are directed to features of preferred embodiments of the invention.

[0009] The present invention has the following advantages: The extract produced according to the present invention, which has a pharmaceutical detoxifying effect, possesses a sedative and hypnotic function without causing physical or psychological dependence. It inhibits excitability caused by morphine and benzedrine and promotes detoxification. After 7 to 15 days of drug administration, the goal of physiological detoxification can be achieved, and a rebound effect will not occur. DETAILED DESCRIPTION

[0010] In connection with fully described embodiments, the present invention is explained in more detail below. It should be noted that the following explanation is only exemplary and does not limit the scope and application of the present invention. Example 1:

[0011] An extract with pharmaceutical detoxifying properties, the main component comprising the following chemical structural features: a cholesteryl compound with a hydroxyl at position 3 and a double bond between positions 5 and 6, structurally characterized by:

[0012] The cholesteryl compound includes β-sitosterol, structurally characterized by R=, or cholesterol, structurally characterized by

[0013] The extract can be obtained by extraction from Agrigremax agrestis, where Agrigremax agrestis comprises one of Limax maximus L., L. flavus L., Agriolimax agrestis L. and Phiolomycus bilineatus.

[0014] The manufacturing process for the extract with pharmaceutical detoxification effect comprises the following steps: S1: Remove impurities from Agrigremax agrestis, break down to 20 mesh and keep as a reserve; S2: Adding 60 kg of Agrigremax agrestis processed in step S1 to a supercritical CO2 extractor and extracting, with an extraction pressure of 25 kPa, a temperature of 65°C, a flow rate of 400 PV and an extraction time of 4 hours, to produce and hold 3.5 kg of oily extract; S3: Adding potassium hydroxide and deionized water to the extract obtained in step S2, stirring to a uniform state with a weight ratio of extract, potassium hydroxide and deionized water of 1:1:1.5. 3.5 kg of extract, 3.5 kg of potassium hydroxide and 5.25 kg of deionized water are placed together in a reactor, heated and stirred so that a saponification reaction occurs, the heating temperature being 85°C and the reaction time being 2 hours to obtain the reaction liquid, which is stored, cooled and kept ready; S4: Adding the reaction liquid prepared in step 3 to an extraction vessel, adding ethyl acetate four times and extracting, with the amount of ethyl acetate added each time being 36.75 kg, washing the ethyl acetate solution layer formed six times with deionized water until the washing liquid is neutral (pH=7), separating the ethyl acetate solution, recovering ethyl acetate under reduced pressure, concentrating to a thick paste of 0.6 kg and keeping ready; S5: Add the thick paste obtained in step 4 to 3.0 kg of methanol, heat, dissolve and filter while warm, cool and store for 48 hours, crystallize and precipitate to obtain crystals, vacuum dry the crystals under reduced pressure, ensuring the drying temperature does not exceed 60°C, to produce 267 g of extract with pharmaceutical detoxifying action.

[0015] The extract can be used to develop detox drugs and detox foods and can be processed into drinks, tablets or capsules. Example 2:

[0016] An extract with pharmaceutical detoxifying properties, wherein the main component comprises the following chemical structural features: a cholesteryl compound with a hydroxyl group at position 3, a double bond between positions 5 and 6, and a double bond between positions 22 and 23, structurally characterized by: The cholesteryl compound comprises rapeseed sterol, structurally characterized by: or stigmasterol, structurally characterized by:

[0017] The extract can be obtained by extraction from Agrigremax agrestis, wherein Agrigremax agrestis comprises one of Limax maximus L., L. flavus L., Agriolimax agrestis L. and Phiolomycus bilineatus.

[0018] The manufacturing process for the extract with pharmaceutical detoxification effect comprises the following steps: S1: Remove impurities from Agrigremax agrestis, break down to 20 mesh and keep as a reserve; S2: Adding 60 kg of Agrigremax agrestis processed in step S1 to a supercritical CO2 extractor and extracting, with an extraction pressure of 25 kPa, a temperature of 65°C, a flow rate of 500 PV and an extraction time of 4 hours, to produce and hold 3.5 kg of oily extract; S3: Adding potassium hydroxide and deionized water to the extract obtained in step S2, stirring to a uniform state with a weight ratio of extract, potassium hydroxide and deionized water of 1:1:1.5. 3.5 kg of extract, 3.5 kg of potassium hydroxide and 5.25 kg of deionized water are placed together in a reactor, heated and stirred so that a saponification reaction occurs, the heating temperature being 100°C and the reaction time being 2 hours to obtain the reaction liquid, which is stored, cooled and kept ready; S4: Adding the reaction liquid prepared in step 3 to an extraction vessel, adding ethyl acetate four times and extracting, with the amount of ethyl acetate added each time being 36.75 kg, washing the ethyl acetate solution layer formed seven times with deionized water until the washing liquid is neutral (pH=7), separating the ethyl acetate solution, recovering ethyl acetate under reduced pressure, concentrating to a thick paste of 0.6 kg and keeping ready; S5: Add the thick paste obtained in step 4 to 3.0 kg of methanol, heat, dissolve and filter while warm, cool and store for 48 hours, crystallize and precipitate to obtain crystals, vacuum dry the crystals under reduced pressure, ensuring the drying temperature does not exceed 60°C, to produce 267 g of extract with pharmaceutical detoxifying action.

[0019] The extract can be used to develop detox drugs and detox foods and can be processed into drinks, tablets or capsules. Example 3:

[0020] An extract with pharmaceutical detoxifying properties, wherein the main component comprises the following chemical structural features: a cholesteryl compound with a hydroxyl group at position 3 and a double bond between positions 5 and 6, structurally characterized by: The cholesteryl compound comprises β-sitosterol, structurally characterized by, or cholesterol, structurally characterized by

[0021] The extract can be obtained by extraction from Agrigremax agrestis, wherein Agrigremax agrestis comprises one of Limax maximus L., L. flavus L., Agriolimax agrestis L. and Phiolomycus bilineatus.

[0022] The manufacturing process for the extract with pharmaceutical detoxification effect comprises the following steps: Step 1: Remove impurities from Agrigremax agrestis, break it down to 20 mesh and keep it as a reserve; Step 2: Weighing 100 kg of Agrigremax agrestis processed in Step 1 and adding it to a multifunctional extraction vessel; adding the solvent under reflux and extracting twice, the first time adding 1000 kg of solvent, extracting for 1.5 hours under reflux and filtering to obtain extraction liquid A; and the second time adding 800 kg of solvent, extracting for 1.0 hour under reflux and filtering to obtain extraction liquid B; mixing extraction liquid A and extraction liquid B, recovering solvent under reduced pressure to obtain an oily, thick paste A of 8.1 kg, and holding it ready; Step 3: Add potassium hydroxide and deionized water to the thick paste A obtained in step 2, stirring to a uniform consistency with a weight ratio of 1:1:1.5 between thick paste B, potassium hydroxide, and deionized water. 8.1 kg of the thick paste, 8.1 kg of potassium hydroxide, and 12.2 kg of deionized water are placed together in a reactor, heated and stirred to initiate a saponification reaction. The heating temperature is 85°C and the reaction time is 2 hours to obtain the reaction liquid, which is then stored, cooled, and kept ready for use. Step 4: Adding the reaction liquid prepared in step 3 to an extraction vessel, adding ethyl acetate four times and extracting four times, the amount of ethyl acetate added each time being 85.2 kg, washing the ethyl acetate solution layer formed six times with deionized water until the washing liquid is neutral (pH=7), separating the ethyl acetate solution, recovering ethyl acetate under reduced pressure, concentrating to a thick paste B of 1.56 kg and keeping it ready; Step 5: Add the thick paste B obtained in step 4 to 7.8 kg of methanol, heat, dissolve and filter while warm, cool and store for 48 hours, crystallize and precipitate to obtain crystals, vacuum dry the crystals under reduced pressure, ensuring the drying temperature does not exceed 60°C, to produce 445 g of extract with pharmaceutical detoxifying properties.

[0023] The solvent in step 2 comprises one or two of n-hexane, ethanol, methanol, oil, gasoline, petroleum ether, diethyl ether and ethyl acetate.

[0024] The extract can be used to develop detox drugs and detox foods and can be processed into drinks, tablets or capsules. Example 4:

[0025] An extract with pharmaceutical detoxifying properties, wherein the main component comprises the following chemical structural features: a cholesteryl compound with a hydroxyl group at position 3 and a double bond between positions 5 and 6, structurally characterized by: The cholesteryl compound comprises β-sitosterol, structurally characterized by, or cholesterol, structurally characterized by

[0026] The extract can be obtained by extraction from Agrigremax agrestis, wherein Agrigremax agrestis comprises one of Limax maximus L., L. flavus L., Agriolimax agrestis L. and Phiolomycus bilineatus.

[0027] The manufacturing process for the extract with pharmaceutical detoxification effect comprises the following steps: Step 1: Remove impurities from Agrigremax agrestis, break it down to 20 mesh and keep it as a reserve; Step 2: Weighing 150 kg of Agrigremax agrestis processed in Step 1 and adding it to a multifunctional extraction vessel; adding mixed solvent chloroformacetone (chloroform:acetone 1:1) under reflux and extracting twice, the first time with 1500 kg of solvent added, extracting for 1.5 hours under reflux and filtering to obtain extraction liquid A; the second time with 1200 kg of solvent added, extracting for 1.0 hour under reflux and filtering to obtain extraction liquid B; mixing extraction liquid A and extraction liquid B, recovering chloroformacetone under reduced pressure to obtain 18.6 kg of an oily, thick paste A, and holding it ready; Step 3: Add potassium hydroxide and deionized water to the thick paste A obtained in step 2, stirring to a uniform consistency with a weight ratio of 1:1:1.5 between thick paste B, potassium hydroxide, and deionized water. 18.6 kg of the thick paste, 18.6 kg of potassium hydroxide, and 27.9 kg of deionized water are placed together in a reactor, heated and stirred to initiate a saponification reaction. The heating temperature is 100°C and the reaction time is 4 hours to obtain the reaction liquid, which is then stored, cooled, and kept ready. Step 4: Adding the reaction liquid prepared in step 3 to an extraction vessel, adding ethyl acetate four times and extracting, with the amount of ethyl acetate added each time being 195.3 kg, washing the ethyl acetate solution layer formed seven times with deionized water until the washing liquid is neutral (pH=7), separating the ethyl acetate solution, recovering ethyl acetate under reduced pressure, concentrating to a thick paste B of 2.7 kg and keeping it ready; Step 5: Add the thick paste B obtained in step 4 to 13.5 kg of methanol, heat, dissolve and filter while warm, cool and store for 48 hours, crystallize and precipitate to obtain crystals, vacuum dry the crystals under reduced pressure, ensuring the drying temperature does not exceed 60°C, to produce 692 g of extract with pharmaceutical detoxifying properties.

[0028] The extract can be used to develop detox drugs and detox foods and can be processed into drinks, tablets or capsules.

[0029] To verify the pharmaceutical detoxification efficacy of the extract of Agrigremax agrestis, the present invention carried out the following experiments: Attempt 1

[0030] Fifty Sprague-Dawley rats, half male and half female, were randomly assigned to five groups. Group 1 served as a blinded control group and received a subcutaneous injection of normal saline. For the remaining groups (2-5), a morphine-dependent rat model was replicated using a dose-increase procedure. Morphine hydrochloride was injected subcutaneously every 12 hours, starting with an initial dose of 5 mg / kg. This dose was successively increased to 80 mg / kg and continued until day seven. The injection volume was 0.2 mL / 100 g, and the administration volume was the same for each group. On day eight, morphine was discontinued, and a naloxone withdrawal test was performed.Each group received different treatments: Group 1 – the blind control group – received the same volume of normal saline solution; Group 2 – the morphine model group – received the same volume of normal saline solution; Group 3 – the positive drug control group – received methadone at a dose of 20 mg / kg; Groups 4 and 5 were the low- and high-dose groups of the Agrigremax agrestis extract prepared according to the present invention, with doses of the Agrigremax agrestis extract of 0.3 g / kg and 0.6 g / kg, respectively. These doses were administered continuously to each group of rats for 3 days. The rats drank water and ate freely. On the first and third days of treatment, the 5 mg / kg rats received naloxone 45 minutes after administration. The withdrawal response of the rats within 30 minutes and changes in body weight before and after (1 hour) administration were observed.The results are shown in the following table:. Table 1 - Values ​​of the withdrawal syndrome in morphine-dependent rats Day 1 Day 3 Blind control group 4,5+3,88 1,4+1,69 Morphine model group 81,3+32,11 44,5+8,09 Positive Drug Control Group 49,35+14,41 35,6+18,73 group with low dose of the extract of Agrigremax agrestis 74,9+42,03 25,5+12,26 Group with high dose of the extract of Agrigremax agrestis 53,8+16,23 22,1+10,90

[0031] The data in the table show that the extract of Agrigremax agrestis can inhibit the withdrawal syndrome of morphine-dependent rats, while the severity of the withdrawal syndrome in the high-dose group is significantly lower than in the model group. Table 2 - Body weight difference value of the rats in the respective groups (body weight before administration - body weight after administration) Day 1 (g) Day 3 (g) Blind control group 0,5+3,20 1,0+1,05 Morphine model group 10,5+5,48 3,6+2,41 Positive Drug Control Group 15,6+6,39 2,6+2,75 group with low dose of the extract of Agrigremax agrestis 11,8+3,25 4,5+2,59 Group with high dose of the extract of Agrigremax agrestis 14,7+4,08 1,9+2,13

[0032] The data in the table show that the two doses of the extract of Agrigremax agrestis had no significant effect on the body weight loss of the morphine-dependent rats. Attempt 2

[0033] Fifty Kunming mice, half male and half female, were randomly assigned to five groups. Group 1 served as a blind control group and received a subcutaneous injection of normal saline. For the remaining groups (2-5), a morphine-dependent rat model was replicated using a dose-increase procedure. Morphine was administered subcutaneously twice daily, once every 12 hours. The initial dose was 25 mg / kg, increasing daily to 160 mg / kg by day six. The injection volume was 0.2 ml / 100 g, and the administration volume was the same for each group. On day seven, morphine administration was stopped, and a naloxone withdrawal test was performed.Each group received different treatments: Group 1 – the blind control group – was administered the same volume of vegetable oil; Group 2 – the morphine model group – was administered the same volume of vegetable oil; Group 3 – the positive drug control group – was administered 20 mg / kg of methadone; Groups 4 and 5 were the low- and high-dose groups of the Agrigremax agrestis extract produced according to the present invention, with doses of the Agrigremax agrestis extract of 0.4 g / kg and 0.8 g / kg, respectively. These doses were administered continuously to each group for 3 days. The rats drank water and ate freely. One hour after administration on the first and third days of treatment, the rats received 8 mg / kg of naloxone. The mice's jumping response within 30 minutes and changes in body weight before and after administration were observed.The results are shown in the following table:. Table 3 - Number of withdrawal jump reactions in morphine-dependent mice Day 1 (Times / 30 min) Day 3 (Times / 30 min) Blind control group 0,4+0,699 0,5+0,84 Morphine model group 63,2+14,65 12,5+6,09 Positive Drug Control Group 25,1+6,9 22,9+6,81 group with low dose of the extract of Agrigremax agrestis 13,5+10,29 6,2+5,86 Group with high dose of the extract of Agrigremax agrestis 35,0+12,28 8,5+2,68

[0034] The data in the table show that the extract of Agrigremax agrestis has a treatment function for the withdrawal syndrome of morphine-dependent mice and can inhibit the jump reaction in the withdrawal syndrome of morphine-dependent mice. Table 4 - Body weight difference value of the mice in the respective groups (body weight before administration - body weight after administration) Day 1 (g) Day 3 (g) Blind control group 0,19+0,17 0,34+0,31 Morphine model group 0,53+0,19 0,55+0,29 Positive Drug Control Group 0,22+0,19 0,46+0,23 group with low dose of the extract of Agrigremax agrestis 0,18+0,13 0,36+0,28 Group with high dose of the extract of Agrigremax agrestis 0,26+0,21 0,43+0,23

[0035] The data in the table shows that the extract of Agrigremax agrestis can promote recovery from weight loss in morphine-dependent mice. Attempt 3

[0036] Forty Kunming mice, half male and half female, were taken and fasted for 12 hours with unlimited access to drinking water. The mice were randomly assigned to four groups: a blind control group, a group receiving a low dose of the Agrigremax agrestis extract prepared according to the present invention (0.4 g / kg), a group receiving a high dose of the Agrigremax agrestis extract prepared according to the present invention (0.8 g / kg), and a drug-positive control group (estazolam 2 mg / kg). Each group of mice was placed in the YLS-1A multifunctional small animal recorder, which, after a 5-minute calibration period, measured the number of spontaneous activities of the mice before administration. The recording time was 10 minutes. Each group of mice was administered the above dose, and the mice in the blind control group received an equal volume of normal saline solution intragastrically.Each mouse was injected intraperitoneally with morphine (10 mg / kg) 30 minutes after administration. After 15 minutes, the mice were placed in a recorder to observe and record the number of activity events within 10 minutes. The results are shown in the following table. Table 5 - Influence of the extract of Agrigremax agrestis on morphine-induced excitability Number of activities before administration (times / min) Number of activities after administration (times / min) Blind control group 164,1+32,41 217,5+23,79 group with low dose of the extract of Agrigremax agrestis 191,5+35,53 102,0+46,29 Group with high dose of the extract of Agrigremax agrestis 185,4+36,93 112,7+23,04 Positive drug control group 171,2+38,94 67,9+40,31

[0037] The data in the table shows that the extract of Agrigremax agrestis has a certain inhibitory effect on the increase in excitability induced by morphine. Attempt 4

[0038] Forty Kunming mice, half male and half female, were taken and fasted for 12 hours with unlimited access to drinking water. The mice were randomly assigned to four groups: a blind control group, a group receiving a low dose of the Agrigremax agrestis extract prepared according to the present invention (0.4 g / kg), a group receiving a high dose of the Agrigremax agrestis extract prepared according to the present invention (0.8 g / kg), and a drug-positive control group (estazolam 2 mg / kg). Each group of mice was placed in the YLS-1A multifunctional small animal recorder, which, after a 5-minute calibration period, measured the number of spontaneous activities of the mice before administration. The recording time was 10 minutes. Each group of mice received the above dose intragastrically, and the mice in the blind control group received an equal volume of normal saline solution intragastrically.Each mouse was injected intraperitoneally with amphetamine (8 mg / kg) 30 minutes after administration. After 15 minutes, the mice were placed in a recorder to observe and record the number of activity events within 10 minutes. The results are shown in the following table. Table 6 - Influence of Agrigremax agrestis extract on amphetamine-induced excitability Number of activities before administration (times / min) Number of activities after administration (times / min) Blind control group 162,3+40,50 233,9+56,445 group with low dose of the extract of Agrigremax agrestis 192,0+45,06 130,6+32,11 Group with high dose of the extract of Agrigremax agrestis 197,4+39,30 132,6+26,26 Positive drug control group 183,7+32,99 83,0+40,14

[0039] The data in the table shows that the extract of Agrigremax agrestis has a certain inhibitory effect on the increase in excitability induced by amphetamine. Attempt 5

[0040] Forty Kunming mice, half male and half female, were taken and fasted for 12 hours with unlimited access to drinking water. The mice were randomly assigned to four groups: a blind control group, a group receiving a low dose of the Agrigremax agrestis extract prepared according to the present invention (0.4 g / kg), a group receiving a high dose of the Agrigremax agrestis extract prepared according to the present invention (0.8 g / kg), and a drug-positive control group (estazolam at 2 mg / kg). Each group was given the above dose, and the mice in the blind control group were given an equal volume of normal saline solution.After 45 minutes, each group of mice received 50 mg / kg of pentobarbital sodium, and then the sleep time of each group of mice was recorded (the disappearance of the righting reflex after administration represents the sleep onset time; the time from the disappearance of the righting reflex until its reappearance represents the sleep time). The results are shown in the following table. Table 7 - Influence of Agrigremax agrestis extract on sleep time after administration of pentobarbital sodium Sleep duration of mice (min) Blind control group 25,8+5,01 Group with low dose of Agrigremax agrestis extract 39,5+11,46 Group with high dose of Agrigremax agrestis extract 32,8+9,56 Positive drug control group 66,22+13,77

[0041] The data in the table show that the extract of Agrigremax agrestis can prolong the sleep time of mice after administration of a threshold dose of pentobarbital sodium. Attempt 6

[0042] Thirty Sprague-Dawley rats, half male and half female, were taken and randomly assigned to three groups: a control group receiving morphine, a group receiving Agrigremax agrestis extract, and a drug-negative control group. Each group consisted of 10 animals. A dose-escalation procedure was used for both the morphine control group and the Agrigremax agrestis extract group. In the morphine control group, morphine hydrochloride was injected twice daily. Following the dose-escalation principle, the morphine dose was increased from 5 mg / kg to 60 mg / kg by day seven. In the control group, the Agrigremax agrestis extract was administered intragastrically twice daily, starting at 0.5 g / kg and increasing daily to 3.0 g / kg until day seven.For the negative control group, the same volume of vegetable oil was administered daily. The administration time and number of doses were the same as for the group receiving the Agrigremax agrestis extract. On day eight, each group of rats received 5 mg / kg of naloxone. The rats' withdrawal response was observed within 30 minutes of withdrawal, and changes in body weight were recorded one hour before and after withdrawal. The results are shown in the following table. Table 8 - Influence of the extract of Agrigremax agrestis on the sleep time of mice after administration of pentobarbital sodium Note on the withdrawal reaction Value of body weight loss (g) Negative drug control group 2,9+2,24 0,2+3,39 Morphine control group 76,9+14,53 9,5+3,62 Group of extract of Agrigremaxagrestis 7,2+3,37 1,1+2,46

[0043] Weight loss is an important indicator of opioid addiction and withdrawal. The data in the table show that the morphine-dependent rats suffered significant weight loss during withdrawal, while the group given the Agrigremax agrestis extract did not experience significant weight loss, suggesting that the Agrigremax agrestis extract did not have body-dependent properties.

[0044] The data in the table showed that withdrawal in morphine-dependent rats was accompanied by significant weight loss, while the sputum extract group did not show significant weight loss, suggesting that the sputum extract did not have any psychoactive properties. The extract is safe in terms of acute toxicity and does not cause physical or psychological dependence. In the future, the extract could be used for the development of food and pharmaceutical products and processed into beverages, tablets, or capsules.

[0045] The foregoing description refers only to a detailed explanation of the present invention in connection with the preferred embodiments described in detail, and the embodiment of the present invention is not limited to such embodiments. A person skilled in the art in the field of the present invention may implement several substitutions or variations for the described embodiments without departing from the concept of the present invention, and these shall be considered to be covered by the scope of protection of the present invention.

Claims

[1] Method for producing an extract with pharmaceutical detoxifying effect, characterized by that the manufacturing process includes the following steps: S1: Remove impurities from Agrigremax agrestis, break down to 20 mesh and keep as a reserve; S2: Feeding Agrigremax agrestis processed in step S1 into an extractor for supercritical CO2 extraction and extraction, wherein the extraction pressure is 25 kPa, the temperature is 65 °C, the flow rate is 400 to 500 PV, and the extraction time is 4 hours to produce and hold the extract; S3: Adding potassium hydroxide and deionized water to the extract obtained in step S2, stirring to a uniform state with a weight ratio of extract, potassium hydroxide and deionized water of 1 : 1 : 1.5; heating and stirring so that a saponification reaction occurs, the heating temperature being 85 to 100°C and the reaction time being 2 hours to obtain the reaction liquid A, which is stored, cooled and kept ready; S4: Fourfold addition of ethyl acetate to the reaction liquid A prepared in step S3 and extraction, wherein the amount of ethyl acetate added each time is three times the amount of reaction liquid A, washing of the ethyl acetate solution layer formed six to seven times with deionized water until the washing liquid is neutral (pH = 7), separation of the ethyl acetate solution, recovery of ethyl acetate under reduced pressure, concentration to a thick paste A and storage of the thick paste A obtained; S5: Adding the thick paste A obtained in step 4 to methanol, wherein the amount of methanol is five times the amount of thick paste A; heating, dissolving and filtering, cooling and storing for 48 hours, crystallizing and precipitating to obtain crystals A, drying the crystals A under reduced pressure, wherein the drying temperature is not more than 60°C to produce the extract with pharmaceutical detoxifying effect. [2] Method for producing an extract with pharmaceutical detoxifying effect, characterized by that the manufacturing process includes the following steps: Step 1: Remove impurities from Agrigremax agrestis, break it down to 20 mesh and keep it as a reserve; Step 2: Feeding the Agrigremax agrestis processed in Step 1 into a multifunctional extraction vessel, adding a solvent under reflux, and extracting twice, the first time with a solvent volume ten times the volume of Agrigremax agrestis, extracting under reflux for 1.5 hours and filtering to obtain extraction liquid A; and the second time with a solvent volume eight times the volume of Agrigremax agrestis, extracting under reflux for 1.0 hour and filtering to obtain extraction liquid B; mixing extraction liquid A and extraction liquid B, recovering solvent under reduced pressure to obtain a thick paste B, and storing the thick paste B; Step 3: Add potassium hydroxide and deionized water to the thick paste B obtained in step 2, stir to a uniform consistency with a weight ratio of thick paste B, potassium hydroxide and deionized water of 1 : 1 : 1.5; heat and stir to initiate a saponification reaction, the heating temperature being 85 to 100°C and the reaction time being 2 to 4 hours to obtain the reaction liquid B, which is stored, cooled and kept ready; Step 4: Add ethyl acetate four times to the reaction liquid B prepared in step 3 and extract, the amount of ethyl acetate added each time being three times the amount of reaction liquid B, wash the ethyl acetate solution layer formed six to seven times with deionized water until the washing liquid is neutral (pH = 7), separate the ethyl acetate solution, recover ethyl acetate under reduced pressure, concentrate to a thick paste C and keep the thick paste C ready; Step 5: Add the thick paste C obtained in step 4 to methanol, wherein the amount of methanol is five times the amount of thick paste C, heat, dissolve and filter, cool and store for 48 hours, crystallize and precipitate to obtain crystals B, dry the crystals B under reduced pressure, wherein the drying temperature is not more than 60°C to produce the extract with pharmaceutical detoxifying effect. [3] Method for producing an extract with pharmaceutical detoxification effect according to claim 2, characterized by , that the solvent in step 2 comprises one or two of n-hexane, ethanol, methanol, acetone, chloroform, oil, gasoline, petroleum ether, diethyl ether and ethyl acetate. [4] Method for producing an extract according to the preceding claims, characterized by, that an extraction from Agrigremax agrestis is carried out as an extraction from a material whose origin includes Limax maximus L., L. flavus L., Agriolimax agrestis L and Phiolomycus bilineatus. [5] Extract with pharmaceutical detoxifying effect, obtainable according to one of claims 1 or 2. [6] Use of an extract according to claim 5 as a detoxification drug.