WO2020211264A1 - 一种血水草总生物碱纳米微粒的制备方法 - Google Patents

一种血水草总生物碱纳米微粒的制备方法 Download PDF

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WO2020211264A1
WO2020211264A1 PCT/CN2019/104655 CN2019104655W WO2020211264A1 WO 2020211264 A1 WO2020211264 A1 WO 2020211264A1 CN 2019104655 W CN2019104655 W CN 2019104655W WO 2020211264 A1 WO2020211264 A1 WO 2020211264A1
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nanoparticles
blood
total
preparing
water
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李小冬
谈满良
李军涛
杨英士
齐书洋
尤雅莉
蒋家阳
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南京康齐生物科技有限公司
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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)
    • A61K36/66—Papaveraceae (Poppy family), e.g. bloodroot
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
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    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

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  • the invention relates to the technical field of medicine, in particular to a method for preparing blood waterweed total alkaloid nanoparticles.
  • Natural products and their derivatives are one of the main sources of clinical medicines in the world today, and Chinese herbal medicines are valuable resources for seeking new active ingredients.
  • Alkaloids are a large class of important active ingredients in Chinese herbal medicine, with a huge number, complex structure and rich physiological functions.
  • Bloodweed is a plant belonging to the celandine family of the Papaveraceae family. It is a unique genus and a unique species in my country. It is a perennial herb. It is widely distributed in Zhejiang, Jiangxi, Sichuan, Hunan and other southern provinces. The root and rhizome are used as medicine. Domestic researches on bloodweed are mostly found in chemical composition and pharmacology, and there are few reports on the extraction, separation and purification process of total alkaloids. Long Lina uses a solvent set method to extract the total alkaloids of blood plants by simulating the extraction process of the tank in industrial production. The product quality is not ideal and the efficiency is low.
  • Chinese invention patents an extraction process for total alkaloids of blood waterweed (application number or patent number CN201010182943.2), a method for separating total alkaloids from celandine, blood waterweed or flying dragon palm blood (application number or patent number CN200710098448 .1) All use conventional extraction methods, the extraction rate of alkaloids is not high, and it is time-consuming and difficult to industrialize.
  • the purpose of the present invention is to provide a method for preparing blood waterweed total alkaloid nanoparticles, using supercritical reverse extraction of non-medicinal components, by changing the polarity of the extraction medium, and changing the ion pair Nature to obtain the total alkaloids in blood plants. This method produces almost no waste water, the process is environmentally friendly, and the extraction rate is high.
  • a preparation method of total alkaloid nanoparticles of blood water grass including the following steps:
  • the medicinal part of the blood plant is an above-ground growth part, which is crushed to a particle size of 60-100 mesh.
  • the alkaline substance is one or more of Ca(OH) 2 , NaHCO 3 , NaOH, and KOH, and the addition ratio is 0.1-2%; the addition ratio of the water is 30 ⁇ 60%.
  • the pH is adjusted to 3 to 4
  • the alcohol is a 90-95% ethanol solution
  • the extraction temperature is 60-72°C.
  • the refrigerating temperature is 5-8°C, and the refrigerating time is 8-12h; the spraying method is spraying from the bottom to the upper part, and the flow rate is 0.01-1L/min.
  • the conditions of the supercritical crystallization kettle in step c) are: the temperature is 15-25°C, the pressure is 15-35MPa, the medium is CO 2 or 2-10% ethanol-CO 2 mixed fluid, and the flow direction is self From top to bottom, the flow rate is 0.5-3L/min.
  • the size of the prepared total alkaloid nanoparticles of Sanguinarium is a minimum diameter of 500 nm, the main part is 1-15 ⁇ m, and the content of the prepared total alkaloids is greater than 60%.
  • the prepared blood waterweed total alkaloid nanoparticles can be used in feed additives, health foods and medicines.
  • the method of the present invention produces almost no waste water, is environmentally friendly in the process, and has a high extraction rate.
  • the total alkaloid content of the product obtained by the method of the present invention exceeds 60%, and the extraction rate is greater than 60%.
  • the alkaloid nanoparticles prepared by the method of the present invention can be used in the fields of feed additives, health foods and medicines, especially in the fields of treating pet parasites.
  • a preparation method of total alkaloid nano particles of blood water grass including the following steps:
  • the filtrate is refrigerated at 5°C for 8 hours, and is sprayed countercurrently into the supercritical crystallization kettle for preparation.
  • the spraying method is spraying from the bottom to the upper part at a flow rate of 0.01L/min; the conditions of the supercritical crystallization kettle are: the temperature is 15°C, The pressure is 15MPa, the medium is CO 2 , the flow direction is from top to bottom, and the flow rate is 0.5L/min;
  • the size of the prepared total alkaloid nano-particles of blood water grass is 500nm with a minimum diameter of 500nm, the main part is 1-15 ⁇ m, and the content of the prepared total alkaloid is 60.5%.
  • a preparation method of total alkaloid nano particles of blood water grass including the following steps:
  • the size of the prepared total alkaloid nanoparticles of Sanguinarium is a minimum diameter of 500 nm, the main part is 1-13.5 ⁇ m, and the content of the prepared total alkaloids is 60.9%.
  • a preparation method of total alkaloid nano particles of blood water grass including the following steps:
  • the filtrate is refrigerated at 6°C for 10 hours, and is sprayed countercurrently into the supercritical crystallization kettle for preparation.
  • the spraying method is spraying from the bottom to the upper part, and the flow rate is 0.5L/min; the conditions of the supercritical crystallization kettle are: the temperature is 20°C, The pressure is 25MPa, the medium is 6% ethanol-CO 2 mixed fluid, the flow direction is from top to bottom, and the flow rate is 1.5L/min;
  • the size of the prepared total alkaloid nano-particles of Sanguinarium is a minimum diameter of 500 nm, the main part is 1-13.5 ⁇ m, and the content of the prepared total alkaloid is 61.7%.
  • a preparation method of total alkaloid nano particles of blood water grass including the following steps:
  • the size of the prepared total alkaloid nanoparticles of Sanguinarium is a minimum diameter of 500 nm, the main part is 1-14 ⁇ m, and the content of the prepared total alkaloids is greater than 61.5%.
  • a preparation method of total alkaloid nano particles of blood water grass including the following steps:
  • the filtrate is refrigerated at 8°C for 12h, and is sprayed countercurrently into the supercritical crystallization kettle for preparation.
  • the spraying method is spraying from the bottom to the top at a flow rate of 1L/min; the conditions of the supercritical crystallization kettle are: temperature 25°C, pressure 35MPa, the medium is a 10% ethanol-CO 2 mixed fluid, the flow direction is from top to bottom, and the flow rate is 3L/min;
  • the size of the prepared total alkaloid nanoparticles of Sanguinarium is a minimum diameter of 500 nm, the main part is 1-15 ⁇ m, and the content of the prepared total alkaloid is 61.5%.

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Abstract

一种血水草总生物碱纳米微粒的制备方法，制备步骤如下：a)将血水草药用部位粉碎，与碱性物质混合，加入水混匀，静置过夜；b)调节pH，收集沉淀，进行干燥，采用醇提取，浓缩过滤；c)滤液经过冷藏，逆流喷入超临界结晶釜中进行制取；d)收集底部纳米颗粒，即得。该方法将生物碱转变为离子对，过滤，产品总生物碱含量达到60％以上，所获得的纳米粒子的最小直径500nm，主体分部为1-15μm，可应用于饲料添加剂、药品及食品领域。

Description

一种血水草总生物碱纳米微粒的制备方法 技术领域
本发明涉及医药技术领域，具体涉及一种血水草总生物碱纳米微粒的制备方法。
背景技术
天然产物及其衍生物是当今世界临床用药的主要来源之一，而中草药是寻求新的活性组分的宝贵资源。生物碱是中草药中一大类重要的活性成分，具有庞大的数量、复杂的结构和丰富的生理功能。
传统的生物碱提取方法通常采用浸渍、回流、渗漉、煎煮等方法，这些方法本质上都属于溶剂法。随着现代分离技术的飞速发展，一些新技术、新方法也被应用到生物碱的提取工艺中来。如超声辅助提取技术、微波辅助萃取技术、超临界流体萃取技术等，这些现代提取技术的应用，有望解决传统提取过程中存在的能耗大、污染重、杂质多、效率较低等问题，因此这些优势显著的新方法也成为当今分离技术的研究热点。
生物碱的分离与精制也有许多经典的方法，如溶剂萃取法、沉淀法与结晶法等。尽管这些技术较为成熟，但效率不高，成本收益率较低，因此，一些先进的分离纯化技术也就应运而生，发展迅速。近年出现的新技术包括色谱分离技术如制备液相色谱，高速逆流色谱，凝胶柱色谱等、树脂吸附技术大孔树脂吸附，离子交换树脂吸附、分子印迹、膜分离技术等。这些新兴的分离技术克服了传统方法存在的溶剂、能源消耗大且效率不高的问题，有效地改善了生物碱的分离与纯化效果，使生物碱的制备向着高效、节能、规模化的方向发展。
血水草是罂粟科白屈菜族血水草属植物，是我国独属、独种的特有物种，系多年生草本植物，广泛分布于我国浙江、江西、四川、湖南等南方各省区，根及根茎入药。国内对血水草的研究多见于化学成分和药理方面，对其总生物碱提取分离及纯化工艺的报道很少。龙丽娜用溶剂套用法提取，模拟工业生产中组罐的提取工艺提取血水草的总生物碱，产品品质不理想，且效率较低。中国发明专利一种血水草总生物碱的提取工艺(申请号或专利号CN201010182943.2)、一种分离白屈菜、血水草或飞龙掌血总生物碱的方法(申请号或专利号CN CN200710098448.1)等均采用常规的提取方式，对生物碱的提取率不高，且耗时、不易产业化等。
发明内容
要解决的技术问题：本发明的目的是提供一种血水草总生物碱纳米微粒的制备方法， 采用超临界反向萃取非药用成分的方式，通过改变萃取介质极性，且改变离子对的性质获取血水草中的总生物碱。此方法几乎不产生废水，过程中环保，提取率高。
技术方案：一种血水草总生物碱纳米微粒的制备方法，包括以下步骤：
a)将血水草药用部位粉碎，与碱性物质混合，加入水混匀，静置过夜；
b)调节pH，收集沉淀，进行干燥，采用醇提取，浓缩过滤；
c)滤液经过冷藏，逆流喷入超临界结晶釜中进行制取；
d)收集底部纳米颗粒，即得血水草总生物碱纳米微粒。
进一步的，所述的步骤a)中血水草的药用部位为地上生长部位，粉碎至粒径为60～100目。
进一步的，所述的步骤a)中碱性物质为Ca(OH) 2、NaHCO 3、NaOH、KOH中的一种或几种，添加比例为0.1～2％；所述水的添加比例为30～60％。
进一步的，所述的步骤b)中pH调节至3～4，所述醇为90-95％乙醇溶液，提取温度为60-72℃。
进一步的，所述的步骤c)中冷藏温度为5～8℃，冷藏时间为8-12h；所述的喷入方式为底部向上部喷射，流速为0.01-1L/min。
进一步的，所述的步骤c)中超临界结晶釜的条件为：温度为15～25℃，压力为15～35MPa，介质为CO 2或2～10％乙醇-CO 2混合流体，流动方向为自上而下，流速为0.5-3L/min。
进一步的，所制备的血水草总生物碱纳米微粒大小为最小直径500nm，主体分部为1-15μm，所制备的总生物碱的含量大于60％。
进一步的，所述制备的血水草总生物碱纳米颗粒可用于饲料添加剂、保健食品和药品。
进一步的，所制备的总生物碱检测方法采用HPLC-DAD，条件为：色谱柱：C18(200mm×4.6mm，5μm)；流动相：乙腈+水＝30+70(V/V)(每100ml水中加0.1ml磷酸)；流速：1.0ml/min；柱温：35℃；检测波长：270nm；进样体积：20μl。
有益效果：
1.本发明方法几乎不产生废水，过程中环保，提取率高。
2.本发明方法获得产品总生物碱的含量超过60％，提取率大于60％。
3.本发明方法制备的生物碱纳米颗粒可用于饲料添加剂、保健食品和药品领域，尤其可用于治疗宠物寄生虫等领域。
具体实施方式
实施例1
一种血水草总生物碱纳米微粒的制备方法，包括以下步骤：
a)将血水草地上生长部位粉碎至粒径为100目，与0.1wt％Ca(OH) 2混合，加入30wt％水混匀， 静置过夜；
b)调节pH至3，收集沉淀，进行干燥，采用95％乙醇溶液提取，提取温度为60℃，浓缩过滤；
c)滤液经过5℃冷藏8h，逆流喷入超临界结晶釜中进行制取，喷入方式为底部向上部喷射，流速为0.01L/min；超临界结晶釜的条件为：温度为15℃，压力为15MPa，介质为CO 2，流动方向为自上而下，流速为0.5L/min；
d)收集底部纳米颗粒，即得血水草总生物碱纳米微粒。
总生物碱检测方法采用HPLC-DAD，条件为：色谱柱：C18(200mm×4.6mm，5μm)；流动相：乙腈：水＝30：70(V/V)(每100ml水中加0.1ml磷酸)；流速：1.0ml/min；柱温：35℃；检测波长：270nm；进样体积：20μl。
所制备的血水草总生物碱纳米微粒大小为最小直径500nm，主体分部为1-15μm，所制备的总生物碱的含量为60.5％。
实施例2
一种血水草总生物碱纳米微粒的制备方法，包括以下步骤：
a)将血水草地上生长部位粉碎至粒径为60目，与0.5wt％NaHCO 3混合，加入40wt％水混匀，静置过夜；
b)调节pH至3，收集沉淀，进行干燥，采用90％乙醇溶液提取，提取温度为63℃，浓缩过滤；
c)滤液经过6℃冷藏9h，逆流喷入超临界结晶釜中进行制取，喷入方式为底部向上部喷射，流速为0.05L/min；超临界结晶釜的条件为：温度为17℃，压力为20MPa，介质为2％乙醇-CO 2混合流体，流动方向为自上而下，流速为1L/min；
d)收集底部纳米颗粒，即得血水草总生物碱纳米微粒。
总生物碱检测方法采用HPLC-DAD，条件为：色谱柱：C18(200mm×4.6mm，5μm)；流动相：乙腈：水＝30：70(V/V)(每100ml水中加0.1ml磷酸)；流速：1.0ml/min；柱温：35℃；检测波长：270nm；进样体积：20μl。
所制备的血水草总生物碱纳米微粒大小为最小直径500nm，主体分部为1-13.5μm，所制备的总生物碱的含量为60.9％。
实施例3
一种血水草总生物碱纳米微粒的制备方法，包括以下步骤：
a)将血水草地上生长部位粉碎至粒径为80目，与1wt％NaOH混合，加入45wt％水混匀，静置过夜；
b)调节pH至3.5，收集沉淀，进行干燥，采用95％乙醇溶液提取，提取温度为65℃，浓缩过滤；
c)滤液经过6℃冷藏10h，逆流喷入超临界结晶釜中进行制取，喷入方式为底部向上部喷射，流速为0.5L/min；超临界结晶釜的条件为：温度为20℃，压力为25MPa，介质为6％乙醇-CO 2混合流体，流动方向为自上而下，流速为1.5L/min；
d)收集底部纳米颗粒，即得血水草总生物碱纳米微粒。
总生物碱检测方法采用HPLC-DAD，条件为：色谱柱：C18(200mm×4.6mm，5μm)；流动相：乙腈：水＝30：70(V/V)(每100ml水中加0.1ml磷酸)；流速：1.0ml/min；柱温：35℃；检测波长：270nm；进样体积：20μl。
所制备的血水草总生物碱纳米微粒大小为最小直径500nm，主体分部为1-13.5μm，所制备的总生物碱的含量为61.7％。
实施例4
一种血水草总生物碱纳米微粒的制备方法，包括以下步骤：
a)将血水草地上生长部位粉碎至粒径为80目，与1.5wt％KOH混合，加入50wt％水混匀，静置过夜；
b)调节pH至4收集沉淀，进行干燥，采用95％乙醇溶液提取，提取温度为68℃，浓缩过滤；c)滤液经过7℃冷藏11h，逆流喷入超临界结晶釜中进行制取，喷入方式为底部向上部喷射，流速为0.8L/min；超临界结晶釜的条件为：温度为22℃，压力为30MPa，介质为8％乙醇-CO 2混合流体，流动方向为自上而下，流速为2.5L/min；
d)收集底部纳米颗粒，即得血水草总生物碱纳米微粒。
总生物碱检测方法采用HPLC-DAD，条件为：色谱柱：C18(200mm×4.6mm，5μm)；流动相：乙腈：水＝30：70(V/V)(每100ml水中加0.1ml磷酸)；流速：1.0ml/min；柱温：35℃；检测波长：270nm；进样体积：20μl。
所制备的血水草总生物碱纳米微粒大小为最小直径500nm，主体分部为1-14μm，所制备的总生物碱的含量大于61.5％。
实施例5
一种血水草总生物碱纳米微粒的制备方法，包括以下步骤：
a)将血水草地上生长部位粉碎至粒径为100目，与0.5wt％Ca(OH) 2、0.5wt％NaHCO 3、0.5wt％NaOH、0.5wt％KOH混合，加入60wt％水混匀，静置过夜；
b)调节pH至3～4，收集沉淀，进行干燥，采用95％乙醇溶液提取，提取温度为72℃，浓缩过滤；
c)滤液经过8℃冷藏12h，逆流喷入超临界结晶釜中进行制取，喷入方式为底部向上部喷射，流速为1L/min；超临界结晶釜的条件为：温度为25℃，压力为35MPa，介质为10％乙醇-CO 2混合流体，流动方向为自上而下，流速为3L/min；
d)收集底部纳米颗粒，即得血水草总生物碱纳米微粒。
总生物碱检测方法采用HPLC-DAD，条件为：色谱柱：C18(200mm×4.6mm，5μm)；流动相：乙腈：水＝30：70(V/V)(每100ml水中加0.1ml磷酸)；流速：1.0ml/min；柱温：35℃；检测波长：270nm；进样体积：20μl。
所制备的血水草总生物碱纳米微粒大小为最小直径500nm，主体分部为1-15μm，所制备的总生物碱的含量为61.5％。

Claims (8)

  1. 一种血水草总生物碱纳米微粒的制备方法，其特征在于：包括以下步骤：
    a)将血水草药用部位粉碎，与碱性物质混合，加入水混匀，静置过夜；
    b)调节pH，收集沉淀，进行干燥，采用醇提取，浓缩过滤；
    c)滤液经过冷藏，逆流喷入超临界结晶釜中进行制取；
    d)收集底部纳米颗粒，即得血水草总生物碱纳米微粒。
  2. 根据权利要求1所述的一种血水草总生物碱纳米微粒的制备方法，其特征在于：所述的步骤a)中血水草的药用部位为地上生长部位，粉碎至粒径为60～100目。
  3. 根据权利要求1所述的一种血水草总生物碱纳米微粒的制备方法，其特征在于：所述的步骤a)中碱性物质为Ca(OH) 2、NaHCO 3、NaOH、KOH中的一种或几种，添加比例为0.1～2％；所述水的添加比例为30～60％。
  4. 根据权利要求1所述的一种血水草总生物碱纳米微粒的制备方法，其特征在于：所述的步骤b)中pH调节至3～4，所述醇为90-95％乙醇溶液，提取温度为60-72℃。
  5. 根据权利要求1所述的一种血水草总生物碱纳米微粒的制备方法，其特征在于：所述的步骤c)中冷藏温度为5～8℃，冷藏时间为8-12h；所述的喷入方式为底部向上部喷射，流速为0.01-1L/min。
  6. 根据权利要求1所述的一种血水草总生物碱纳米微粒的制备方法，其特征在于：所述的步骤c)中超临界结晶釜的条件为：温度为15～25℃，压力为15～35MPa，介质为CO 2或2～10％乙醇-CO 2混合流体，流动方向为自上而下，流速为0.5-3L/min。
  7. 根据权利要求1所述的一种血水草总生物碱纳米微粒的制备方法，其特征在于：所制备的血水草总生物碱纳米微粒大小为最小直径500nm，主体分部为1-15μm，所制备的总生物碱的含量大于60％。
  8. 根据权利要求7所述的一种血水草总生物碱纳米微粒的制备方法，其特征在于：所述制备的血水草总生物碱纳米颗粒可用于饲料添加剂、保健食品和药品。
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