WO2022048176A1 - 溪黄草的应用和溪黄草组合物 - Google Patents

溪黄草的应用和溪黄草组合物 Download PDF

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WO2022048176A1
WO2022048176A1 PCT/CN2021/092060 CN2021092060W WO2022048176A1 WO 2022048176 A1 WO2022048176 A1 WO 2022048176A1 CN 2021092060 W CN2021092060 W CN 2021092060W WO 2022048176 A1 WO2022048176 A1 WO 2022048176A1
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Prior art keywords
xihuangcao
alcohol
dependence
nicotine
parts
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PCT/CN2021/092060
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English (en)
French (fr)
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郭海彪
李淑如
王德勤
李楚源
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广州白云山和记黄埔中药有限公司
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Priority claimed from CN202010917817.0A external-priority patent/CN114129615B/zh
Priority claimed from CN202010916751.3A external-priority patent/CN114129613B/zh
Priority claimed from CN202010917816.6A external-priority patent/CN114129614B/zh
Application filed by 广州白云山和记黄埔中药有限公司 filed Critical 广州白云山和记黄埔中药有限公司
Publication of WO2022048176A1 publication Critical patent/WO2022048176A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/42—Cucurbitaceae (Cucumber family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34—Tobacco-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse

Definitions

  • the invention relates to the technical field of biomedicine, in particular to the application of Xihuangcao and a Xihuangcao composition.
  • Acute alcohol intoxication refers to the abnormal body function that occurs after a drinker ingests a large amount of alcohol at one time, manifested as decreased self-control, slurred speech, weakness of limbs, etc. In severe cases, it can lead to death; alcoholic liver disease is a liver disease caused by long-term excessive drinking. , the initial manifestation is fatty liver, and then it can develop into alcoholic hepatitis, liver fibrosis and cirrhosis.
  • Alcohol dependence is a physical or psychological disease caused by repeated drinking, manifested as a strong and compulsive craving for drinking (mental dependence). sex).
  • Alcoholism is considered a bad habit worldwide, the number of people with alcohol dependence is increasing day by day. Since alcohol can cause serious damage to many tissues and organs of the human body, especially the liver, the treatment of alcohol dependence is the first step in the treatment of alcohol-related diseases. However, options for the treatment of alcohol dependence are limited.
  • the opioid receptor antagonist naltrexone and the GABA receptor agonist acamprosate calcium are FDA-approved for the prevention of excessive drinking and relapse.
  • Another drug approved to prevent alcohol use is disulfiram, which reduces alcohol intake by increasing the drinker's sensitivity to alcohol.
  • the drugs currently used for the treatment of alcohol dependence have serious adverse reactions, poor patient compliance, and many limitations in clinical use, which cannot meet the needs of many current alcohol-dependent patients.
  • Nicotine is an important addictive substance for the human body to rely on tobacco, which acts on the central nervous system to cause the release of neurotransmitters such as dopamine.
  • the essence of smoking addiction is nicotine dependence, which is a chronic and highly relapsing disease characterized by uncontrollable nicotine-seeking urges and compulsive and continuous use of nicotine to experience the euphoria it brings.
  • nicotine dependence is a chronic and highly relapsing disease characterized by uncontrollable nicotine-seeking urges and compulsive and continuous use of nicotine to experience the euphoria it brings.
  • When dependents stop taking nicotine they are prone to agitation, inattention, insomnia, anxiety and other withdrawal symptoms, which is one of the reasons why most smoking patients cannot get rid of nicotine.
  • Smoking cessation can reduce the morbidity and mortality of many major diseases and improve health status and quality of life. Therefore, reducing or avoiding nicotine intake is an effective measure to prevent the occurrence of chronic major diseases.
  • the treatment of nicotine (tobacco) dependence mainly includes drug, psychological, behavioral therapy and other methods.
  • FDA-approved nicotine therapy drugs include nicotine replacement drugs, bupropion, and a selective partial agonist of the ⁇ 4 ⁇ 2 subtype of the nicotine acetylcholine receptor ( varenicline).
  • Nicotine replacement drugs are mainly in the form of nicotine chewable tablets, nicotine patches, and nicotine lozenges, which provide part of the nicotine that can be obtained from tobacco, thereby reducing the smoking desire of the dependent and adapting to a life without cigarettes .
  • this treatment method only changes and reduces the intake method and intake of nicotine.
  • Varenicline is a high choice Sexual ⁇ 4 ⁇ 2 receptor partial agonists, mainly by blocking the binding of nicotine to the receptor, reducing the release of dopamine in the nucleus accumbens brain region, thereby reducing the rewarding effect of smoking.
  • Xihuangcao belongs to the genus Lamiaceae, and is the mainstream variety in Guangdong. Among them, Isodon lophanthoides var.gerardianus (Benth) H.Hara was approved by the national health plan in 2013. It is listed in the catalogue of new food raw materials. It has the functions of clearing dampness and heat, relieving jaundice and gallbladder, cooling blood and dissipating blood stasis. Studies have shown that Xihuangcao mainly contains flavonoids, terpenes, phenolic acids, volatile oils and coumarin.
  • the purpose of the present invention is to provide the application of Xihuangcao in the prevention or treatment of addictive substance dependence products, especially in the prevention or treatment of alcohol dependence and nicotine dependence products.
  • the addictive substance dependence is alcohol dependence or nicotine dependence.
  • Another object of the present invention is to provide the application of Xihuangcao in the preparation of a product for improving anxiety-like behaviors caused by acute alcohol withdrawal.
  • Another object of the present invention is to provide the application of Xihuangcao in the preparation of alcohol withdrawal products.
  • Another object of the present invention is to provide the application of Xihuangcao in the preparation of smoking cessation products.
  • the Xihuangcao is a Xihuangcao crude drug or a Xihuangcao extract or a Xihuangcao preparation.
  • the extract of Huangcao is water extract of Huangcao or alcohol extract of Huangcao.
  • the alcoholic extract of Xihuangcao is ethanolic extract of Xihuangcao.
  • the product is a health product, functional food or medicine.
  • the dosage form of the product is oral liquid, capsule, tablet, granule, solid beverage, injection, pill, syrup, powder, ointment, emulsion or suspension.
  • Another object of the present invention is to provide a product for preventing or treating addiction to substances, comprising an active ingredient and an auxiliary material, and the active ingredient is a crude drug of Xihuangcao or a Xihuangcao extract or a Xihuangcao preparation.
  • the extract of Huangcao is water extract of Huangcao or alcohol extract of Huangcao.
  • the alcoholic extract of Xihuangcao is preferably Xihuangcao ethanol extract.
  • the Xihuangcao preparation is Xihuangcao tea.
  • the Xihuangcao tea is prepared by the following steps: withering, rolling, fermenting, air-cooling, stripping and drying the fresh leaves of Xihuangcao in sequence.
  • the Xihuang herbal tea is prepared by the following steps:
  • withering treatment is carried out with the fresh leaves of the yellow grass
  • step (b) rolling the withered leaves after the withering in step (a) are processed by rolling, and the rolling time is (20 ⁇ 10) min;
  • Fermentation ferment the kneaded kneaded leaves, the fermentation temperature is (40 ⁇ 5)°C, and the fermentation time is (6 ⁇ 1) h;
  • the preparation process of the ethanolic extract of Huangcao xiguang includes: taking Huangcao xiguangcao, adding 50-80wt% ethanol aqueous solution, extracting, filtering, and concentrating. Further, the ethanol aqueous solution is 60-80 wt% ethanol aqueous solution, and further, the extraction time is 10-40 min, preferably 20-30 min. Further, the quality of the ethanol aqueous solution is 10-30 times that of Xihuangcao.
  • the preparation process of the water extract of Huangxi Huangcao comprises: taking Xihuangcao, decocting with water for 1 to 3 times, and concentrating the obtained decoction into a thick paste.
  • the relative density of the thick paste at 40-60° C. is 1.1-1.25. Further, the relative density at 50 to 60°C is 1.1 to 1.25.
  • the time for each decoction with water is 0.5-2 h, preferably 0.8-1.2 h.
  • Another object of the present invention is to provide a product for preventing or treating dependence on addictive substances, the active ingredients of which are prepared from Xihuangcao and at least one selected from the group consisting of sweet-scented osmanthus, jujube, Luo Han Guo and Chinese wolfberry.
  • the addictive substance dependence is alcohol dependence or nicotine dependence.
  • the active ingredients of the product are prepared from Xihuangcao and Osmanthus fragrans.
  • the active ingredients of the product are prepared from Xihuangcao, jujube and wolfberry.
  • the active ingredients of the product are prepared from Xihuangcao, sweet-scented osmanthus, and Luo Han Guo.
  • the active ingredients of the product are prepared from Xihuangcao, jujube, sweet-scented osmanthus and wolfberry.
  • Another object of the present invention is to provide a Xihuangcao composition for preventing or treating addiction substance dependence, the active components of which are prepared from the following raw materials: Xihuangcao and Araliaceae ginseng.
  • the active ingredient is prepared from the following raw materials in parts by weight: 1-100 parts of Xihuangcao and 1-100 parts of Araliaceae ginseng.
  • the Araliaceae Panax plant comprises at least one of American ginseng, Panax ginseng and Panax notoginseng.
  • the active ingredients are prepared from the following raw materials in parts by weight: 1-20 parts of Xihuangcao and 1-20 parts of Araliaceae ginseng; further, 1-10 parts of Xihuangcao and 1-10 parts of Araliaceae ginseng, or 1-10 parts of Xihuangcao and 1-2 parts of Araliaceae ginseng.
  • the mass ratio of described Xihuangcao and Araliaceae ginseng plant is selected from 1:1, 2:1, 2:3, 3:1, 3:2, 3:4, 4:1, 4: 3, 4:5, 5:1, 5:3, 5:4, 5:6, 10:1, 20:1, 30:1, 40:1, 1:2:, 1:3, 1:4 , 1:5, or a range between any of the above.
  • the present invention also provides another Xihuangcao composition for preventing or treating addictive substance dependence with improved taste, and its active ingredients are prepared from the following raw materials: Xihuangcao and Araliaceae ginseng, and sweet-scented osmanthus, red dates , at least one of wolfberry, longan and monk fruit.
  • the active ingredients of the Xihuangcao composition are prepared from the following raw materials in parts by weight: 1-100 parts of Xihuangcao, 1-100 parts of Araliaceae ginseng, and 1-100 parts of osmanthus At least one of 100 parts, 1-100 parts of red dates, 1-100 parts of wolfberry, 1-100 parts of longan and 1-100 parts of monk fruit.
  • the active ingredients of the Xihuangcao composition are prepared from the following raw materials: Xihuangcao, Araliaceae ginseng and sweet-scented osmanthus.
  • the active ingredients of the Xihuangcao composition are prepared from the following raw materials in parts by weight: 1-100 parts of Xihuangcao, 1-100 parts of Araliaceae ginseng and 1-100 parts of osmanthus share.
  • the active ingredients of the Xihuangcao composition are prepared from the following raw materials in parts by weight: 1-20 parts of Xihuangcao, 1-2 parts of Araliaceae ginseng and 1-2 parts of sweet-scented osmanthus further, 1-10 parts of Xihuangcao, 1-2 parts of Araliaceae ginseng and 1-2 parts of osmanthus; further, 3-10 parts of Xihuangcao, 1-2 parts of Araliaceae ginseng 1 to 2 parts of osmanthus; further, 3 to 5 parts of Xihuangcao, 1 part of Araliaceae ginseng and 0.5 to 2 parts of osmanthus, further 4 parts of Dixihuangcao and 1 part of Araliaceae ginseng and 1 serving of osmanthus.
  • the active ingredients of the Xihuangcao composition are prepared from the following raw materials: Xihuangcao, Araliaceae ginseng and red dates.
  • the active ingredients of the Xihuangcao composition are prepared from the following raw materials in parts by weight: 1-100 parts of Xihuangcao, 1-100 parts of Araliaceae ginseng and 1-100 parts of red dates 1 to 10 parts of Xihuangcao, 1 to 10 parts of Araliaceae ginseng and 1 to 10 parts of red dates; further, 1 to 10 parts of Xihuangcao, 1 to 10 parts of Araliaceae ginseng ⁇ 2 servings and 1-2 servings of red dates.
  • the active ingredients of the Xihuangcao composition are prepared from the following raw materials: Xihuangcao, Araliaceae ginseng, sweet-scented osmanthus and red dates.
  • the active ingredients of the Xihuangcao composition are prepared from the following raw materials in parts by weight: 1-100 parts of Xihuangcao, 1-100 parts of Araliaceae ginseng, 1-100 parts of osmanthus 1 to 100 servings and red dates. Further, it is 1-25 parts of Xihuangcao, 1-2 parts of Araliaceae ginseng, 1-2 parts of sweet-scented osmanthus and 1-2 parts of red dates. Further, it is 3-10 parts of Xihuangcao, 1-2 parts of Araliaceae ginseng, 1-2 parts of sweet-scented osmanthus and 1-2 parts of red dates.
  • Another object of the present invention is to provide an application of the above-mentioned Huangcao composition in the preparation of a product for preventing or treating dependence on addictive substances.
  • the addictive substance dependence is alcohol or nicotine dependence.
  • Another object of the present invention is to provide an application of the above-mentioned Huangcao composition in the preparation of alcohol or smoking cessation products.
  • Another object of the present invention is to provide a product for preventing or treating addiction to substances, comprising the above-mentioned composition of Xihuangcao and auxiliary materials.
  • the product is a health product, food or medicine.
  • the food is in the form of tea bags, beverages, granular food, powdered food, capsule food or tablet food.
  • the dosage form of the health product is a liquid health product, a granular health product, a powder health product, a capsule health product or a tablet health product.
  • the dosage form of the medicine is oral liquid, granule, powder, capsule or tablet.
  • the excipients include excipients, fillers, compatibilizers, binders, humectants, disintegrants, retarders, absorption accelerators, adsorbents, diluents, solubilizers, emulsifiers , at least one of lubricants, wetting agents, suspending agents, flavoring agents and fragrances.
  • the present invention has the following beneficial effects:
  • the present invention uses a variety of animal models of addictive drug mental dependence to conduct experimental research on Xihuangcao, and finds for the first time that Xihuangcao has a good effect of preventing and treating addictive drug spiritual dependence, such as a good effect of preventing and treating alcohol dependence, which is beneficial to Promote abstinence from alcohol.
  • Xihuangcao has a good effect of preventing and treating addictive drug spiritual dependence, such as a good effect of preventing and treating alcohol dependence, which is beneficial to Promote abstinence from alcohol.
  • the above-mentioned effect of Xihuangcao on preventing and treating alcohol dependence does not affect the blood alcohol concentration, and is not produced by affecting the absorption and metabolism of alcohol in the blood. Its mechanism is completely different from the conventional mechanism of hangover and liver protection.
  • Xihuangcao can significantly reduce the place preference effect on alcohol in mice, interfere with the formation of behavioral sensitization induced by alcohol dependence, and effectively improve the effects of acute alcohol withdrawal in mice.
  • Anxiety-like behavior reduce alcohol preference, so as to achieve a good role in preventing and treating alcohol dependence.
  • the present invention discovers the effect of Xihuangcao in treating nicotine dependence for the first time.
  • the present invention uses a variety of addictive drug mental dependence animal models to test, and the results prove that Xihuangcao can weaken the reward effect caused by nicotine, inhibit the formation and expression of behavioral sensitization caused by nicotine, and improve the neuropsychiatric symptoms caused by nicotine. (such as anxiety-like symptoms, behavioral sensitization), has a good role in preventing and treating nicotine dependence, can effectively prevent nicotine relapse, and is conducive to smoking cessation by smokers.
  • the Xihuangcao composition of the present invention is compounded by Xihuangcao and Araliaceae ginseng plants, which can weaken the reward effect caused by alcohol or nicotine dependence, inhibit the formation and expression of behavioral sensitization caused by alcohol or nicotine, and effectively It can effectively prevent and treat alcohol and nicotine dependence, and promote smoking and drinking in people addicted to tobacco and alcohol. At the same time, it also has a good anti-fatigue effect and can improve taste.
  • Figure 1 shows the effect of Xihuangcao on alcohol-induced conditioned place preference
  • A Base value pre-test stage
  • B Test stage
  • Figure 2 shows the effect of Xihuangcao on alcohol-induced behavioral sensitization
  • Figure 3 shows the effect of Xihuangcao on blood alcohol concentration in mice
  • Figure 4 shows the effect of Xihuangcao on the amount of drinking and alcohol preference in mice
  • C Basic value of alcohol preference
  • D Alcohol preference
  • Figure 5 shows the effect of Xihuangcao on drinking in the dark in mice ** P ⁇ 0.01vs model group;
  • Figure 6 shows the effect of Xihuangcao on light and dark box experiments after acute alcohol withdrawal in mice
  • P ⁇ 0.01vs control group The incubation period of entering the dark box
  • * P ⁇ 0.01, ** P ⁇ 0.01vs model group The number of crossings between the light and dark boxes.
  • the "plurality” mentioned in the present invention means two or more.
  • "And/or" which describes the association relationship of the associated objects means that there can be three kinds of relationships, for example, A and/or B, which can mean that A exists alone, A and B exist at the same time, and B exists alone.
  • the character "/" generally indicates that the associated objects are an "or" relationship.
  • One of the embodiments of the present invention provides the application of Xihuangcao in the preparation of addictive substance-dependent products.
  • the addictive substance dependence is alcohol dependence or nicotine dependence.
  • Another embodiment of the present invention provides the application of Xihuangcao in the preparation of a product for improving anxiety-like behaviors caused by acute alcohol withdrawal.
  • Another embodiment of the present invention also provides the application of Xihuangcao in the preparation of alcohol withdrawal products.
  • Another embodiment of the present invention provides the application of Xihuangcao in preparing a smoking cessation product.
  • the Xihuangcao is a crude drug of Xihuangcao, that is, a dried product of the whole grass.
  • the yellow grass is the extract of the yellow grass, for example, it can be the water extract of the yellow grass, or the alcohol extract of the yellow grass, whether it is the water extract of the yellow grass or the alcohol extract of the yellow grass, its It can be obtained according to the conventional method in the industry.
  • the Xihuangcao is a Xihuangcao preparation.
  • the products for preventing or treating alcohol dependence according to the present invention can be medicines, health products, or functional foods, and the products can also be Xihuangcao and other common health-care foods (such as sweet-scented osmanthus, jujube, Luo Han Guo and wolfberry) etc.) together, as long as it does not affect the activity of Xihuangcao in preventing and treating alcohol dependence.
  • Xihuangcao and other common health-care foods such as sweet-scented osmanthus, jujube, Luo Han Guo and wolfberry
  • the present embodiment also provides a product for preventing or treating addictive substance dependence with improved taste, the active ingredients of which are prepared from at least one selected from osmanthus, jujube, mangosteen and wolfberry.
  • the active ingredients of which are prepared from at least one selected from osmanthus, jujube, mangosteen and wolfberry.
  • Xihuangcao can be combined with at least one of sweet-scented osmanthus, jujube, Luo Han Guo and wolfberry in any proportion.
  • the active ingredients of the product are prepared including Xihuangcao and Osmanthus fragrans.
  • the Xihuangcao and sweet-scented osmanthus can be combined in any mass ratio, for example, can be selected from 1-100: 0.5-100, 50-100: 0.5-1 or 1-20: 1-20, and further can be selected from 1-5: 1 to 5, specifically can be selected from: 80:0.5, 100:1, 1:1, 1:2, 1:3, 1:4, 1:5, 2:1, 3:1, 4:1, 5 :1.
  • the sweet-scented osmanthus of the present invention can be selected from the dried product of sweet-scented sweet-scented osmanthus or the extract of sweet-scented sweet-scented osmanthus (such as water extract, alcohol extract or oil of sweet-scented osmanthus), and can also be selected from other conventional processed products that do not affect the activity of sweet-scented osmanthus.
  • the active ingredients of the product are prepared from Xihuangcao, jujube and wolfberry.
  • the Xihuangcao, jujube and wolfberry can be combined in any mass ratio, such as can be selected from 1-5:1-5:1-5, specifically can be selected from: 1:1:1, 1:2:1, 1:3:1, 1:4:1, 1:5:1, 2:1:1, 3:1:1, 4:1:1, 5:1:1, 1:1:2, 1: 1:3, 1:1:4, 1:1:5.
  • the active ingredients of the product are prepared from Xihuangcao, sweet-scented osmanthus, jujube, and wolfberry.
  • the Xihuangcao, sweet-scented osmanthus, jujube, and wolfberry can be combined in any mass ratio, for example, can be selected from 0.5-10:1-5:1-5:1-5, specifically can be selected from: 1:1:1 :1, 1:2:1:1, 1:3:1:1, 1:4:1:1, 1:5:1:1, 2:1:1:1, 3:1:1:1 , 4:1:1:1, 5:1:1:1, 6:1:1:1, 7:1:1:1, 1:1:2:1, 1:1:3:1, 1 :1:4:1, 1:1:5:1, 1:1:1:2, 1:1:1:3, 1:1:1:4, 1:1:1:5.
  • the active ingredients of the product are prepared from Xihuangcao, sweet-scented osmanthus, and Luo Han Guo.
  • the Xihuangcao, sweet-scented osmanthus, and Luohanguo can be combined in any mass ratio, such as can be selected from 1-100:0.5-5:1-100, further can be selected from 80-100:0.5-2:20-40 or 1 ⁇ 5:1 ⁇ 5:1 ⁇ 5, can be selected from: 100:0.5:20, 1:1:1, 1:2:1, 1:3:1, 1:4:1, 1:5: 1, 2:1:1, 3:1:1, 4:1:1, 5:1:1, 1:1:2, 1:1:3, 1:1:4, 1:1:5.
  • the product of the present invention can also be in the form of a drug.
  • the present embodiment also provides a product for preventing or treating dependence on an addictive substance, comprising a crude drug of Xihuangcao or an extract of Xihuangcao or a preparation of Xihuangcao, and an auxiliary material.
  • the Xihuangcao preparation can be selected as Xihuangcao tea
  • the Xihuangcao tea refers to the tea leaves prepared from the fresh leaves of Xihuangcao according to the conventional black tea preparation method, which includes withering, rolling, fermentation step, further, can also include air cooling, stripping, drying steps.
  • the extract of Huangcao is water extract of Huangcao or alcohol extract of Huangcao. Regardless of whether it is the water extract of Xihuangcao or the alcohol extract of Xihuangcao, it can be obtained according to conventional methods in the industry.
  • the product described in this embodiment is not limited in dosage form, and can be any conventional dosage form such as oral liquid, capsule, tablet, granule, injection, pill, syrup, powder, ointment, emulsion or suspension.
  • the adjuvant described in this embodiment is any conventional adjuvant acceptable in the preparation of health products, food and medicine, such as selected from excipients, fillers, compatibilizers, adhesives, humectants, disintegrants, slow solvents, Any one or more of absorption accelerators, adsorbents, diluents, solubilizers, emulsifiers, lubricants, wetting agents, suspending agents, flavoring agents and fragrances.
  • Another embodiment of the present invention provides a Xihuangcao composition for preventing or treating addictive substance dependence, the active ingredients of which are prepared from the following raw materials: Xihuangcao and Araliaceae ginseng.
  • the Xihuangcao can be combined with Araliaceae ginseng plants in any mass ratio, for example, in parts by weight, 1-100 parts of Xihuangcao and 1-100 parts of Araliaceae ginseng plants 100 parts; for example, 1-20 parts of Xihuangcao and 1-20 parts of Araliaceae ginseng; further, 1-10 parts of Xihuangcao and 1-10 parts of Araliaceae ginseng. Or 1-10 parts of Xihuangcao and 1-2 parts of Araliaceae ginseng.
  • the mass ratio of Xihuangcao to Araliaceae ginseng is selected from 1:1, 2:1, 2:3, 3:1, 3:2, 3:4, 4:1, 4:3 , 4:5, 5:1, 5:3, 5:4, 5:6, 10:1, 20:1, 30:1, 40:1, 1:2:, 1:3, 1:4, 1:5, or a range between any of the above.
  • the Xihuangcao includes the crude drug of Xihuangcao or the extract of Xihuangcao, and other processed products that do not affect the activity of Xihuangcao;
  • the Araliaceae ginseng plant includes its crude drug or extract, And other processed products that do not affect the activity of Araliaceae ginseng plants.
  • the Araliaceae Panax plant includes at least one of American ginseng, Panax ginseng, and Panax notoginseng.
  • This embodiment also provides a Xihuangcao composition for preventing or treating addictive substance dependence with improved taste, and its active ingredients are prepared from the following raw materials: Xihuangcao and Araliaceae ginseng, and sweet-scented osmanthus, red dates , at least one of wolfberry and monk fruit.
  • the above-mentioned Xihuangcao and Araliaceae ginseng can be combined with at least one of sweet-scented osmanthus, red dates, wolfberry, longan and Luo Han Guo in any proportion.
  • the Osmanthus fragrans includes Osmanthus fragrans medicinal or Osmanthus fragrans extract or Osmanthus fragrans oil.
  • the red dates include red dates crude drug; the wolfberry includes wolfberry crude drug; and the Luo Han Guo includes Luo Han Guo crude drug.
  • the raw materials of the active ingredients of the Xihuangcao composition are Xihuangcao, Araliaceae ginseng and sweet-scented osmanthus.
  • Xihuangcao and Araliaceae ginseng can be combined with the sweet-scented osmanthus in any parts by weight, for example, in parts by weight, 1-100 parts of Xihuangcao, 1-100 parts of Araliaceae ginseng and osmanthus 1 to 100 servings.
  • the raw materials of the active ingredients of the Xihuangcao composition are Xihuangcao, Araliaceae ginseng, sweet-scented osmanthus and red dates.
  • Xihuangcao and Araliaceae ginseng can be combined with the sweet-scented osmanthus and red dates in any weight portion. For example, in parts by weight, it is 1-100 parts of Xihuangcao, 1-100 parts of Araliaceae ginseng, 1-100 parts of sweet-scented osmanthus, and 1-100 parts of red dates.
  • Another embodiment of the present invention also provides an application of the above-mentioned Huangcao composition in the preparation of a product for preventing or treating dependence on addictive substances.
  • the addictive substance dependence is alcohol or nicotine dependence.
  • Another embodiment of the present invention also provides the application of the above-mentioned Huangcao composition in the preparation of alcohol or smoking cessation products.
  • Another object of the present invention is to provide a product for preventing or treating addiction to substances, comprising the above-mentioned composition of Xihuangcao and auxiliary materials.
  • the product described in this embodiment may be a health product, a food or a medicine.
  • the product described in this embodiment is not limited to the dosage form, and the food can be any conventional dosage form such as tea bag, beverage, granular food, powdered food, capsule food or tablet food.
  • the health care product is any conventional dosage form such as liquid health product, granular health product, powder health product, capsule health product or tablet health product; the medicine is oral liquid, granule, powder, capsule or tablet Any conventional dosage form
  • the adjuvant is any adjuvant that is acceptable in the preparation of medicines, health products and food, such as excipients, fillers, compatibilizers, adhesives, humectants, disintegrants, slow solvents, absorption Any one or more of accelerators, adsorbents, diluents, solubilizers, emulsifiers, lubricants, wetting agents, suspending agents, flavoring agents and fragrances.
  • Preparation of water extract of Xihuangcao take 100g dried product of Xihuangcao whole grass, add 600ml of water and decoct for 2 times, each time is 1h, the decoctions are combined, and concentrated to a viscosity with a relative density of 1.1 ⁇ 1.25 (50 ⁇ 60 °C). Ointment, for use (1g of Xihuangcao crude drug is equivalent to 0.1g of Xihuangcao extract).
  • Example 1.1 The water extract of Xihuangcao prepared in Example 1.1 (modeling is intraperitoneal injection, and treatment is intragastric administration).
  • C57BL/6J mice, male, 150 mice, at least 60 mice that can be used for the experiment were screened out by the conditioned place preference test (CPP), and divided into 6 groups of 10 mice; the normal control group (normal saline) , Simple Xihuangcao group ( Xihuangcao crude drug 1.0g/kg + normal saline), alcohol dependence model group (normal saline + alcohol), Xihuangcao low-dose group ( Xihuangcao crude drug 0.25g/kg + alcohol), Xihuangcao crude drug 0.25g/kg + alcohol Huangcao medium dose group (Xihuangcao crude drug 0.5g/kg + alcohol), Xihuangcao high dose group (Xihuangcao crude drug 1.0g/kg + alcohol).
  • the normal control group normal saline
  • Simple Xihuangcao group Xihuangcao crude drug 1.0g/kg + normal saline
  • mice with too much or too little activity were eliminated, and the remaining mice were randomly and evenly divided into groups: 60 mice were divided into 6 groups, 10 mice in each group, and the grouping was consistent with the above.
  • CPP video experiment system (Guangzhou Feidi Biotechnology Co., Ltd.): CPP box (400mm ⁇ 150mm ⁇ 200mm).
  • Conditioned place preference (CPP) animal model is a common method to evaluate the reward effect and dependence effect of alcohol. After being associated with a specific environment, experimental animals experience a rewarding effect in reproducing the environment associated with an addictive drug.
  • the general experiment consists of three stages: base value pre-test stage, conditioned place preference training stage and test stage.
  • base value pre-test stage On the first day of the experiment, the isolation door in the middle of the CPP box was opened, allowing the mice to freely explore between the black and white boxes. The residence time in the black and white boxes within 15 minutes was recorded, and the preference of each mouse for the CPP black and white boxes was determined. Mice with natural preference for black box or white box (retention time > 500s) will be excluded based on basal values. Days 2 to 9 of the experiment consisted of 4 rounds of training.
  • the non-preferred box of mice was used as the companion medicine box.
  • the white box was used as the medicine companion box
  • the black box was the non medicine companion box.
  • intraperitoneal injection of normal saline was performed for 5 minutes and then placed in a non-accompanied medicine box, and then taken out after staying for 30 minutes.
  • alcohol was given for 5 minutes and then placed in the companion medicine box, and then taken out after staying for 30 minutes.
  • Mice in the normal control group and model group were given normal saline by gavage 30 minutes before training on days 2-9, while the Xihuangcao group were given different doses of Xihuangcao 30 minutes before training on days 2-9.
  • the behavioral sensitization experiment was divided into four phases: baseline pre-test phase, acute alcohol induction phase, sensitization phase and test phase.
  • Basal value pre-test stage (1st to 2nd day), the purpose is to make mice adapt to intraperitoneal injection and establish basal activity value.
  • the mice were adapted to the test room for at least 1 h, weighed and injected intraperitoneally with normal saline according to their body weight. The mice were immediately placed in the center of the open box, and the mice were allowed to explore freely in the open box for 15 minutes, and the number of mouse activities was recorded as Basal activity values in mice.
  • mice in the alcohol-dependent model group, the low-dose group, the middle-dose group, and the high-dose group were injected with alcohol (2.0g/kg) according to their body weight after adapting to the test environment.
  • the control group and the pure Xihuangcao group were injected with the same volume of normal saline, and immediately placed in the center of the open box, the mice were free to explore, and the number of activities was recorded.
  • Sensitization stage (4th to 13th day): Mice in each group were given normal saline or Xihuangcao by intragastric administration for 30 minutes every day, and then intraperitoneally injected alcohol (2.5g/kg) once a day, and put them back immediately after the injection. cage.
  • mice After 1 week of adaptation to the environment, the mice were raised in a single cage and given two bottles, one of which was filled with pure water and the other with 10% alcohol. The mice foraged for food and water freely for 3 weeks; weighed at 4:30-6:00 pm every day Measure the water and alcohol weights and replace with fresh water and alcohol every other day. To prevent mice from developing position preference, the two bottle positions were alternated daily. According to the 24-hour alcohol consumption and alcohol preference of the mice in the last 3 days of training, the mice with too high or too low alcohol consumption were eliminated, and the remaining mice were randomly divided into 3 groups. The intraperitoneal injection was administered after the weighing of the water bottle every day, once a day for 1 week.
  • mice were stroked before the experiment, and each mouse was stroked for 1 min every day for 3 consecutive days.
  • Alcoholism is defined by the National Institute on Alcohol Abuse and Alcoholism as heavy drinking over a short period of time resulting in a blood alcohol concentration of more than 0.08%. Alcohol abuse is common among young people and is a risk factor for later development of alcohol abuse and dependence.
  • the dark drinking experiment is a commonly used animal model to simulate human drinking behavior, that is, the behavior of drinking a large amount of high concentration in a short period of time.
  • this experiment is usually carried out after the lights are turned off, the water is replaced with 20% alcohol, and the animals are allowed to drink continuously for 2 to 4 hours.
  • Natural high drinking strain mice C57BL/6J mice
  • This model is commonly used to study the neurochemical pathways and neural circuits of alcohol dependence or relapse behavior.
  • the circadian rhythm of drinking in mice more drinking at night and less during the day, the experiment started 1 h after the lights were turned off. The water bottle was removed, and only one bottle containing 20% alcohol was provided. The mice drank by themselves for 4 hours, and weighed the bottle before and after drinking.
  • mice in each group were intraperitoneally injected with corresponding drugs or physiological saline 30 minutes before the start of the experiment, once a day for 1 week.
  • the light-dark box test is a commonly used animal model for evaluating anxiety-like behaviors.
  • the light and dark box is divided into a light box and a dark box by a baffle with a circular hole with a diameter of 4cm in the center, and a 40w light bulb is provided above the 60cm of the light box.
  • the experimenter placed the mice in the light box with their backs facing the dark box, and recorded the latency of the mice passing from the light box into the dark box, the residence time in the light box and the number of crossings between the light and dark boxes within 5 minutes. Wash the device with toilet water after each animal experiment.
  • mice in the simplex Huangcao group and the low-dose, medium-dose, and high-dose groups were given Xihuangcao by gavage, while the normal control group and the alcohol-dependent model group were given the same volume of normal saline by gavage. Dosing for 7 days for light and dark box experiments.
  • Conditioned place preference experiment is based on Pavlovian conditioning theory and establishes an animal model to study the rewarding effect of drugs. produce a reward effect.
  • mice in each group were given normal saline or Xihuangcao by intragastric administration, and alcohol (2.5g/kg) was injected intraperitoneally. ), and 1 hour later, the mouse serum was collected for detection and analysis), and the whole blood alcohol concentration was determined by headspace gas chromatography-mass spectrometry.
  • the mouse drinking experiment in the dark is a commonly used animal model to simulate the behavior of heavy drinking in a short period of time (ie, binge drinking behavior).
  • the experimental results showed that after the light was turned off for 1 hour, the alcohol consumption of the mice reached 4.575 ⁇ 0.7259g/kg within 4 hours, and the high dose of Xihuangcao could significantly reduce the alcohol consumption of the mice (P ⁇ 0.01, Figure 5).
  • the light and dark box is also a commonly used animal model for evaluating the anxiety state of animals.
  • the experimental results are shown in Figure 6.
  • the Latency of the mice in the model group was significantly shortened (P ⁇ 0.01, Figure 6A), and the duration of stay in the light box (Duration) was significantly shortened.
  • P ⁇ 0.01, Figure 6B the number of transitions (Transitions) between the light and dark boxes were also significantly reduced (P ⁇ 0.01, Figure 6C), and the administration of Xihuangcao medium and high doses could reverse these changes to varying degrees (P ⁇ 0.01, Figure 6C).
  • ⁇ 0.05, P ⁇ 0.01) significantly improving the anxiety-like behavior of mice.
  • the Xihuangcao of the present invention does not inhibit the action of acetaldehyde deaminase in the liver and the activity of monoamine oxidase in the body, thereby avoiding the damage of acetaldehyde to the liver and the blood pressure caused by the accumulation of monoamine substances such as norepinephrine.
  • Adverse reactions such as increased heart rate and increased heart rate have improved the safety of treatment and the compliance of patients.
  • Preparation of water extract of Xihuangcao take 100g dried product of Xihuangcao whole grass and add 600ml of water to decoct twice, each time for 1 hour, combine the decoctions, and concentrate to relative density of 1.1 ⁇ 1.20 (50 ⁇ 60°C) for use (1g)
  • the crude drug of Xihuangcao is equivalent to 0.1g of Xihuangcao water extract).
  • Nicotine (subcutaneous injection dose 0.5mg/kg, Shanghai Times Biotechnology Co., Ltd.); 0.9% saline;
  • Example 1.2 The water extract of Xihuangcao prepared in Example 1.2 (modeling was intraperitoneal injection, and treatment was intragastric administration).
  • mice Male, 150 mice, at least 50 mice that can be used for the experiment were screened out by the conditioned place preference test (CPP), and divided into 5 groups of 10 mice, the normal control group (normal saline + normal saline) ), nicotine dependence model group (normal saline + nicotine), Xihuangcao low-dose group (Xihuangcao crude drug 0.25g/kg + nicotine), Xihuangcao middle-dose group (Xihuangcao crude drug 0.5g/kg + nicotine), Xihuangcao crude drug 0.5g/kg + nicotine Grass high dose group (Xihuangcao crude drug 1.0g/kg + nicotine).
  • the normal control group normal saline + normal saline
  • nicotine dependence model group normal saline + nicotine
  • Xihuangcao low-dose group Xihuangcao crude drug 0.25g/kg + nicotine
  • Xihuangcao middle-dose group Xih
  • CPP video experiment system (Guangzhou Feidi Biotechnology Co., Ltd.): CPP box (400mm ⁇ 150mm ⁇ 200mm), multifunctional mouse activity recorder (equipment station of Shandong Academy of Medical Sciences), elevated plus maze behavior analysis system (Shanghai Shift Information Technology Co., Ltd.).
  • the conditioned place preference (CPP) animal model is a commonly used method to evaluate the reward and dependence effects of addictive substances.
  • the general experiment consists of three stages: base value pre-test stage, conditioned place preference training stage and test stage.
  • base value pre-test stage On the first day of the experiment, the isolation door in the middle of the CPP box was opened, allowing the mice to freely explore between the black and white boxes.
  • the residence time in the black and white boxes within 15 minutes was recorded, and the preference of each mouse for the CPP black and white boxes was determined. Mice with natural preference for black box or white box (retention time > 500s) will be excluded based on basal values.
  • Days 2 to 9 of the experiment consisted of 4 rounds of training. According to the basic value, the non-preferred box of mice is used as the companion medicine box.
  • the white box is used as the medicine companion box
  • the black box is the non medicine companion box.
  • intraperitoneal injection of normal saline was performed for 5 minutes and then placed in the non-accompanied medicine box, and then taken out after staying for 30 minutes.
  • nicotine was given for 5 minutes and then put into the companion medicine box, and then taken out after 30 minutes of stay.
  • Mice in the normal control group and model group were given normal saline by gavage 30 minutes before training on days 2-9, and the Xihuangcao group was given different doses of Xihuangcao 30 minutes before training on days 2-9.
  • Behavioral sensitization refers to the process of progressive enhancement of the body's behavioral response caused by chronic intermittent administration of addictive substances.
  • the mice were adapted to the test room for at least 1 h, intraperitoneally injected with physiological saline according to their body weight, and the mice were immediately placed in the center of the open box, allowing the mice to explore freely in the open box for 15 minutes, and the number of mouse activities was recorded as the mouse's Base activity value.
  • the normal control group and the nicotine dependence model group were given the same volume of normal saline by gavage, and the drug group was given the corresponding dose of drugs according to body weight, once a day for 7 consecutive days.
  • the control group was subcutaneously injected with physiological saline, and the other groups were subcutaneously injected with nicotine (0.5 mg/kg), once a day for 7 consecutive days;
  • the elevated plus maze test is a test method to evaluate the anxiety response of rodents. It mainly evaluates the anxiety behavior of mice by comparing the residence time and distance in the open arm and the closed arm. This test applies it to evaluate anxiety-like behavior in nicotine-dependent mice.
  • the mice in the nicotine-dependent group were injected subcutaneously with 0.5 mg/kg of nicotine every day for 7 consecutive days to prepare a nicotine-dependent model.
  • Mice in the normal control group were subcutaneously injected with an equal volume of normal saline every day for 7 consecutive days.
  • the mice in the normal control group and the nicotine-dependent group were given normal saline by gavage 30 minutes before modeling, and the Xihuangcao group was given different doses of Xihuangcao.
  • mice At the beginning of the experiment, hold the mouse with its back to the experimenter, and place it in the center of the junction of the open arm and the closed arm, so that the mice face the open arm, and all mice need to face the same open arm. After the mice were placed, the experimenter quickly moved away. When the mice entered the elevated plus maze, they began to record the activities of the mice in the elevated plus maze within 5 minutes. After the experiment, wipe the detection equipment with 75% alcohol and dry it before proceeding to the next animal experiment, so as to avoid the influence of smell on the experimental results.
  • SPSS statistical software was used for analysis, and the experimental data were expressed as mean ⁇ standard error. All data were analyzed by one-way analysis of variance. After the homogeneity of variance test, if the variance is homogeneous, the LSD method is used for pairwise comparison between groups; if the variance is unequal, the Dunnett's T3 method is used for comparison between groups. P ⁇ 0.05 was regarded as a statistically significant difference.
  • the middle and high doses of Xihuangcao significantly reduced the number of spontaneous activities in behaviorally sensitized mice (P ⁇ 0.01, P ⁇ 0.001), indicating that Xihuangcao can effectively inhibit the formation of behavioral sensitization in nicotine-dependent mice.
  • the number of spontaneous activities of nicotine mice increased significantly compared with the normal control group (P ⁇ 0.01). Sensitized expression, the difference was statistically significant.
  • the nicotine-dependent mice had a significant reduction in the time of open arms and the percentage of times they entered the open arms (P ⁇ 0.01), indicating that the nicotine-dependent mice developed obvious anxiety-like behaviors.
  • Xihuangcao significantly increased the residence time of nicotine mice in the open arm and the percentage of the number of times of entering the open arm, of which the middle and high doses were statistically significant.
  • the results of the elevated plus maze experiment showed that Xihuangcao can improve the anxiety response of nicotine-dependent mice.
  • the preparation method of the ethanol extract of Xihuangcao take a certain amount of Xihuangcao, add 20 times the amount of 70% ethanol, extract for 25 minutes, filter, and concentrate under reduced pressure.
  • This embodiment provides a product for preventing and treating alcohol dependence or nicotine dependence.
  • the liquids were combined and concentrated to a relative density of 1.12 to 1.20 (55 to 60° C.), and obtained.
  • Preparation method (a) picking: select the fresh leaves of Xihuangcao; (b) withering: placing the fresh leaves in a withering tank for withering treatment; (c) rolling: placing the withered tea leaves in a rolling machine for rolling treatment , the rolling time is 20min; (d) fermentation: the tea leaves after rolling are fermented, the fermentation temperature is 40 °C, and the fermentation time is 6h; (e) air cooling: the fermented tea leaves are spread out to cool down, and the spread thickness is 1cm (f) stripping: the air-cooled tea leaves are processed for stripping, the stripping temperature is 240°C, and the stripping time is 30min. After the stripping is finished, it cools and naturally regains moisture to redistribute the moisture on the leaf surface; (g) Drying: drying the tea leaves after stripping to obtain Xihuangcao tea.
  • This embodiment provides a tablet for preventing and treating alcohol dependence or nicotine dependence, which is weighed according to the following formula, and prepared according to the tablet process;
  • Preparation method the above three flavors, add 10000ml of water to decoct twice, each decoction time is 1h, the decoctions are combined and concentrated to a relative density of 1.12-1.25 or 1.1-1.20 (50-60 °C), the above-mentioned concentrate and an appropriate amount of auxiliary materials It is made into granules, dried, mixed uniformly, compressed into 1000 tablets, coated with sugar or film, and obtained.
  • the present embodiment provides a granule with good taste for preventing and treating alcohol dependence or nicotine dependence, which is weighed according to the following formula, and prepared according to the process of granule
  • Xihuangcao 1000g sweet-scented osmanthus oil 10g, appropriate amount of accessories, total 1000g;
  • Preparation method the above Xihuangcao is extracted twice with 25 times the amount of 50%-60% ethanol, each time for 0.5h, the filtrates are combined, the filtrate is concentrated to a relative density of 1.12-1.25 or 1.1-1.20 (55-60 °C), the concentrated solution It is made into granules with an appropriate amount of auxiliary materials, dried, added with osmanthus oil, and mixed to make 1000g granules.
  • the present embodiment provides a tea preparation with good taste for preventing and treating alcohol dependence or nicotine dependence, which is weighed according to the following formula, and prepared according to the technology of the tea preparation
  • Xihuangcao 1000g Luo Han Guo 200g, osmanthus oil 5g, appropriate amount of accessories, total 1000g;
  • Preparation method add 5000ml of water to decoct the above Xihuangcao and Luohanguo for 2 times, 1 hour each time, combine the decoction, filter, concentrate the filtrate to a relative density of 1.20 (50 ° C), add ethanol to make the alcohol content reach 60% , stand for precipitation, take the supernatant, recover ethanol and concentrate to an appropriate amount, add osmanthus oil and an appropriate amount of auxiliary materials, mix well, press into a block, and dry to obtain the final product.
  • This embodiment provides a tea bag that is convenient to take and has a good taste for preventing and treating alcohol dependence or nicotine dependence.
  • Preparation method mix the above four flavors into a small bag to make a tea bag.
  • Xihuangcao 2000g appropriate amount of accessories, 1000 hollow capsules, total 1000 capsules;
  • Preparation method take the above crude drug Xihuangcao to prepare the water extract of Xihuangcao according to the method of Example 1.1, concentrate and dry to powder (or directly use the crude drug of Xihuangcao for powdering), add appropriate amount of auxiliary materials and mix, put into capsule, and get final product.
  • Xihuangcao 800g sweet-scented osmanthus oil 5g, appropriate amount of accessories, total 1000ml;
  • Preparation method add 8000ml of water to decoct the above crude drug of Xihuangcao for two times, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.10-1.30 (50-60°C), let it cool, and add ethanol to make it.
  • the alcohol content reaches 50% ⁇ 80%, stand, filter, recover ethanol from the filtrate and concentrate to clear paste with relative density of 1.10 ⁇ 1.30 (50 ⁇ 60°C)
  • add osmanthus oil and appropriate amount of water mix well, adjust pH value, refrigerate, filter, add water to 1000ml, stir well, sub-pack, sterilize, and that’s it.
  • Preparation method soak the above two crude drugs in 60L of water for 30min, heat and decoct for 1h, filter, add appropriate amount of auxiliary materials, add water to 100L, pack and sterilize.
  • Healthy male C57 mice (body weight 18-22g) were provided by Beijing Weitong Lihua Laboratory Animal Co., Ltd., the license number is SCXK (Beijing) 2016-0006. Raised in an ordinary animal laboratory (temperature: 22°C ⁇ 1°C, humidity: 60% ⁇ 5%), fed with standard feed and drank purified water.
  • mice were acclimated to a 12h:12h day-night alternation environment for 7 days.
  • 105 C57 mice were randomly divided into 7 groups with 15 mice in each group: normal control group (normal saline 0.5g/kg + normal saline), Model group (normal saline 0.5g/kg + alcohol or nicotine), Xihuangcao group (Xihuangcao 0.5g/kg + alcohol or nicotine), American ginseng group (American ginseng 0.5g/kg + alcohol or nicotine), Xihuangcao + American ginseng group 1 (Xihuangcao 0.5g/kg + American ginseng 0.5g/kg + alcohol or nicotine), Xihuangcao + American ginseng group 2 (Xihuangcao 0.6g/kg + American ginseng 0.3g/kg + alcohol or nicotine), Xihuangcao + American ginseng group 3 (Xihuangcao 0.8g/kg + American ginseng 0.2g
  • the dose of alcohol is 2g/kg each time
  • the dose of nicotine is 0.5mg/kg.
  • the Xihuangcao used for administration is a water extract, and the preparation process is as follows: take 100 g of the dried product of the whole grass of Xihuangcao, add 600 ml of water to decoct for 2 times, and the decoction time is 1h each time, and the decoctions are combined and concentrated to a relative density of 1.12 ⁇ 1.20 (55 ⁇ 60°C), set aside.
  • the American ginseng used for administration is American ginseng water extract, and the preparation method of the American ginseng water extract refers to the water extract of Xihuangcao.
  • the Xihuangcao + American ginseng group used for administration was the water extract of both.
  • the Xihuangcao group, the American ginseng group and the combined drug group were given drugs, while the normal control group and the model group were given the same volume of normal saline.
  • Conditioned place preference (CPP) animal model is a common method to evaluate the reward and dependence effects of alcohol, nicotine and other addictive substances.
  • the general experiment consists of three stages: base value pre-test stage, conditioned place preference training stage and test stage.
  • base value pre-test stage On the first day of the experiment, the isolation door in the middle of the CPP box was opened, allowing the mice to freely explore between the black and white boxes. The residence time in the black and white boxes within 15 minutes was recorded, and the preference of each mouse for the CPP black and white boxes was determined. Mice with natural preference for black box or white box (retention time > 500s) will be excluded based on basal values. Days 2 to 9 of the experiment consisted of 4 rounds of training. According to the basic value, the non-preferred box of mice was used as the companion medicine box.
  • the white box was used as the medicine companion box, and the black box was the non medicine companion box.
  • intraperitoneal injection of normal saline was performed for 5 minutes and then placed in the non-accompanied medicine box, and then taken out after staying for 30 minutes.
  • addictive substances alcohol or nicotine
  • mice in the normal control group and model group were given normal saline by gavage 30 minutes before training on days 2 to 9, and the Xihuangcao group, American ginseng group, and combined administration group (1, 2, 3) were given before training on days 2 to 9. The corresponding drugs were given by gavage for 30 minutes.
  • Behavioral sensitization refers to the process of progressive enhancement of the body's behavioral response caused by chronic intermittent administration of addictive substances.
  • the mice were adapted to the test room for at least 1 h, intraperitoneally injected with physiological saline according to their body weight, and the mice were immediately placed in the center of the open box, allowing the mice to explore freely in the open box for 15 minutes, and the number of mouse activities was recorded as the mouse's Base activity value.
  • the control group and model group were given the same volume of normal saline by gavage, and the Xihuangcao group, American ginseng group, and combination (1, 2, 3) group were given corresponding doses of drugs according to body weight, once a day for 7 consecutive days. .
  • the control group was subcutaneously injected with normal saline, and the other groups were subcutaneously injected with alcohol or nicotine, once a day for 7 consecutive days.
  • mice After adaptive feeding of C57 mice for 1 week, the mice were randomly divided into blank control group, Xihuangcao group (0.5g/kg), American ginseng group (0.5g/kg), and combination group (group 1: Xihuangcao 0.5 g/kg + American ginseng 0.5 g/kg, group 2: Xihuangcao 0.6 g/kg + American ginseng 0.3 g/kg, group 3: Xihuangcao 0.8 g/kg + American ginseng 0.2 g/kg). Mice in each group were given intragastric administration, once a day, for 14 consecutive days.
  • a lead wire with 6% body weight was placed on the tail of the mice, and they were placed in water for swimming, and the time from entering the water to swimming exhaustion was recorded.
  • the exhaustion standard was the time when the head was completely submerged in the water and could not float up .
  • the serum of the mice was collected, and the content of serum urea nitrogen (BUN) and serum lactate (LA) were determined by semi-automatic spectrophotometer.
  • mice in the pre-test stage of the basic value showed that there was no significant difference in the residence time of the mice in each group in the accompanying medicine box, and the difference was not statistically significant (P>0.05), indicating that the mice in each group had no significant difference in the time spent in the accompanying medicine box.
  • the degree of preference is similar.
  • mice in the nicotine dependence model group stayed in the concomitant medicine box (white box) for a significantly longer time, and their preference for the concomitant medicine box was significantly increased (P ⁇ 0.01), indicating that nicotine produced a significant amount of nicotine.
  • mice in the pre-test phase of the basic value showed that there was no significant difference in the stay time of the mice in the accompanying medicine box in each group, and the difference was not statistically significant (P>0.05), indicating that the mice in each group had no effect on the accompanying medicine box.
  • the degree of preference is similar.
  • the mice in the alcohol dependence model group stayed in the medicine box (white box) for a longer time, and their preference for the medicine box was significantly increased (P ⁇ 0.01), indicating that alcohol produced a significant effect.
  • Reward effect mice established an association between the reward effect of alcohol and the companion medicine box.
  • the time from swimming to exhaustion is a comprehensive response of mice's physical fitness, which not only reflects the body's ability to resist fatigue, but also reflects the body's ability to resist stress and adapt to adverse environments.
  • the results of this test show that American ginseng and its combination with Xihuangcao can significantly prolong the swimming time of mice to exhaustion. The drug has no significant effect.
  • American ginseng and its combination with Xihuangcao can significantly reduce serum urea nitrogen and lactic acid content in exercise mice. This result indicates that American ginseng and its combination with Xihuangcao have anti-fatigue effect.
  • Xihuangcao has a special grassy taste and a bitter taste, which is not widely accepted by the public.
  • the following table shows the substances and ratios that taste better.
  • Xihuangcao American ginseng, Panax notoginseng, ginseng, sweet-scented osmanthus and red dates are all dried products, and then brewed with hot water after the combination shown in Table 9.
  • the ratio of Xihuangcao composition to water is 1:50, Take a taste test.
  • Preparation method the above four crude drugs are decocted twice by adding 12000ml of water, each decoction time is 1h, the decoctions are combined and concentrated to a relative density of 1.12 ⁇ 1.20 (55 ⁇ 60°C), the above concentrate is prepared with an appropriate amount of conventional excipients. Granulate, dry, mix well, compress into 1000 tablets, and coat with sugar or film.
  • Xihuangcao 900g American ginseng 200g, osmanthus oil 10g, appropriate amount of accessories, total 1000g granules;
  • Preparation method add 5000ml of water to decoct the above Xihuangcao for 2 times, 1h each time, combine the decoction, filter, and concentrate the filtrate to a relative density of 1.12-1.20 (55-60°C), and the concentrated solution is for use; pulverize American ginseng into fine powder , add the above-mentioned concentrated liquid and an appropriate amount of conventional auxiliary materials, mix well, make into granules, dry, add osmanthus oil, mix well, and make 1000g granules, that is.
  • Xihuangcao 1000g American ginseng 200g, Luo Han Guo 50g, appropriate amount of accessories, total 1000g granules;
  • Preparation method add 4000ml of water for 2 times, 1 hour each time, combine the decoction, filter, concentrate the filtrate to an appropriate concentration to obtain a concentrated solution, pulverize the crude drug of American ginseng into fine powder, add The concentrate and an appropriate amount of conventional auxiliary materials are mixed, pressed into a block, and dried.
  • Preparation method mix the above three crude drugs into a small bag to make a tea bag.
  • Preparation method The above two crude drugs are crushed into fine powder, sieved, mixed, and put into capsules.
  • Preparation method add 4000ml of water to the crude drug of Xihuangcao and American ginseng and decoct twice, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.10 ⁇ 1.30 (50 ⁇ 60°C), let it cool, add Ethanol is used to make the alcohol content reach 50% to 60%, stand still, and filter. The filtrate recovers ethanol and concentrates to a clear paste with a relative density of 1.10 to 1.30 (50 to 60°C). Add osmanthus oil and an appropriate amount of water, and mix well. Adjust the pH value, refrigerate, filter, add water to 1000ml, stir well, sub-pack, sterilize, and that’s it.
  • Beverage preparation Weigh according to the following formula and prepare according to the beverage process:
  • Preparation method extract Xihuangcao with 10 times the amount of ethanol, soak American ginseng and sweet-scented osmanthus in appropriate amount of water for 30 minutes, heat and cook for 1 hour, filter, add an appropriate amount of conventional auxiliary materials, add water to 100L, package and sterilize.
  • Beverage preparation Weigh according to the following formula and prepare according to the beverage process:
  • Preparation method soak the above three crude drugs in 70L of water for 30min, heat and decoct for 1h, filter, add an appropriate amount of conventional excipients, add water to 100L, package and sterilize.
  • Preparation method mix the above two crude drugs into a small bag to make a tea bag.
  • Preparation method mix the above four crude drugs into small bags to make tea bags.
  • Preparation method mix the above two crude drugs into a small bag to make a tea bag.
  • Preparation method Mix the above three crude drugs into a small bag, and make a tea bag.
  • Xihuangcao 600g Panax notoginseng 50g, sweet-scented osmanthus oil 6g, appropriate amount of accessories, total 1000ml;
  • Preparation method Add 2000ml of water to decoct the two crude drugs of Xihuangcao and Panax notoginseng for two times, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.10-1.30 (50-60°C), and let it stand. , filter, concentrate, add sweet-scented osmanthus oil, appropriate amount of water and conventional auxiliary materials, mix well, adjust pH value, refrigerate, filter, add water to 1000ml, stir well, package, sterilize, and that's it.

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Abstract

溪黄草的应用和溪黄草组合物。溪黄草能够显著减轻小鼠对酒精的位置偏爱效应，干扰酒精诱导行为敏化的形成，减少小鼠的饮酒量、降低酒精偏爱度，且不影响酒精吸收和代谢，对于酒精依赖具有优异的防治效果。同时溪黄草可减弱尼古丁的奖赏效应，抑制尼古丁引起的行为敏化的形成和表达，从而具有良好地防治尼古丁依赖的作用，可有效防治尼古丁复吸，有利于吸烟人群戒烟。该溪黄草组合物的活性成分由以下原料制备而成：溪黄草和五加科人参属植物。溪黄草组合物可以有效地防治酒精和尼古丁依赖，促进烟酒成瘾人群戒烟和戒酒，还具有抗疲劳作用，并可以改善口感。

Description

溪黄草的应用和溪黄草组合物 技术领域
本发明涉及生物医药技术领域，特别是涉及溪黄草的应用和溪黄草组合物。
背景技术
长期无节制的饮酒会导致酒精相关的健康问题如急性酒精中毒(醉酒)、酒精性肝病和酒精依赖(成瘾)等。急性酒精中毒是指饮酒者一次性大量酒精摄入后发生的机体机能异常，表现为自控力下降、言语含糊、四肢无力等，严重者可致死；酒精性肝病是由于长期过量饮酒导致的肝脏疾病，初期表现为脂肪肝，进而可发展成酒精性肝炎、肝纤维化和肝硬化，严重酗酒时可诱发广泛性肝细胞坏死，甚至引起肝功能衰竭；与急性酒精中毒和酒精性肝病不同的是，酒精依赖是由于反复饮酒导致躯体或心理性疾病，表现为强烈和强制的饮酒渴求(精神依赖性)，停止饮酒时，可见焦虑、烦躁、抑郁、心悸，甚至震颤等戒断症状(躯体依赖性)。尽管酗酒在世界范围均被视为陋习，但是酒精依赖患者的数量却与日俱增。由于酒精可对人体多个组织器官尤其是肝脏造成严重损害，故酒精性依赖的治疗是治疗酒精性相关疾病的第一步。然而，对于酒精依赖的治疗来讲，可选用的药物十分有限，阿片受体拮抗剂纳曲酮和GABA受体激动剂阿坎酸钙被FDA批准用于预防过度饮酒和戒酒复发。而另一个批准用于防止饮酒的药物为戒酒硫，通过增加饮酒者对酒精的敏感性而减少饮酒。目前用于治疗酒精依赖的药物存在严重的不良反应，病人依从性差，临床使用有诸多限制，无法满足当前众多酒精依赖患者的需求。
尼古丁是人类机体对烟草产生依赖的重要成瘾物质，其作用于中枢神经系统引起多巴胺等神经递质的释放。吸烟成瘾的实质是尼古丁依赖，是一种慢性高复发性疾病，其特征为无法克制的尼古丁寻求冲动以及强迫性地、连续性地使用尼古丁，以体验其带来的欣快感。当依赖者停止尼古丁的摄入时，易产生激惹、注意力不集中、失眠、焦虑等戒断症状，这也是大部分吸烟患者无法摆脱尼古丁的原因之一。戒烟可减少很多重大疾病的发病率及病死率，改善健康状况和生活质量。因此，减少或避免尼古丁的摄入是预防慢性重大疾病发生的有效措施。对于尼古丁(烟草)依赖的治疗主要包括药物、心理、行为治疗等方法。目前，美国FDA批准的尼古丁治疗药物包括尼古丁替代药物、安非他酮及尼古丁乙酰胆碱受体α 4β 2亚型的选择性部分激动药(伐尼克兰)。
然而上述药物在防治尼古丁依赖上或多或少存在不足。具体如下：(1)尼古丁替代药物主要以尼古丁咀嚼片、尼古丁贴片、尼古丁含片形式替代治疗，提供部分原来可从烟草中获 得的尼古丁，从而减低依赖者的吸烟欲望以适应没有香烟的生活。但这种治疗方法只是改变了降低了尼古丁的摄入方式和摄入量，长期使用容易产生局部不良反应如口鼻皮肤过敏、口腔溃疡、不良味觉和咽部烧灼感、呃逆；(2)安非他酮是一种抗抑郁药，其长期使用易产生耐受性，会增加患有抑郁症、癫痫、肝硬化的吸烟人群临床症状恶化的风险；(3)伐尼克兰是一种高选择性α4β2受体部分激动药，主要通过阻断尼古丁与受体的结合，减少伏隔核脑区释放多巴胺，从而降低吸烟的奖赏效应。临床上使用易出现恶心、失眠、幻觉、头痛、便秘和腹痛、神经精神性风险(如抑郁、焦虑、自杀行为)等不良反应。因此，尽管尼古丁替代药物、安非他酮、伐尼克兰被国内外公认为一线戒烟药物，但戒烟率却不高，这可能是因为它们存在的不良反应导致用药依从性变差，进而诱发香烟复吸。因此，通过改善日常生活方式，采用药食同源的中草药防治烟草和酒精依赖是值得选择的一种治疗手段。
溪黄草为唇形科香茶菜属植物，是广东地区的主流品种，其中的狭基线纹香茶菜(Isodon lophanthoides var.gerardianus(Benth)H.Hara)在2013年更是被国家卫计委列为新食品原料目录，具有清利湿热、退黄利胆、凉血散瘀的功效，民间常用于治疗急性黄疸型肝炎、急性胆囊炎、咽喉炎、跌打瘀肿等疾病。研究表明，溪黄草主要含有黄酮类、萜类、酚酸、挥发油和香豆素等成分。
近年来研究表明，溪黄草水提物能抑制二甲苯致小鼠耳部炎症反应，对四氯化碳(CCl 4)所致小鼠急性肝损伤、酒精所致小鼠急性肝损伤、D-胺基半乳糖(D-CalN)所致大鼠急性肝损伤、醋氨酚所致小鼠急性肝损伤、刀豆蛋白A(ConA)、脂多糖加卡介苗(LPS+BCG)所致小鼠免疫性肝损伤均具有保护作用。但至今并未有关于溪黄草对酒精或尼古丁等成瘾物质依赖的研究报道。
发明内容
基于此，本发明的目的是提供一种溪黄草在预防或治疗成瘾物质依赖产品中的应用，尤其是在预防或治疗酒精依赖和尼古丁依赖产品中的应用。
具体技术方案如下：
溪黄草在制备预防或治疗成瘾物质依赖的产品中的应用。
在其中一些实施例中，所述成瘾物质依赖为酒精依赖或尼古丁依赖。
本发明的另一目的是提供溪黄草在制备改善急性酒精戒断引起的焦虑样行为的产品中的应用。
本发明的另一目的是提供一种溪黄草在制备戒酒的产品中的应用。
本发明的另一目的是提供一种溪黄草在制备戒烟的产品中的应用。
在其中一些实施例中，所述溪黄草为溪黄草生药或溪黄草提取物或溪黄草制剂。
在其中一些实施例中，所述溪黄草提取物为溪黄草水提取物或溪黄草醇提取物。所述溪黄草醇提取物为溪黄草乙醇提取物。
在其中一些实施例中，所述产品为保健品、功能性食品或药物。
在其中一些实施例中，所述产品的剂型为口服液、胶囊剂、片剂、颗粒剂、固体饮料、注射剂、丸剂、糖浆剂、散剂、膏剂、乳液或悬浮液。
本发明的再一目的是提供一种预防或治疗成瘾物质依赖的产品，包括活性成分和辅料，所述活性成分为溪黄草生药或溪黄草提取物或溪黄草制剂。
在其中一些实施例中，所述溪黄草提取物为溪黄草水提取物或溪黄草醇提取物。所述溪黄草醇提取物优选为溪黄草乙醇提取物。
在其中一些实施例中，所述溪黄草制剂为溪黄草茶。
在其中一些实施例中，所述溪黄草茶由包括以下的步骤制备而成：将溪黄草鲜叶依次进行萎凋、揉捻、发酵、风冷、理条和干燥处理。
在其中一些实施例中，所述溪黄草茶由包括以下的步骤制备而成：
(a)萎凋：将溪黄草鲜叶进行萎凋处理；
(b)揉捻：将步骤(a)萎凋后的萎凋叶进行揉捻处理，揉捻时间为(20±10)min；
(c)发酵：将揉捻后的揉捻叶进行发酵，发酵温度为(40±5)℃，发酵时间为(6±1)h；
(e)风冷：将发酵叶进行摊放，摊放厚度为(1±0.2)cm；
(f)理条：将风冷叶进行理条处理，理条温度为(240±20)℃，理条时间为(30±5)min，再进行摊凉；
(g)干燥：将理条叶进行干燥处理，得到溪黄草茶。
在其中一些实施例中，所述溪黄草乙醇提取物的制备过程包括：取溪黄草，加入50～80wt％乙醇水溶液，提取，过滤，浓缩而得。进一步地，所述乙醇水溶液为60～80wt％乙醇水溶液，进一步地，所述提取的时间为10～40min，优选为20～30min。进一步地，所述乙醇水溶液的质量为溪黄草的10～30倍。
在其中一些实施例中，所述溪黄草水提取物的制备过程包括：取溪黄草，用水煎煮1～3次，所得煎液浓缩成稠膏，即得。
在其中一些实施例中，所述稠膏在40～60℃下的相对密度为1.1～1.25。进一步地，在50～60℃下的相对密度为1.1～1.25。
在其中一些实施例中，溪黄草水提取物的制备过程中，每次用水煎煮的时间为0.5～2h， 优选为0.8～1.2h。
本发明的另一目的是提供一种预防或治疗成瘾物质依赖的产品，其活性成分由溪黄草，以及选自桂花、大枣、罗汉果以及枸杞中的至少一种制备而成。
在其中一些实施例中，所述成瘾物质依赖为酒精依赖或尼古丁依赖。
在其中一些实施例中，所述产品的活性成分由溪黄草和桂花制备而成。
在其中一些实施例中，所述产品的活性成分由溪黄草、大枣以及枸杞制备而成。
在其中一些实施例中，所述产品的活性成分由溪黄草、桂花、以及罗汉果制备而成。
在其中一些实施例中，所述产品的活性成分由溪黄草、大枣、桂花以及枸杞制备而成。
本发明的再一目的提供一种预防或治疗成瘾物质依赖的溪黄草组合物，其活性成分由以下的原料制备而成：溪黄草和五加科人参属植物。
在其中一些实施例中，其活性成分由以下重量份的原料制备而成：溪黄草1～100份和五加科人参属植物1～100份。
在其中一些实施例中，所述五加科人参属植物包括西洋参、人参和三七中的至少一种。
在其中一些实施例中，其活性成分由以下重量份的原料制备而成：溪黄草1～20份和五加科人参属植物1～20份；进一步地，溪黄草1～10份和五加科人参属植物1～10份，或者溪黄草1～10份和五加科人参属植物1～2份。进一步地，所述溪黄草与五加科人参属植物的质量比选自1:1、2:1、2:3、3:1、3:2、3:4、4:1、4:3、4:5、5:1、5:3、5:4、5:6、10:1、20:1、30:1、40:1、1:2:、1:3、1:4、1:5，或者选自以上任意两者之间的范围。
本发明还提供另一种改善口感的预防或治疗成瘾物质依赖的溪黄草组合物，其活性成分由以下的原料制备而成：溪黄草和五加科人参属植物，以及桂花、红枣、枸杞、桂圆和罗汉果中的至少一种。
在其中一些实施例中，所述溪黄草组合物的活性成分由以下重量份的原料制备而成：溪黄草1～100份和五加科人参属植物1～100份，以及桂花1～100份、红枣1～100份、枸杞1～100份、桂圆1～100份和罗汉果1～100份中的至少一种。
在其中一些实施例中，所述溪黄草组合物的活性成分由以下的原料制备而成：溪黄草、五加科人参属植物和桂花。
在其中一些实施例中，所述溪黄草组合物的活性成分由以下重量份的原料制备而成：溪黄草1～100份、五加科人参属植物1～100份和桂花1～100份。
在其中一些实施例中，所述溪黄草组合物的活性成分由以下重量份的原料制备而成：溪黄草1～20份、五加科人参属植物1～2份和桂花1～2份；进一步地，溪黄草1～10份、五加科人参属植物1～2份和桂花1～2份；进一步地，溪黄草3～10份、五加科人参属植物1～2份和 桂花1～2份；进一步地，溪黄草3～5份、五加科人参属植物1份和桂花0.5～2份，进一步地溪黄草4份、五加科人参属植物1份和桂花1份。
在其中一些实施例中，所述溪黄草组合物的活性成分由以下的原料制备而成：溪黄草、五加科人参属植物和红枣。
在其中一些实施例中，所述溪黄草组合物的活性成分由以下重量份的原料制备而成：溪黄草1～100份、五加科人参属植物1～100份和红枣1～100份，进一步地，为溪黄草1～10份、五加科人参属植物1～10份和红枣1～10份；进一步地，为溪黄草1～10份、五加科人参属植物1～2份和红枣1～2份。
在其中一些实施例中，所述溪黄草组合物的活性成分由以下的原料制备而成：溪黄草、五加科人参属植物、桂花和红枣。
在其中一些实施例中，所述溪黄草组合物的活性成分由以下重量份的原料制备而成：溪黄草1～100份、五加科人参属植物1～100份、桂花1～100份和红枣1～100份。进一步地，为溪黄草1～25份、五加科人参属植物1～2份、桂花1～2份和红枣1～2份。进一步地，为溪黄草3～10份、五加科人参属植物1～2份、桂花1～2份和红枣1～2份。
本发明的另一目的是提供一种上述的溪黄草组合物在制备预防或治疗成瘾物质依赖的产品中的应用。
在其中一些实施例中，所述成瘾物质依赖为酒精或尼古丁依赖。
本发明的另一目的是提供一种上述的溪黄草组合物在制备戒酒或戒烟的产品中的应用。
本发明的再一目的是提供一种预防或治疗成瘾物质依赖的产品，包括上述的溪黄草组合物，以及辅料。
在其中一些实施例中，所述产品为保健品、食品或药品。
在其中一些实施例中，所述食品的剂型为袋泡茶、饮料、颗粒状食品、粉末状食品、胶囊状食品或片状食品。
在其中一些实施例中，所述保健品的剂型为液体状保健品、颗粒状保健品、粉末状保健品、胶囊保健品或片状保健品。
在其中一些实施例中，所述药品的剂型为口服液、颗粒剂、散剂、胶囊剂或片剂。
在其中一些实施例中，所述辅料包括赋形剂、填料、增容剂、粘合剂、保湿剂、崩解剂、缓溶剂、吸收加速剂、吸附剂、稀释剂、增溶剂、乳化剂、润滑剂、润湿剂、悬浮剂、矫味剂和香料中的至少一种。
与现有技术相比，本发明具有以下有益效果：
本发明采用多种成瘾性药物精神依赖的动物模型对溪黄草进行试验研究，首次发现溪黄 草具有良好的防治成瘾性药物精神依赖作用，如良好的防治酒精依赖的作用，有利于促进戒酒。并且溪黄草的上述防治酒精依赖的作用不影响血液的酒精浓度，不是通过影响血液中酒精的吸收和代谢而产生的，其机理与常规解酒护肝的机理截然不同。本发明溪黄草的防治酒精依赖的作用具体体现在：溪黄草能够显著减轻小鼠对酒精的位置偏爱效应，干扰酒精依赖诱导的行为敏化的形成，有效改善小鼠急性酒精戒断后的焦虑样行为，降低酒精偏爱度，从而实现很好的防治酒精依赖的作用。
同时，本发明首次发现了溪黄草在治疗尼古丁依赖中的作用。本发明采用多种成瘾性药物精神依赖的动物模型进行试验，结果证明溪黄草可减弱尼古丁引起的奖赏效应，抑制尼古丁引起的行为敏化的形成和表达，改善尼古丁引起的神经精神性症状(如焦虑样症状、行为敏化)，具有良好地防治尼古丁依赖的作用，可有效防止尼古丁复吸，利于吸烟人群戒烟。
此外，本发明的溪黄草组合物选择溪黄草和五加科人参属植物复配，可以减弱酒精或尼古丁依赖引起的奖赏效应，抑制酒精或尼古丁引起的行为敏化的形成和表达，有效地防治酒精和尼古丁依赖，促进烟酒成瘾人群戒烟和戒酒，同时，还具有良好的抗疲劳作用，并可以很好地改善口感。
此外本发明的溪黄草的长期使用安全性好，使用依从性好。
附图说明
图1为溪黄草对酒精诱导条件性位置偏爱的影响
Figure PCTCN2021092060-appb-000001
A：基础值前测阶段；B：测试阶段； ##P<0.01vs对照组； **P<0.01vs模型组；
图2为溪黄草对酒精诱导行为敏化的影响
Figure PCTCN2021092060-appb-000002
A：基础值前测阶段；B：急性酒精刺激阶段；C：测试阶段； ##P<0.01vs对照组； *P<0.05、 **P<0.01vs模型组；
图3为溪黄草对小鼠血液酒精浓度的影响
Figure PCTCN2021092060-appb-000003
图4为溪黄草对小鼠饮酒量和酒精偏爱度的影响
Figure PCTCN2021092060-appb-000004
A：饮酒量基础值；B：饮酒量；C：酒精偏爱度基础值；D：酒精偏爱度； **P<0.01vs模型组；
图5为溪黄草对小鼠黑暗中饮酒的影响
Figure PCTCN2021092060-appb-000005
**P<0.01vs模型组；
图6为溪黄草对小鼠急性酒精戒断后明暗箱实验的影响
Figure PCTCN2021092060-appb-000006
A：进入暗箱的潜伏期；B：明箱内的停留时间；C：明暗箱之间的穿越次数； ##P<0.01vs对照组； *P<0.01、 **P<0.01vs模型组。
具体实施方式
本发明下列实施例中未注明具体条件的实验方法，通常按照常规条件，或按照制造厂商所建议的条件。实施例中所用到的各种常用化学试剂，均为市售产品。
除非另有定义，本发明所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本发明的说明书中所使用的术语只是为了描述具体的实施例的目的，不用于限制本发明。
本发明的术语“包括”和“具有”以及它们任何变形，意图在于覆盖不排他的包含。例如包含了一系列步骤的过程、方法、装置、产品或设备没有限定于已列出的步骤或模块，而是可选地还包括没有列出的步骤，或可选地还包括对于这些过程、方法、产品或设备固有的其它步骤。
在本发明中提及的“多个”是指两个或两个以上。“和/或”，描述关联对象的关联关系，表示可以存在三种关系，例如，A和/或B，可以表示：单独存在A，同时存在A和B，单独存在B这三种情况。字符“/”一般表示前后关联对象是一种“或”的关系。
本发明实施方式之一提供了一种溪黄草在制备成瘾物质依赖的产品中的应用。
其中，在一些实施例中，所述成瘾物质依赖为酒精依赖或尼古丁依赖。
本发明另一实施方式提供了溪黄草在制备改善急性酒精戒断引起的焦虑样行为的产品中的应用。
本发明另一实施方式还提供溪黄草在制备戒酒的产品中的应用。
本发明另一实施方式提供了溪黄草在制备戒烟的产品中的应用。
其中，在一些实施例中，所述溪黄草为溪黄草生药，即可以为全草干燥品。
在一些实施例中，所述溪黄草为溪黄草提取物，例如可以为溪黄草水提取物，或者是溪黄草醇提取物，不管是溪黄草水提取物还是溪黄草醇提取物，其按照行业内常规方法所得即可。
在一些实施例中，所述溪黄草为溪黄草制剂。
本发明所述预防或治疗酒精依赖的产品可以为药品、保健品，也可以是功能性食品，所述产品也可以是溪黄草以其他常见的保健食品(例如桂花、大枣、罗汉果以及枸杞等)一起联用，只要不影响溪黄草防治酒精依赖的活性即可。
本实施方式还提供一种改善口感的预防或治疗成瘾物质依赖的产品，其活性成分由包括溪黄草，以及选自桂花、大枣、罗汉果以及枸杞中的至少一种制备而成。其中溪黄草可以任意比例与桂花、大枣、罗汉果以及枸杞中的至少一种进行组合。
在一些实施方式中，所述产品的活性成分由包括溪黄草和桂花制备而成。所述溪黄草和 桂花可以任意质量比例进行组合，如可选自1～100：0.5～100，50～100:0.5～1或1～20:1～20，进一步可选自1～5：1～5，具体可选自：80:0.5、100:1、1:1、1:2、1:3、1:4、1:5、2:1、3:1、4:1、5:1。本发明所述桂花可以选自桂花干燥品或桂花提取物(如水提物、醇提物或桂花油)，还可以选自其他不影响桂花活性的常规加工品。
在其中一些实施方式中，所述产品的活性成分由溪黄草、大枣以及枸杞制备而成。所述溪黄草、大枣以及枸杞可以任意质量比例进行组合，如可选自1～5：1～5：1～5，具体可选自：1:1:1、1:2:1、1:3:1、1:4:1、1:5:1、2:1:1、3:1:1、4:1:1、5:1:1、1:1:2、1:1:3、1:1:4、1:1:5。
在一些实施方式中，所述产品的活性成分由溪黄草、桂花、大枣、以及枸杞制备而成。所述溪黄草、桂花、大枣、以及枸杞可以任意质量比例进行组合，如可选自0.5～10:1～5:1～5:1～5，具体可选自：1:1:1:1、1:2:1:1、1:3:1:1、1:4:1:1、1:5:1:1、2:1:1:1、3:1:1:1、4:1:1:1、5:1:1:1、6:1:1:1、7:1:1:1、1:1:2:1、1:1:3:1、1:1:4:1、1:1:5:1、1:1:1:2、1:1:1:3、1:1:1:4、1:1:1:5。
在一些实施方式中，所述产品的活性成分由溪黄草、桂花、以及罗汉果制备而成。所述溪黄草、桂花、以及罗汉果可以任意质量比例进行组合，如可选自1～100:0.5～5:1～100，进一步可选自80～100:0.5～2:20～40或1～5:1～5:1～5，具体可选自：100:0.5:20、1:1:1、1:2:1、1:3:1、1:4:1、1:5:1、2:1:1、3:1:1、4:1:1、5:1:1、1:1:2、1:1:3、1:1:4、1:1:5。
本发明所述产品也可以是以药物的形式存在。
本实施方式还提供一种预防或治疗成瘾物质依赖的产品，包括溪黄草生药或溪黄草提取物或溪黄草制剂，以及包括辅料。其中所述溪黄草制剂可选为溪黄草茶，所述溪黄草茶是指以溪黄草鲜叶为原料，按照常规的红茶制备方法制备得到的茶叶，其包括萎凋、揉捻、发酵步骤，进一步地，还可以包括风冷、理条、干燥步骤。
在其中一些实施方式中，所述溪黄草提取物为溪黄草水提取物或溪黄草醇提取物。不管是溪黄草水提取物还是溪黄草醇提取物，其按照行业内常规方法所得即可。
本实施方式所述产品不限制剂型，可以为口服液、胶囊剂、片剂、颗粒剂、注射剂、丸剂、糖浆剂、散剂、膏剂、乳液或悬浮液等任意常规剂型。
本实施方式中所述辅料为制备保健品、食品以及药品中可接受的任意常规辅料，如选自赋形剂、填料、增容剂、粘合剂、保湿剂、崩解剂、缓溶剂、吸收加速剂、吸附剂、稀释剂、增溶剂、乳化剂、润滑剂、润湿剂、悬浮剂、矫味剂和香料中的任意一种或多种。
本发明再实施方式之一提供了一种预防或治疗成瘾物质依赖的溪黄草组合物，其活性成分由以下的原料制备而成：溪黄草和五加科人参属植物。
其中，在一些实施方式中，所述溪黄草可以任意质量比与五加科人参属植物进行组合，例如，按重量份计，溪黄草1～100份和五加科人参属植物1～100份；例如，溪黄草1～20份和 五加科人参属植物1～20份；进一步地，溪黄草1～10份和五加科人参属植物1～10份。或者溪黄草1～10份和五加科人参属植物1～2份。例如，所述溪黄草与五加科人参属植物的质量比选自1:1、2:1、2:3、3:1、3:2、3:4、4:1、4:3、4:5、5:1、5:3、5:4、5:6、10:1、20:1、30:1、40:1、1:2:、1:3、1:4、1:5，或者选自以上任意两者之间的范围。
在一些实施方式中，所述溪黄草包括溪黄草生药或溪黄草提取物，以及其他不影响溪黄草活性的加工制品；所述五加科人参属植物包括其生药或提取物，以及其他不影响五加科人参属植物活性的加工制品。
在一些实施方式中，所述五加科人参属植物包括西洋参、人参和三七中的至少一种。
本实施方式还提供一种改善口感的预防或治疗成瘾物质依赖的溪黄草组合物，其活性成分由以下的原料制备而成：溪黄草和五加科人参属植物，以及桂花、红枣、枸杞和罗汉果中的至少一种。上述溪黄草与五加科人参属植物可以任意比例与桂花、红枣、枸杞、桂圆和罗汉果中的至少一种组合。
在一些实施方式中，所述桂花包括桂花生药或桂花提取物或桂花油。进一步地，所述红枣包括红枣生药；所述枸杞包括枸杞生药；所述罗汉果包括罗汉果生药。
在其中一些实施方式中，所述溪黄草组合物的活性成分的原料为溪黄草、五加科人参属植物和桂花。其中，溪黄草和五加科人参属植物可以任意重量份与所述桂花组合，例如，按重量份计，为溪黄草1～100份、五加科人参属植物1～100份和桂花1～100份。
在其中一些实施方式中，所述溪黄草组合物的活性成分的原料为溪黄草、五加科人参属植物、桂花和红枣。其中，溪黄草和五加科人参属植物可以任意重量份与所述桂花和红枣组合。例如，按重量份计，为溪黄草1～100份、五加科人参属植物1～100份、桂花1～100份和红枣1～100份。
本发明的另一实施方式还提供一种上述的溪黄草组合物在制备预防或治疗成瘾物质依赖的产品中的应用。
在其中一些实施方式中，所述成瘾物质依赖为酒精或尼古丁依赖。
本发明的另一实施方式还提供一种上述的溪黄草组合物在制备戒酒或戒烟的产品中的应用。
本发明的再一目的是提供一种预防或治疗成瘾物质依赖的产品，包括上述的溪黄草组合物，以及辅料。
本实施方式所述产品可以为保健品、食品或药品。
本实施方式所述产品不限制剂型，所述食品可以为袋泡茶、饮料、颗粒状食品、粉末状食品、胶囊状食品或片状食品等任意常规剂型。所述保健品为液体状保健品、颗粒状保健品、 粉末状保健品、胶囊保健品或片状保健品等任意常规剂型；所述药品为口服液、颗粒剂、散剂、胶囊剂或片剂等任意常规剂型
本实施方式中所述辅料为制备药品、保健品以及食品中可接受的任意辅料，如选自赋形剂、填料、增容剂、粘合剂、保湿剂、崩解剂、缓溶剂、吸收加速剂、吸附剂、稀释剂、增溶剂、乳化剂、润滑剂、润湿剂、悬浮剂、矫味剂和香料中的任意一种或多种。
以下结合具体实施例对本发明作进一步详细的说明。
实施例1.1
溪黄草水提物的制备：取100g溪黄草全草干燥品，加600ml水煎煮2次，每次煎煮时间为1h，煎液合并，浓缩至相对密度1.1～1.25(50～60℃)的稠膏，备用(1g溪黄草生药相当于0.1g溪黄草提取物)。
1.实验试剂
酒精：(腹腔注射剂量2g/kg，浓度15％)；0.9％生理盐水；
实施例1.1制备的溪黄草水提物(造模是腹腔注射，治疗是灌胃给药)。
2.实验动物与分组
C57BL/6J小鼠，雄性，150只，经条件位置偏爱实验(CPP)剔除筛选至少60只可用于实验的小鼠，分为6组、每组10只；依次为正常对照组(生理盐水)、单纯溪黄草组(溪黄草生药1.0g/kg+生理盐水)、酒精依赖性模型组(生理盐水+酒精)、溪黄草低剂量组(溪黄草生药0.25g/kg+酒精)、溪黄草中剂量组(溪黄草生药0.5g/kg+酒精)、溪黄草高剂量组(溪黄草生药1.0g/kg+酒精)。根据基础值前测阶段测定的实验结果，剔除活动过多或过少的小鼠剔除，剩下小鼠随机均匀分组：60只小鼠分为6组，每组10只，分组与上述一致。
3.试验设备
CPP视频实验系统(广州飞迪生物科技有限公司)：CPP箱(400mm×150mm×200mm)。
4.试验步骤
4.1条件位置偏爱实验
条件性位置偏爱(CPP)动物模型是评价酒精奖赏效应和依赖性作用的一种常用手段，是根据巴普洛夫条件反射理论而建立研究药物奖赏效应的动物模型，将成瘾药物的奖赏效应与特定环境相关联后，实验动物在重现成瘾药物相关环境中即产生奖赏效应。一般实验包括三个阶段：基础值前测阶段、条件性位置偏爱训练阶段和测试阶段。实验第1天，将CPP箱中间隔离门打开，让小鼠在黑、白两箱之间自由探索。记录15min内分别在黑和白箱内的停留时间，测定各小鼠对CPP黑、白箱的偏爱度。根据基础值将对黑箱或白箱存在天然偏爱的小鼠(停留时间>500s)剔除。实验第2～9天，共包含4轮训练。根据基础值将小鼠非偏爱箱 作为伴药箱，本实验中将白箱作为伴药箱，黑箱为非伴药箱。训练的第2、4、6和8天腹腔注射生理盐水5min后放入非伴药箱内，停留30min后取出。训练的第3、5、7和9天给予酒精5min后放入伴药箱，停留30min后取出。正常对照组和模型组小鼠在第2～9天训练前30min给予灌胃生理盐水，溪黄草组在第2～9天训练前30分钟灌胃给予不同剂量的溪黄草。
经过4轮训练后，于第10天进行测试，测试当天不给药。撤去中间隔离门，从中间隔离间将小鼠放入，让小鼠在两箱之间自由选择，记录15min内小鼠分别在伴药箱和非伴药箱内的停留时间。
4.2行为敏化实验
行为敏化实验分为四个阶段：基础值前测阶段、急性酒精诱导阶段、敏化阶段和测试阶段。(1)基础值前测阶段(第1～2d)，目的是让小鼠适应腹腔注射并建立基础活动值。实验开始前小鼠适应测试房间至少1h，称重并按体重腹腔注射生理盐水，立即将小鼠放入敞箱中央，让小鼠在敞箱内自由探索15min，记录其小鼠活动次数，作为小鼠的基础活动值。(2)急性酒精刺激(第3d)：酒精依赖性模型组、溪黄草低剂量组、中剂量组、高剂量组小鼠适应测试环境后按体重腹腔注射酒精(2.0g/kg)，正常对照组和单纯溪黄草组等体积注射生理盐水，立即放入敞箱中央，小鼠自由探索，记录其活动次数。(3)敏化阶段(第4～13d)：各组小鼠每天灌胃给予生理盐水或溪黄草30min后，腹腔注射酒精(2.5g/kg)，每天1次，注射完之后立即放回笼子。(4)测试阶段(第14d)，也称为激发实验：与第3d—样，在适应测试环境1h后，小鼠腹腔注射给以小剂量酒精(2.0g/kg)进行激发，立即放入敞箱中央，小鼠自由探索15min，并记录总活动次数。每只动物实验结束后用花露水搽洗装置(通常实验使用酒精擦拭，但为避免酒精对实验造成影响，故改用稀释的花露水代替酒精)。
4.3自动顶空-气相色谱-质谱法测定血液酒精浓度
将标准溶液和血液样品制备好后，精密量取标准溶液或样品溶液于顶空气瓶中，加入叔丁醇内标溶液，马上用钳口器将顶空瓶用硅胶密封垫密封。放入自动顶空恒温炉中恒温后，进行测定。
4.4两瓶子实验(Two bottle choice)
小鼠适应环境1周后，单笼饲养并给以两瓶子，其中一瓶装纯水，另一瓶装10％酒精，小鼠自由觅食觅水3周；每天下午4:30-6:00称量水和酒精重量，隔天更换新鲜的水和酒精。为防止小鼠产生位置偏爱，每天交替两瓶子位置。根据训练饮酒最后3天小鼠24h饮酒量和酒精偏爱度，将饮酒量过高或过低的小鼠剔除，剩余小鼠随机分为3组。每天于水瓶称量结束后进行腹腔注射给药，每天1次，连续1周。将最后3天实验数据纳入统计，饮酒量计算公式：(酒精溶液消耗量×10％酒精质量比)/体重，单位是g/kg/24h；酒精偏爱度计算公式： 酒精溶液消耗量/(酒精溶液消耗量+水消耗量)。为减少应激对自行饮酒行为的影响，于实验开始前抚摸小鼠，每只每天抚摸1min，连续3天。
4.5黑暗中饮酒实验(Drink in dark)
酗酒行为被美国国立酗酒和酒精中毒研究所定义为短时间内大量饮酒导致血液酒精浓度超过0.08％。酗酒行为在年轻人中比较常见，是日后发展为酒精滥用和依赖的风险因素。黑暗中饮酒实验是模拟人类酗酒行为的常用动物模型，即在短时间内大量高浓度饮酒行为。
依据动物饮酒行为的昼夜节律性，本实验通常在关灯后进行，将水换成20％酒精，让动物持续饮酒2～4h，测定短时间内动物饮酒量/体重比。天然高饮酒品系小鼠(C57BL/6J小鼠)可大量饮酒使血液酒精浓度≥0.1％，并产生醉酒行为。该模型通常被用于研究酒精依赖或复饮行为的神经化学通路及神经环路。根据小鼠饮酒的昼夜节律性，晚上饮酒较多，白天较少，本实验在关灯1h后开始。将水瓶撤去，仅提供一个装有20％酒精瓶，小鼠自行饮酒4h，称量饮酒前、后瓶子重量，本实验连续测试1周，取最后3d实验结果进行统计。饮酒量计算公式：(酒精溶液消耗量×20％酒精质量比)/体重。为测定溪黄草水提物是否影响小鼠酗酒行为，各组小鼠于实验开始30min前腹腔注射给予相应药物或生理盐水，每天一次，连续1周。
4.6明暗箱实验(light/dark box test)
明暗箱实验是评价焦虑样行为常用的动物模型。明暗箱由中央带直径4cm圆孔的挡板隔成明箱和暗箱，明箱60cm上方提供40w灯泡。实验者将小鼠背对暗箱放入明箱内，记录5min内小鼠从明箱穿越入暗箱内的潜伏期、在明箱内的停留时间和明暗箱之间的穿越次数。每只动物实验结束后用花露水搽洗装置。实验前7天，单纯溪黄草组和溪黄草低剂量组、中剂量组、高剂量组小鼠灌胃给予溪黄草，正常对照小组和酒精依赖模型组灌胃给予同等容积生理盐水，给药7天进行明暗箱实验。
5.统计分析处理
采用统计软件进行分析，实验数据均采用均数±标准误表示。除酒精诱导行为敏化实验结果采用单因素重复测量方差分析外，其余数据采用单因素方差分析进行统计。经方差齐性检验，若方差齐，则釆用LSD法进行组间两两比较；若方差不齐则采用Dunnett’s T3法进行组间比较。P<0.05定为差异有统计学意义。
6.试验结果
6.1溪黄草减弱酒精诱导条件性位置偏爱
条件性位置偏爱实验是根据巴甫洛夫条件反射理论而建立研究药物奖赏效应的动物模型，将成瘾药物的奖赏效应与特定环境相关联后，实验动物在重现成瘾药物相关环境中即产生奖赏效应。基础值前测阶段实验结果表明，各组小鼠的基础值均无明显差别(p＝0.7656， 图1A)。经过历时8天4个轮回生理盐水酒精训练后，与训练前相比，正常对照组对伴药箱的偏爱度无明显差异，表明生理盐水不产生奖赏效应；与正常对照组相比，纯溪黄草处理组对伴药箱内的滞留时间无明显差异，酒精处理组(即模型组)在伴药箱内的停留时间明显延长，其对伴药箱的偏爱度明显提高(P<0.01，图1B)，表明纯溪黄草处理并不会引起小鼠对伴药箱的偏爱程度，而酒精产生了明显的奖赏刺激作用，经过训练后，小鼠建立了酒精奖赏效应与伴药箱之间的关联性，酒精诱导条件性位置偏爱模型制备成功。与酒精依赖性模型组相比，溪黄草中、高剂量组处理后的小鼠对伴药箱的偏爱度显著降低(P<0.01，图1B)，表明溪黄草干扰了酒精奖赏效应与特定环境关联性的建立。
6.2溪黄草对酒精诱导行为敏化的影响
反复、间断性给以精神活性药物处理可显著增加个体对药物的反应性，在动物身上表现为自发性活动明显增加。成瘾药物诱导行为敏化与强迫性用药有关。基础值前测阶段实验结果表明，各组间小鼠活动次数无明显差异(p＝0.4057，图2A)。在急性酒精刺激阶段，模型组、溪黄草低剂量组、中剂量组、高剂量组给以酒精刺激小鼠活动次数明显增加，表明酒精引起小鼠行为敏化，模型建立成功(P<0.01，图2B)。在敏化训练阶段，注射酒精前给予溪黄草明显减少酒精刺激引起的敏化小鼠活动增加现象(P<0.05，P<0.01，图2C)，表明溪黄草干扰酒精诱导行为敏化的形成。
6.3溪黄草对小鼠血液酒精浓度的影响
为评价溪黄草是否通过影响酒精的吸收和代谢而产生作用的，于行为学测试结束后采血(各组小鼠灌胃给予生理盐水或溪黄草药物后，腹腔注射酒精(2.5g/kg)，1小时后收集小鼠血清进行检测分析)，顶空气相色谱质谱法测定全血酒精浓度。结果显示，各组间血液酒精浓度无显著差异(p＝0.4057，图3)。表明溪黄草不影响血液酒精浓度，溪黄草抑制酒精诱导行为敏化的获得不是通过影响酒精吸收和代谢而产生作用的。
6.4溪黄草对小鼠饮酒量和酒精偏爱度的影响
小鼠饮酒量和酒精偏爱的实验结果如图4所示，各组间小鼠的饮酒量及酒精偏爱度基础值无明显差异，而在经过训练饮酒后，与空白对照组相比较，溪黄草中、高剂量组均能不同程度减少小鼠的饮酒量和酒精偏爱度(P<0.05,P<0.01)。
6.5溪黄草对小鼠黑暗中饮酒的影响
小鼠黑暗中饮酒实验是常用模拟人类短时间内大量饮酒行为(即酗酒行为)的动物模型。实验结果表明，在关灯1h后，仅4h内小鼠饮酒量就达到4.575±0.7259g/kg，而给予溪黄草中高剂量能明显减少小鼠的饮酒量(P<0.01，图5)。
6.6溪黄草对小鼠急性酒精戒断后明暗箱实验的影响
明暗箱也是用于评价动物焦虑状态的常用动物模型。实验结果图6所示，与对照组小鼠相比较，模型组小鼠在进入暗箱的潜伏期(Latency)明显缩短(P<0.01，图6A)，在明箱内的停留时间(Duration)明显缩短(P<0.01，图6B)，以及明暗箱之间的穿越次数(Transitions)也显著减少(P<0.01，图6C)，而给予溪黄草中高剂量后均能不同程度的逆转这些变化(P<0.05，P<0.01)，明显改善小鼠的焦虑样行为。
此外，本发明溪黄草不抑制肝脏内乙醛脱氨酶的作用及体内单胺氧化酶的活性，从而避免了乙醛对肝脏的损害和由于去甲肾上腺素等单胺类物质的蓄积而造成的血压升高、心率增快等不良反应，提高了治疗的安全性及患者的依从性。
实施例1.2
溪黄草水提物的制备：取100g溪黄草全草干燥品加600ml水煎煮2次，每次煎煮时间为1h，煎液合并，浓缩至相对密度1.1～1.20(50～60℃)备用(1g溪黄草生药相当于0.1g溪黄草水提取物)。
1.试验试剂
尼古丁(皮下注射剂量0.5mg/kg，上海时代生物科技有限公司)；0.9％生理盐水；
实施例1.2制备的溪黄草水提物(造模是腹腔注射，治疗是灌胃给药)。
2.实验动物与分组
C57BL/6J小鼠，雄性，150只，经条件位置偏爱实验(CPP)剔除筛选至少50只可用于实验的小鼠，分为5组，每组10只，正常对照组(生理盐水+生理盐水)、尼古丁依赖性模型组(生理盐水+尼古丁)、溪黄草低剂量组(溪黄草生药0.25g/kg+尼古丁)、溪黄草中剂量组(溪黄草生药0.5g/kg+尼古丁)、溪黄草高剂量组(溪黄草生药1.0g/kg+尼古丁)。
3.实验设备
CPP视频实验系统(广州飞迪生物科技有限公司)：CPP箱(400mm×150mm×200mm)，多功能小鼠自主活动记录仪(山东省医学科学院设备站)，高架十字迷宫行为学分析系统(上海移数信息科技有限公司)。
4.实验方法
4.1条件位置偏爱实验
条件性位置偏爱(CPP)动物模型是评价成瘾性物质奖赏效应和依赖性作用的一种常用方法。一般实验包括三个阶段：基础值前测阶段、条件性位置偏爱训练阶段和测试阶段。实验第1天，将CPP箱中间隔离门打开，让小鼠在黑、白两箱之间自由探索。记录15min内分别在黑和白箱内的停留时间，测定各小鼠对CPP黑、白箱的偏爱度。根据基础值将对黑箱或白箱存在天然偏爱的小鼠(停留时间>500s)剔除。实验第2～9天，共包含4轮训练。根据基 础值将小鼠非偏爱箱作为伴药箱，本实验中将白箱作为伴药箱，黑箱为非伴药箱。训练的第2、4、6和8天腹腔注射生理盐水5min后放入非伴药箱内，停留30min后取出。训练的第3、5、7和9天给予尼古丁5min后放入伴药箱，停留30min后取出。正常对照组和模型组小鼠在第2～9天训练前30min给予灌胃生理盐水，溪黄草组在第2～9天训练前30分钟灌胃给予不同剂量的溪黄草。
经过4轮训练后，于第10天进行测试，测试当天不给药。撤去中间隔离门，从中间隔离间将小鼠放入，让小鼠在两箱之间自由选择，记录15min内小鼠分别在伴药箱和非伴药箱内的停留时间。
4.2行为敏化实验
行为敏化是指慢性间隙性给予成瘾性物质可以引起机体行为反应渐进性增强过程。实验开始前小鼠适应测试房间至少1h，按体重腹腔注射生理盐水，立即将小鼠放入敞箱中央，让小鼠在敞箱内自由探索15min，记录其小鼠活动次数，作为小鼠的基础活动值。
次日起，正常对照组和尼古丁依赖模型组灌胃给予等容量生理盐水，药物组按体重给予相应剂量药物，每天1次，连续7天。每天给药后1小时，对照组皮下注射生理盐水，其他组别皮下注射尼古丁(0.5mg/kg)，每天1次，连续7天；(1)行为敏化的形成：第8天起停用尼古丁4天，不做任何处理；第12天所有动物皮下注射尼古丁0.25mg/kg激发，立即测定小鼠30分钟内的自主活动次数。(2)行为敏化的表达：第8天起停用尼古丁4天，对照组和模型给予等容量生理盐水，药物组给予溪黄草，连续4天。第12天所有动物皮下注射尼古丁0.25mg/kg激发，立即测定小鼠30分钟内的自主活动次数。
4.3高架十字迷宫实验
高架十字迷宫实验是评价啮齿类动物焦虑反应的试验方法，主要通过比较小鼠在开臂和闭臂内的滞留时间和路程来评价小鼠的焦虑行为。本试验将其应用于评价尼古丁依赖小鼠的焦虑样行为。尼古丁依赖性组小鼠每天皮下注射尼古丁0.5mg/kg，连续7天，制备尼古丁依赖模型。正常对照组小鼠，每天皮下注射等体积生理盐水，连续7天。正常对照组和尼古丁依赖组小鼠在造模前30min灌胃给予生理盐水，溪黄草组给与不同剂量的溪黄草。实验开始时手持小鼠，使其背对实验人员，放置在开臂与闭臂接合处的中心区，让小鼠面对开放臂，且所有小鼠需要面对同一开放臂。放置好小鼠后，实验人员迅速远离，小鼠进入高架十字迷宫的同时开始记录5分钟内小鼠在高架十字迷宫内的活动情况。实验结束后，用75％的酒精擦拭检测设备，晾干后方可进行下一只动物的实验，以避免气味对实验结果产生的影响。统计各组小鼠进入开臂和闭臂的总次数，计算进开臂次数百分比(进入开臂的次数/进入开臂和闭臂的总次数)和开臂停留时间的百分比(进入开臂的时间/进入开臂和闭臂的总时间)。
5.统计分析处理
采用SPSS统计软件进行分析，实验数据均采用均数±标准误表示。所有数据采用单因素方差分析进行统计。经方差齐性检验，若方差齐，则釆用LSD法进行组间两两比较；若方差不齐则采用Dunnett’s T3法进行组间比较。P<0.05定为差异有统计学意义。
6.实验结果
6.1溪黄草对尼古丁诱导条件性位置偏爱的影响
如表1所示，各组小鼠基础值前测阶段实验结果表明，各组小鼠在伴药箱均无明显差别(P>0.05)。经过历时8天4个轮回生理盐水和尼古丁训练后，与训练前相比，生理盐水组对伴药箱的偏爱度无明显差异，表明生理盐水不产生奖赏效应。与正常对照组相比，尼古丁模型处理组在伴药箱内的停留时间明显延长，其对伴药箱的偏爱度明显提高(P<0.01)，表明尼古丁产生了明显的奖赏刺激作用，经过训练后，小鼠建立了尼古丁奖赏效应与伴药箱之间的关联性，尼古丁诱导的条件性位置偏爱模型制备成功。与尼古丁模型组相比，中、高溪黄草均显著降低小鼠对伴药箱的停留时间(P<0.01)，表明溪黄草干扰了尼古丁奖赏效应与特定环境关联性的建立，对尼古丁的奖赏效应具有减弱作用。
表1溪黄草对尼古丁诱导条件性位置偏爱的影响
Figure PCTCN2021092060-appb-000007
Figure PCTCN2021092060-appb-000008
###P<0.001vs正常对照组； *P<0.05， **P<0.01vs尼古丁依赖模型组。
6.2溪黄草对尼古丁诱导行为敏化的影响
反复、间断性给以精神活性药物处理可显著增加个体对药物的反应性，在动物身上表现为自发性活动明显增加。如表2所示，实验开展前，各组间小鼠自发活动次数无明显差异(P>0.05)，即小鼠无明显行为异常差异。在行为敏化形成阶段，与正常对照组相比，尼古丁依赖小鼠的活动次数显著增加，表明尼古丁引起小鼠行为敏化形成(P<0.01)。与尼古丁模型组比较，溪黄草中、高剂量显著减少行为敏化小鼠的自发活动次数(P<0.01,P<0.001)， 表明溪黄草能有效抑制尼古丁依赖小鼠的行为敏化形成。在行为敏化表达阶段即尼古丁戒断期间保持给药，与正常对照组比较，尼古丁小鼠的自发活动次数显著增加(P<0.01)；溪黄草剂量依赖性地降低小剂量尼古丁激发的行为敏化表达，差异具有统计学意义。
表2溪黄草对尼古丁诱导行为敏化的影响
Figure PCTCN2021092060-appb-000009
Figure PCTCN2021092060-appb-000010
###P<0.001vs正常对照组； *P<0.05， **P<0.01， ***P<0.001vs尼古丁依赖模型组。
6.3溪黄草对尼古丁依赖小鼠的焦虑反应影响
如表3所示，与正常对照组相比，尼古丁依赖小鼠开臂停留的时间和进入开臂次数的百分比显著减少(P<0.01)，表明尼古丁小鼠出现明显的焦虑样行为。溪黄草在不影响进臂总次数和总时间的前提下，显著增加尼古丁小鼠在开臂的停留时间和进入开臂次数的百分比，其中中、高剂量具有统计学意义。高架十字迷宫实验结果表明，溪黄草具有改善尼古丁依赖性小鼠的焦虑反应。
表3溪黄草对尼古丁依赖小鼠焦虑样行为的影响
Figure PCTCN2021092060-appb-000011
Figure PCTCN2021092060-appb-000012
###P<0.001vs正常对照组； **P<0.01， ***P<0.001vs尼古丁依赖模型组。
实施例2
溪黄草乙醇提取物的制备方法：取一定量溪黄草加入20倍量70％乙醇，提取25min，过滤，减压浓缩而得。
实施例3
本实施例提供一种防治酒精依赖或尼古丁依赖的产品，制备方法：取100g溪黄草全草干燥品、100g桂花(干燥品)，加1000ml水煎煮2次，每次煎煮时间为1h，煎液合并，浓缩至相对密度1.12～1.20(55～60℃)，即得。
实施例4
本实施例提供一种防治酒精依赖或尼古丁依赖的溪黄草茶
按照下列配方称重，按照茶的工艺制备：溪黄草1000g；
制备方法：(a)采摘：选取溪黄草鲜叶；(b)萎凋：将鲜叶置于萎凋槽中进行萎凋处理；(c)揉捻：将萎凋后的茶叶置于揉捻机中进行揉捻处理，揉捻时间为20min；(d)发酵：将揉捻后的茶叶进行发酵，发酵温度为40℃，发酵时间为6h；(e)风冷：将发酵好的茶叶摊开降温，摊放厚度为1cm；(f)理条：将风冷后的茶叶进行理条处理，理条温度为240℃，理条时间为30min，理条结束后摊凉自然回潮，使叶面水分重新分布；(g)干燥：将理条后的茶叶进行干燥处理，得到溪黄草茶。
实施例5
本实施例提供一种防治酒精依赖或尼古丁依赖的片剂按照下列配方称重，按照片剂的工艺制备；溪黄草1000g，大枣500g，枸杞500g，辅料适量，总量1000片；
制备方法：以上三味，加水10000ml煎煮2次，每次煎煮时间为1h，煎液合并，浓缩至相对密度1.12～1.25或1.1～1.20(50～60℃)，上述浓缩液与适量的辅料制成颗粒，干燥，混匀，压制成1000片，包糖衣或薄膜衣，即得。
实施例6
本实施例提供一种防治酒精依赖或尼古丁依赖的口感优良的颗粒剂按照下列配方称重，按照颗粒剂的工艺制备
溪黄草1000g，桂花油10g，辅料适量，总量1000g；
制备方法：以上溪黄草加25倍量的50％-60％乙醇提取2次，每次0.5h，合并滤液，滤液浓缩至相对密度1.12～1.25或1.1～1.20(55～60℃)，浓缩液与适量的辅料制成颗粒，干燥，加入桂花油，混匀，制成1000g颗粒，即得。
实施例7
本实施例提供一种防治酒精依赖或尼古丁依赖的口感优良的茶剂按照下列配方称重，按照茶剂的工艺制备
溪黄草1000g，罗汉果200g，桂花油5g，辅料适量，总量1000g；
制备制法：以上溪黄草和罗汉果加5000ml水煎煮2次，每次1h，合并煎液，滤过，滤 液浓缩至相对密度为1.20(50℃)，加乙醇使含醇量达60％，静置使沉淀，取上清液，回收乙醇并浓缩至适量，加入桂花油和适量的辅料，混匀，压制成块，干燥，即得。
实施例8
本实施例提供一种防治酒精依赖或尼古丁依赖的方便服用且口感优良的袋泡茶按照下列配方称重，按照袋泡茶的工艺制备
溪黄草700g，大枣100g，枸杞100g，桂花100g，总量1000g；
制备制法：将以上四味混合装进小袋，制成袋泡茶，即得。
实施例9
防治酒精依赖或尼古丁依赖的胶囊的制备
按照下列配方称重，按照胶囊的工艺制备：
溪黄草2000g，辅料适量，空心胶囊1000粒，总量1000粒；
制法：取以上的溪黄草生药按照实施例1.1的方法制备溪黄草水提取物，浓缩干燥打粉(或者直接用溪黄草生药进行打粉)，加入适量辅料混匀，装入胶囊，即得。
实施例10
防治酒精依赖或尼古丁依赖的口服液的制备
按照下列配方称重，按照口服液的工艺制备：
溪黄草800g，桂花油5g，辅料适量，总量1000ml；
制法：以上溪黄草生药加8000ml水煎煮二次，合并煎液，滤过，滤液减压浓缩至相对密度为1.10～1.30(50～60℃)的清膏，放冷，加乙醇使含醇量达50％～80％，静置，滤过，滤液回收乙醇并浓缩至相对密度为1.10～1.30(50～60℃)的清膏，加入桂花油及适量水，混匀，调节pH值，冷藏，滤过，加水至1000ml，搅匀，分装，灭菌，即得。
实施例11
防治酒精依赖或尼古丁依赖的饮料的制备
按照下列配方称重，按照饮料的工艺制备：
溪黄草2kg，桂花100g，辅料适量，总量100L
制法：以上两味生药加60L水浸泡30min，加热煎煮1h，过滤，加入辅料适量，加水至100L，分装，灭菌，即得。
实施例12溪黄草组合物的活性研究
一、活性研究
1活性研究方法
1.1试验动物、试剂及分组
健康雄性C57小鼠(体重18-22g)由北京维通利华实验动物公司提供，许可证编号为SCXK(京)2016-0006。饲养于普通级动物实验室(温度：22℃±1℃，湿度：60％±5％)，以标准饲料喂养并饮用纯净水。
实验前使小鼠在12h：12h昼夜交替环境中适应7天，105只C57小鼠随机分为7组，每组15只，分别为：正常对照组(生理盐水0.5g/kg+生理盐水)、模型组(生理盐水0.5g/kg+酒精或尼古丁)、溪黄草组(溪黄草0.5g/kg+酒精或尼古丁)、西洋参组(西洋参0.5g/kg+酒精或尼古丁)、溪黄草+西洋参组1(溪黄草0.5g/kg+西洋参0.5g/kg+酒精或尼古丁)、溪黄草+西洋参组2(溪黄草0.6g/kg+西洋参0.3g/kg+酒精或尼古丁)、溪黄草+西洋参组3(溪黄草0.8g/kg+西洋参0.2g/kg+酒精或尼古丁)。其中，每次给予酒精的剂量为2g/kg，给予尼古丁的剂量为0.5mg/kg。给药所用的溪黄草为水提取物，制备过程为：取100g溪黄草全草干燥品，加600ml水煎煮2次，每次煎煮时间为1h，煎液合并，浓缩至相对密度1.12～1.20(55～60℃)，备用。给药所用的西洋参为西洋参水提物，所述西洋参水提物的制备方法参考溪黄草水提取物。给药所用的溪黄草+西洋参组为两者水提物。
1.2给药方法
溪黄草组、西洋参组及联合用药组(溪黄草+西洋参组1，2，3)给予药物，正常对照组和模型组大鼠则灌胃等体积的生理盐水。
1.3酒精/尼古丁依赖模型制作
1.3.1条件位置偏爱模型
条件性位置偏爱(CPP)动物模型是评价酒精、尼古丁等成瘾性物质奖赏效应和依赖性作用的一种常用方法。一般实验包括三个阶段：基础值前测阶段、条件性位置偏爱训练阶段和测试阶段。实验第1天，将CPP箱中间隔离门打开，让小鼠在黑、白两箱之间自由探索。记录15min内分别在黑和白箱内的停留时间，测定各小鼠对CPP黑、白箱的偏爱度。根据基础值将对黑箱或白箱存在天然偏爱的小鼠(停留时间>500s)剔除。实验第2～9天，共包含4轮训练。根据基础值将小鼠非偏爱箱作为伴药箱，本实验中将白箱作为伴药箱，黑箱为非伴药箱。训练的第2、4、6和8天腹腔注射生理盐水5min后放入非伴药箱内，停留30min后取出。训练的第3、5、7和9天给予成瘾性物质(酒精或尼古丁)5min后放入伴药箱，停留30min后取出。正常对照组和模型组小鼠在第2～9天训练前30min给予灌胃生理盐水，溪黄草组、西洋参组、联合给药组(1，2，3)在第2～9天训练前30分钟灌胃给予相应的药物。
经过4轮训练后，于第10天进行测试，测试当天不给药。撤去中间隔离门，从中间隔离间将小鼠放入，让小鼠在两箱之间自由选择，记录15min内小鼠分别在伴药箱和非伴药箱内的停留时间。
1.3.2行为敏化实验
行为敏化是指慢性间隙性给予成瘾性物质可以引起机体行为反应渐进性增强过程。实验开始前小鼠适应测试房间至少1h，按体重腹腔注射生理盐水，立即将小鼠放入敞箱中央，让小鼠在敞箱内自由探索15min，记录其小鼠活动次数，作为小鼠的基础活动值。次日起，对照组和模型组灌胃给予等容量生理盐水，溪黄草组、西洋参组、联合用药(1，2，3)组按体重给予相应剂量的药物，每天1次，连续7天。每天给药后1小时，对照组皮下注射生理盐水，其他组别皮下酒精或尼古丁，每天1次，连续7天。(1)行为敏化的形成：第8天起停用酒精或尼古丁4天，不做任何处理；第12天所有动物皮下注射酒精或尼古丁激发，立即测定小鼠30分钟内的自主活动次数。(2)行为敏化的表达：第8天起停用酒精或尼古丁4天，对照组和模型组给予等容量生理盐水，药物组给予溪黄草、西洋参或联合用药组(1，2，3)，连续4天。第12天所有动物皮下注射成瘾性物质激发，立即测定小鼠30分钟内的自主活动次数
1.3.3抗疲劳研究
C57小鼠适应性喂养1周后，将小鼠进行随机分组，分为空白对照组、溪黄草组(0.5g/kg)、西洋参组(0.5g/kg)、联合用药组(组1：溪黄草0.5g/kg+西洋参0.5g/kg，组2：溪黄草0.6g/kg+西洋参0.3g/kg，组3：溪黄草0.8g/kg+西洋参0.2g/kg)。各组小鼠均采用灌胃给药，每日1次，连续14d。末次给药后30min，在小鼠尾部负体质量6％的铅丝，置于水中进行游泳，记录小鼠从进入水中至游泳力竭的时间，力竭标准为头部完全没入水中不能上浮的时间。游泳结束30min后，采集小鼠血清，半自动分光光度计测定血清尿素氮(BUN)、血清乳酸(LA)含量。
1.4数据分析
实验数据以
Figure PCTCN2021092060-appb-000013
形式表示，运用SPSS19.0软件对数据进行单因素方差分析，组间两两比较用LSD法。
2.研究结果
3.1溪黄草与西洋参不同配比对尼古丁依赖的作用
如表4所示，基础值前测阶段结果表明，各组小鼠在伴药箱在停留时间无明显区别，差异不具统计学意义(P>0.05)，说明各组小鼠对伴药箱的偏爱程度相似。与正常对照组相比，尼古丁依赖模型组小鼠在伴药箱(白箱)内的停留时间明显延长，其对伴药箱的偏爱度明显提高(P<0.01)，表明尼古丁产生了明显的奖赏效应，小鼠建立了尼古丁奖赏效应与伴药箱之间的关联性。与尼古丁依赖模型组相比，溪黄草及不同配比的溪黄草与西洋参组合物均显著降低尼古丁依赖小鼠在伴药箱的停留时间(P<0.01)，而西洋参组小鼠在伴药箱停留时间 较模型组无明显差别。
表4溪黄草与西洋参对尼古丁诱导条件性位置偏爱的影响
Figure PCTCN2021092060-appb-000014
组别 剂量(g/kg) 基础值(s) 伴药箱停留时间(s)
正常对照组 - 217.4±53.2 234.6±82.5
尼古丁依赖模型组 - 202.7±55.5 729.3±127.3###
溪黄草组 0.5 221.2±41.8 474.4±153.2**
西洋参组 0.5 215.3±62.4 747.2±159.4
溪黄草+西洋参组 0.5:0.5 212.5±57.1 456.8±171.4**
溪黄草+西洋参组 0.6:0.3 208.9±54.1 401.7±148.3**
溪黄草+西洋参组 0.8:0.2 207.3±47.5 382.3±152.9***
###P<0.001vs正常对照组；*P<0.05，**P<0.01vs尼古丁依赖模型组。
3.2溪黄草与西洋参不同配比对酒精依赖的作用
如表5所示，基础值前测阶段结果表明，各组小鼠在伴药箱的停留时间无明显区别，差异不具统计学意义(P>0.05)，说明各组小鼠对伴药箱的偏爱程度相似。与正常对照组相比，酒精依赖模型组小鼠在伴药箱(白箱)内的停留时间明显延长，其对伴药箱的偏爱度明显提高(P<0.01)，表明酒精产生了明显的奖赏效应，小鼠建立了酒精奖赏效应与伴药箱之间的关联性。与酒精依赖模型组相比，溪黄草及不同配比的溪黄草与西洋参组合物均显著降低酒精依赖小鼠在伴药箱的停留时间(P<0.01)，而西洋参组小鼠在伴药箱停留时间较模型组无明显差别。
表5溪黄草与西洋参不同配比对酒精诱导条件性位置偏爱的影响
Figure PCTCN2021092060-appb-000015
组别 剂量(g/kg) 基础值(s) 伴药箱停留时间(s)
正常对照组 - 221.3±47.8 247.6±82.5
酒精依赖模型组 - 215.6±76.2 841.6±92.1###
溪黄草组 0.5 241.2±56.1 505.1±103.1**
西洋参组 0.5 232.1±53.2 847.2±119.2
溪黄草+西洋参组 0.5:0.5 231.1±62.6 497.7±127.3**
溪黄草+西洋参组 0.6:0.3 228.4±55.7 421.4±108.4***
溪黄草+西洋参组 0.8:0.2 227.2±51.6 402.9±102.3***
###P<0.001vs正常对照组；*P<0.05，**P<0.01vs酒精依赖模型组。
3.3溪黄草与西洋参不同配比对尼古丁诱导行为敏化的影响
如表6所示，各组间小鼠的基础活动值无明显差异(P>0.05)，即小鼠的自主活动行为相似。在行为敏化形成阶段，与正常对照组相比，尼古丁依赖小鼠的活动次数显著增加，表明尼古丁使小鼠行为敏化形成(P<0.01)。与尼古丁依赖模型组比较，溪黄草及不同配比的溪黄草与西洋参组合物均显著减少行为敏化小鼠的自主活动次数(P<0.01,P<0.001)，表明溪黄草能有效抑制尼古丁引起的小鼠行为敏化的形成。在行为敏化表达阶段即尼古丁戒断期间保持给药，与正常对照组比较，尼古丁依赖小鼠的自主活动次数显著增加(P<0.01)； 溪黄草及不同配比的溪黄草与西洋参组合物均降低小剂量尼古丁激发的行为敏化表达，差异具有统计学意义，而西洋参单独给药对尼古丁诱导的行为敏化的形成与表达均无作用。
表6溪黄草与西洋参不同配比对尼古丁诱导行为敏化的影响
Figure PCTCN2021092060-appb-000016
Figure PCTCN2021092060-appb-000017
##～P<0.001vs正常对照组；*P<0.05，**P<0.01，***P<0.001vs尼古丁依赖模型组。
3.4溪黄草与西洋参不同配比对酒精诱导行为敏化的影响
如表7所示，各组间小鼠的基础活动值无明显差异(P>0.05)，即小鼠的自主活动行为相似。在行为敏化形成阶段，与正常对照组相比，酒精依赖小鼠的活动次数显著增加，表明酒精使小鼠行为敏化形成(P<0.01)。与酒精依赖模型组比较，溪黄草及不同配比的溪黄草与西洋参组合物均显著减少行为敏化小鼠的自主活动次数(P<0.01,P<0.001)，表明溪黄草能有效抑制酒精引起的小鼠行为敏化的形成。在行为敏化表达阶段即酒精戒断期间保持给药，与正常对照组比较，酒精依赖小鼠的自主活动次数显著增加(P<0.01)；溪黄草及不同配比的溪黄草与西洋参组合物均降低小剂量酒精激发的行为敏化表达，差异具有统计学意义，而西洋参单独给药对酒精诱导的行为敏化的形成与表达均无作用。
表7溪黄草与西洋参不同配比对酒精诱导行为敏化的影响
Figure PCTCN2021092060-appb-000018
Figure PCTCN2021092060-appb-000019
##～P<0.001vs正常对照组；**P<0.01，***P<0.001vs酒精依赖模型组。
3.5溪黄草与西洋参不同配比抗疲劳作用
游泳至力竭的时间是小鼠体能的综合反应，其不仅反映机体抵抗疲劳的能力，也反映机体的抗应激能力及对不良环境的适应能力。本试验结果显示，西洋参及其与溪黄草的组合物 均可明显延长小鼠游泳至力竭的时间，其中以西洋参与溪黄草1:1配比效果最为明显，而溪黄草单独给药无显著作用。此外，西洋参及其与溪黄草组合物能显著减少运动小鼠血清尿素氮和乳酸含量。该结果表明西洋参及其与溪黄草的组合物具有抗疲劳作用。
表8溪黄草与西洋参不同配比抗疲劳作用
Figure PCTCN2021092060-appb-000020
Figure PCTCN2021092060-appb-000021
*P<0.05，**P<0.01vs溶剂对照组。
二、溪黄草组合物不同配比的口感度
溪黄草有特殊的青草味，口感苦涩，大众接受程度不高，我们通过不同药材筛选及配比的筛选，改善口感。下表展示了口感较好的物质及配比。
材料：溪黄草、西洋参、三七、人参、桂花和红枣均为干燥品，按表9所示配比组合后用热水冲泡，溪黄草组合物与水的比例为1：50，进行口感度测试。
结果如表9所示，本试验结果显示，溪黄草组合物的汤色透亮美观均可接受，苦涩味道与其他配比均可降低，其中以第7组、8组的口感度效果最佳。
表9溪黄草组合物不同配比的口感度
Figure PCTCN2021092060-appb-000022
Figure PCTCN2021092060-appb-000023
三、溪黄草产品的制备
实施例一
片剂的制备：按照下列配方称重，按照片剂的工艺制备：
溪黄草2000g，西洋参200g，大枣50g，枸杞50g，辅料适量，总量1000片；
制备方法：以上四味生药，加水12000ml煎煮2次，每次煎煮时间为1h，煎液合并，浓缩至相对密度1.12～1.20(55～60℃)，上述浓缩液与适量的常规辅料制成颗粒，干燥，混匀，压制成1000片，包糖衣或薄膜衣，即得。
实施例二
颗粒剂的制备：按照下列配方称重，按照颗粒剂的工艺制备：
溪黄草900g，西洋参200g，桂花油10g，辅料适量，总量1000g颗粒；
制备方法：以上溪黄草加5000ml水煎煮2次，每次1h，合并煎液，滤过，滤液浓缩至相对密度1.12～1.20(55～60℃)，浓缩液备用；将西洋参粉碎成细粉，加入上述浓缩液和适量的常规辅料，混匀，制成颗粒，干燥，加入桂花油，混匀，制成1000g颗粒，即得。
实施例三
茶剂的制备：按照下列配方称重，按照茶剂的工艺制备：
溪黄草1000g，西洋参200g，罗汉果50g，辅料适量，总量1000g颗粒；
制备制法：以上溪黄草和罗汉果两味加4000ml水煎煮2次，每次1h，合并煎液，滤过，滤液浓缩至适量浓度，得浓缩液，将西洋参生药粉碎成细粉，加入浓缩液和适量的常规辅料，混匀，压制成块，干燥，即得。
实施例四
袋泡茶的准备：按照下列配方称重，按照袋泡茶的工艺制备：
溪黄草800g，西洋参40g，桂花40g，总量880g；
制备制法：将以上三味生药混合装进小袋，制成袋泡茶，即得。
实施例五
胶囊的制备：按照下列配方称重，按照胶囊的工艺制备：
溪黄草200g，西洋参200g，空心胶囊1000粒，总量1000粒；
制法：以上两味生药粉碎成细粉，过筛，混匀，装入胶囊，即得。
实施例六
口服液的制备：按照下列配方称重，按照口服液的工艺制备：
溪黄草600g，西洋参100g，桂花油6g，辅料适量，总量1000ml；
制法：以上溪黄草和西洋参生药中加水4000ml煎煮二次，合并煎液，滤过，滤液减压浓缩至相对密度为1.10～1.30(50～60℃)的清膏，放冷，加乙醇使含醇量达50％～60％，静置，滤过，滤液回收乙醇并浓缩至相对密度为1.10～1.30(50～60℃)的清膏，加入桂花油及适量水，混匀，调节pH值，冷藏，滤过，加水至1000ml，搅匀，分装，灭菌，即得。
实施例七
饮料的制备：按照下列配方称重，按照饮料的工艺制备：
溪黄草4kg，西洋参2kg，桂花100g，辅料适量，总量100L；
制法：溪黄草加10倍量乙醇提取，西洋参、桂花加适量水浸泡30min，加热煎煮1h，过滤，加入常规辅料适量，加水至100L，分装，灭菌，即得。
实施例八
饮料的制备：按照下列配方称重，按照饮料的工艺制备：
溪黄草4kg，西洋参2kg，红枣1kg，辅料适量，总量100L；
制法：以上三味生药加70L水浸泡30min，加热煎煮1h，过滤，加入常规辅料适量，加水至100L，分装，灭菌，即得。
实施例九
袋泡茶的制备：按照下列配方称重，按照袋泡茶的工艺制备：
溪黄草100g，西洋参500g，总量600g；
制备制法：将以上两味生药混合装进小袋，制成袋泡茶，即得。
实施例十
袋泡茶的制备：按照下列配方称重，按照袋泡茶的工艺制备：
溪黄草200g，西洋参200g，桂圆300g，枸杞300g，总量1000g；
制备制法：将以上四味生药混合装进小袋，制成袋泡茶，即得。
实施例十一
袋泡茶的准备：按照下列配方称重，按照袋泡茶的工艺制备：
溪黄草800g，人参20g，总量820g；
制备制法：将以上两味生药混合装进小袋，制成袋泡茶，即得。
实施例十二
袋泡茶的准备：按照下列配方称重，按照袋泡茶的工艺制备：
溪黄草800g，西洋参40g，桂花40g，总量880g；
制备制法：将以上三味生药混合装进小袋，制成袋泡茶，即得。
实施例十三
口服液的制备：按照下列配方称重，按照口服液的工艺制备：
溪黄草600g，三七50g，桂花油6g，辅料适量，总量1000ml；
制法：以上溪黄草和三七两味生药加水2000ml煎煮二次，合并煎液，滤过，滤液减压浓缩至相对密度为1.10～1.30(50～60℃)的清膏，静置，滤过，浓缩，加入桂花油及适量水和常规辅料，混匀，调节pH值，冷藏，滤过，加水至1000ml，搅匀，分装，灭菌，即得。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。

Claims (22)

  1. 溪黄草在制备预防或治疗成瘾物质依赖的产品中的应用。
  2. 根据权利要求1所述的应用，其特征在于，所述成瘾物质依赖为酒精依赖或尼古丁依赖。
  3. 溪黄草在制备改善急性酒精戒断引起的焦虑样行为的产品中的应用。
  4. 溪黄草在制备戒酒的产品中的应用。
  5. 溪黄草在制备戒烟的产品中的应用。
  6. 根据权利要求1～5任一项所述的应用，其特征在于，所述溪黄草为溪黄草生药或溪黄草提取物或溪黄草制剂。
  7. 根据权利要求6所述的应用，其特征在于，所述溪黄草提取物为溪黄草水提取物或溪黄草醇提取物。
  8. 根据权利要求1～5任一项所述的应用，其特征在于，所述产品为保健品、功能性食品或药物。
  9. 一种预防或治疗成瘾物质依赖的产品，其特征在于，包括活性成分和辅料，所述活性成分为溪黄草生药或溪黄草提取物或溪黄草制剂。
  10. 根据权利要求9所述的产品，其特征在于，所述溪黄草提取物为溪黄草水提取物或溪黄草醇提取物；和/或，所述溪黄草制剂为溪黄草茶；和/或，所述成瘾物质依赖为酒精依赖或尼古丁依赖。
  11. 一种改善口感的预防或治疗成瘾物质依赖的产品，其特征在于，其活性成分由溪黄草，以及选自桂花、大枣、罗汉果以及枸杞中的至少一种制备而成。
  12. 根据权利要求11所述的产品，其特征在于，所述成瘾物质依赖为酒精依赖或尼古丁依赖。
  13. 一种预防或治疗成瘾物质依赖的溪黄草组合物，其特征在于，其活性成分由以下的原料制备而成：溪黄草和五加科人参属植物。
  14. 根据权利要求13所述的溪黄草组合物，其特征在于，其活性成分由以下重量份的原料制备而成：溪黄草1～100份和五加科人参属植物1～100份；优选地，其活性成分由以下重量份的原料制备而成：溪黄草1～10份和五加科人参属植物1～10份；进一步优选地，其活性成分由以下重量份的原料制备而成：溪黄草1～10份和五加科人参属植物1～2份。
  15. 根据权利要求13或14所述的溪黄草组合物，其特征在于，所述五加科人参属植物 包括西洋参、人参和三七中的至少一种。
  16. 一种改善口感的预防或治疗成瘾物质依赖的溪黄草组合物，其特征在于，其活性成分由以下的原料制备而成：溪黄草和五加科人参属植物，以及桂花、红枣、枸杞、桂圆和罗汉果中的至少一种。
  17. 根据权利要求16所述的溪黄草组合物，其特征在于，其活性成分由以下重量份的原料制备而成：溪黄草1～100份、五加科人参属植物1～100份和桂花1～100份；
    或者，其活性成分由以下重量份的原料制备而成：溪黄草1～100份、五加科人参属植物1～100份、红枣1～100份和桂花1～100份。
  18. 权利要求13～17任一项所述的溪黄草组合物在制备预防或治疗成瘾物质依赖的产品中的应用。
  19. 根据权利要求18所述的应用，其特征在于，所述成瘾物质依赖为酒精依赖或尼古丁依赖。
  20. 权利要求13～17任一项所述的溪黄草组合物在制备戒酒或戒烟的产品中的应用。
  21. 一种预防或治疗成瘾物质依赖的产品，其特征在于，包括权利要求13～17任一项所述的溪黄草组合物，以及辅料。
  22. 根据权利要求21所述的产品，其特征在于，所述产品为保健品、食品或药品；进一步地，所述食品为袋泡茶、饮料、颗粒状食品、粉末状食品、胶囊状食品或片状食品；所述保健品为液体状保健品、颗粒状保健品、粉末状保健品、胶囊保健品或片状保健品；所述药品的为口服液、颗粒剂、散剂、胶囊剂或片剂。
PCT/CN2021/092060 2020-09-03 2021-05-07 溪黄草的应用和溪黄草组合物 WO2022048176A1 (zh)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103798478A (zh) * 2014-03-05 2014-05-21 饶平县云盖月茶叶专业合作社 一种溪黄草茶的制作方法
CN104940284A (zh) * 2015-06-25 2015-09-30 广西梧州制药（集团）股份有限公司 溪黄草在制备治疗和/或预防高脂血症药物方面的新用途
CN106720834A (zh) * 2017-01-18 2017-05-31 邢台医学高等专科学校 一种解酒糖果及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103798478A (zh) * 2014-03-05 2014-05-21 饶平县云盖月茶叶专业合作社 一种溪黄草茶的制作方法
CN104940284A (zh) * 2015-06-25 2015-09-30 广西梧州制药（集团）股份有限公司 溪黄草在制备治疗和/或预防高脂血症药物方面的新用途
CN106720834A (zh) * 2017-01-18 2017-05-31 邢台医学高等专科学校 一种解酒糖果及其制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HONG, HUI-WEN ET AL.: "Observation on the Treatment of Chronic Cholecystitis with Chinese Medicine of Self-made Square Addition and Subtraction", CHINESE JOURNAL OF INTEGRATED TRADITIONAL AND WESTERN MEDICINE ON LIVER DISEASES, vol. 28, no. 4, 30 April 2018 (2018-04-30), pages 220 - 221,237, XP055907605 *
XIE, XINGLIANG ET AL.: "Research progress of Xihuangcao", HERALD OF MEDICINE, vol. 30, no. 4, 30 April 2011 (2011-04-30), pages 494 - 497, XP055907562 *

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