WO2018099493A1 - 一种金莲花颗粒剂及其制备方法 - Google Patents

一种金莲花颗粒剂及其制备方法 Download PDF

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WO2018099493A1
WO2018099493A1 PCT/CN2018/072853 CN2018072853W WO2018099493A1 WO 2018099493 A1 WO2018099493 A1 WO 2018099493A1 CN 2018072853 W CN2018072853 W CN 2018072853W WO 2018099493 A1 WO2018099493 A1 WO 2018099493A1
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parts
powder
sweet potato
ultrafine
granules
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PCT/CN2018/072853
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English (en)
French (fr)
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高旭华
高仪
王一飞
王巧利
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广东大鹏医药科技有限公司
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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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • 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)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/894—Dioscoreaceae (Yam family)
    • A61K36/8945—Dioscorea, e.g. yam, Chinese yam or water yam
    • 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
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
    • 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
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • 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
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • 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
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • 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

Definitions

  • the invention belongs to the field of traditional Chinese medicine preparations, and particularly relates to a golden lotus granule and a preparation method thereof.
  • the golden lotus is a dry flower of the plant Golden Lotus of the genus Ranunculaceae. It has the functions of clearing away heat and detoxifying. It has been made into tablets, powder injections, capsules, oral liquids and other dosage forms. It is used clinically for acute and chronic diseases. Infectious diseases such as tonsillitis, acute otitis media, acute tympanitis, acute conjunctivitis, acute lymphangitis, upper respiratory tract infection, pharyngitis.
  • Sweet potato is a sweet potato of Convolvulaceae, commonly known as sweet potato, sweet potato, sweet potato, sweet potato, etc. It is native to Mexico in the Americas and was introduced into China in the middle of the 16th century. It has high nutritional value. At present, there are many researches on the development of sweet potato roots and their products at home and abroad, and the analysis of sweet potato stems and leaves and the development of food or medicine have just started.
  • Sweet potato stems and leaves contain a variety of active ingredients, reported from the Asian Vegetable Research and Development Center, each 100g fresh sweet potato stems and leaves containing crude protein 3.56g, crude fiber 4.10g, crude fat 0.67g, calcium 81.2mg, phosphorus 67.3mg, carotene 3.61 mg, VC 25.0 mg, and niacin 0.94 mg. It is not only nutritious, but also has high medicinal value.
  • Artemisia scoparia is the stem and leaf of the compositae, Artemisia scoparia, which is warm and sweet, and enters the liver and kidney. It has the effects of clearing blood, nourishing the heart, reducing blood pressure, moistening the lungs and clearing the phlegm.
  • Licorice is the dry root of legume licorice, licorice licorice or licorice licorice; sweet and sweet; spleen and qi, clearing away heat and detoxification, relieving cough, relieving pain, and reconciling various medicines.
  • nasturtium granules Since the granules have the advantages of convenient taking, quick absorption, rapid effect, and the like, various kinds of nasturtium granules appear on the market. For example, the aconite brand of Golden Lotus granules, whose main component is nasturtium, has the effect of clearing away heat and detoxifying.
  • Chinese Patent Application No. 201110122227.X discloses a golden lotus granule preparation having heat-clearing, detoxifying antibacterial and anti-viral anti-inflammatory, which is prepared from the following Chinese herbal medicines by weight ratio: 1 to 100 parts of nasturtium and 100 to 1 part of scutellaria.
  • the traditional Chinese medicine compound preparation of the invention has good antibacterial, anti-viral and anti-inflammatory effects, and is prepared into a granule agent which is convenient to carry, fast to absorb, and quick in effect, and is favorable for large-scale production thereof.
  • an object of the present invention is to provide a golden lotus granule and a preparation method thereof to solve the above drawbacks.
  • the invention provides a golden lotus granule comprising the following raw materials in parts by weight: 10-20 parts of golden lotus, 3-8 parts of artemisia argyi, 3-5 parts of ultrafine powder of sweet potato stems and leaves, 1-10 parts of licorice, wood 1 to 3 parts of sugar alcohol and 18 to 45 parts of mixed adjuvant, wherein the mixed auxiliary material is composed of dextrin, 0.5 to 3% (W/W) PVP alcohol solution and corncob ultrafine powder: 1: (0.5 to 0.8) : (0.05 to 0.1) by weight composition.
  • the nasturtium granules comprise the following raw materials in parts by weight: 15 parts of nasturtium, 6 parts of Artemisia selengensis, 4 parts of sweet potato stem and leaf ultrafine powder, 5 parts of licorice, 2 parts of xylitol and 26 parts of mixed auxiliary materials.
  • the mixed adjuvant consists of dextrin, 2% (w/w) PVP alcohol solution and corncob ultrafine powder in a weight ratio of 1:0.6:0.06.
  • the nasturtium granules comprise the following raw materials by weight: 10 parts of nasturtium, 3 parts of sage, 3 parts of sweet potato stem and leaf powder, 1 part of licorice, 1 part of xylitol and 18 parts of mixed adjuvant
  • the mixed adjuvant consists of dextrin, 0.5% (w/w) PVP alcohol solution and corncob ultrafine powder in a weight ratio of 1:0.5:0.05.
  • the nasturtium granules comprise the following raw materials in parts by weight: 20 parts of nasturtium, 8 parts of sage, 8 parts of sweet potato stem and leaf ultrafine powder, 10 parts of licorice, 3 parts of xylitol and 45 parts of mixed auxiliary materials.
  • the mixed auxiliary material is composed of dextrin, 3% (W/W) PVP alcohol solution and corncob ultrafine powder in a weight ratio of 1:0.8:0.1.
  • the sweet potato stem and leaf ultrafine powder is obtained by the following steps:
  • the corncob ultrafine powder is prepared by the following steps:
  • the dried corn cob is chopped, pre-pulverized to 30 to 50 mesh, and then crushed into a powder having a particle diameter of 32 to 45 ⁇ m by an ultrafine pulverizer.
  • the granule further comprises 0.1 to 0.3 parts of magnesium lauryl sulfate.
  • the present invention also provides a method of preparing the above-described Golden Lotus granules, comprising the steps of:
  • A) Preparation of raw material fine powder The preparation of the raw material fine powder includes four steps of S1 to S4:
  • the filtrate II is concentrated to a thick paste having a relative density of 1.30 to 1.35 at 80 to 90 ° C, and the thick paste is spray-dried into an extract powder, and the ultrafine powder of sweet potato stems and leaves is added and uniformly mixed to obtain a fine powder of the raw material;
  • the sweet potato stem and leaf ultrafine powder in the step A) is prepared by the following steps:
  • the mixed auxiliary material in the step B) is composed of dextrin, 0.5-3% (W/W) PVP alcohol solution and corncob ultrafine powder: 1: (0.5-0.8): (0.05-0.1) Weight ratio composition.
  • the mixed auxiliary material in the step B) is composed of dextrin, 0.5-3% (W/W) PVP alcohol solution and corncob ultrafine powder in a weight ratio of 1:0.6:0.06.
  • the step B) further comprises adding 0.1 to 0.3 parts of magnesium lauryl sulfate to the raw material fine powder.
  • the ultrafine powder of nasturtium, sage, sweet potato stem and leaf and licorice are the main traditional Chinese medicine components, among which, the golden lotus is preferably Yunnan golden lotus, and its temperature is warm and sweet, and it has heat and detoxification, hurricane and cold. Solving the table, eliminating the effect, etc.; the ultrafine powder of sweet potato stems and leaves is obtained by ultrafine grinding of sweet potato stems and leaves. Compared with the sweet potato stem and leaf extract, it completely retains most of the active components of sweet potato stems and leaves, and its ultrafine powder state has It is beneficial to reduce the viscosity of traditional Chinese medicine thick paste, shorten the subsequent spray drying time, and improve the production efficiency.
  • the components in the formula complement each other, and the effects of dispelling cold and medium, clearing away heat and dampness, soothing the liver and stomach, etc., are used to treat the loss of appetite caused by cold invasion or damp heat, and the symptoms of fatigue are significant.
  • the inventors found that the particles obtained by adding the paste alone were generally moldable, and the particles were easy to adhere, and it was easy to absorb moisture and agglomerate in the later storage, and the shelf life was short; PVP had good solubility and stability, and the invention Attempts to add PVP alcohol solution on the basis of the addition of dextrin resulted in a significant increase in the formability of the obtained granules; however, the inventors also found a problem in that the reproducibility of the granules was poor, and different concentrations of PVP alcohol solution were used. The product properties of the obtained granules are quite different. The inventors have determined that the particles prepared by 0.5 to 3% (w/w) PVP alcohol solution have the best effect through a large number of tests.
  • the particles obtained by adding the dextrin and the PVP alcohol solution also have the problems of being hygroscopic and having poor stability, and the specific performance is that the granules to which the dextrin and the PVP alcohol solution are added are the most
  • the long shelf life is only 12 months, and in the 12th month, moisture absorption and agglomeration appear.
  • adding corncob ultrafine powder on the above basis can greatly improve the hygroscopicity of the particles, and the obtained particles dissolve quickly, and no precipitation occurs after dissolution. Unexpected.
  • the inventors also found that the particle size and dosage of the corncob ultrafine powder have a great influence on its effect.
  • the inventors made unremitting efforts to control the particle size of the ultrafine powder of corn to 32-45 ⁇ m, and controlling its specific gravity with dextrin to be 1:0.05 can greatly improve the hygroscopicity of the particles, and improve The dissolution of the particles.
  • the golden lotus has a bitter taste
  • the addition of xylitol enhances the taste of the granules.
  • the traditional Chinese medicine extract is generally extracted by the method of boiled alcohol precipitation.
  • the method has the advantages of easy operation, high accuracy and low cost, but there are also many reports that the alcohol precipitation process often loses a large amount while removing impurities.
  • the active ingredient The inventors have found that concentrating the drug solution to a certain concentration before the second alcohol precipitation can significantly reduce the loss of the active ingredient.
  • the effect test proves that the granules prepared by the traditional Chinese medicine extract extracted by the method of the present invention have less appetite for treatment caused by cold invasion or damp heat, and the body weight is compared with the existing boiled alcohol precipitation method. The symptoms of fatigue have a more pronounced effect.
  • the granules of the invention have the following advantages:
  • the granule of the present invention has the advantages of good moldability, low moisture absorption, high stability, good dissolution property and fast dissolution rate.
  • the granules of the present invention are used for treating loss of appetite caused by cold invasion or damp heat, and the symptoms of fatigue are significant, and the total effective rate is as high as 100%.
  • the corncob ultrafine powder is prepared by the following steps:
  • the dried corn cob was taken, chopped, pre-pulverized to 40 mesh, and then crushed into a powder having a particle diameter of 38 ⁇ m by an ultrafine pulverizer.
  • the corncob ultrafine powder is prepared by the following steps:
  • the dried corn cob was taken, chopped, pre-pulverized to 30 mesh, and then crushed into a powder having a particle diameter of 32 ⁇ m by an ultrafine pulverizer.
  • the corncob ultrafine powder is prepared by the following steps:
  • the dried corn cob is taken, chopped, pre-pulverized to 50 mesh, and then crushed into a powder having a particle diameter of 45 ⁇ m by an ultrafine pulverizer.
  • the golden lotus granules according to the fifth embodiment of the present invention are prepared from the following parts by weight of raw materials: 15 parts of nasturtium, 6 parts of Artemisia selengensis, 4 parts of sweet potato stem and leaf ultrafine powder, and 5 parts of licorice, 2 parts of xylitol and 26 parts of mixed adjuvant, wherein the mixed adjuvant is composed of dextrin, 2% (w/w) PVP alcohol solution and corn cob ultrafine powder of Example 2 at a weight of 1:0.6:0.06 Than composition.
  • A) Preparation of raw material fine powder The preparation of the raw material fine powder includes four steps of S1 to S4:
  • the filtrate I is evaporated again and concentrated to a concentrated liquid II having a relative density of 1.20 at 85 ° C, and a second solution of the concentrate II 2 times of 85% ethanol is added for secondary alcohol precipitation. After standing overnight, the supernatant is taken, and the precipitate is taken. Washing with 85% ethanol solution, washing the supernatant and the supernatant to obtain filtrate II, and recovering the ethanol under reduced pressure;
  • the filtrate II is concentrated to a thick paste having a relative density of 1.32 at 85 ° C, and the thick paste is spray-dried into an extract powder, and the ultrafine powder of sweet potato stems and leaves is added and uniformly mixed to obtain a fine powder of the raw material;
  • Example 6 a golden lotus granule
  • the golden lotus granules according to the sixth embodiment of the present invention are prepared from the following parts by weight of the preparation raw materials: 10 parts of nasturtium, 3 parts of sage, 3 parts of sweet potato stem and leaf ultrafine powder described in Example 1, 1 part of licorice, 1 part of xylitol and 18 parts of mixed adjuvant, wherein the mixed adjuvant is composed of dextrin, 0.5% (w/w) PVP alcohol solution and the corncob ultrafine powder described in Example 3 at 1:0.5:0.05 Weight ratio composition.
  • Example 5 The preparation method is referred to Example 5.
  • the golden lotus granules according to the seventh embodiment of the present invention are prepared from the following parts by weight of the preparation raw materials: 20 parts of nasturtium, 8 parts of sage, 8 parts of sweet potato stem and leaf ultrafine powder described in Example 1, 10 parts of licorice, 3 parts of xylitol and 45 parts of mixed adjuvant, wherein the mixed adjuvant is composed of dextrin, 3% (w/w) PVP alcohol solution and corncob ultrafine powder described in Example 4 at 1:0.8:0.1 Weight ratio composition.
  • Example 5 The preparation method is referred to Example 5.
  • Comparative Example 1 differs from Example 5 in that the licorice was removed and the weight fraction of the sweet potato ultrafine powder was increased to 9 parts, and the remaining parameters and operations were as in Example 5.
  • Comparative Example 2 differs from Example 5 in that the mixed adjuvant is dextrin, and the remaining parameters and operations are as in Example 5.
  • Comparative Example 3 differs from Example 5 in that the mixed adjuvant was composed of dextrin and a 2% (w/w) PVP alcohol solution in a weight ratio of 1:0.6, and the remaining parameters and operations were as in Example 5.
  • Comparative Example 4 differs from Example 5 in that the mixed adjuvant consists of dextrin, 2% (w/w) PVP alcohol solution and corncob ultrafine powder in a weight ratio of 1:1:1.
  • Example 5 The preparation method described in Example 5 was repeated in the same manner, but the step of concentrating the filtrate I was removed in the step S3), and the remaining parameters and operations were as in Example 5.
  • the granules prepared in Examples 5 to 7 and Comparative Examples 1 to 5 were respectively subjected to an acute toxicity test, a 30-day feeding test, and a 90-day feeding test.
  • RESULTS The growth of the feeding animals was good, and the hematology and physical and chemical examinations were normal. Therefore, the present invention provides that the Golden Lotus granules have food safety and are suitable for long-term drinking.
  • the granules according to Examples 5 to 7 of the present invention have the characteristics of uniform particles and uniform color, and are easy to granulate and excellent in elution properties.
  • Comparative Example 4 changed the ratio of dextrin, PVP alcohol solution and corncob ultrafine powder in the mixed adjuvant, and the obtained granules decreased compared with Example 5, but the granules of Comparative Examples 2 to 3 were compared. It’s better.
  • Examples 5 to 7 and Comparative Examples 2 to 4 were subjected to long-term sample retention test under room temperature conditions. Samples were taken at the end of the 3rd, 6th, 12th and 18th months to examine their appearance, solubility, moisture content and microbial limits. The results are shown in Table 2.
  • the samples of Comparative Examples 2 to 4 have different degrees of changes after long-term room temperature retention test.
  • the samples in Comparative Examples 2 and 3 had strong hygroscopicity, and moisture absorption occurred in the 6th and 12th months, respectively, and agglomeration and mildew occurred in the 12th and 18th months.
  • the stability of the two groups of samples is poor, which is not conducive to long-term preservation.
  • Group 5 The Golden Lotus granules (10 g/bag) described in Example 5 of the present invention are taken twice a day, each time taking 1 sachet with warm water, 7 days for 1 course of treatment, and taking 2 courses continuously;
  • Group 6 The golden lotus granules (10 g/bag) described in Example 6 of the present invention, 2 times a day, each time taking 1 sachet with warm water, 7 days for 1 course of treatment, taking 1 course of treatment;
  • Group 7 The golden lotus granules (10 g/bag) described in Example 7 of the present invention, 2 times a day, each time taking 1 sachet with warm water, 7 days for 1 course of treatment, taking 1 course of treatment;
  • Comparative Example 1 group The golden lotus granules (10 g/bag) of Comparative Example 1 of the present invention were taken twice a day, each time taking 1 sachet with warm water, 7 days for 1 course of treatment, taking 1 course of treatment;
  • Comparative Example 5 The golden lotus granules (10 g/bag) according to the comparative example 5 of the present invention were taken twice a day, and 1 pouch was taken with warm water each time, 7 days was a course of treatment, and 1 course of treatment was taken.
  • the granules according to Examples 5 to 7 of the present invention treat the loss of appetite caused by cold invasion or damp heat, and the symptoms of fatigue are significant, and the total effective rate is as high as 100%, which is much higher than Comparative Example 1 and Comparative Example 5 The therapeutic effect of the granules.

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Abstract

一种金莲花颗粒剂及其制备方法，所述颗粒剂按重量份数计包括金莲花10～20份、茼蒿3～8份、甘薯茎叶超微粉3～5份、甘草1～10份、木糖醇1～3份以及混合辅料18～45份，其中，所述混合辅料由糊精、0.5～3％(W/W)的PVP醇溶液和玉米芯超微粉按1:(0.5～0.8):(0.05～0.1)的重量比组成。该颗粒剂成型性好、不易稀释、稳定性高、溶出性好且溶解速度快。

Description

一种金莲花颗粒剂及其制备方法 技术领域
本发明属于中药制剂领域，具体涉及一种金莲花颗粒剂及其制备方法。
背景技术
金莲花为毛茛科金莲花属的植物金莲花的干燥花朵，具有清热解毒的功效，现已被制成片剂、粉针剂、胶囊剂、口服液等多种剂型，临床上多用于急、慢性扁桃炎、急性中耳炎、急性鼓膜炎、急性结膜炎、急性淋巴管炎、上呼吸道感染、咽炎等感染性疾病。
甘薯属旋花科甘薯属，俗称红薯、白薯、番薯、甜薯等，原产于美洲墨西哥，大约16世纪中叶传入我国，具有很高的营养价值。目前，国内外对甘薯块根及其制品开发研究很多，而对甘薯茎叶的分析研究及其食品或药品的开发才刚刚起步。甘薯茎叶含有多种活性成分，距亚洲蔬菜研究所发展中心报道，每100g新鲜甘薯茎叶含粗蛋白3.56g、粗纤维4.10g、粗脂肪0.67g、钙81.2mg、磷67.3mg、胡萝卜素3.61mg、VC 25.0mg、烟酸0.94mg。其不仅营养丰富，而且还具有较高的药用价值。
茼蒿为菊科植物茼蒿的茎叶，性温，味甘涩，入肝、肾经，有清血、养心、降压、润肺、清痰的功效。
甘草为豆科植物甘草、胀果甘草或光果甘草的干燥根；性味甘、平；补脾益气，清热解毒，祛痰止咳，缓急止痛，调和诸药。
目前，以金莲花、甘薯茎叶超微粉、茼蒿以及甘草为主要有效成分的制剂还未见有报道。
由于颗粒剂具有服用方便，吸收快、显效迅速等优点，市场上出现了各种各样的金莲花颗粒剂。如锥子山牌金莲花颗粒，其主要成分为金莲花，具有清热解毒的功效。
中国专利申请201110122227.X公开了一种具有清热解毒抗菌和抗病毒消炎的金莲花颗粒制剂，由下述按重量比的中药材制成:金莲花1～100份、黄芩100～1份。该发明的中药复方制剂具有良好的抗菌、抗病毒消炎作用，制成携带服用方便、吸收更快、见效快的颗粒剂，有利于其大规模生产。但由于中药稠膏本身含水分较多，其在实际生产时不易与糊精混合均匀，容易形成结块，且中药类的颗粒剂本身易吸潮，该颗粒剂还加入了大量的蔗糖，进一步加剧了颗粒的吸湿性，其所制得的颗粒剂稳定性较差，容易回潮，不利于颗粒的保存。
因此，针对上述现有技术中存在的技术问题，有必要提供一种体系稳定，易于制备和成型的金莲花颗粒剂。
发明内容
为了解决现有技术中存在的技术问题，本发明的目的在于提供一种金莲花颗粒剂及其制备方法，以解决以上缺陷。
本发明提供了一种金莲花颗粒剂，包括以下重量份数的制备原料：金莲花10～20份、茼蒿3～8份、甘薯茎叶超微粉3～5份、甘草1～10份、木糖醇1～3份以及混合辅料18～45份，其中，所述混合辅料由糊精、0.5～3％(W/W)的PVP醇溶液和玉米芯超微粉按1:(0.5～0.8):(0.05～0.1)的重量比组成。
优选地，所述的金莲花颗粒剂包括以下重量份数的制备原料：金莲花15份、茼蒿6份、甘薯茎叶超微粉4份、甘草5份、木糖醇2份以及混合辅料26份，其中，所述混合辅料由糊精、2％(W/W)的PVP醇溶液和玉米芯超微粉按1:0.6:0.06的重量比组成。
优选地，所述的金莲花颗粒剂包括以下重量份数的制备原料：金莲花10份、茼蒿3份、甘薯茎叶超微粉3份、甘草1份、木糖醇1份以及混合辅料18份，其中，所述混合辅料由糊精、0.5％(W/W)的PVP醇溶液和玉米芯超微粉按1:0.5:0.05的重量比组成。
优选地，所述的金莲花颗粒剂包括以下重量份数的制备原料：金莲花20份、茼蒿8份、甘薯茎叶超微粉5份、甘草10份、木糖醇3份以及混合辅料45份，其中，所述混合辅料由糊精、3％(W/W)的PVP醇溶液和玉米芯超微粉按1:0.8:0.1的重量比组成。
优选地，所述甘薯茎叶超微粉由以下步骤制得：
取新鲜甘薯茎叶，去杂质，洗净，晾干，干燥，预粉碎至30～50目后经超微粉碎机碎成粒径为20～50μm的粉体，即得。
优选地，所述玉米芯超微粉由以下步骤制得：
取晒干后的玉米芯，切碎，预粉碎至30～50目后经超微粉碎机碎成粒径为32～45μm的粉体，即得。
优选地，所述颗粒剂还包括月桂醇硫酸镁0.1～0.3份。
相应地，本发明还提供了一种制备上述的金莲花颗粒剂的方法，包括以下步骤：
A)原料细粉的制备：所述原料细粉的制备包括S1～S4四个步骤：
S1、取金莲花、茼蒿和甘草，洗净，晾干，粉碎成60～70目，加入药材3～6倍量的蒸馏水煎煮1～3次，过滤，合并煎煮液，将煎煮液蒸发浓缩至80～90℃下相对密度为1.05～1.10的浓缩液Ⅰ，冷却，备用；
S2、往上述浓缩液Ⅰ中边搅拌边缓慢滴加所述浓缩液Ⅰ1～2倍量的50～60％的乙醇溶液进行一次醇沉，静置过夜后取上清液，沉淀物用50～60％的乙醇溶液洗涤，洗涤液与上清液合并得滤液Ⅰ，减压回收乙醇；
S3、将滤液Ⅰ再次蒸发浓缩至80～90℃下相对密度为1.15～1.25的浓缩液Ⅱ，加入浓缩液Ⅱ2～3倍量的80～90％的乙醇溶液进行二次醇沉，静置过夜后取上清液，沉淀物用80～90％的乙醇溶液洗涤，洗涤液与上清液合并得滤液Ⅱ，减压回收乙醇；
S4、将滤液Ⅱ浓缩至80～90℃下相对密度为1.30～1.35的稠膏，将上述稠膏经喷雾干燥成浸膏粉，加入甘薯茎叶超微粉，混合均匀，得原料细粉；
B)往上述原料细粉中加入木糖醇、0.5～3％(W/W)的PVP醇溶液和混合辅料，混匀，预压成粗片，粉碎，过筛，即得。
优选地，所述步骤A)中所述甘薯茎叶超微粉由以下步骤制得：
取新鲜甘薯茎叶，去杂质，洗净，晾干，干燥，预粉碎至30～50目后经超微粉碎机碎成粒径为20～50μm的粉体，即得。
优选地，所述步骤B)中所述混合辅料由糊精、0.5～3％(W/W)的PVP醇溶液和玉米芯超微粉按1:(0.5～0.8):(0.05～0.1)的重量比组成。
优选地，所述步骤B)中所述混合辅料由糊精、0.5～3％(W/W)的PVP醇溶液和玉米芯超微粉按1:0.6:0.06的重量比组成。
优选地，所述步骤B)还包括往所述原料细粉中加入月桂醇硫酸镁0.1～0.3份。
本发明颗粒剂中，金莲花、茼蒿、甘薯茎叶超微粉以及甘草为主要的中药成分，其中，金莲花优选为云南金莲花，其性温、味甘辛，具有清热解毒，祛风散寒，解表，消结等功效；甘薯茎叶超微粉由甘薯茎叶经超微粉碎得到，与甘薯茎叶提取物相比，其完整地保留了甘薯茎叶的大部分有效成分，且其超微粉状态有利于降低中药稠膏的粘度，缩短后续喷雾干燥时间，提高了生产效率。配方中各组分相辅相成，共奏散寒和中，清热祛湿，疏肝和胃等功效，用于治疗由寒邪入侵或湿热等引起的食欲不振，身重乏力症状具有显著的效果。
发明人在试验过程中发现单独加入糊精制得的颗粒成型性一般，且颗粒间易粘连，在后期储藏中容易吸潮结块，保存期较短；PVP具有良好的溶解性和稳定性，发明人尝试在加入糊精的基础上加入PVP醇溶液，结果所制得的颗粒的成型性有明显提升；但发明人同时发现一个问题，颗粒的重现性较差，不同浓度的PVP醇溶液所制得的颗粒之间产品性能差异较大，发明人通过大量的试验，最终确定0.5～3％(W/W)的PVP醇溶液所制得的颗粒效果最好。
但是，由于中药浸膏本身易吸潮，加入了糊精和PVP醇溶液制得的颗粒还存在易吸湿，稳定性差的问题，具体表现为，加入了糊精和PVP醇溶液的颗粒剂其最长保存期仅为12个月，在第12个月即出现了吸潮结块现象。发明人通过大量长期的试验，终于发现，在上述基础上再加入玉米芯超微粉能大大地 改善颗粒的吸湿性，且制得的颗粒溶解速度快，在溶解后无沉淀产生，这一点是发明人意想不到的。同时发明人也发现，玉米芯超微粉的粒径和用量对其效果有较大的影响。最终，发明人通过不懈的努力得出，将玉米超微粉的粒径控制在32～45μm，且控制其与糊精的比重在1:0.05之间能极大改善颗粒的吸湿性，并且提高了颗粒的溶出性。
本发明中金莲花味偏苦，加入了木糖醇提升了颗粒的口感。
现有技术中一般采用水煮醇沉的方法提取中药提取物，该方法具有操作容易，准确度高，成本低廉的优点，但也有许多报道指出醇沉过程在除去杂质的同时，往往损失较大量的有效成分。发明人发现，在第二次醇沉前先将药液浓缩到一定的浓度，能够明显减少有效成分的损失。效果试验证明，与现有的水煮醇沉方法相比，由经本发明所述方法提取得到的中药提取液所制得的颗粒剂对治疗由寒邪入侵或湿热等引起的食欲不振，身重乏力症状具有更显著的效果。
发明人在制粒过程中发现，在将浸膏和辅料混合时，仍然会有些小粒团聚在一起。为了解决该问题，发明人尝试了多种方法，最后终于发现，在将浸膏与辅料混合前，先将浸膏经喷雾干燥成粉状，再与辅料混合，容易将两者混合均匀，且无团聚现象。月桂醇硫酸镁能够避免制粒过程中产生较多的细粉。
与现有技术相比，本发明颗粒剂有以下优势：
1)本发明颗粒剂具有成型性好，不易吸湿，稳定性高，溶出性好且溶解速度快的优点。
2)本发明颗粒剂用于治疗由寒邪入侵或湿热等引起的食欲不振，身重乏力症状具有显著的效果，总有效率高达100％。
具体实施方式：
以下通过具体实施方式的描述对本发明作进一步说明，但这并非是对本发明的限制，本领域技术人员根据本发明的基本思想，可以做出各种修改或改进，但是只要不脱离本发明的基本思想，均在本发明的范围之内。
实施例1、甘薯茎叶超微粉的制备
取新鲜甘薯茎叶，去杂质，洗净，晾干，干燥，预粉碎至40目后经超微粉碎机碎成粒径为30μm的粉体，即得。
实施例2、玉米芯超微粉的制备
所述玉米芯超微粉由以下步骤制得：
取晒干后的玉米芯，切碎，预粉碎至40目后经超微粉碎机碎成粒径为38μm的粉体，即得。
实施例3、玉米芯超微粉的制备
所述玉米芯超微粉由以下步骤制得：
取晒干后的玉米芯，切碎，预粉碎至30目后经超微粉碎机碎成粒径为32μm的粉体，即得。
实施例4、玉米芯超微粉的制备
所述玉米芯超微粉由以下步骤制得：
取晒干后的玉米芯，切碎，预粉碎至50目后经超微粉碎机碎成粒径为45μm的粉体，即得。
实施例5、一种金莲花颗粒剂
本发明实施例5所述金莲花颗粒剂由以下重量份数的制备原料制备而成：金莲花15份、茼蒿6份、实施例1所述的甘薯茎叶超微粉4份、甘草5份、木糖醇2份以及混合辅料26份，其中，所述混合辅料由糊精、2％(W/W)的PVP醇溶液和实施例2所述玉米芯超微粉按1:0.6:0.06的重量比组成。
制备方法：
A)原料细粉的制备：所述原料细粉的制备包括S1～S4四个步骤：
S1、取金莲花、茼蒿和甘草，洗净，晾干，粉碎成70目，加入药材5倍量的蒸馏水煎煮3次，过滤，合并煎煮液，将煎煮液蒸发浓缩至85℃下相对密度为1.10的浓缩液Ⅰ，冷却，备用；
S2、往上述浓缩液Ⅰ中边搅拌边缓慢滴加所述浓缩液Ⅰ2倍量的55％的乙醇溶液进行一次醇沉，静置过夜后取上清液，沉淀物用55％的乙醇溶液洗涤，洗涤液与上清液合并得滤液Ⅰ，减压回收乙醇；
S3、将滤液Ⅰ再次蒸发浓缩至85℃下相对密度为1.20的浓缩液Ⅱ，加入浓缩液Ⅱ2倍量的85％的乙醇溶液进行二次醇沉，静置过夜后取上清液，沉淀物用85％的乙醇溶液洗涤，洗涤液与上清液合并得滤液Ⅱ，减压回收乙醇；
S4、将滤液Ⅱ浓缩至85℃下相对密度为1.32的稠膏，将上述稠膏经喷雾干燥成浸膏粉，加入甘薯茎叶超微粉，混合均匀，得原料细粉；
B)往上述原料细粉中加入木糖醇、2％(W/W)的PVP醇溶液和混合辅料，混匀，预压成粗片，粉碎，过筛，按10g/袋分装，即得。
实施例6、一种金莲花颗粒剂
本发明实施例6所述金莲花颗粒剂由以下重量份数的制备原料制备而成：金莲花10份、茼蒿3份、实施例1所述的甘薯茎叶超微粉3份、甘草1份、木糖醇1份以及混合辅料18份，其中，所述混合辅料由糊精、0.5％(W/W)的PVP醇溶液和实施例3所述的玉米芯超微粉按1:0.5:0.05的重量比组成。
制备方法参考实施例5。
实施例7、一种金莲花颗粒剂
本发明实施例7所述金莲花颗粒剂由以下重量份数的制备原料制备而成：金莲花20份、茼蒿8份、实施例1所述的甘薯茎叶超微粉5份、甘草10份、木糖醇3份以及混合辅料45份，其中，所述混合辅料由糊精、3％(W/W)的PVP醇溶液和实施例4所述的玉米芯超微粉按1:0.8:0.1的重量比组成。
制备方法参考实施例5。
对比例1、一种金莲花颗粒剂
对比例1与实施例5的区别在于：去掉甘草，甘薯超微粉的重量份数增加至9份，其余参数及操作如实施例5。
对比例2、一种金莲花颗粒剂
对比例2与实施例5的区别在于：所述混合辅料为糊精，其余参数及操作如实施例5。
对比例3、一种金莲花颗粒剂
对比例3与实施例5的区别在于：所述混合辅料由糊精和2％(W/W)的PVP醇溶液按1:0.6的重量比组成，其余参数及操作如实施例5。
对比例4一种金莲花颗粒剂
对比例4与实施例5的区别在于：所述混合辅料由糊精、2％(W/W)的PVP醇溶液和玉米芯超微粉按1:1:1的重量比组成。
对比例5、一种金莲花颗粒剂
按相同的步骤重复进行实施例5所述制备方法，但步骤S3)中去掉浓缩滤液Ⅰ步骤，其余参数及操作如实施例5。
试验例一、安全性试验
分别取实施例5～7以及对比例1～5制得的颗粒剂，进行急性毒性试验、30天喂养试验和90天喂养试验。结果：喂养动物的生长情况良好，血液学和理化检查正常。因此，本发明提供金莲花颗粒剂具有食用安全性，适宜长期饮用。
试验例二、质量评价
取本发明实施例5～7以及对比例1～5所述颗粒剂，按照《中国药典》2010版一部附录对各组颗粒剂的性状、粒度、水分含量、全部溶解时间、微生物限度、干燥失重以及制粒效果进行评价，评价结果如表1所示。
表1 评价结果
Figure PCTCN2018072853-appb-000001
注：【性状】：棕黄色颗粒，颗粒均匀，色泽一致为合格；【粒度】：按照粒度测定法测定，不能通过一号筛与能通过五号筛的总和不能超过15％；【水分含量】：按照水分测定法测定，取供试品约1g，置75℃减压干燥5小时，冷却30分钟，精密称定，再在上述温度干燥1小时，冷却，称重，至连续两次称重的差异不超过5mg为止，含水量未超过6％为合格；【溶化性】：取供试品1袋，加热水200ml， 搅拌5min，立即观察，全部溶化，无浑浊为合格；【微生物限度】：按照微生物限度检查法检查；【干燥失重】在80℃减压干燥至恒重，减失重量不超过2％为合格。
由上表1可知：
本发明实施例5～7所述颗粒剂具有颗粒均匀，色泽一致的特点，且其制粒容易，溶出性优异。
与实施例5所述颗粒剂相比，对比例1～5所述颗粒剂各方面指标均有所下降。
需要指出的是：从对比例2结果可看出，单独加入糊精，不易制粒，难成型，且所得颗粒的溶出性较差，不能通过一号筛与能通过五号筛的总和为各组最高，达到19.8％；对比例3在对比例2的基础上加入PVP醇溶液，其所得的颗粒与对比例2相比，制粒效果有明显提升，但颗粒的溶出性和粒度无明显变化；对比例4改变了混合辅料中糊精、PVP醇溶液和玉米芯超微粉的配比，其所得的颗粒剂与实施例5相比有所下降，但比对比例2～3所述颗粒剂要好。
试验例二、稳定性试验
2.1长期室温留样试验
取实施例5～7以及对比例2～4市售样品，室温条件下，进行长期留样试验。分别于第3、6、12和18个月末取样，考察其外观性状、溶化性、水分含量及微生物限度，结果见表2所示。
表2 长期室温留样试验结果
Figure PCTCN2018072853-appb-000002
Figure PCTCN2018072853-appb-000003
由上表2可知，本发明实施例5～7经长期室温留样试验后，样品的外观形状、溶化性、水分含量和微生物限度均无明显变化，有效期长达一年半，具有优异的稳定性。
需要指出的是：与实施例5所述样品相比，对比例2～4所述样品经长期室温留样试验后，样品均有不同程度的变化。其中，对比例2、3所述样品吸湿性较强，其分别在第6个月和第12个月就有吸潮现象发生，在第12个月和第18个月有结块、霉变现象发生，两组样品的稳定性较差，不利于长期保存。
试验例三、临床疗效观察
1.一般资料
选择有由寒邪入侵或湿热等引起的食欲不振，身重乏力症状的自愿者250例，年龄18～35岁之间，将250例自愿者随机分成5组，每组50人，分别是实施例5～7组、对比例1组以及对比例5组。
2、治疗方法
实施例5组：本发明实施例5所述金莲花颗粒剂(10g/袋)，每日2次，每次取1小袋用温水冲服，7天为1疗程，连续服用2个疗程；
实施例6组：本发明实施例6所述金莲花颗粒剂(10g/袋)，每日2次，每次取1小袋用温水冲服，7天为1疗程，服用1个疗程；
实施例7组：本发明实施例7所述金莲花颗粒剂(10g/袋)，每日2次，每次取1小袋用温水冲服，7天为1疗程，服用1个疗程；
对比例1组：本发明对比例1所述金莲花颗粒剂(10g/袋)，每日2次，每次取1小袋用温水冲服，7天为1疗程，服用1个疗程；
对比例5组：本发明对比例5所述金莲花颗粒剂(10g/袋)，每日2次，每次取1小袋用温水冲服，7天为1疗程，服用1个疗程。
3、疗效观察。
3.1疗效指标
(1)显效：服药1～3天后进食明显增加，身重乏力现象完全消失者；
(2)有效：服药3～7天后症状已有改善，进食好转，身重乏力现象明显减轻者；
(3)无效：服药7天后症状无明显改善者。
3.2统计学分析应用SPSS13.0软件进行统计学处理，数据以表示，计数资料用x2检验，计量资料用t检验。
3.3疗效结果
表3 疗效结果
组别 例数 显效(显效率％) 有效(有效率％) 无效(无效率％) 总有效率(％)
实施例5组 50 43(86％) 7(14％) 0 100
实施例6组 50 40(80％) 10(20％) 0 100
实施例7组 50 38(76％) 12(24％) 0 100
对比例1组 50 25(50％) 16(32％) 9(18％) 82
对比例5组 50 20(40％) 18(36％) 12(24％) 76
由上表3可知，本发明实施例5～7所述颗粒剂治疗由寒邪入侵或湿热等引起的食欲不振，身重乏力症状具有显著的效果，其总有效率高达100％，远远高于对比例1和对比例5组所述颗粒剂的治疗效果。

Claims (10)

  1. 一种金莲花颗粒剂，其特征在于，包括以下重量份数的制备原料：金莲花10～20份、茼蒿3～8份、甘薯茎叶超微粉3～5份、甘草1～10份、木糖醇1～3份以及混合辅料18～45份，其中，所述混合辅料由糊精、0.5～3％(W/W)的PVP醇溶液和玉米芯超微粉按1:(0.5～0.8):(0.05～0.1)的重量比组成。
  2. 如权利要求1所述的金莲花颗粒剂，其特征在于，包括以下重量份数的制备原料：金莲花15份、茼蒿6份、甘薯茎叶超微粉4份、甘草5份、木糖醇2份以及混合辅料26份，其中，所述混合辅料由糊精、2％(W/W)的PVP醇溶液和玉米芯超微粉按1:0.6:0.06的重量比组成。
  3. 如权利要求1或2所述的金莲花颗粒剂，其特征在于，所述甘薯茎叶超微粉由以下步骤制得：
    取新鲜甘薯茎叶，去杂质，洗净，晾干，干燥，预粉碎至30～50目后经超微粉碎机碎成粒径为20～50μm的粉体，即得。
  4. 如权利要求1或2所述的金莲花颗粒剂，其特征在于，所述玉米芯超微粉由以下步骤制得：
    取晒干后的玉米芯，切碎，预粉碎至30～50目后经超微粉碎机碎成粒径为32～45μm的粉体，即得。
  5. 如权利要求1或2所述的金莲花颗粒剂，其特征在于，所述颗粒剂还包括月桂醇硫酸镁0.1～0.3份。
  6. 一种制备如权利要求1～4任一所述的金莲花颗粒剂的方法，其特征在于，包括以下步骤：
    A)原料细粉的制备：所述原料细粉的制备包括S1～S4四个步骤：
    S1、取金莲花、茼蒿和甘草，洗净，晾干，粉碎成60～70目，加入药材3～6倍量的蒸馏水煎煮1～3次，过滤，合并煎煮液，将煎煮液蒸发浓缩至80～90℃下相对密度为1.05～1.10的浓缩液Ⅰ，冷却，备用；
    S2、往上述浓缩液Ⅰ中边搅拌边缓慢滴加所述浓缩液Ⅰ1～2倍量的50～60％的乙醇溶液进行一次醇沉，静置过夜后取上清液，沉淀物用50～60％的乙醇溶液洗涤，洗涤液与上清液合并得滤液Ⅰ，减压回收乙醇；
    S3、将滤液Ⅰ再次蒸发浓缩至80～90℃下相对密度为1.15～1.25的浓缩液Ⅱ，加入浓缩液Ⅱ2～3倍量的80～90％的乙醇溶液进行二次醇沉，静置过夜后取上清液，沉淀物用80～90％的乙醇溶液洗涤，洗涤液与上清液合并得滤液Ⅱ，减压回收乙醇；
    S4、将滤液Ⅱ浓缩至80～90℃下相对密度为1.30～1.35的稠膏，将上述稠膏经喷雾干燥成浸膏粉，加入甘薯茎叶超微粉，混合均匀，得原料细粉；
    B)往上述原料细粉中加入木糖醇和混合辅料，混匀，预压成粗片，粉碎，过筛，即得。
  7. 如权利要求6所述的金莲花颗粒剂的方法，其特征在于，所述步骤A)中所述甘薯茎叶超微粉由以下步骤制得：
    取新鲜甘薯茎叶，去杂质，洗净，晾干，干燥，预粉碎至30～50目后经超微粉碎机碎成粒径为20～50μm的粉体，即得。
  8. 如权利要求6所述的金莲花颗粒剂的方法，其特征在于，所述步骤B)中所述混合辅料由糊精、0.5～3％(W/W)的PVP醇溶液和玉米芯超微粉按1:(0.5～0.8):(0.05～0.1)的重量比组成。
  9. 如权利要求8所述的金莲花颗粒剂的方法，其特征在于，所述步骤B)中所述混合辅料由糊精、0.5～3％(W/W)的PVP醇溶液和玉米芯超微粉按1:0.6:0.06的重量比组成。
  10. 如权利要求6所述的金莲花颗粒剂的方法，其特征在于，所述步骤B)还包括往所述原料细粉中加入月桂醇硫酸镁0.1～0.3份。
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