WO2021184636A1 - Shouhui tongbian microcapsule preparation and preparation method therefor - Google Patents

Shouhui tongbian microcapsule preparation and preparation method therefor 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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French (fr)
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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Publication of WO2021184636A1 publication Critical patent/WO2021184636A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/70Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704Polygonum, e.g. knotweed
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/36Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/25Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258Panax (ginseng)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284Atractylodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/482Cassia, e.g. golden shower tree
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/75Rutaceae (Rue family)
    • A61K36/752Citrus, e.g. lime, orange or lemon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/81Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815Lycium (desert-thorn)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/886Aloeaceae (Aloe family), e.g. aloe vera
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules 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
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5036Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules 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
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5052Proteins, e.g. albumin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10Laxatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/53Liquid-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

A Shouhui Tongbian microcapsule preparation is prepared from Shouhui Tongbian extract fine powder, a capsule material, an anti-sticking agent, and a plasticizer. The Shouhui Tongbian extract fine powder is prepared from fallopia multiflora, aloe vera, semen cassia, radix ginseng, fructus lycii, colla corii asini, fructus aurantii immaturus, and rhizoma atractylodis macrocephalae. The preparation method of the Shouhui Tongbian microcapsule preparation comprises the preparation of the Shouhui Tongbian extract fine powder and the preparation of microcapsules. The Shouhui Tongbian microcapsules spherical or sphere-like, have good fluidity and low hygroscopicity, and are not prone to caking. The microcapsule preparation has obvious slow-release and targeting effects; because the release is mainly concentrated in target regions of small and large intestines, the microcapsule preparation has a direct effect, high bioavailability, and good constipation treatment effect; in addition, the microcapsule preparation can mask objectionable odors, improve taste, and enhance medication compliance.

Description

一种首荟通便微囊制剂及其制备方法Shouhui laxative microcapsule preparation and preparation method thereof 技术领域Technical field
本发明涉及一种中药微囊制剂及其制备方法,尤其涉及一种首荟通便微囊制剂及其制备方法,属于中药制剂领域。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.
背景技术Background technique
中国专利CN100453105C公开了一种具有通便排毒、减肥降脂功能的中药组合物及制备方法,产品为治疗功能性便秘的中药复方制剂“顺益舒®”“首荟通便胶囊”。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.
技术解决方案Technical solutions
针对现有首荟通便胶囊存在的不足和产品升级换代的需要,本发明为一种首荟通便微囊制剂,按重量百分比计,微囊制剂配方包括以下成分:A、首荟通便提取物细粉13.5%-27.5%      B、囊材67%-81%   C、抗粘剂0.9%-2.5%      D、增塑剂3.6%-5.0%。             In view of the shortcomings of the existing Shouhui laxative capsules and the need for product upgrades, the present invention is a Shouhui laxative microcapsule preparation. In terms of weight percentage, 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%.
所述囊材为阿拉伯胶、麦芽糊精、变性淀粉、辛烯基琥珀酸酯化淀粉、淀粉糖浆干粉、酪蛋白酸钠、β-乳球蛋白、大豆分离蛋白、黄原胶中的一种或几种;所述抗粘剂为单硬脂酸甘油酯、十八醇、微粉硅胶、二氧化钛中的一种或几种;所述增塑剂为甘油、聚乙二醇6000、聚乙二醇400、丙二醇、柠檬酸中的一种或几种。The capsule material is a kind of gum arabic, maltodextrin, modified starch, octenyl succinate starch, dry starch syrup powder, sodium caseinate, β-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.
其中,所述首荟通便提取物细粉由下列原料制成(重量份):何首乌60-150、芦荟100-200、决明子80-180、人参20-80 、枸杞子30-100、阿胶30-100、枳实80-150、白术20-80;优选之一,所述首荟通便提取物细粉由下列原料制成(重量份):何首乌120、芦荟160 、决明子140、人参50、枸杞子75、阿胶75、枳实120、白术50。Wherein, 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.
优选地,按重量百分比计,制剂配方包含以下成分:A、首荟通便提取物细粉17.5%-23.5%    B、囊材71.5%-77.5%   C、抗粘剂1.1%-1.9%        D、增塑剂3.8%-4.7%;优选地,按重量百分比计,制剂配方包含以下成分:A、首荟通便提取物细粉19.7%-22.5%     B、囊材72.3%-74.1%   C、抗粘剂1.3%-1.8%      D、增塑剂3.9%-4.4%; Preferably, in terms of weight percentage, 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%;
所述囊材按重量计为络蛋白酸钠:淀粉糖浆干粉=3:2、麦芽糊精:β-乳球蛋白=3:2、麦芽糊精:大豆分离蛋白:变性淀粉:阿拉伯胶=5:3:2:1或辛烯基琥珀酸酯化淀粉:β-乳球蛋白=3:2中的一种;所述抗粘剂按重量计为十八醇:二氧化钛=2:1或单硬脂酸甘油酯;所述增塑剂按重量计为聚乙二醇6000:柠檬酸=2-6:1或丙二醇。The capsule material is sodium complex protein by weight: starch syrup dry powder=3:2, maltodextrin: β-lactoglobulin=3:2, maltodextrin: soy protein isolate: modified starch: gum arabic=5 :3:2:1 or octenyl succinate starch: β-lactoglobulin=3:2; the anti-sticking agent is stearyl alcohol by weight: titanium dioxide=2:1 or single Glyceryl stearate; the plasticizer is polyethylene glycol 6000 by weight: citric acid=2-6:1 or propylene glycol.
本发明的另一个目的是提供所述首荟通便微囊制剂的制备方法,主要包括首荟通便提取物细粉的制备、乳化液的制备以及喷雾干燥。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.
一种首荟通便微囊制剂的制备方法,包括下列步骤:A preparation method of Shouhui laxative microcapsule preparation includes the following steps:
1)提取、纯化工艺:A、按配方量称取阿胶,粉碎成超细粉,过筛,备用;1) Extraction and purification process: A. Weigh the donkey-hide gelatin according to the formula, pulverize it into ultra-fine powder, sieving, and set aside;
B、人参、何首乌、决明子和芦荟加50%-70%乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;B. Ginseng, Polygonum multiflorum, Cassia Seeds and Aloe are refluxed and extracted twice with 50%-70% ethanol, the first time is 10 times the amount, the second time is 8 times the amount, each 2 hours, respectively, filtered, and the filtrate was combined;
C、枸杞子、枳实、白术加水煎煮二次,第一次加8倍量水,浸泡1小时,煎煮1.5小时,第二次加6倍量水,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.10-1.20(80℃时)的清膏,放至室温,搅拌加乙醇使乙醇浓度达50%-70%(25℃时),冷藏静置24-48小时,滤过;C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.10-1.20 (at 80°C), put it at room temperature, stir and add ethanol to make the ethanol concentration reach 50%-70% (at 25°C), keep it in the refrigerator for 24-48 hours, Filter
D、步骤B醇提液与步骤C水煎液合并,浓缩成相对密度为1.30-1.35(70℃时)的稠膏,干燥,粉碎成细粉,过筛,备用;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;
E、将步骤A阿胶超细粉、步骤D细粉混匀,即得首荟通便提取物细粉,备用;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;
2)制剂工艺:F、按配方量称取步骤E首荟通便提取物细粉、囊材、抗粘剂和增塑剂,将囊材、抗粘剂和增塑剂加入纯化水,45℃-58℃条件下加热搅拌使溶解,配置成质量分数为22%-42%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和乳化剂,均质乳化,得乳化液,备用;2) 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 ℃-58℃ 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;
G、步骤F乳化液在进风温度165℃-175℃、喷雾压力0.36MPa-0.42MPa、进料速度15ml/min-25ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。G. 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.
优选地,步骤1)提取、纯化工艺包括下列步骤:A、按配方量称取阿胶,粉碎成超细粉,过150-200目筛,备用;Preferably, 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;
B、人参、何首乌、决明子和芦荟加60%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;B. Ginseng, Polygonum multiflorum, Cassia seeds and Aloe are refluxed with 60% ethanol for two extractions, 10 times the amount for the first time, and 8 times the amount for the second time, for 2 hours each time, filter separately, and combine the filtrate;
C、枸杞子、枳实、白术加水煎煮二次,第一次加8倍量水,浸泡1小时,煎煮1.5小时,第二次加6倍量水,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.10-1.20(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达60%(25℃时),冷藏静置36小时,滤过;C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.10-1.20 (at 80°C), put it at room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), keep it in the refrigerator for 36 hours, and filter;
D、步骤B醇提液与步骤C水煎液合并,浓缩成相对密度为1.30-1.35(70℃)的稠膏,带式真空干燥,粉碎成细粉,过筛,备用;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;
E、将步骤A阿胶超细粉、步骤D细粉混匀,即得首荟通便提取物细粉,备用。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.
优选地,所述1)提取、纯化工艺步骤D中带式真空干燥的参数条件为真空度-0.08Mpa--0.10Mpa,干燥温度50℃-60℃。Preferably, 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.
优选地,所述步骤2)制剂工艺包括下列步骤:F、按配方量称取步骤E首荟通便提取物细粉、囊材、抗粘剂和增塑剂,将囊材、抗粘剂和增塑剂加入纯化水,52℃条件下加热搅拌使溶解,配置成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和乳化剂,均质乳化,得乳化液,备用;Preferably, 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;
G、步骤F乳化液在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。G. 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.
优选地,步骤2)F中所述乳化剂为Tween80、大豆磷脂、卵磷脂、泊洛沙姆、蔗糖脂肪酸酯中的一种或几种,用量按质量分数计为制剂配方总量的0.4%-1.2%;Preferably, 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%;
优选地,步骤F所述乳化剂按重量比计为大豆磷脂:蔗糖脂肪酸酯=4∶6的复合乳化剂,用量按质量分数计为制剂配方总量的0.9%。Preferably, the emulsifier in step F is a composite emulsifier of soybean phospholipid: sucrose fatty acid ester=4:6 in terms of weight ratio, and the amount is 0.9% of the total preparation formula in terms of mass fraction.
进一步地,本发明所述首荟通便的微囊制剂的制备方法含有如下步骤:Further, the preparation method of the first hydrangea laxative microcapsule preparation of the present invention includes the following steps:
1)提取、纯化工艺:A、按配方量称取阿胶,粉碎成超细粉,过150-200目筛备用;1) 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;
B、人参、何首乌、决明子和芦荟加60%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;B. Ginseng, Polygonum multiflorum, Cassia seeds and Aloe are refluxed with 60% ethanol for two extractions, 10 times the amount for the first time, and 8 times the amount for the second time, for 2 hours each time, filter separately, and combine the filtrate;
C、枸杞子、枳实、白术加水煎煮二次,第一次加8倍量水,浸泡1小时,煎煮1.5小时,第二次加6倍量水,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.15(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达60%(25℃时),冷藏静置36小时,滤过;C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.15 (at 80°C), place it at room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), keep it in the refrigerator for 36 hours, and filter;
D、步骤B醇提液与步骤C水煎液合并,浓缩成相对密度为1.30-1.35(70℃)的稠膏,带式真空干燥-0.09pa,粉碎成细粉,过筛,备用;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;
E、将步骤A阿胶超细粉、步骤D细粉混匀,即得首荟通便提取物细粉,备用;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;
2)制剂工艺:F、取步骤E首荟通便提取物细粉、囊材、抗粘剂和增塑剂,将囊材、抗粘剂和增塑剂加入纯化水,52℃条件下加热搅拌使溶解,配置成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和、大豆磷脂:蔗糖脂肪酸酯=4∶6的复合乳化剂,用量按质量分数计为制剂配方总量的0.9%。,均质乳化,得乳化液,备用;2) Preparation process: F, step E, take the fine powder, capsule material, anti-sticking agent and plasticizer of the first hydrangea laxative extract, add the capsule material, anti-sticking agent and plasticizer to purified water, and heat at 52℃ Stir to dissolve, configure it into a 36% mass fraction of the capsule material solution, cool to room temperature, add the fine powder of Shouhui laxative extract and soybean phospholipid: sucrose fatty acid ester = 4:6 composite emulsifier under stirring. The dosage is 0.9% of the total amount of the formulation in terms of mass fraction. , Homogeneous emulsification to obtain the emulsion for use;
G、步骤F乳化液在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。G. 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.
本发明微囊除了可作为普通散剂或颗粒剂使用外,还可进一步作为中间体灌装成胶囊,压制成片剂等,从而得到首荟通便微囊胶囊和首荟通便微囊片。In addition to being used as ordinary powders or granules, 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.
有益效果Beneficial effect
1)首荟通便微囊制剂为药库型微型胶囊,呈球形或类球形,流动性好,引湿性小,稳定性好,不易结块,可改善首荟通便胶囊成品易吸潮、不稳定等问题;1) 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;
2)首荟通便为治疗便秘的药物,其起效部位集中在小肠及大肠部位,本发明首荟通便微囊制剂具有具明显缓释和靶向作用,药物主要集中于小肠与大肠靶区释放,直接作用于起效部位,生物利用度高,且不受胃肠节律的影响,可发挥最佳的治疗便秘的效果;2) 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;
3)首荟通便提取物细粉通过囊材的包埋和掩盖,可掩盖首荟通便制剂固有的的不良气味及口感,患者用药依从性好。3) The fine powder of Shouhui laxative extract can conceal the inherent bad smell and taste of Shouhui laxative preparations by embedding and concealing the capsule material, and the patients have good medication compliance.
本发明首荟通便微囊制剂呈白色或灰白色粉末,呈疏松状,无不良气味,流动性较好,分散性和稳定性均佳。微囊颗粒表面除有个别存在凹痕外,颗粒较圆整并接近球形,表面致密无孔隙,基本无黏连,囊粒径分布相对均匀,粒径分布较窄,多数集中在20μm附近,且呈近似的正态分布。包封率测定结果表明,本发明制剂配方及制备工艺所得的首荟通便微囊制剂,其包封率均在80%以上,最高达93.8%,微囊化效果较好。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 20μm, 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.
体外累积溶出度试验表明,本发明首荟通便微囊胶囊、首荟通便微囊片在1h内累积溶出百分率小于55%,2h内均达到80%以上的溶出,3h内基本释放完全。与传统胶囊相比,本发明首荟通便微囊制剂具有一定的缓释作用。In vitro cumulative dissolution test shows that the cumulative dissolution percentage of Shouhui laxative microcapsule capsules and Shouhui laxative microcapsule tablets of the present invention is less than 55% within 1 hour, reaches more than 80% dissolution within 2 hours, and is basically completely released within 3 hours. Compared with traditional capsules, the Shouhui laxative microcapsule preparation of the present invention has a certain slow-release effect.
加速稳定性试验结果表明,在加速试验条件(40±2℃、RH 75%±5)下放置6个月,首荟通便微囊片及微囊胶囊性状无变化,含量无明显变化,水分、溶散时限及卫生学各项考察指标均符合要求。由上述实验数据可知,本发明所制备的首荟通便微囊制剂稳定性好,质量可控。The results of the accelerated stability test showed that after 6 months of storage under accelerated test conditions (40±2℃, RH 75%±5), the properties of Shouhui laxative microcapsule tablets and microcapsule capsules did not change, and the content did not change significantly. , Dissolution time limit and various inspection indicators of hygiene meet the requirements. It can be known from the above experimental data that the Shouhui laxative microcapsule preparation prepared by the present invention has good stability and controllable quality.
附图说明Description of the drawings
图1为实施例5首荟通便微囊粒径分布图;图2为实施例11首荟通便微囊粒径分布图;图3为首荟通便微囊胶囊、首荟通便微囊片及首荟通便胶囊累积溶出度百分率曲线图。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.
本发明的实施方式Embodiments of the present invention
以下通过具体实施例进一步描述本发明,但本发明并不仅仅限于以下实施例,任何形式的等同替换对本领域普通技术人员来说都是显而易见且包含在本发明之中的。The present invention is further described by specific embodiments below, but the present invention is not limited to the following embodiments, and any form of equivalent replacement is obvious to a person of ordinary skill in the art and is included in the present invention.
实施例Example 1 首荟通便微囊胶囊Shouhui laxative microcapsules
1)提取、纯化工艺:何首乌120g 、芦荟160g、决明子150g、人参20g、枸杞子50g、阿胶40g、枳实120g 、白术30g,以上8味,取阿胶,粉碎成超细粉,过180目筛,备用;人参、何首乌、决明子、芦荟加60%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.10(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达70%(25℃时),冷藏静置36小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.35(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度50℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉243g。1) Extraction and purification process: Polygonum multiflorum 120g, aloe vera 160g, cassia 150g, ginseng 20g, wolfberry 50g, donkey-hide gelatin 40g, Citrus aurantium 120g, Atractylodes macrocephala 30g, the above 8 flavors, take donkey-hide gelatin, crush into superfine powder, pass through a 180 mesh sieve , Spare; ginseng, multiflora multiflora, cassia, aloe plus 60% ethanol reflux extraction twice, the first time increase 10 times the amount, the second time increase 8 times the amount, each 2 hours, respectively, filter and combine the filtrate; Chinese wolfberry , Fructus Aurantii, Atractylodes macrocephala, decocted twice with water, the first time increased 8 times, soaked for 1 hour, decocted for 1.5 hours, the second time increased 6 times, decocted for 1.5 hours, filtered, combined the filtrate, concentrated to relative A clear paste with a density of 1.10 (at 80°C), put it to room temperature, stir and add ethanol to make the concentration reach 70% (at 25°C), keep it in the refrigerator for 36 hours, and filter; combine the above alcohol extract and decoction, and concentrate A thick paste with a relative density of 1.35 (70°C), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature 50°C, crushed into fine powder, sieved, and mixed with the above superfine powder of donkey-hide gelatin. Get 243g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:135g     B、阿拉伯胶:540g    麦芽糊精:270g    C、单硬脂酸甘油酯:10g    二氧化钛:5g    D、聚乙二醇400:40g2) Preparation process: A. Shouhui laxative extract fine powder: 135g B. Gum Arabic: 540g Maltodextrin: 270g C. Glyceryl monostearate: 10g Titanium dioxide: 5g D. Polyethylene glycol 400: 40g
将以上配方量的阿拉伯胶、麦芽糊精、单硬脂酸甘油酯、二氧化钛、聚乙二醇400加入纯化水,50℃条件下加热搅拌使溶解,配制成质量分数为40%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及泊洛沙姆6g,均质乳化,得乳化液,在进风温度170℃、喷雾压力0.38MPa、进料速度17.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊826g。Add acacia gum, maltodextrin, glyceryl monostearate, titanium dioxide, polyethylene glycol 400 in the above formula into purified water, heat and stir at 50 ℃ to dissolve, and prepare a capsule material solution with a mass fraction of 40% , Cool to room temperature, add the above formula amount of laxative extract powder and 6g of poloxamer under stirring, homogenize and emulsify to obtain an emulsified liquid. At the inlet temperature of 170℃, the spray pressure of 0.38MPa, the feed Spray drying was performed at a speed of 17.5 ml/min, and the microcapsules were collected and cooled to obtain 826 g of microcapsules.
取步骤2)微囊,加入淀粉174g,灌装,磨光机中抛光,剔除破损胶囊,即得。Take step 2) microcapsules, add 174g starch, fill, polish in a grinder, remove damaged capsules, and get ready.
实施例Example 2 首荟通便微囊片Shouhui laxative microcapsule tablets
1)提取、纯化工艺:何首乌80g    芦荟120g    决明子100g     人参50g      枸杞子80g   阿胶80g   枳实80g      白术50g,以上8味,取阿胶,粉碎成超细粉,过180目筛,备用;人参、何首乌、决明子、芦荟加70%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.11(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达70%(25℃时),冷藏静置24小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.30(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度60℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉256g。 1) Extraction and purification process: Polygonum multiflorum 80g aloe 120g cassia 100g ginseng 50g wolfberry 80g donkey-hide gelatin 80g  Fructus Aurantii 80g Atractylodes 50g, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass through a 180-mesh sieve, and set aside; ginseng, fleeceflower root, cassia seed, aloe plus 70% ethanol reflux extraction for the second time, the first time increase 10 times the amount , Add 8 times the amount for the second time, 2 hours each time, filter separately and combine the filtrate; add water to decoct wolfberry, citrus fruit and atractylodes macrocephalae twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours , Add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.11 (at 80℃), put it to room temperature, stir and add ethanol to make the concentration reach 70% (25℃) Time), refrigerate and stand for 24 hours, and then filter; combine the above alcohol extract and decoction to concentrate into a thick paste with a relative density of 1.30 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa , The drying temperature is 60 ℃, pulverized into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 256g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:175g      B、辛烯基琥珀酸酯化淀粉:775g2) Preparation process: A. Shouhui laxative extract fine powder: 175g B. Octenyl succinate starch: 775g
C、微粉硅胶:13g     D、丙二醇:37g,将以上配方量的辛烯基琥珀酸酯化淀粉、微粉硅胶、丙二醇加入纯化水,48℃条件下加热搅拌使溶解,配制成质量分数为28%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及吐温-80 12g,均质乳化,得乳化液,在进风温度166℃、喷雾压力0.40MPa、进料速度16ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊784g。C. Micro-powder silica gel: 13g D. 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.
取步骤2)微囊,加入蔗糖粉201g,混匀,制成粗颗粒,干燥,粉碎,过筛,制颗粒,低温干燥,整粒,加入7g硬脂酸镁和8g的滑石粉,混匀,压片,即得。Take 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.
实施例Example 3 首荟通便微囊胶囊Shouhui laxative microcapsules
1)提取、纯化工艺:何首乌150g   芦荟200g     决明子180g    人参20g      枸杞子30g    阿胶30g  枳实150g     白术20g,以上8味,取阿胶,粉碎成超细粉,过200目筛,备用;人参、何首乌、决明子、芦荟加50%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.17(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达50%(25℃时),冷藏静置36小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.32(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度55℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉331g。1) Extraction and purification process: Polygonum multiflorum 150g, Aloe 200g Cassia Seed 180g Ginseng 20g Wolfberry 30g Ejiao 30g Fructus aurantii 150g 20g Atractylodes macrocephala, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass a 200-mesh sieve, and set aside; ginseng, fleece-flower root, cassia seed, aloe plus 50% ethanol are refluxed for the second time, and the first time is 10 times the amount , Add 8 times the amount for the second time, 2 hours each time, filter separately and combine the filtrate; add water to decoct wolfberry, citrus fruit and atractylodes macrocephalae twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours , Add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.17 (at 80 ℃), put it to room temperature, stir and add ethanol to make the concentration reach 50% (25 ℃) Time), refrigerate and stand for 36 hours, and filter; combine the above alcohol extract and water decoction, concentrate into a thick paste with a relative density of 1.32 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa , The drying temperature is 55 ℃, crushed into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 331g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:217g      B、淀粉糖浆干粉:572g   β-乳球蛋白:143g     C、十八醇:21g      D、甘油:28g   柠檬酸:19g,将以上配方量的淀粉糖浆干粉、β-乳球蛋白、十八醇、甘油、柠檬酸加入纯化水,46℃条件下加热搅拌使溶解,配制成质量分数为37%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及蔗糖脂肪酸酯10g,均质乳化,得乳化液,在进风温度168℃、喷雾压力0.42MPa、进料速度15ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊796g。取步骤2)微囊,加入微粉硅胶204g,灌装,磨光机中抛光,剔除破损胶囊即得。 2) Preparation process: A. Shouhui laxative extract fine powder: 217g B. Dry starch syrup powder: 572g β-lactoglobulin: 143g C. Stearyl alcohol: 21g D. Glycerin: 28g Citric acid: 19g, add the starch syrup powder, β-lactoglobulin, stearyl alcohol, glycerin, and citric acid of the above formula to purified water, heat and stir at 46℃ Dissolve it and prepare it into a capsule material solution with a mass fraction of 37%, cool it to room temperature, add the above formula amount of the laxative extract powder of the above formula and 10g of sucrose fatty acid ester under stirring, and homogenize and emulsify to obtain an emulsion. 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. Take step 2) microcapsules, add 204g of micro-powder silica gel, fill, polish in a grinder, and remove damaged capsules.
实施例Example 4 首荟通便微囊片Shouhui laxative microcapsule tablets
1)提取、纯化工艺:何首乌60g    芦荟100g      决明子80g   人参80g      枸杞子100g    阿胶100g枳实120g      白术80g,以上8味,取阿胶,粉碎成超细粉,过150目筛,备用;人参、何首乌、决明子、芦荟加70%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.15(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达60%(25℃时),冷藏静置48小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.34(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度60℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉311g。1) Extraction and purification process: Polygonum multiflorum 60g, aloe 100g Cassia seed 80g ginseng 80g wolfberry 100g donkey-hide gelatin 100g citrus fruit 120g Atractylodes macrocephala 80g, the above 8 flavors, take donkey-hide gelatin, crush it into ultra-fine powder, pass through a 150-mesh sieve, and set aside; ginseng, fleece-flower root, cassia seed, aloe plus 70% ethanol reflux extraction 2 Add 10 times the amount for the first time, add 8 times the amount for the second time, filter separately and combine the filtrate for 2 hours each time; decoct wolfberry, citrus fruit, and Atractylodes macrocephala twice with water, add 8 times the amount for the first time , Soak for 1 hour, decoct for 1.5 hours, add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.15 (at 80 ℃), put it to room temperature, stir and add Ethanol makes the concentration reach 60% (at 25℃), keep it in the refrigerator for 48 hours, and filter; combine the above alcohol extract and water decoction, concentrate to a thick paste with a relative density of 1.34 (70℃), belt vacuum drying, Vacuum degree -0.08MPa-0.10Mpa, drying temperature 60℃, crushed into fine powder, sieved, and mixed with the above-mentioned donkey-hide gelatin superfine powder to obtain 311g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:275g  B、大豆分离蛋白:372g   麦芽糊精:224g   黄原胶:74g      C、微粉硅胶:9g      D、聚乙二醇6000:46g,将以上配方量的大豆分离蛋白、麦芽糊精、黄原胶、微粉硅胶、聚乙二醇6000加入纯化水,51℃条件下加热搅拌使溶解,配制成质量分数为27%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及卵磷脂5g,均质乳化,得乳化液,在进风温度174℃、喷雾压力0.39MPa、进料速度20ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊806g。取步骤2)微囊,加入糊精178g,混匀,制成粗颗粒,干燥,粉碎,过筛,制颗粒,低温干燥,整粒,加入8g硬脂酸镁和8g的滑石粉,混匀,压片,即得。2) Preparation process: A. Shouhui laxative extract powder: 275g B. Soy protein isolate: 372g Maltodextrin: 224g Xanthan gum: 74g C, micronized silica gel: 9g D, polyethylene glycol 6000: 46g, add the above formula amount of soy protein isolate, maltodextrin, xanthan gum, micronized silica gel, and polyethylene glycol 6000 to purified water, Heat and stir at 51℃ to dissolve, prepare a 27% mass fraction of the capsule material solution, cool to room temperature, add the above formula amount of the laxative extract powder of the above formula and 5g of lecithin, homogenize and emulsify, The obtained emulsion was spray-dried at an inlet temperature of 174°C, a spray pressure of 0.39 MPa, and a feed rate of 20 ml/min. The microcapsules were collected and cooled to obtain 806 g of microcapsules. Take 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.
实施例Example 5 首荟通便微囊胶囊Shouhui laxative microcapsules
1)提取、纯化工艺(10倍处方量)  :何首乌1200g   芦荟1600g     决明子1400g   人参500g      枸杞子750g    阿胶750g    枳实1200g     白术500g,以上8味,取阿胶,粉碎成超细粉,过200目筛,备用;人参、何首乌、决明子、芦荟加60%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.15(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达60%(25℃时),冷藏静置48小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.32(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度60℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉2650g。 1) Extraction and purification process (10 times the prescription amount): Polygonum multiflorum 1200g, aloe 1600g, cassia 1400g, ginseng 500g, medlar 750g, donkey-hide gelatin 750g Fructus Aurantii 1200g Atractylodes 500g, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass through a 200-mesh sieve, and set aside; ginseng, fleece-flower root, cassia, aloe plus 60% ethanol reflux extraction twice, the first time increase 10 times the amount , Add 8 times the amount for the second time, 2 hours each time, filter separately and combine the filtrate; add water to decoct wolfberry, citrus fruit and atractylodes macrocephalae twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours , Add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.15 (at 80 ℃), put it to room temperature, stir and add ethanol to make the concentration reach 60% (25 ℃) Time), refrigerate and stand for 48 hours, and filter; combine the above alcohol extract and water decoction, concentrate into a thick paste with a relative density of 1.32 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa , The drying temperature is 60 ℃, pulverized into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 2650g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:225g   B、酪蛋白酸钠:445g   淀粉糖浆干粉:296g    C、单硬脂酸甘油酯:13g    D、聚乙二醇6000:30g  柠檬酸:9g,将以上配方量的麦芽糊精、β-乳球蛋白、单硬脂酸甘油酯、聚乙二醇6000、柠檬酸加入纯化水,52℃条件下加热搅拌使溶解,配制成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和大豆磷脂3.6g、蔗糖脂肪酸酯5.4g,均质乳化,得乳化液,在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊867g。取步骤2)微囊,加入微粉硅胶133g,灌装,磨光机中抛光,剔除破损胶囊即得。 2) Preparation process: A. Shouhui laxative extract powder: 225g B. Sodium caseinate: 445g Dry starch syrup powder: 296g C, glyceryl monostearate: 13g D. Polyethylene glycol 6000: 30g Citric acid: 9g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000, citric acid into purified water, 52℃ Under the conditions, heat and stir to dissolve, prepare a 36% mass fraction of capsule material solution, cool to room temperature, add the fine powder of Shouhui laxative extract, 3.6g of soybean phospholipid, and 5.4g of sucrose fatty acid ester under stirring, and homogenize Emulsify to obtain an emulsion, which is spray-dried at an inlet temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min. The microcapsules are collected and cooled to obtain 867 g of microcapsules. Take step 2) microcapsules, add 133g of micro-powder silica gel, fill, polish in a grinder, and get rid of damaged capsules.
实施例Example 6 首荟通便微囊片Shouhui laxative microcapsule tablets
1)提取、纯化工艺:何首乌130g    芦荟180g     决明子150g   人参70g      枸杞子60g     阿胶70g枳实120g      白术60g,以上8味,取阿胶,粉碎成超细粉,过150目筛,备用;人参、何首乌、决明子、芦荟加70%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.19(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达60%(25℃时),冷藏静置24小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.33(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度55℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉325g。1) Extraction and purification process: Polygonum multiflorum 130g, Aloe 180g, Cassia seed 150g, Ginseng 70g Wolfberry 60g Ejiao 70g Citrus aurantium 120g Atractylodes macrocephala 60g, the above 8 flavors, take donkey-hide gelatin, crush it into superfine powder, pass through a 150-mesh sieve, and set aside; ginseng, fleece-flower root, cassia seed, aloe plus 70% ethanol reflux extraction twice, the first time 10 times the amount, the second Add 8 times the amount each time, 2 hours each time, filter separately, and combine the filtrate; add water to decoct wolfberry, Citrus aurantium, and Atractylodes macrocephala twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours, and second Add 6 times the amount each time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.19 (at 80°C), put it to room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), Refrigerate and stand for 24 hours, then filter; combine the above alcohol extract and water decoction, concentrate into thick paste with relative density of 1.33 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature Crushed into fine powder at 55°C, sieved, and mixed with the above-mentioned superfine donkey-hide gelatin powder to obtain 325g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:260g     B、阿拉伯胶:510g  大豆分离蛋白:170g   C、十八醇:8g   微粉硅胶:4g    D、聚乙二醇6000:48g,将以上配方量的阿拉伯胶、大豆分离蛋白、十八醇、微粉硅胶、聚乙二醇6000加入纯化水,58℃条件下加热搅拌使溶解,配制成质量分数为42%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及蔗糖脂肪酸酯7g,均质乳化,得乳化液,在进风温度166℃、喷雾压力0.36MPa、进料速度20.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊798g。取步骤2)微囊,加入微晶纤维素180g,混匀,制成粗颗粒,干燥,粉碎,过筛,制颗粒,低温干燥,整粒,加入10g硬脂酸镁和12g的滑石粉,混匀,压片,即得。 2) Preparation process: A. Shouhui laxative extract powder: 260g B. Arabic gum: 510g soy protein isolate: 170g C, stearyl alcohol: 8g Micro-powder silica gel: 4g D, polyethylene glycol 6000: 48g, add the above formula amount of gum arabic, soy protein isolate, stearyl alcohol, micro-powder silica gel, polyethylene glycol 6000 into purified water, heat and stir at 58℃ to dissolve , Formulated into a capsule material solution with a mass fraction of 42%, cooled to room temperature, added the above formula amount of laxative extract powder of the above formula and 7g of sucrose fatty acid ester under stirring, and homogenized emulsification to obtain an emulsified liquid. 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. Take 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.
实施例Example 7 首荟通便微囊Shouhui laxative microcapsules
1)提取、纯化工艺:何首乌75g     芦荟150g      决明子90g   人参50g       枸杞子70g     阿胶80g枳实120g      白术60g,以上8味,取阿胶,粉碎成超细粉,过200目筛,备用;人参、何首乌、决明子、芦荟加50%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.17(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达50%(25℃时),冷藏静置36小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.30(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度60℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉289g。1) Extraction and purification process: Polygonum multiflorum 75g Aloe 150g Cassia seed 90g Ginseng 50g Wolfberry 70g Ejiao 80g Citrus aurantium 120g Atractylodes macrocephala 60g, the above 8 flavors, take donkey-hide gelatin, crush it into superfine powder, pass through a 200-mesh sieve, and set aside; ginseng, fleece-flower root, cassia seed and aloe are refluxed with 50% ethanol for two times, the first time is 10 times the amount, the second time Add 8 times the amount each time, 2 hours each time, filter separately, and combine the filtrate; add water to decoct wolfberry, Citrus aurantium, and Atractylodes macrocephala twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours, and second Add 6 times the amount each time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.17 (at 80°C), put it to room temperature, stir and add ethanol to make the concentration reach 50% (at 25°C), Refrigerate and stand for 36 hours, then filter; combine the above alcohol extract and water decoction, concentrate into thick paste with relative density of 1.30 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature At 60°C, pulverize into fine powder, sieving, and mix with the above-mentioned superfine Ejiao powder to obtain 289g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:150g     B、辛烯基琥珀酸酯化淀粉:468g   β-乳球蛋白:312g    C、单硬脂酸甘油酯:20g     D、丙二醇:50g,将以上配方量的辛烯基琥珀酸酯化淀粉、β-乳球蛋白、单硬脂酸甘油酯、丙二醇加入纯化水,49℃条件下加热搅拌使溶解,配制成质量分数为29%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及吐温-80 8g,均质乳化,得乳化液,在进风温度165℃、喷雾压力0.41MPa、进料速度24ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊806g。 2) Preparation process: A. Shouhui laxative extract powder: 150g B. Octenyl succinate starch: 468g β-lactoglobulin: 312g C. Glyceryl monostearate: 20g D. Propylene glycol: 50g, add the octenyl succinate starch, β-lactoglobulin, glyceryl monostearate, and propylene glycol in the above formula into purified water, heat and stir at 49℃ to dissolve, and prepare the quality The capsule material solution with a fraction of 29%, cool to room temperature, add the above formula amount of Shouhui laxative extract powder and Tween-80 8g under stirring, homogenize and emulsify to obtain an emulsion, at the inlet temperature of 165℃ , Spray drying under the conditions of spray pressure 0.41MPa and feed rate 24ml/min, collect the microcapsules, and cool to obtain 806g microcapsules.
实施例Example 8 首荟通便微囊胶囊Shouhui laxative microcapsules
1)提取、纯化工艺:何首乌100g    芦荟130g       决明子120g    人参40g       枸杞子70g      阿胶60g枳实100g  白术40g,以上8味,取阿胶,粉碎成超细粉,过150目筛,备用;人参、何首乌、决明子、芦荟加60%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.19(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达70%(25℃时),冷藏静置48小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.32(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度60℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉281g。 1) Extraction and purification process: Polygonum multiflorum 100g, Aloe 130g, Cassia seed 120g Ginseng 40g wolfberry 70g Ejiao 60g Citrus aurantium 100g Atractylodes 40g, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass through a 150-mesh sieve, and set aside; ginseng, fleece-flower root, cassia, aloe plus 60% ethanol reflux extraction twice, Add 10 times the amount for the first time, add 8 times the amount for the second time, filter separately and combine the filtrate for 2 hours each time; decoct medlar, citrus fruit, and atractylodes macrocephala twice with water, add 8 times the amount for the first time, soak 1 hour, decocting for 1.5 hours, adding 6 times the amount for the second time, decocting for 1.5 hours, filtering, combining the filtrate, and concentrating to a clear paste with a relative density of 1.19 (at 80°C), placing it at room temperature, stirring and adding ethanol to make Concentration reaches 70% (at 25°C), keep it in the refrigerator for 48 hours, and filter; combine the above alcohol extract and water decoction to concentrate into a thick paste with a relative density of 1.32 (70°C), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature 60℃, crushed into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 281g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:190g      B、麦芽糊精:474g   大豆分离蛋白:273g   C、十八醇:25g     D、丙二醇:41g,将以上配方量的麦芽糊精、大豆分离蛋白、十八醇、丙二醇加入纯化水,45℃条件下加热搅拌使溶解,配制成质量分数为22%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及泊洛沙姆4g,均质乳化,得乳化液,在进风温度174℃、喷雾压力0.42MPa、进料速度25ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊839g。取步骤2)微囊,加入微粉硅胶161g,灌装,磨光机中抛光,剔除破损胶囊即得。 2) Preparation process: A. Shouhui laxative extract powder: 190g B, maltodextrin: 474g soy protein isolate: 273g C, stearyl alcohol: 25g D. Propylene glycol: 41g, add the above formula amount of maltodextrin, soy protein isolate, stearyl alcohol, and propylene glycol to purified water, heat and stir at 45°C to dissolve, prepare a 22% mass fraction of capsule material solution, and cool To room temperature, add the above formula amount of laxative extract powder and 4g of poloxamer under stirring, homogenize and emulsify to obtain an emulsion. At the inlet temperature of 174℃, the spray pressure of 0.42MPa, and the feed rate of 25ml Under the condition of spray drying, the microcapsules were collected and cooled to obtain 839 g of microcapsules. Take step 2) microcapsules, add 161g of micro-powder silica gel, fill, polish in a grinder, and get rid of damaged capsules.
实施例Example 9 首荟通便微囊片Shouhui laxative microcapsule tablets
1)提取、纯化工艺:何首乌70g     芦荟110g       决明子90g    人参60g       枸杞子80g      阿胶80g  枳实100g   白术30g,以上8味,取阿胶,粉碎成超细粉,过150目筛,备用;人参、何首乌、决明子、芦荟加50%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.12(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达50%(25℃时),冷藏静置48小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.31(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度50℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉263g。 1) Extraction and purification process: Polygonum multiflorum 70g, Aloe 110g, Cassia 90g Ginseng 60g wolfberry 80g donkey-hide gelatin 80g Citrus aurantium 100g and Atractylodes 30g, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass through a 150-mesh sieve, and set aside; ginseng, fleece-flower root, cassia, aloe plus 50% ethanol reflux extraction twice, the first time increase 10 times the amount , Add 8 times the amount for the second time, 2 hours each time, filter separately and combine the filtrate; add water to decoct wolfberry, citrus fruit and atractylodes macrocephalae twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours , Add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.12 (at 80℃), put it to room temperature, stir and add ethanol to make the concentration reach 50% (25℃) Time), refrigerate and stand for 48 hours, and filter; combine the above alcohol extract and water decoction, concentrate into a thick paste with a relative density of 1.31 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa , The drying temperature is 50 ℃, pulverized into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 263g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:183g     B、阿拉伯胶:756g    C、单硬脂酸甘油酯:10g    二氧化钛:6g   D、柠檬酸:45g,将以上配方量的阿拉伯胶、单硬脂酸甘油酯、二氧化钛、柠檬酸加入纯化水,50℃条件下加热搅拌使溶解,配制成质量分数为32%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及卵磷脂5g,均质乳化,得乳化液,在进风温度175℃、喷雾压力0.38MPa、进料速度18.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊811g。取步骤2)微囊,加入淀粉173g,混匀,制成粗颗粒,干燥,粉碎,过筛,制颗粒,低温干燥,整粒,加入5g硬脂酸镁和11g的滑石粉,混匀,压片,即得。 2) Preparation process: A. Shouhui laxative extract powder: 183g B. Gum Arabic: 756g   C. Glyceryl monostearate: 10g Titanium dioxide: 6g D. Citric acid: 45g, add acacia, glyceryl monostearate, titanium dioxide, and citric acid in the above formula into purified water, heat and stir at 50℃ to dissolve, and prepare a 32% mass fraction of capsule material solution , Cool to room temperature, add the above formula amount of laxative extract powder and 5g of lecithin under stirring, homogenize and emulsify to obtain an emulsified liquid, at the inlet temperature of 175℃, the spray pressure of 0.38MPa, and the feed rate of 18.5 Spray drying is performed under the condition of ml/min, and the microcapsules are collected and cooled to obtain 811 g of microcapsules. Take 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.
实施例Example 10  10 首荟通便微囊胶囊Shouhui laxative microcapsules
1)提取、纯化工艺:何首乌90g    芦荟130g       决明子120g   人参40g      枸杞子70g      阿胶50g  枳实90g   白术40g,以上8味,取阿胶,粉碎成超细粉,过180目筛,备用;人参、何首乌、决明子、芦荟加60%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;枸杞子、枳实、白术加水煎煮二次,第一次加8倍量,浸泡1小时,煎煮1.5小时,第二次加6倍量,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.16(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达70%(25℃时),冷藏静置36小时,滤过;合并上述醇提液与水煎液,浓缩成相对密度为1.34(70℃)的稠膏,带式真空干燥,真空度-0.08MPa--0.10Mpa,干燥温度50℃,粉碎成细粉,过筛,与上述阿胶超细粉混匀,即得首荟通便提取物细粉303g。 1) Extraction and purification process: Polygonum multiflorum 90g, Aloe 130g, Cassia seed 120g Ginseng 40g wolfberry fruit 70g donkey-hide gelatin 50g citrus fruit 90g atractylodes 40g, the above 8 flavors, take donkey-hide gelatin, crush into superfine powder, pass through a 180-mesh sieve, and set aside; ginseng, fleece-flower root, cassia, aloe plus 60% ethanol reflux extraction twice, Add 10 times the amount for the first time, add 8 times the amount for the second time, filter separately and combine the filtrate for 2 hours each time; decoct medlar, citrus fruit, and atractylodes macrocephala twice with water, add 8 times the amount for the first time, soak 1 hour, decocting for 1.5 hours, adding 6 times the amount for the second time, decocting for 1.5 hours, filtering, combining the filtrate, and concentrating to a clear paste with a relative density of 1.16 (at 80°C), placing it at room temperature, stirring and adding ethanol to make Concentration reaches 70% (at 25°C), keep it in refrigeration for 36 hours, and filter; combine the above alcohol extract and water decoction to concentrate into a thick paste with a relative density of 1.34 (70°C), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature 50℃, crushed into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 303g of fine powder of Shouhui laxative extract.
2)制剂工艺:A、首荟通便提取物细粉:176g    B、麦芽糊精:349g  大豆分离蛋白:210g    变性淀粉:140g      阿拉伯胶:70g    C、单硬脂酸甘油酯:16g      D、甘油:39g,将以上配方量的麦芽糊精、大豆分离蛋白、变性淀粉、阿拉伯胶、单硬脂酸甘油酯、甘油加入纯化水,47℃条件下加热搅拌使溶解,配制成质量分数为39%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及吐温-80 11g,均质乳化,得乳化液,在进风温度169℃、喷雾压力0.41MPa、进料速度21ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊837g。 2) Preparation process: A. Shouhui laxative extract powder: 176g B. Maltodextrin: 349g Soy protein isolate: 210g Modified starch: 140g Gum arabic: 70g C, Glyceryl monostearate: 16g D. 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. At the inlet temperature of 169℃, 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.
取步骤2)微囊,加入乳糖163g,灌装,磨光机中抛光,剔除破损胶囊,即得。Take step 2) microcapsules, add 163g lactose, fill, polish in a grinder, remove damaged capsules, and get ready.
实施例Example 11  11 首荟通便微囊片Shouhui laxative microcapsule tablets
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。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.
制剂工艺:A、首荟通便提取物细粉:197g    B、酪蛋白酸钠:445g   淀粉糖浆干粉:296g   C、十八醇:12g  二氧化钛:6g       D、丙二醇:44g,将以上配方量的酪蛋白酸钠、淀粉糖浆干粉、十八醇、二氧化钛、丙二醇加入纯化水,52℃条件下加热搅拌使溶解,配制成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入以上配方量的首荟通便提取物细粉以及大豆磷脂3.6g和蔗糖脂肪酸酯5.4g,均质乳化,得乳化液,在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊852g。取步骤2)微囊,加入糊精131g,混匀,制成粗颗粒,干燥,粉碎,过筛,制颗粒,低温干燥,整粒,加入8g硬脂酸镁和9g的滑石粉,混匀,压片,即得。 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℃ 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. At the inlet temperature of 172℃, 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. Take 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.
对比实施例Comparative example 1 首荟通便微囊Shouhui laxative microcapsules
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。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.
制剂工艺:A、首荟通便提取物细粉:225g    B、麦芽糊精:506g   β-乳球蛋白:217g   C、单硬脂酸甘油酯:13g   D、聚乙二醇6000:39g,将以上配方量的麦芽糊精、β-乳球蛋白、单硬脂酸甘油酯、聚乙二醇6000加入纯化水,52℃条件下加热搅拌使溶解,配制成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和大豆磷脂3.6g、蔗糖脂肪酸酯5.4g,均质乳化,得乳化液,在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊785g。Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C. Glyceryl monostearate: 13g D. Polyethylene glycol 6000: 39g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, and polyethylene glycol 6000 to purified water ,Heat and stir at 52℃ to dissolve, prepare a 36% mass fraction of capsule material solution, cool to room temperature, add Shouhui laxative extract powder, 3.6g soy phospholipid, and 5.4g sucrose fatty acid ester under stirring. , Homogeneous emulsification to obtain an emulsion, spray drying at an inlet temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min. The microcapsules are collected and cooled to obtain 785 g of microcapsules.
对比实施例Comparative example 2 首荟通便微囊Shouhui laxative microcapsules
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。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.
制剂工艺:A、首荟通便提取物细粉:225g     B、麦芽糊精:506g   β-乳球蛋白:217g    C、单硬脂酸甘油酯:13g    D、柠檬酸:39g,将以上配方量的麦芽糊精、β-乳球蛋白、单硬脂酸甘油酯、聚乙二醇6000加入纯化水,52℃条件下加热搅拌使溶解,配制成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和大豆磷脂3.6g、蔗糖脂肪酸酯5.4g,均质乳化,得乳化液,在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊794g。 Preparation process: A, Shouhui laxative extract powder: 225g B, maltodextrin: 506g β-lactoglobulin: 217g C, glycerol monostearate: 13g D. Citric acid: 39g, add the above formula amount of maltodextrin, β-lactoglobulin, glycerol monostearate, polyethylene glycol 6000 to purified water, heat and stir at 52℃ to dissolve, and prepare the quality 36% of the capsule material solution, cool to room temperature, add Shouhui laxative extract powder, 3.6g of soy phospholipids, and 5.4g of sucrose fatty acid ester under stirring, homogenize and emulsify to obtain an emulsion, at the inlet temperature Spray drying was performed under the conditions of 172°C, spray pressure 0.39 MPa, and feed rate 22.5 ml/min. The microcapsules were collected and cooled to obtain 794 g of microcapsules.
对比实施例Comparative example 3 首荟通便微囊Shouhui laxative microcapsules
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。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.
制剂工艺:A、首荟通便提取物细粉:225g     B、麦芽糊精:506g    β-乳球蛋白:217g   C、单硬脂酸甘油酯:13g   D、聚乙二醇6000:26g   柠檬酸:13g,将以上配方量的麦芽糊精、β-乳球蛋白、单硬脂酸甘油酯、聚乙二醇6000加入纯化水,52℃条件下加热搅拌使溶解,配制成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和大豆磷脂3.6g、蔗糖脂肪酸酯5.4g,均质乳化,得乳化液,在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊791g。 Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C, glycerol monostearate: 13g D, polyethylene glycol 6000: 26g Citric acid: 13g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000 to purified water, heat and stir at 52℃ to dissolve, and prepare the mass fraction as 36% of the capsule material solution, cool to room temperature, add Shouhui laxative extract powder, 3.6g soy phospholipid, 5.4g sucrose fatty acid ester under stirring, homogenize and emulsify to obtain an emulsified liquid, at the inlet temperature of 172℃ , Spray drying under the conditions of spray pressure 0.39MPa and feed rate 22.5ml/min, collect microcapsules and cool to obtain 791g microcapsules.
对比实施例Comparative example 4 首荟通便微囊Shouhui laxative microcapsules
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。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.
制剂工艺:A、首荟通便提取物细粉:225g    B、麦芽糊精:506g   β-乳球蛋白:217g   C、单硬脂酸甘油酯:13g     D、聚乙二醇6000:31.2g    柠檬酸:7.8g,将以上配方量的麦芽糊精、β-乳球蛋白、单硬脂酸甘油酯、聚乙二醇6000加入纯化水,52℃条件下加热搅拌使溶解,配制成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和大豆磷脂3.6g、蔗糖脂肪酸酯5.4g,均质乳化,得乳化液,在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊823g。 Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C, glycerol monostearate: 13g D. Polyethylene glycol 6000: 31.2g Citric acid: 7.8g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000 to purified water, heat and stir at 52℃ to dissolve, and prepare the mass fraction It is a 36% capsule material solution, cooled to room temperature, and while stirring, add the fine powder of Shouhui laxative extract, 3.6g of soybean phospholipid, and 5.4g of sucrose fatty acid ester, and homogenize and emulsify to obtain an emulsion. At the inlet temperature of 172 Under the conditions of ℃, spray pressure of 0.39MPa, and feed rate of 22.5ml/min, spray drying was performed, and the microcapsules were collected and cooled to obtain 823g of microcapsules.
对比实施例Comparative example 5 首荟通便微囊Shouhui laxative microcapsules
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。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.
制剂工艺:A、首荟通便提取物细粉:225g     B、麦芽糊精:506g   β-乳球蛋白:217g  C、单硬脂酸甘油酯:13g     D、聚乙二醇6000:32.5g     柠檬酸:6.5g,将以上配方量的麦芽糊精、β-乳球蛋白、单硬脂酸甘油酯、聚乙二醇6000加入纯化水,52℃条件下加热搅拌使溶解,配制成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和大豆磷脂3.6g、蔗糖脂肪酸酯5.4g,均质乳化,得乳化液,在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊817g。 Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C. Glyceryl monostearate: 13g D. Polyethylene glycol 6000: 32.5g Citric acid: 6.5g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000 into purified water, heat and stir at 52℃ to dissolve, and prepare the mass fraction It is a 36% capsule material solution, cooled to room temperature, and under stirring, add Shouhui laxative extract powder, 3.6g of soybean phospholipid, and 5.4g of sucrose fatty acid ester, homogenize and emulsify to obtain an emulsified liquid, at an inlet temperature of 172 Under the conditions of ℃, spray pressure of 0.39MPa, and feed rate of 22.5ml/min, spray drying was performed, and the microcapsules were collected and cooled to obtain 817g of microcapsules.
对比实施例Comparative example 6 首荟通便微囊Shouhui laxative microcapsules
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。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.
制剂工艺:A、首荟通便提取物细粉:225g    B、麦芽糊精:506g   β-乳球蛋白:217g  C、单硬脂酸甘油酯:13g    D、聚乙二醇6000:33.4g   柠檬酸:5.6g,将以上配方量的麦芽糊精、β-乳球蛋白、单硬脂酸甘油酯、聚乙二醇6000加入纯化水,52℃条件下加热搅拌使溶解,配制成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和大豆磷脂3.6g、蔗糖脂肪酸酯5.4g,均质乳化,得乳化液,在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊805g。 Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C. Glyceryl monostearate: 13g D. Polyethylene glycol 6000: 33.4g Citric acid: 5.6g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000 into purified water, heat and stir at 52℃ to dissolve, and prepare the mass fraction It is a 36% capsule material solution, cooled to room temperature, and while stirring, add the fine powder of Shouhui laxative extract, 3.6g of soybean phospholipid, and 5.4g of sucrose fatty acid ester, and homogenize and emulsify to obtain an emulsion. At the inlet temperature of 172 Under the conditions of ℃, spray pressure 0.39MPa, and feed rate of 22.5ml/min, spray drying was performed, and the microcapsules were collected and cooled to obtain 805 g of microcapsules.
对比实施例Comparative example 7 首荟通便颗微囊的制备Preparation of Shouhui laxative microcapsules
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。所用微囊制备方法参照中国专利“一种复方陈醋微囊及其制备方法与应用(授权公告号CN106036829B)”的最佳效果实施例5,以此考察现有技术微囊制备方法应用于首荟通便提取物细粉时所达到的制剂效果。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.
制剂工艺:A、首荟通便提取物细粉:222g    B、3%海藻酸钠溶液:778g,将上述配方量的首荟通便提取物细粉加入到质量分数为3%的海藻酸钠溶液,制得微囊囊芯混合液,其中海藻酸钠与首荟通便提取物细粉的重量比为3.5:1;将上述囊芯混合液混合均匀,在搅拌状态下滴入1.5%的壳聚糖与3.5%的氯化钙混合液体系中进行微囊化包埋; Preparation process: A. Shouhui laxative extract fine powder: 222g B. 3% sodium alginate solution: 778g, add the fine powder of the first hydrangea laxative extract of the above formula to the 3% sodium alginate solution to prepare the microcapsule core mixture, in which the sodium alginate The weight ratio of the fine powder of Shouhui laxative extract is 3.5:1; mix the above-mentioned capsule core mixture uniformly, and drip into the 1.5% chitosan and 3.5% calcium chloride mixture system under stirring. Microencapsulation and embedding;
用泵将上述制得的微囊送到喷雾干燥机进行喷雾干燥,控制进风口温度为185℃,喷雾压力0.185MPa,最终微囊沥出得到微囊成品245g。The 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.
对比实施例Comparative example 8 首荟通便微囊的制备Preparation of Shouhui laxative microcapsules
本实施例所用首荟通便提取物细粉为实施例5步骤1)提取、纯化工艺所得的首荟通便提取物细粉。所用微囊制备方法参照“胡锐,周广萍,宋维春.喷雾干燥法中药益生元微囊的制备及体外控释分析[J].安徽农业科学,2016,44(29):89-94.”中最佳的微囊制备工艺,即囊材为明胶:海藻酸钠=1:3,芯材质量分数为20%,进风口温度187℃、出风口温度60℃、进料速度为32mL/min。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." The best microcapsule preparation process is that the capsule material is gelatin: sodium alginate=1:3, the mass fraction of the core material is 20%, the air inlet temperature is 187℃, the air outlet temperature is 60℃, and the feed rate is 32mL/min.
制剂工艺:A、首荟通便提取物细粉:200g    B、明胶:200g    海藻酸钠:600g,将以上配方量的明胶、海藻酸钠加入纯化水,50℃条件下加热搅拌使溶解,配制成质量分数为4%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉,均质乳化,得乳化液,在进风温度187℃、出风口温度60℃、喷雾压力0.39MPa、进料速度32ml/min条件下进行喷雾干燥,收集微囊,冷却,得微囊329g。 Preparation process: A. Shouhui laxative extract fine powder: 200g B. Gelatin: 200g Sodium alginate: 600g, add the gelatin and sodium alginate of the above formula into purified water, heat and stir at 50℃ to dissolve, prepare a capsule material solution with a mass fraction of 4%, cool to room temperature, add the first under stirring The fine powder of Hui laxative extract was homogenized and emulsified to obtain an emulsion, which was spray-dried under the conditions of air inlet temperature of 187°C, air outlet temperature of 60°C, spray pressure of 0.39MPa, and feed rate of 32ml/min, and the microcapsules were collected. After cooling, 329g of microcapsules were obtained.
工业实用性Industrial applicability
实验例Experimental example 1 微囊形态及粒径分布Microcapsule morphology and particle size distribution
一、形态:取实施例5、实施例11微囊样品适量,置蒸发皿中,于自然光处或相当于自然光的室内,观察其色泽、形状。肉眼观测到微囊样品呈白色或灰白色粉末,呈疏松状,无不良气味,流动性较好,分散性和稳定性均佳。1. 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.
将上述样品分别加入少量丙酮,超声2min(使重叠粘连的微囊分散),蘸取并滴加在玻片上,加盖玻片,置于Winner99C型静态颗粒图像仪(济南微纳颗粒仪器股份有限公司)放大1000倍观察,微囊颗粒表面除有个别存在凹痕外,颗粒较圆整并接近球形,表面致密无孔隙,基本无黏连,符合微囊要求。Add a small amount of acetone to the above samples, ultrasonic for 2 minutes (to disperse the overlapping and adhered microcapsules), dip and drop on the glass slide, add a cover glass, and place it on the Winner99C static particle imager (Jinan Micro Nano Particle Instrument Co., Ltd. Company) Observed at 1000 times magnification. Except for individual dents on the surface of the microcapsule particles, the particles are relatively round and close to spherical, and the surface is compact and non-porous, basically free of adhesion, which meets the requirements of microcapsules.
二、粒径分布:取实施例5、实施例11微囊样品约0.03 g,以50%乙醇作为分散介质,置Winner2005B智能型激光粒度分析仪(济南微纳颗粒仪器股份有限公司)中测定粒径(D),结果见表1(表中D10、D50、D90分别表示分布曲线中累积分布为10%、50%、90%时最大颗粒的等效直径,Dav表示平均粒径,下表同)和附图1、附图2。2. 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.
Figure 851609dest_path_image001
Figure 851609dest_path_image001
从附图1和附图2可以看出,首荟通便微囊粒径分布相对均匀,多数集中在20μm附近,其中实施例5微囊的平均粒径为22.69μm,实施例11微囊的平均粒径为23.03μm,两份样品的微囊粒径分布较窄,且呈近似的正态分布,微囊化效果较好。It can be seen from Figure 1 and Figure 2 that the particle size distribution of the laxative microcapsules of Shouhui is relatively uniform, most of which are concentrated in the vicinity of 20μm. The average particle size of the microcapsules of Example 5 is 22.69μm, and that of the microcapsules of Example 11 The average particle size is 23.03μm, 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.
实验例Experimental example 2 首荟通便微囊包封率测定Determination of the encapsulation rate of Shouhui laxative microcapsules
包封率指微囊中的实际含药量占微囊样品中总药量(即载药量)的百分比,即制得的微囊含药量占系统总含药量的百分比。包封率越高,表明药物被包埋的程度越好,首荟通便微囊包封率测定的具体方法如下。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.
色谱条件与系统适用性试验   以十八烷基键合硅胶为填充剂;以乙腈-甲醇-水=20:8:72为流动相;检测波长为320nm。理论板数按2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷峰计算应不低于2000。 Chromatographic conditions and system suitability test   Use octadecyl-bonded silica gel as filler; use acetonitrile-methanol-water=20:8:72 as mobile phase; detection wavelength is 320nm. The number of theoretical plates should not be less than 2000 calculated based on the peak of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside.
对照品溶液的制备   精密称取2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷对照品适量,加稀乙醇制成每1ml含0.06mg的溶液,即得。 Preparation of reference solution   Accurately weigh an appropriate amount of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside reference substance, add dilute ethanol to make a solution containing 0.06mg per 1ml, and get it.
供试品溶液的制备   精密称取适量首荟通便微囊样品,置100mL容量瓶中,以75%的乙醇定容至100mL,摇匀,使微囊外表面首荟通便提取物全部溶解在乙醇溶液中,精密移取10ml上述溶液置另一25mL容量瓶中,并以75%的乙醇溶液定容至刻度,取5ml样品溶液,转移至分液漏斗中,用乙醚提取2次,每次15ml,弃去乙醚液,再用稀盐酸调pH值至1-2,用乙酸乙酯提取(15ml,15ml,15ml,10ml)4次,合并乙酸乙酯液,蒸干,残渣用稀乙醇溶解并转移至2ml量瓶中,定容,摇匀,滤过,即得微囊外2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷供试品溶液。 Preparation of 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. Pipette 10ml of the above solution into another 25ml volumetric flask, and dilute to the mark with 75% ethanol solution, take 5ml sample solution, transfer to a separatory funnel, extract twice with ether, 15ml each time, discard the ether Then adjust the pH value 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, dissolve the residue with dilute ethanol and transfer to 2ml volume In the bottle, dilute to volume, shake well, and filter to obtain the test solution of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside outside the microcapsule.
另精密称取适量首荟通便微囊样品,置100mL容量瓶中,以pH=7.6的磷酸二氢钾-氢氧化钠缓冲液溶解并定容至100mL,摇匀,使微囊外表面及微囊内首荟通便提取物全部溶解于缓冲液中,其余操作同上,即得微囊2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷供试品溶液。In addition, accurately weigh an appropriate amount of Shouhui laxative microcapsule sample, place it in a 100mL volumetric flask, dissolve it with a pH=7.6 potassium dihydrogen phosphate-sodium hydroxide buffer solution and dilute to 100mL, shake it well, so that the outer surface of the microcapsule is All the laxative extracts of Shouhui in the microcapsules are dissolved in the buffer, and the rest of the operations are the same as above to obtain the microcapsules 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside. Test solution.
测定法   取标准溶液及供试品溶液,分别进样20ul,采用外标两点法对数方程计算样品中2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷的含量,通过2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷的含量计算微囊外表面提取物细粉的量(m)及微囊总提取物细粉的量(M)。 Assay   Take the standard solution and the test solution, respectively inject 20ul samples, and use the external standard two-point method to calculate the 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucose in the sample The content of glycosides, calculated by the content of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside The amount of fine powder of the extract (M).
包封率=(微囊样品中总药量M−微囊外药量m)×100%/微囊样品中总药量M。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.
Figure 329995dest_path_image002
Figure 329995dest_path_image002
由表2可得,在增塑剂为聚乙二醇6000和柠檬酸复合物,且用量固定为制剂配方总量3.9%时,随着聚乙二醇6000与柠檬酸用量比例的变化,首荟通便微囊的包封率和合格微囊的收率也随之变化,从实验结果来看,聚乙二醇6000:柠檬酸=3:1时,其包封率最好,成品收率最高,并明显高于增塑剂为单味聚乙二醇6000的对比实施例1以及增塑剂为单味柠檬酸的对比实施例2。From Table 2, when the plasticizer is a compound of polyethylene glycol 6000 and citric acid, and the dosage is fixed at 3.9% of the total formulation formula, as the ratio of polyethylene glycol 6000 to citric acid changes, the first The encapsulation rate of Hui laxative microcapsules and the yield of qualified microcapsules also change accordingly. From the experimental results, when polyethylene glycol 6000: citric acid = 3:1, the encapsulation rate is the best, and the finished product yields The rate is the highest, and is significantly higher than Comparative Example 1 where the plasticizer is a single-flavor polyethylene glycol 6000 and Comparative Example 2 where the plasticizer is a single-flavor citric acid.
对比实施例7和对比实施例8所得微囊包封率较差,分别为44.1%和37.6%;其收率较低,分别为24.5%和32.9%。可见,以现有技术微囊制剂配方及微囊制备方法进行首荟通便胶囊的制备,其包封率及产品收率无法达到相应的要求,无法实现工业化生产。The encapsulation rates of the microcapsules obtained in Comparative Example 7 and Comparative Example 8 were poor, 44.1% and 37.6%, respectively; the yields were low, 24.5% and 32.9%, respectively. It can be seen that the encapsulation rate and product yield of Shouhui laxative capsules prepared by the prior art microcapsule preparation formula and microcapsule preparation method cannot meet the corresponding requirements, and industrial production cannot be realized.
实验例Experimental example 3 体外累积溶出度试验In vitro cumulative dissolution test
本发明实施例5首荟通便微囊胶囊、实施例11首荟通便微囊片及首荟通便胶囊(鲁南厚普制药有限公司,规格:0.35g/粒×6粒/盒,批号:26190032)参照溶出度测定法(《中国药典》2015年版四部通则0931缓释或控释制剂)于250ml磷酸盐缓冲液(pH6.8)为溶出介质、水浴温度为37℃±0.5℃、转速100r˙min -1的条件下进行体外溶出试验,以2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷(C 20H 22O 9)为指标进行考察。 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) Refer to the dissolution test method (Chinese 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℃±0.5℃, The in vitro dissolution test was carried out at a speed of 100r˙min -1 , with 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (C 20 H 22 O 9 ) as an indicator Conduct an inspection.
色谱条件与系统适用性试验   以十八烷基键合硅胶为填充剂;以乙腈-甲醇-水=20:8:72为流动相;检测波长为320nm。理论板数按2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷峰计算应不低于2000。 Chromatographic conditions and system suitability test   Use octadecyl-bonded silica gel as filler; use acetonitrile-methanol-water=20:8:72 as mobile phase; detection wavelength is 320nm. The number of theoretical plates should not be less than 2000 calculated based on the peak of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside.
对照品溶液的制备   精密称取2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷对照品适量,加稀乙醇制成每1ml含0.06mg的溶液,即得。 Preparation of reference solution   Accurately weigh an appropriate amount of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside reference substance, add dilute ethanol to make a solution containing 0.06mg per 1ml, and get it.
供试品溶液的制备   取各时间点样品10ml,同时补加10ml的同温蒸馏水,样品经0.45μm微孔滤膜滤过,取5ml续滤液,转移至分液漏斗中,用乙醚提取2次,每次15ml,弃去乙醚液,再用稀盐酸调pH值至1-2,用乙酸乙酯提取(15ml,15ml,15ml,10ml)4次,合并乙酸乙酯液,蒸干,残渣用稀乙醇溶解并转移至2ml量瓶中,定容,摇匀,滤过,即得。 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 0.45μm 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.
测定法   取标准溶液,样品溶液,分别进样20ul,采用外标两点法对数方程计算样品中2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷的含量,计算各时间点2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷的累积溶出百分率,结果见表3。 Assay   Take the standard solution and the sample solution, respectively inject 20ul, and use the external standard two-point method to calculate the logarithmic equation of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside Calculate the cumulative dissolution percentage of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside at each time point. The results are shown in Table 3.
Figure 301362dest_path_image003
Figure 301362dest_path_image003
以溶出时间(min)为横坐标,累积溶出百分率(%)为纵坐标,绘制溶出曲线,见附图3。由附图3可以看出,首荟通便微囊胶囊和首荟通便微囊片在1h内累积溶出百分率小于54%,2h内均达到了82%以上的溶出,3h内基本释放完全,首荟通便微囊制剂具有一定的缓释效果。Take the dissolution time (min) as the abscissa and the cumulative dissolution percentage (%) as the ordinate to draw the dissolution curve, see Figure 3. It can be seen from Figure 3 that the cumulative dissolution rate of Shouhui laxative microcapsule capsules and Shouhui laxative microcapsule tablets within 1 hour is less than 54%, and both reached more than 82% dissolution within 2 hours, and the release is basically complete within 3 hours. Shouhui laxative microcapsule preparation has a certain slow-release effect.
实验例Experimental example 4 加速稳定性考察Accelerated stability investigation
本发明两批样品(实施例5微囊胶囊、实施例11微囊片)在铝塑包装下(6粒/版),采用加速试验箱(40±2℃、RH75%±5)保存6个月,分别按0个月,1个月,2个月,3个月,6个月取样)进行加速稳定性考查,其中二苯乙烯苷含量测定方法与实验例2同,其它指标的检测方法参照《中国药典》2015年版四部。两批产品加速稳定性试验数据见表4、表5。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℃, 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.
Figure 715157dest_path_image004
Figure 715157dest_path_image004
Figure 912920dest_path_image005
Figure 912920dest_path_image005
表4、表5加速稳定性试验结果表明,在加速试验条件(40±2℃、RH75%±5)下放置6个月,首荟通便微囊胶囊及微囊片性状无变化,含量无明显变化,水分、崩解(溶散)时限及卫生学各项考察指标均符合要求。由上述加速稳定性试验结果可知,本发明所制备的首荟通便微囊制剂稳定性好,质量可控。The results of accelerated stability test in Table 4 and Table 5 show that when placed for 6 months under accelerated test conditions (40±2℃, RH75%±5), the properties of Shouhui laxative microcapsule capsules and microcapsule tablets have no change, and the content has no change. Obvious changes, moisture, disintegration (dissolution) time limit and various inspection indicators of hygiene meet the requirements. It can be known from the above accelerated stability test results that the Shouhui laxative microcapsule preparation prepared by the present invention has good stability and controllable quality.

Claims (10)

  1. 一种首荟通便微囊制剂,其特征在于,按重量百分比计,微囊制剂配方包括以下成分:A Shouhui laxative microcapsule preparation, characterized in that, in terms of weight percentage, the microcapsule preparation formula includes the following ingredients:
    A、首荟通便提取物细粉13.5%-27.5%  B、囊材67%-81%                 A. Shouhui laxative extract fine powder 13.5%-27.5% B. Capsule material 67%-81%
    C、抗粘剂0.9%-2.5%                     D、增塑剂3.6%-5.0%             C. Anti-sticking agent 0.9%-2.5% D. Plasticizer 3.6%-5.0%
    所述囊材为阿拉伯胶、麦芽糊精、变性淀粉、辛烯基琥珀酸酯化淀粉、淀粉糖浆干粉、酪蛋白酸钠、β-乳球蛋白、大豆分离蛋白、黄原胶中的一种或几种;所述抗粘剂为单硬脂酸甘油酯、十八醇、微粉硅胶、二氧化钛中的一种或几种;所述增塑剂为甘油、聚乙二醇6000、聚乙二醇400、丙二醇、柠檬酸中的一种或几种。The capsule material is a kind of gum arabic, maltodextrin, modified starch, octenyl succinate starch, dry starch syrup powder, sodium caseinate, β-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.
  2. 如权利要求1所述的微囊制剂,其特征在于,所述首荟通便提取物细粉由下列原料制成:何首乌60-150重量份、芦荟100-200重量份 、决明子80-180重量份、人参20-80重量份、枸杞子30-100重量份、阿胶30-100重量份、枳实80-150重量份、白术20-80重量份;The microcapsule preparation according to claim 1, wherein the fine powder of Shouhui laxative extract is made of the following raw materials: 60-150 parts by weight of Polygonum multiflorum, 100-200 parts by weight of aloe, and 80-180 parts by weight of Cassia seed Parts, 20-80 parts by weight of ginseng, 30-100 parts by weight of wolfberry, 30-100 parts by weight of donkey-hide gelatin, 80-150 parts by weight of Citrus aurantium, 20-80 parts by weight of Baizhu;
    优选之一,所述首荟通便提取物细粉由下列原料制成:何首乌120重量份、芦荟160重量份、决明子140重量份、人参50重量份、枸杞子75重量份、阿胶75重量份、枳实120重量份、白术50重量份。Preferably, the fine powder of Shouhui laxative extract is made from the following raw materials: 120 parts by weight of Polygonum multiflorum, 160 parts by weight of aloe, 140 parts by weight of cassia, 50 parts by weight of ginseng, 75 parts by weight of wolfberry, and 75 parts by weight of donkey-hide gelatin , Citrus aurantium 120 parts by weight, and Atractylodes macrocephala 50 parts by weight.
  3. 如权利要求1或2所述的微囊制剂,其特征在于,按重量百分比计,制剂配方包含以下成分:A、首荟通便提取物细粉17.5%-23.5%    B、囊材71.5%-77.5%   C、抗粘剂1.1%-1.9%     D、增塑剂3.8%-4.7%;优选之一,按重量百分比计,制剂配方包含以下成分:A、首荟通便提取物细粉19.7%-22.5%    B、囊材72.3%-74.1%    C、抗粘剂1.3%-1.8%      D、增塑剂3.9%-4.4%;所述囊材按重量计为络蛋白酸钠:淀粉糖浆干粉=3:2、麦芽糊精:β-乳球蛋白=3:2、麦芽糊精:大豆分离蛋白:变性淀粉:阿拉伯胶=5:3:2:1或辛烯基琥珀酸酯化淀粉:β-乳球蛋白=3:2中的一种;所述抗粘剂按重量计为十八醇:二氧化钛=2:1或单硬脂酸甘油酯;所述增塑剂按重量计为聚乙二醇6000:柠檬酸=2-6:1或丙二醇。The microcapsule preparation according to claim 1 or 2, characterized in that, in terms of weight percentage, the preparation formula 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%; the preferred one, in terms of weight percentage, the formulation contains the following ingredients: A, Shouhui laxative extract fine powder 19.7%-22.5 % B, bag material 72.3%-74.1% C. Anti-sticking agent 1.3%-1.8% D. Plasticizer 3.9%-4.4%; the capsule material is sodium complex protein by weight: starch syrup dry powder = 3:2, maltodextrin: β-lactosphere Protein=3:2, Maltodextrin: Soy protein isolate: Modified starch: Arabic gum=5:3:2:1 or octenyl succinate starch: β-lactoglobulin=3:2 The anti-sticking agent is stearyl alcohol by weight: titanium dioxide = 2:1 or glyceryl monostearate; the plasticizer is polyethylene glycol 6000 by weight: citric acid = 2-6:1 Or propylene glycol.
  4. 如权利要求1-3中任一项所述首荟通便微囊制剂的制备方法,其特征在于,包括下列步骤:1)提取、纯化工艺The preparation method of Shouhui laxative microcapsule preparation according to any one of claims 1 to 3, characterized by comprising the following steps: 1) extraction and purification process
    A、按配方量称取阿胶,粉碎成超细粉,过筛,备用;A. Weigh the donkey-hide gelatin according to the formula, crush it into superfine powder, sieving, and set aside;
    B、人参、何首乌、决明子和芦荟加50%-70%乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;B. Ginseng, Polygonum multiflorum, Cassia Seeds and Aloe are refluxed and extracted twice with 50%-70% ethanol, the first time is 10 times the amount, the second time is 8 times the amount, each 2 hours, respectively, filtered, and the filtrate was combined;
    C、枸杞子、枳实、白术加水煎煮二次,第一次加8倍量水,浸泡1小时,煎煮1.5小时,第二次加6倍量水,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.10-1.20(80℃时)的清膏,放至室温,搅拌加乙醇使乙醇浓度达50%-70%(25℃时),冷藏静置24-48小时,滤过;C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.10-1.20 (at 80°C), put it at room temperature, stir and add ethanol to make the ethanol concentration reach 50%-70% (at 25°C), keep it in the refrigerator for 24-48 hours, Filter
    D、步骤B醇提液与步骤C水煎液合并,浓缩成相对密度为1.30-1.35(70℃时)的稠膏,干燥,粉碎成细粉,过筛,备用;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;
    E、将步骤A阿胶超细粉、步骤D细粉混匀,即得首荟通便提取物细粉,备用;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;
    2)制剂工艺2) Preparation process
    F、按配方量称取步骤E首荟通便提取物细粉、囊材、抗粘剂和增塑剂,将囊材、抗粘剂和增塑剂加入纯化水,45℃-58℃条件下加热搅拌使溶解,配置成质量分数为22%-42%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和乳化剂,均质乳化,得乳化液,备用;F. Weigh the laxative extract powder, capsule material, anti-adhesive agent and plasticizer of step E according to the formula quantity, add the capsule material, anti-adhesive agent and plasticizer to purified water at 45℃-58℃ Under heating and stirring to dissolve, configure it into a 22%-42% mass fraction of capsule material solution, cool to room temperature, add the fine powder of Shouhui laxative extract and emulsifier under stirring, homogenize and emulsify to obtain an emulsified liquid, and set aside ;
    G、步骤F乳化液在进风温度165℃-175℃、喷雾压力0.36MPa-0.42MPa、进料速度15ml/min-25ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。G. 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.
  5. 根据权利要求4所述的方法,其特征在于,步骤1)所述提取、纯化工艺包括下列步骤:The method according to claim 4, wherein step 1) said extraction and purification process comprises the following steps:
    A、按配方量称取阿胶,粉碎成超细粉,过150-200目筛,备用;A. Weigh the donkey-hide gelatin according to the formula, crush it into superfine powder, pass through a 150-200 mesh sieve, and set aside;
    B、人参、何首乌、决明子和芦荟加60%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;B. Ginseng, Polygonum multiflorum, Cassia seeds and Aloe are refluxed with 60% ethanol for two extractions, 10 times the amount for the first time, and 8 times the amount for the second time, for 2 hours each time, filter separately, and combine the filtrate;
    C、枸杞子、枳实、白术加水煎煮二次,第一次加8倍量水,浸泡1小时,煎煮1.5小时,第二次加6倍量水,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.10-1.20(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达60%(25℃时),冷藏静置36小时,滤过;C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.10-1.20 (at 80°C), put it at room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), keep it in the refrigerator for 36 hours, and filter;
    D、步骤B醇提液与步骤C水煎液合并,浓缩成相对密度为1.30-1.35(70℃)的稠膏,带式真空干燥,粉碎成细粉,过筛,备用;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;
    E、将步骤A阿胶超细粉、步骤D细粉混匀,即得首荟通便提取物细粉,备用。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.
  6. 根据权利要求5所述的方法,其特征在于,步骤1)D中带式真空干燥的条件为真空度-0.08MPa--0.10Mpa,干燥温度50℃-60℃。The method according to claim 5, characterized in that the conditions of the belt vacuum drying in step 1) D are vacuum degree -0.08MPa-0.10Mpa, and drying temperature 50°C-60°C.
  7. 根据权利要求4-6中任一项所述的方法,其特征在于,步骤2)所述制剂工艺包括下列步骤:F、按配方量称取步骤E首荟通便提取物细粉、囊材、抗粘剂和增塑剂,将囊材、抗粘剂和增塑剂加入纯化水,52℃条件下加热搅拌使溶解,配置成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和乳化剂,均质乳化,得乳化液,备用;The method according to any one of claims 4-6, characterized in that step 2) the preparation process comprises the following steps: F. Weighing step E according to the amount of the formula. , Anti-sticking agent and plasticizer, add the capsule material, anti-sticking agent and plasticizer to purified water, heat and stir at 52℃ to dissolve, configure into a capsule material solution with a mass fraction of 36%, cool to room temperature, and stir In the state, add the fine powder of Shouhui laxative extract and emulsifier, homogenize and emulsify to obtain the emulsified liquid for use;
    G、步骤F乳化液在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。G. 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.
  8. 如权利要求7所述的方法,其特征在于,步骤F所述乳化剂为Tween80、大豆磷脂、卵磷脂、泊洛沙姆、蔗糖脂肪酸酯中的一种或几种,用量按质量分数计为制剂配方总量的0.4%-1.2%。The method of claim 7, wherein the emulsifier in step F is one or more of Tween 80, soybean phospholipid, lecithin, poloxamer, and sucrose fatty acid ester, and the amount is calculated by mass fraction It is 0.4%-1.2% of the total preparation formula.
  9. 如权利要求8所述的方法,其特征在于,步骤F所述乳化剂按重量比计为大豆磷脂:蔗糖脂肪酸酯=4∶6的复合乳化剂,用量按质量分数计为制剂配方总量的0.9%。The method according to claim 8, wherein the emulsifier in step F is a composite emulsifier of soybean phospholipid: sucrose fatty acid ester = 4:6 in weight ratio, and the amount is calculated as the mass fraction of the total formulation formula Of 0.9%.
  10. 根据权利要求1所述的方法,其特征在于,步骤1)所述提取、纯化工艺包括下列步骤:1)提取、纯化工艺The method according to claim 1, wherein step 1) said extraction and purification process comprises the following steps: 1) extraction and purification process
    A、按配方量称取阿胶,粉碎成超细粉,过150-200目筛,备用;A. Weigh the donkey-hide gelatin according to the formula, crush it into superfine powder, pass through a 150-200 mesh sieve, and set aside;
    B、人参、何首乌、决明子和芦荟加60%的乙醇回流提取二次,第一次加10倍量,第二次加8倍量,每次2小时,分别滤过,合并滤液;B. Ginseng, Polygonum multiflorum, Cassia seeds and Aloe are refluxed with 60% ethanol for two extractions, 10 times the amount for the first time, and 8 times the amount for the second time, for 2 hours each time, filter separately, and combine the filtrate;
    C、枸杞子、枳实、白术加水煎煮二次,第一次加8倍量水,浸泡1小时,煎煮1.5小时,第二次加6倍量水,煎煮1.5小时,滤过,合并滤液,浓缩成相对密度为1.15(80℃时)的清膏,放至室温,搅拌加乙醇使浓度达60%(25℃时),冷藏静置36小时,滤过;C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.15 (at 80°C), place it at room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), keep it in the refrigerator for 36 hours, and filter;
    D、步骤B醇提液与步骤C水煎液合并,浓缩成相对密度为1.30-1.35(70℃)的稠膏,带式真空干燥-0.09pa,粉碎成细粉,过筛,备用;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;
    E、将步骤A阿胶超细粉、步骤D细粉混匀,即得首荟通便提取物细粉,备用;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;
    2)制剂工艺2) Preparation process
    F、取步骤E首荟通便提取物细粉、囊材、抗粘剂和增塑剂,将囊材、抗粘剂和增塑剂加入纯化水,52℃条件下加热搅拌使溶解,配置成质量分数为36%的囊材溶液,冷却至室温,搅拌状态下加入首荟通便提取物细粉和、大豆磷脂:蔗糖脂肪酸酯=4∶6的复合乳化剂,用量按质量分数计为制剂配方总量的0.9%。,均质乳化,得乳化液,备用;F. Take the laxative extract powder, capsule material, anti-sticking agent and plasticizer of step E, add the capsule material, anti-sticking agent and plasticizer to purified water, heat and stir at 52℃ to dissolve, configure Into a capsule material solution with a mass fraction of 36%, cool to room temperature, add the fine powder of Shouhui laxative extract and a composite emulsifier of soybean phospholipid: sucrose fatty acid ester = 4:6 under stirring, and the amount is calculated by mass fraction This is 0.9% of the total formulation formula. , Homogeneous emulsification to obtain the emulsion for use;
    G、步骤F乳化液在进风温度172℃、喷雾压力0.39MPa、进料速度22.5ml/min条件下进行喷雾干燥,收集微囊,冷却,即得。G. 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.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115944667A (en) * 2022-12-29 2023-04-11 江中药业股份有限公司 Lingguizhu gan decoction extract and preparation method thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111375019A (en) * 2020-03-20 2020-07-07 鲁南制药集团股份有限公司 Aloe microcapsule preparation for relieving constipation and preparation method thereof
CN112426468A (en) * 2020-12-22 2021-03-02 王焜 Traditional Chinese medicine composition and preparation for constipation and preparation method thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1748765A (en) * 2004-09-17 2006-03-22 鲁南制药集团股份有限公司 Composition with catharsis and toxin expelling, fat reducing and weight reducing function and preparing method
CN1965944A (en) * 2006-03-03 2007-05-23 上海中医药大学 Microsphere of dried tangerine peel oil and method for preparing same
CN106123496A (en) * 2016-06-30 2016-11-16 鲁南制药集团股份有限公司 A kind of drying means of Chinese medical concrete
CN109464570A (en) * 2018-11-23 2019-03-15 鲁南制药集团股份有限公司 A kind of head luxuriant growth Tongbian capsule preparation process
CN111375019A (en) * 2020-03-20 2020-07-07 鲁南制药集团股份有限公司 Aloe microcapsule preparation for relieving constipation and preparation method thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1748765A (en) * 2004-09-17 2006-03-22 鲁南制药集团股份有限公司 Composition with catharsis and toxin expelling, fat reducing and weight reducing function and preparing method
CN1965944A (en) * 2006-03-03 2007-05-23 上海中医药大学 Microsphere of dried tangerine peel oil and method for preparing same
CN106123496A (en) * 2016-06-30 2016-11-16 鲁南制药集团股份有限公司 A kind of drying means of Chinese medical concrete
CN109464570A (en) * 2018-11-23 2019-03-15 鲁南制药集团股份有限公司 A kind of head luxuriant growth Tongbian capsule preparation process
CN111375019A (en) * 2020-03-20 2020-07-07 鲁南制药集团股份有限公司 Aloe microcapsule preparation for relieving constipation and preparation method thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
FENG, YI; ZHANG, YING; YANG, YIN; XU, DESHENG: "Influencing Factors on Microencapsulation of Volatile Oil Microcapsules", CHINESE TRADITIONAL PATENT MEDICINE, vol. 29, no. 2, 20 February 2007 (2007-02-20), CN, pages 202 - 208, XP009530862, ISSN: 1001-1528 *
ZHANG TAN,TAN TIAN-WEI,LING PEIXUE: "Research Progress of Microcapsule Wall-materials in Food Industry Extracts", FOOD AND FERMENTATION INDUSTRIES, vol. 37, no. 5, 31 May 2011 (2011-05-31), pages 132 - 138, XP055852496, DOI: 10.13995/j.cnki.11-1802/ts.2011.05.029 *
ZHANG YUN-HUI , REN SI-JIA , HU WEN-WEN , ZHANG WANG , ZHANG SONG: "Advances in Effect of Spray Drying to Microcapsules Properties in Food", FOOD AND MACHINERY, vol. 29, no. 2, 18 March 2013 (2013-03-18), pages 214 - 217, XP055852493 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115944667A (en) * 2022-12-29 2023-04-11 江中药业股份有限公司 Lingguizhu gan decoction extract and preparation method thereof
CN115944667B (en) * 2022-12-29 2023-09-22 江中药业股份有限公司 Poria, cassia bark, rhizoma atractylodis and sweet soup extract and preparation method thereof

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