WO2021184636A1 - Préparation de microcapsule de shouhui tongbian et procédé de préparation associé - Google Patents

Préparation de microcapsule de shouhui tongbian et procédé de préparation associé Download PDF

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WO2021184636A1
WO2021184636A1 PCT/CN2020/105564 CN2020105564W WO2021184636A1 WO 2021184636 A1 WO2021184636 A1 WO 2021184636A1 CN 2020105564 W CN2020105564 W CN 2020105564W WO 2021184636 A1 WO2021184636 A1 WO 2021184636A1
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shouhui
add
fine powder
laxative
amount
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PCT/CN2020/105564
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Chinese (zh)
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张贵民
高艳红
刘金宇
关永霞
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鲁南厚普制药有限公司
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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)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704—Polygonum, e.g. knotweed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
    • 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
    • A61K36/258—Panax (ginseng)
    • 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
    • A61K36/284—Atractylodes
    • 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
    • A61K36/482—Cassia, e.g. golden shower tree
    • 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)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • 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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • 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)
    • A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
    • 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)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5052—Proteins, e.g. albumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • 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
    • A61K2236/33—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
    • A61K2236/39—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 relates to a Chinese medicine microcapsule preparation and a preparation method thereof, in particular to a Shouhui laxative microcapsule preparation and a preparation method thereof, and belongs to the field of Chinese medicine preparations.
  • Chinese patent CN100453105C discloses a traditional Chinese medicine composition with laxative detoxification, weight loss and lipid-lowering functions and a preparation method thereof.
  • the product is a traditional Chinese medicine compound preparation "Shunyishu®” and “Shouhui laxative capsule” for the treatment of functional constipation.
  • the present invention is a Shouhui laxative microcapsule preparation.
  • the microcapsule preparation formula includes the following ingredients: A. Shouhui laxative Extract fine powder 13.5%-27.5% B. Capsule material 67%-81% C, anti-adhesive agent 0.9%-2.5% D. Plasticizer 3.6%-5.0%.
  • the capsule material is a kind of gum arabic, maltodextrin, modified starch, octenyl succinate starch, dry starch syrup powder, sodium caseinate, ⁇ -lactoglobulin, soy protein isolate, and xanthan gum Or several;
  • the anti-sticking agent is one or more of glycerol monostearate, stearyl alcohol, micronized silica gel, and titanium dioxide;
  • the plasticizer is glycerin, polyethylene glycol 6000, polyethylene glycol One or more of alcohol 400, propylene glycol, and citric acid.
  • the fine powder of Shouhui laxative extract is made of the following raw materials (parts by weight): Polygonum multiflorum 60-150, aloe 100-200, cassia 80-180, ginseng 20-80, wolfberry 30-100, donkey-hide gelatin 30 -100, Fructus Aurantii 80-150, Atractylodes 20-80; one of the preferred ones, the fine powder of Shouhui laxative extract is made of the following raw materials (parts by weight): Polygonum multiflorum 120, Aloe 160, Cassia 140, Ginseng 50, Lycium barbarum 75, donkey-hide gelatin 75, Zhishi 120, Baizhu 50.
  • the formulation contains the following ingredients: A, Shouhui laxative extract fine powder 17.5%-23.5% B, capsule material 71.5%-77.5% C. Anti-sticking agent 1.1%-1.9% D. Plasticizer 3.8%-4.7%; preferably, in terms of weight percentage, the preparation formula contains the following ingredients: A, Shouhui laxative extract fine powder 19.7%-22.5% B, capsule material 72.3%-74.1% C , Anti-sticking agent 1.3%-1.8% D, plasticizer 3.9%-4.4%;
  • Another object of the present invention is to provide a preparation method of the first hydrangea laxative microcapsule preparation, which mainly includes the preparation of the fine powder of the first hydrangea laxative extract, the preparation of the emulsion and the spray drying.
  • a preparation method of Shouhui laxative microcapsule preparation includes the following steps:
  • Extraction and purification process A. Weigh the donkey-hide gelatin according to the formula, pulverize it into ultra-fine powder, sieving, and set aside;
  • step D The alcohol extract of step B is combined with the decoction of step C, concentrated into a thick paste with a relative density of 1.30 to 1.35 (at 70°C), dried, crushed into fine powder, sieved, and set aside;
  • step E Mix the superfine powder of donkey-hide gelatin in step A and the fine powder in step D to obtain the fine powder of laxative extract of Shouhui, for use;
  • Step E Preparation process: F. Weigh the laxative extract powder, capsule material, anti-sticking agent and plasticizer of step E according to the formula quantity, and add the capsule material, anti-sticking agent and plasticizer to purified water, 45 Heat and stir at °C-58°C to dissolve, prepare a 22%-42% mass fraction of capsule material solution, cool to room temperature, add Shouhui laxative extract powder and emulsifier under stirring, homogenize emulsification, Obtain the emulsion for use;
  • Step F The emulsion is spray-dried under the conditions of inlet air temperature of 165°C-175°C, spray pressure of 0.36MPa-0.42MPa, and feed rate of 15ml/min-25ml/min, collect the microcapsules, and cool to obtain.
  • step 1) the extraction and purification process includes the following steps: A. Weigh the donkey-hide gelatin according to the formula, pulverize it into ultra-fine powder, pass through a 150-200 mesh sieve, and set aside;
  • step D Combine the alcohol extract of step B with the decoction of step C, concentrate into a thick paste with a relative density of 1.30 to 1.35 (70°C), dry with belt vacuum, pulverize into fine powder, sieved, and set aside;
  • step E Mix the superfine powder of donkey-hide gelatin in step A and the fine powder in step D to obtain the fine powder of laxative extract of Shouhui, for use.
  • the parameter conditions of the belt vacuum drying in step D of the 1) extraction and purification process are the vacuum degree -0.08Mpa-0.10Mpa, and the drying temperature is 50°C-60°C.
  • the step 2) preparation process includes the following steps: F, weighing step E according to the formula amount, the fine powder of the first hydrangea laxative extract, the capsule material, the anti-adhesive agent and the plasticizer, the capsule material, the anti-adhesive agent Add purified water and plasticizer into purified water, heat and stir at 52°C to dissolve, prepare a 36% mass fraction of capsule material solution, cool to room temperature, add the fine powder of Shouhui laxative extract and emulsifier under stirring, evenly Quality emulsification to obtain emulsion for use;
  • Step F The emulsion is spray-dried under the conditions of an inlet air temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min, collects the microcapsules, and cools them to obtain.
  • the emulsifier in step 2) F is one or more of Tween 80, soybean phospholipid, lecithin, poloxamer, and sucrose fatty acid ester, and the amount is 0.4 of the total preparation formula by mass fraction. %-1.2%;
  • the preparation method of the first hydrangea laxative microcapsule preparation of the present invention includes the following steps:
  • Extraction and purification process A. Weigh the donkey-hide gelatin according to the formula, crush it into superfine powder, and pass it through a 150-200 mesh sieve for use;
  • step D Combine the alcohol extract of step B with the decoction of step C, concentrate into a thick paste with a relative density of 1.30 to 1.35 (70°C), vacuum-dry it with -0.09pa, pulverize into fine powder, sieving, and set aside;
  • step E Mix the superfine powder of donkey-hide gelatin in step A and the fine powder in step D to obtain the fine powder of laxative extract of Shouhui, for use;
  • Step F The emulsion is spray-dried under the conditions of an inlet air temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min, collects the microcapsules, and cools them to obtain.
  • the microcapsules of the present invention can be further used as intermediates to be filled into capsules and compressed into tablets, etc., thereby obtaining Shouhui laxative microcapsule capsules and Shouhui laxative microcapsule tablets.
  • Shouhui laxative microcapsule preparation is a drug storage type microcapsule, which is spherical or quasi-spherical, with good fluidity, low moisture absorption, good stability, and not easy to agglomerate. It can improve the easy moisture absorption of the finished product of Shouhui laxative capsule. Instability and other issues;
  • Shouhui laxative is a drug for the treatment of constipation, and its effective site is concentrated in the small intestine and large intestine.
  • the Shouhui laxative microcapsule preparation of the present invention has obvious slow-release and targeting effects, and the drugs are mainly concentrated in the small intestine and large intestine.
  • Regional release which directly acts on the site of effect, has high bioavailability, and is not affected by gastrointestinal rhythms, which can exert the best effect in treating constipation;
  • the shouhui laxative microcapsule preparation of the invention is white or off-white powder, in a loose shape, no bad smell, good fluidity, and good dispersibility and stability. Except for individual dents on the surface of the microcapsule particles, the particles are relatively round and close to spherical, and the surface is dense and non-porous, basically without adhesion, the particle size distribution of the capsules is relatively uniform, and the particle size distribution is relatively narrow, most of which are concentrated near 20 ⁇ m, and Approximately normal distribution.
  • the measurement result of the encapsulation rate shows that the encapsulation rate of the Shouhui laxative microcapsule preparation obtained by the preparation formula and preparation process of the present invention is above 80%, up to 93.8%, and the microencapsulation effect is good.
  • Figure 1 is the particle size distribution diagram of Shouhui laxative microcapsules in Example 5;
  • Figure 2 is the particle size distribution diagram of Shouhui laxative microcapsules in Example 11;
  • Figure 3 is the Shouhui laxative microcapsules and Shouhui laxative microcapsules The cumulative dissolution percentage curve of tablets and Shouhui laxative capsules.
  • step 2 microcapsules, add 174g starch, fill, polish in a grinder, remove damaged capsules, and get ready.
  • Micro-powder silica gel 13g
  • Propylene glycol 37g, add the octenyl succinate starch, micro-powder silica gel, and propylene glycol in the above formula into purified water, heat and stir at 48°C to dissolve, and prepare a mass fraction of 28%
  • the capsule material solution cool to room temperature, add the above formula amount of Shouhui laxative extract powder and Tween-80 under stirring 12g, homogeneously emulsified to obtain an emulsion, spray-dried under the conditions of an inlet air temperature of 166°C, a spray pressure of 0.40MPa, and a feed rate of 16ml/min, collect the microcapsules, and cool to obtain 784g of microcapsules.
  • step 2 microcapsules, add 201g of sucrose powder, mix well, make coarse granules, dry, pulverize, sieving, granulate, dry at low temperature, whole granules, add 7g magnesium stearate and 8g talcum powder, mix well , Press the tablet and get it.
  • Spray drying was performed under the conditions of an inlet air temperature of 168°C, a spray pressure of 0.42 MPa, and a feed rate of 15 ml/min.
  • the microcapsules were collected and cooled to obtain 796 g of microcapsules.
  • step 2) microcapsules, add 204g of micro-powder silica gel, fill, polish in a grinder, and remove damaged capsules.
  • microcapsules were collected and cooled to obtain 806 g of microcapsules.
  • step 2) microcapsules, add 178g of dextrin, mix well to make coarse particles, dry, pulverize, sieving, granulate, dry at low temperature, whole, add 8g magnesium stearate and 8g talcum powder, mix well , Press the tablet and get it.
  • Spray drying was performed under the conditions of a wind temperature of 166°C, a spray pressure of 0.36 MPa, and a feed rate of 20.5 ml/min.
  • the microcapsules were collected and cooled to obtain 798 g of microcapsules.
  • step 2) microcapsules, add 180g of microcrystalline cellulose, mix well, make coarse particles, dry, pulverize, sieving, granulate, dry at low temperature, sizing, add 10g magnesium stearate and 12g talc, Mix well, press tablets, and get ready.
  • microcapsules were collected and cooled to obtain 839 g of microcapsules.
  • step 2 microcapsules, add 173g starch, mix well, make coarse granules, dry, pulverize, sieving, granulate, dry at low temperature, whole granules, add 5g magnesium stearate and 11g talcum powder, mix well, Press the tablet and get it.
  • Glycerin 39g, add the above formula amount of maltodextrin, soy protein isolate, modified starch, acacia, glycerol monostearate, and glycerin to purified water, heat and stir at 47°C to dissolve, and prepare the mass fraction It is a 39% capsule material solution, cooled to room temperature, and under stirring, add the above formula amount of Shouhui laxative extract powder and Tween-80 11g, homogenize and emulsify to obtain an emulsion.
  • Spray drying was performed under the conditions of a spray pressure of 0.41 MPa and a feed rate of 21 ml/min. The microcapsules were collected and cooled to obtain 837 g of microcapsules.
  • step 2 microcapsules, add 163g lactose, fill, polish in a grinder, remove damaged capsules, and get ready.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • Preparation process A, Shouhui laxative extract powder: 197g B, sodium caseinate: 445g Starch syrup dry powder: 296g C. Stearyl alcohol: 12g Titanium dioxide: 6g D. Propylene glycol: 44g, add sodium caseinate, dry starch syrup powder, stearyl alcohol, titanium dioxide, propylene glycol in the above formula into purified water, heat and stir at 52°C to dissolve, and prepare a capsule material with a mass fraction of 36% The solution was cooled to room temperature, and the above formula was added with the above formula amount of laxative extract powder, 3.6g of soy phospholipid and 5.4g of sucrose fatty acid ester, homogenized and emulsified to obtain an emulsified liquid.
  • Spray drying was performed under the conditions of spray pressure of 0.39MPa and feed rate of 22.5ml/min, and the microcapsules were collected and cooled to obtain 852g of microcapsules.
  • step 2) microcapsules, add 131g of dextrin, mix well, make coarse particles, dry, pulverize, sieving, make granules, dry at low temperature, and sizing, add 8g magnesium stearate and 9g talcum powder, and mix well , Press the tablet and get it.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • microcapsules are collected and cooled to obtain 785 g of microcapsules.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • the microcapsule preparation method used refers to the best effect example 5 of the Chinese patent "A compound vinegar microcapsule and its preparation method and application (authorization announcement number CN106036829B)" to investigate the application of the prior art microcapsule preparation method to Shouhui The preparation effect achieved when the laxative extract is fine powder.
  • microcapsules prepared above are sent to a spray dryer for spray drying with a pump, and the air inlet temperature is controlled to be 185°C and the spray pressure is 0.185MPa. Finally, the microcapsules are drained to obtain 245g of finished microcapsules.
  • the fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.
  • the microcapsule preparation method used refers to "Hu Rui, Zhou Guangping, Song Weichun. Preparation and in vitro controlled release analysis of Chinese medicine prebiotic microcapsules by spray drying method[J]. Anhui Agricultural Sciences, 2016, 44(29): 89-94.”
  • Morphology Take an appropriate amount of the microcapsule samples of Example 5 and Example 11, place them in an evaporating dish, and place them in natural light or a room equivalent to natural light to observe their color and shape.
  • the microcapsule sample was observed to be white or off-white powder, loose, no bad smell, good fluidity, good dispersibility and stability.
  • Particle size distribution Take about 0.03 g of the microcapsule samples of Example 5 and Example 11, use 50% ethanol as the dispersion medium, and set the Winner2005B intelligent laser particle size analyzer (Jinan Micronano Particle Instrument Co., Ltd.) to determine the particle size. Diameter (D), the results are shown in Table 1 (D10, D50, D90 in the table represent the equivalent diameter of the largest particle when the cumulative distribution in the distribution curve is 10%, 50%, and 90%, respectively. Dav represents the average particle diameter. The table below is the same ) And Figure 1 and Figure 2.
  • the particle size distribution of the laxative microcapsules of Shouhui is relatively uniform, most of which are concentrated in the vicinity of 20 ⁇ m.
  • the average particle size of the microcapsules of Example 5 is 22.69 ⁇ m, and that of the microcapsules of Example 11
  • the average particle size is 23.03 ⁇ m, the particle size distribution of the microcapsules of the two samples is relatively narrow, and the distribution is approximately normal, and the microencapsulation effect is better.
  • Encapsulation rate refers to the percentage of the actual drug content in the microcapsule to the total drug content (ie, drug loading) in the microcapsule sample, that is, the percentage of the drug content of the prepared microcapsule to the total drug content of the system. The higher the encapsulation rate, the better the degree of drug encapsulation.
  • the specific method for determining the encapsulation rate of Shouhui laxative microencapsulation is as follows.
  • Preparation of reference solution Accurately weigh an appropriate amount of 2,3,5,4'-tetrahydroxystilbene-2-O- ⁇ -D-glucoside reference substance, add dilute ethanol to make a solution containing 0.06mg per 1ml, and get it.
  • test solution Accurately weigh an appropriate amount of Shouhui laxative microcapsule sample, place it in a 100mL volumetric flask, dilute to 100mL with 75% ethanol, and shake it up so that all the Shouhui laxative extract on the outer surface of the microcapsule is dissolved in the ethanol solution.
  • Encapsulation rate (total drug amount in the microcapsule sample M ⁇ the amount of drug outside the microcapsule m) ⁇ 100%/total drug amount M in the microcapsule sample.
  • Example 5 of the present invention Shouhui laxative microcapsules, Example 11 Shouhui laxative microcapsule tablets and Shouhui laxative capsules (Lunan Houpu Pharmaceutical Co., Ltd., specifications: 0.35g/capsule ⁇ 6 capsules/box, Batch number: 26190032)
  • the dissolution test method Choinese Pharmacopoeia 2015 Edition Four General Principles 0931 Sustained Release or Controlled Release Preparation) in 250ml phosphate buffer (pH6.8) as the dissolution medium, and the temperature of the water bath is 37°C ⁇ 0.5°C
  • the in vitro dissolution test was carried out at a speed of 100r ⁇ min -1 , with 2,3,5,4'-tetrahydroxystilbene-2-O- ⁇ -D-glucoside (C 20 H 22 O 9 ) as an indicator Conduct an inspection.
  • Preparation of reference solution Accurately weigh an appropriate amount of 2,3,5,4'-tetrahydroxystilbene-2-O- ⁇ -D-glucoside reference substance, add dilute ethanol to make a solution containing 0.06mg per 1ml, and get it.
  • Preparation of test solution Take 10ml of samples at each time point and add 10ml of distilled water at the same temperature at the same time. The sample is filtered through 0.45 ⁇ m microporous membrane. 5ml of the additional filtrate is transferred to the separatory funnel. Extracted twice with ether, 15ml each time, discarded Remove the ether solution, adjust the pH to 1-2 with dilute hydrochloric acid, extract with ethyl acetate (15ml, 15ml, 15ml, 10ml) 4 times, combine the ethyl acetate solution, evaporate to dryness, and dissolve the residue with dilute ethanol and transfer to In a 2ml measuring flask, make the volume constant, shake well, filter, and get ready.
  • Example 5 microcapsules Two batches of samples of the present invention (Example 5 microcapsules, Example 11 microcapsule tablets) are stored in an aluminum-plastic package (6 tablets/plate) in an accelerated test box (40 ⁇ 2°C, RH75% ⁇ 5). Months, samples were taken at 0 months, 1 month, 2 months, 3 months, and 6 months respectively) for accelerated stability testing.
  • the stilbene glycoside content determination method is the same as that of Experimental Example 2, and the testing methods for other indicators Refer to the four volumes of the 2015 edition of the Chinese Pharmacopoeia.
  • the accelerated stability test data of the two batches of products are shown in Table 4 and Table 5.

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Abstract

Une préparation de microcapsule de Shouhui Tongbian est préparée à partir d'une poudre fine d'extrait de Shouhui Tongbian, d'un matériau de capsule, d'un agent anti-collant et d'un plastifiant. La poudre fine d'extrait de Shouhui Tongbian est préparée à partir de fallopia multiflora, aloe vera, semen cassia, radix ginseng, fructus lycii, colla corii asini, fructus aurantii immaturus, et rhizoma atractylodis macrocephalae. Le procédé de préparation de la préparation de microcapsule de Shouhui Tongbian comprend la préparation de la poudre fine d'extrait de Shouhui Tongbian et la préparation de microcapsules. Les microcapsules de Shouhui Tongbian de type sphérique ou de type sphère présentent une bonne fluidité et une faible hygroscopicité, et ne sont pas sujettes à l'agglomération. La préparation de microcapsules présente des effets de libération lente et de ciblage évidents ; du fait que la libération est principalement concentrée dans des régions cibles de petits et grands intestins, la préparation de microcapsules a un effet direct, une biodisponibilité élevée et un bon effet de traitement de la constipation ; de plus, la préparation de microcapsules peut masquer les odeurs désagréables, améliorer le goût et améliorer la compliance aux médicaments.
PCT/CN2020/105564 2020-03-20 2020-07-29 Préparation de microcapsule de shouhui tongbian et procédé de préparation associé WO2021184636A1 (fr)

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