CN106943354A - A kind of preparation method of novel biochemical particles - Google Patents
A kind of preparation method of novel biochemical particles Download PDFInfo
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- CN106943354A CN106943354A CN201710128515.3A CN201710128515A CN106943354A CN 106943354 A CN106943354 A CN 106943354A CN 201710128515 A CN201710128515 A CN 201710128515A CN 106943354 A CN106943354 A CN 106943354A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/236—Ligusticum (licorice-root)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/286—Carthamus (distaff thistle)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/533—Leonurus (motherwort)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Abstract
The invention discloses a kind of preparation method of novel biochemical particles, the present invention is to the active ingredient in prescription, specific aim enrichment is carried out for structure type, motherwort is using ultrafiltration and the combined process for purification enriched biological alkali of nanofiltration, the organic compounds such as flavones, saponin(e, phenolic acid, amarogentin in safflower, peach kernel, Ligusticum wallichii, Radix Angelicae Sinensis, Radix Glycyrrhizae, rhizoma zingiberis are enriched with using polyamide, further prepared using certain density ethanol elution, recovery；Wherein Radix Angelicae Sinensis, the volatile oil of Ligusticum wallichii are difficult to extract in big production obtains, distillate is prepared using steam distillation, distillate adds after β rings paste stirring inclusion, the method of nanofiltration concentration lifts rejection of the nanofiltration to solute component again, high content extractive of volatile oil is obtained, volatile oil in Ligusticum wallichii, Radix Angelicae Sinensis production is solved and waves and be difficult to extract and influence the technical barrier of product quality, realize efficiently concentrating, Improving The Quality of Products homogeneity and production technology level, reduce patient's dosage.
Description
Technical field
The invention belongs to the formulation art of secondary exploitation for Chinese materia medica, and in particular to one kind is based on prescription active ingredient materialization
Matter, using modern pharmaceutical technological improvement preparation method, more particularly to a kind of preparation method of novel biochemical particles.
Background technology
Novel biochemical particles derive from gynaecology's masterpiece in Qing Dynasty Fu green hill《Fu Qingzhu works on obstetrics and gynecology》" Shenghua Tang ", by Radix Angelicae Sinensis, river
Rhizome of chuanxiong, peach kernel, motherwort, safflower, honey-fried licorice root and the taste Chinese medicine of carbonized Rhizoma Zingiberis 7 composition, there is promoting blood circulation, dissolving stasis, analgesic, always by
Referred to as " postpartum first party ".Prescription Chinese medicine meal feeds intake, and extracts after volatile oil, is ground into meal and extracts volatile oil.After distillation
The another device of the aqueous solution collect.The dregs of a decoction, which are added water, to be decocted secondary, 2 hours first times, second 1.5 hours, collecting decoction, filtration,
Filtrate merges with above-mentioned solution, is condensed into thick paste, adds brown sugar in right amount, mixes, particle is made；In 60 DEG C of drying, crush, use second
Particle is made in alcohol, sprays into volatile oil, produces.There is dosage greatly in the novel biochemical particles prepared using traditional handicraft, production technology
And quality standard awaits lifting.
Containing the medicinal material rich in volatility effective component such as Radix Angelicae Sinensis, Ligusticum wallichii in prescription, its composition boiling point is high, volatile oil extracting
Difficulty, and profit layering is difficult during steam distillation, conventional method cannot get volatile oil.Safflower, Radix Angelicae Sinensis, Ligusticum wallichii in prescription is rich
Containing flavones, liposoluble ingredient, contain phenolic hydroxyl group, double bond etc. in structure, with thermal instability, during composition separation and purification
Decomposition has been converted to influence product quality, cause the wasting of resources.
Resin purification includes macroreticular resin, polyamide, the moon according to its separation characteristic（Sun）Ion exchange resin etc., according into
Point with the Van der Waals force of interlaminar resin, hydrogen bond and molecular sieve are equivalent should be to the active ingredient of Chinese medicine preparation progress enriching and purifying.
Based on above-mentioned background there is provided a kind of preparation method of novel biochemical particles, the efficiently concentrating of active ingredient is realized, is lifted
Product quality homogeneity and production technology level, reduce patient's dosage, significant.
The content of the invention
For the defect of prior art, it is an object of the invention to provide a kind of preparation method of novel biochemical particles, with reality
The active ingredient efficiently concentrating of existing Chinese medicine preparation, Improving The Quality of Products homogeneity and production technology level, reduce patient's dosage.
The present invention is achieved by the following technical solutions：
A kind of preparation method of novel biochemical particles, is comprised the steps of：
A. raw material is weighed by following weight：20-40 parts of motherwort, 20-30 parts of Radix Angelicae Sinensis, 8-10 parts of Ligusticum wallichii, peach kernel 2-5
Part, 1-5 parts of honey-fried licorice root, 1-5 parts of carbonized Rhizoma Zingiberis, 1-5 parts of safflower；
B. take motherwort to add water to cook 1-3 times, be every time 8-10 times of amount of water, extraction time is 1 hour, and extract solution is used
1000-5000 Da milipore filters remove big molecular impurity, and small molecular weight impurity is removed using molecular cut off 100-800 Da NF membranes
And dehydration is concentrated into proportion 1.10, obtains motherwort total alkaloid；
C. Radix Angelicae Sinensis, Ligusticum wallichii is taken to be ground into meal, supercritical extraction unit extracts volatile oil, and 50-90% ethanol is entrainer, extraction
Pressure is 30-45Mpa, and 35-55 DEG C of temperature prepares volatile oil, 400-800 parts of purifying dissolvings of beta-schardinger dextrin is weighed, to waving
Hair oil carries out scattered inclusion, and inclusion solution uses the Ultra filtration membrane of 10000-50000 Da molecular cut offs, collects inclusion compound
Ultrafiltrate；
D. peach kernel, honey-fried licorice root, carbonized Rhizoma Zingiberis, safflower is taken to merge with the Radix Angelicae Sinensis in step c, the Ligusticum wallichii dregs of a decoction, plus 8-12 times is measured water progress
Steam distillation collects distillate, and distillate is added 80-160 parts of stirrings of beta-schardinger dextrin, received using molecular cut off 100-500 Da
Filter membrane dehydration concentration, to proportion 1.10, obtains extractive of volatile oil；
E. the aqueous extract after step d distillations is released, and the dregs of a decoction add 8-10 times of water again, decoct 1-2 hours, merge extract solution, 10%
Aqueous hydrochloric acid solution adjusts pH value 2-3, is separated using macroporous resin adsorption, after 2-4 times of column volume of washing, using concentration 50-85% concentration
Ethanol elution, collects eluent, is recycled to proportion 1.10, obtains flavones, polyphenol, glycoside extracts；
F. by step b motherwort total alkaloids, step c inclusion compound ultrafiltrates, step d extractive of volatile oil is step e flavones, more
Phenol, glycoside extracts merge, and add brown sugar powder and are pelletized using marumerization, and whole grain produces novel biochemical particles granulation.
Further improvement of the present invention scheme is：
A kind of preparation method of novel biochemical particles, is comprised the steps of：
A. raw material is weighed by following weight：30 parts of motherwort, 24 parts of Radix Angelicae Sinensis, 9 parts of Ligusticum wallichii, 3 parts of peach kernel, honey-fried licorice root 3
Part, 3 parts of carbonized Rhizoma Zingiberis, 3 parts of safflower；
B. take motherwort to add water to cook 2 times, be every time 10 times of amount of water, extraction time is 1 hour, 1000 Da of extract solution
Milipore filter remove big molecular impurity, using the Da composite polyamide materials NF membrane of molecular cut off 300 remove small molecular weight impurity and
Dehydration concentration, to proportion 1.10, obtains motherwort total alkaloid;
C. Radix Angelicae Sinensis, Ligusticum wallichii is taken to be ground into meal, supercritical extraction unit extracts volatile oil, and 80% ethanol is entrainer, extracting pressure
For 35Mpa, temperature 45 C, the mL of volatile oil 55 prepared weighs the purifying dissolving of 600g beta-schardinger dextrins, volatile oil is carried out
Scattered inclusion, inclusion solution uses the Ultra filtration membrane of 50,000 molecular cut offs, collects inclusion compound ultrafiltrate;
D. take peach kernel, honey-fried licorice root, carbonized Rhizoma Zingiberis, safflower to merge with the Radix Angelicae Sinensis in step c, the Ligusticum wallichii dregs of a decoction, add water 10 times and measure water progress
Steam distillation, collects distillate, distillate adds beta-schardinger dextrin 100g to stir 20min, compound using the Da of molecular cut off 300
The dehydration concentration of polyamide material NF membrane, to proportion 1.10, obtains extractive of volatile oil；
E. the aqueous extract after step d distillations is released, the dregs of a decoction 8 times of water of dosage, decoction 1.5 hours again, merges extract solution, 10% salt
Aqueous acid adjusts pH value 2, is separated using macroporous resin adsorption, after 3 times of column volumes of washing, is eluted using the concentration ethanol of concentration 75%,
Eluent is collected, proportion 1.10 is recycled to, obtains flavones, polyphenol, glycoside extracts；
F. by step b motherwort total alkaloids, step c inclusion compound ultrafiltrates, step d extractive of volatile oil is step e flavones, more
Phenol, glycoside extracts merge, and add brown sugar powder and are pelletized using marumerization, and whole grain produces novel biochemical particles granulation.
Further improvement of the present invention scheme is：
Cationic ion-exchange resin model D-001, D-113 in the step b, one kind in 001 × 8.
The material of milipore filter in the step b and c is one kind in polyether sulfone, Kynoar and cellulose.
NF membrane in the step b and d is aromatic polyamides class composite membrane, polypiperazine-amide class composite membrane and sulfonation are poly-
One kind in ether sulfone class composite membrane.
Punching resin model in the step e is one kind in D-101, AB-8, HPD-800.
The parts by weight of brown sugar are 180-340 parts in the step f.
The present invention carries out specific aim enrichment to the active ingredient in prescription for structure type, motherwort using ultrafiltration with
The combined process for purification enriched biological alkali of nanofiltration, using polyamide to safflower, peach kernel, Ligusticum wallichii, Radix Angelicae Sinensis, Radix Glycyrrhizae, rhizoma zingiberis
The organic compounds such as middle flavones, saponin(e, phenolic acid, amarogentin are enriched with, further using certain density ethanol elution, recovery system
It is standby；Wherein Radix Angelicae Sinensis, the volatile oil of Ligusticum wallichii are difficult to extract in big production obtains, and prepares distillate using steam distillation, distills
Liquid adds after β-ring paste stirring inclusion, then the method for nanofiltration concentration lifts nanofiltration to the rejection of solute component, obtains high content and waves
Hair oil extract, solves volatile oil in Ligusticum wallichii, Radix Angelicae Sinensis production and waves and be difficult to extract and influence the technical barrier of product quality, realize
Efficiently concentrating.
The present invention can be to the effective enrichment of volatile ingredient using supercritical extract.Meanwhile, by it is cyclodextrin encapsulated with it is super
Filter technology is combined, water miscible simultaneously in lifting volatile oil, and associated in the aqueous solution state and trip are realized by UF membrane interfacial effect
Amorph volatile oil is efficiently separated, and reduces free state volatile oil and novel biochemical particles finished product is damaged in transport, storage because of composition
Lose the technical barrier of influence product quality.The present invention combines the technical advantage of UF membrane, and its extract solution is entered using nanofiltration
Row enrichment method, is handled by normal temperature, and active ingredient is effectively enriched with.
Compared with prior art, beneficial effects of the present invention are：
（1）The method being combined using supercritical extract with steam distillation, has ensured the extraction effect of volatile ingredient in prescription
Rate, and and then use cyclodextrin inclusion technique, lifted drug effect, realize resource rational utilization while, improve particle matter
Amount.
（2）Heat-sensitive ingredients realize that normal temperature enrichment is enriched with by nanofiltration in prescription medicinal material, have prevented using conventional heat concentration
The loss of effective components caused, while the present invention more standard, controllable for being also.
（3）The efficiently concentrating of active ingredient is realized, using resin purification technology, the macromolecular substances such as removing protein, tanning are removed,
Preparation intermediate medicinal extract amount is reduced, while ensureing curative effect, patient's dosage is reduced.
Embodiment
Embodiment 1：The preparation of novel biochemical particles
Weigh the kg of motherwort 30, the kg of Radix Angelicae Sinensis 24, the kg of Ligusticum wallichii 9, the kg of peach kernel 3, the kg of honey-fried licorice root 3 respectively, carbonized Rhizoma Zingiberis 3 kg is red
Spend 3 kg；
Take motherwort to add water to cook 1 time, be every time 10 times of amount of water, extraction time is 1 hour, and extract solution is super with 1000 Da
Filter membrane removes big molecular impurity, and small molecular weight impurity is removed and de- using the Da composite polyamide materials NF membrane of molecular cut off 300
Water is concentrated, and to proportion 1.10, obtains motherwort total alkaloid.
Radix Angelicae Sinensis, Ligusticum wallichii is taken to be ground into meal, supercritical extraction unit extracts volatile oil, and 80% ethanol is entrainer, extraction pressure
Power is 35Mpa, and temperature 45 C, the mL of volatile oil 55 prepared weighs the purifying dissolving of 600g beta-schardinger dextrins, volatile oil is entered
The scattered inclusion of row, inclusion solution uses the Ultra filtration membrane of 50,000 molecular cut offs, collects inclusion compound ultrafiltrate.
Peach kernel, honey-fried licorice root, carbonized Rhizoma Zingiberis, safflower is taken to merge with the Radix Angelicae Sinensis in above-mentioned steps, the Ligusticum wallichii dregs of a decoction, plus 10 times of amount water enter
Water-filling steam distillation, collects distillate, distillate adds beta-schardinger dextrin 100g to stir 20min, multiple using the Da of molecular cut off 300
The dehydration concentration of polyamide material NF membrane is closed, to proportion 1.10, extractive of volatile oil is obtained；
Aqueous extract after above-mentioned steps distillation is released, the dregs of a decoction 8 times of water of dosage, decoction 1.5 hours again, merges extract solution, 10% salt
Aqueous acid adjusts pH value 2, is separated using D101 types macroporous resin adsorption, after 3 times of column volumes of washing, using the concentration second of concentration 75%
Alcohol is eluted, and is collected eluent, is recycled to proportion 1.10, obtains flavones, polyphenol, glycoside extracts.
Merge motherwort total alkaloid, inclusion compound ultrafiltrate, extractive of volatile oil and flavones, polyphenol, glycoside extracts, use
Brown sugar powder 250g marumerizations are pelletized, and whole grain produces novel biochemical particles granulation.
Embodiment 2：The preparation of novel biochemical particles
The kg of motherwort 20, the kg of Radix Angelicae Sinensis 20, the kg of Ligusticum wallichii 8, peach kernel 2 kg, honey-fried licorice root 1kg, the kg of carbonized Rhizoma Zingiberis 1, safflower are weighed respectively
1kg；
Take motherwort to add water to cook 2 times, be every time 8 times of amount of water, extraction time is 1 hour, extract solution is with 1000 Da ultrafiltration
Film removes big molecular impurity, and small molecular weight impurity and dehydration are removed using the Da composite polyamide materials NF membrane of molecular cut off 300
Concentration, to proportion 1.10, obtains motherwort total alkaloid.
Radix Angelicae Sinensis, Ligusticum wallichii is taken to be ground into meal, supercritical extraction unit extracts volatile oil, and 5% ethanol is entrainer, extraction pressure
Power is 30Mpa, and 35 DEG C of temperature, the mL of volatile oil 55 prepared weighs the purifying dissolving of 400g beta-schardinger dextrins, volatile oil is entered
The scattered inclusion of row, inclusion solution uses the Ultra filtration membrane of 50,000 molecular cut offs, collects inclusion compound ultrafiltrate.
Peach kernel, honey-fried licorice root, carbonized Rhizoma Zingiberis, safflower is taken to merge with the Radix Angelicae Sinensis in above-mentioned steps, the Ligusticum wallichii dregs of a decoction, plus 8 times of amount water enter
Water-filling steam distillation, collects distillate, distillate adds beta-schardinger dextrin 80g to stir 20min, compound using the Da of molecular cut off 300
The dehydration concentration of polyamide material NF membrane, to proportion 1.10, obtains extractive of volatile oil；
Aqueous extract after above-mentioned steps distillation is released, the dregs of a decoction 8 times of water of dosage, decoction 1 hour again, merges extract solution, 10% hydrochloric acid
The aqueous solution adjusts pH value 2, is separated using D101 types macroporous resin adsorption, after 2 times of column volumes of washing, using the concentration ethanol of concentration 55%
Elution, collects eluent, is recycled to proportion 1.10, obtains flavones, polyphenol, glycoside extracts.
Merge motherwort total alkaloid, inclusion compound ultrafiltrate, extractive of volatile oil and flavones, polyphenol, glycoside extracts, use
Brown sugar powder 180g marumerizations are pelletized, and whole grain produces novel biochemical particles granulation.
Embodiment 3：The preparation of novel biochemical particles
Weigh the kg of motherwort 40, the kg of Radix Angelicae Sinensis 30, Ligusticum wallichii 10 kg, peach kernel 5kg, the kg of honey-fried licorice root 5 respectively, carbonized Rhizoma Zingiberis 5 kg is red
Spend 5 kg；
Take motherwort to add water to cook 3 times, be every time 10 times of amount of water, extraction time is 1 hour, and extract solution is super with 1000 Da
Filter membrane removes big molecular impurity, and small molecular weight impurity is removed and de- using the Da composite polyamide materials NF membrane of molecular cut off 300
Water is concentrated, and to proportion 1.10, obtains motherwort total alkaloid.
Radix Angelicae Sinensis, Ligusticum wallichii is taken to be ground into meal, supercritical extraction unit extracts volatile oil, and 90% ethanol is entrainer, extraction pressure
Power is 45Mpa, and 55 DEG C of temperature, the mL of volatile oil 55 prepared weighs the purifying dissolving of 800g beta-schardinger dextrins, volatile oil is entered
The scattered inclusion of row, inclusion solution uses the Ultra filtration membrane of 50,000 molecular cut offs, collects inclusion compound ultrafiltrate.
Take peach kernel, honey-fried licorice root, carbonized Rhizoma Zingiberis, safflower to merge with the Radix Angelicae Sinensis in above-mentioned steps, the Ligusticum wallichii dregs of a decoction, add water 12 times and measure water
Steam distillation is carried out, distillate is collected, distillate adds beta-schardinger dextrin 160g to stir 20min, using the Da of molecular cut off 300
The dehydration concentration of composite polyamide material NF membrane, to proportion 1.10, obtains extractive of volatile oil；
Aqueous extract after above-mentioned steps distillation is released, the dregs of a decoction 10 times of water of dosage, decoction 2 hours again, merges extract solution, 10% salt
Aqueous acid adjusts pH value 3, is separated using D101 types macroporous resin adsorption, after 4 times of column volumes of washing, using the concentration second of concentration 75%
Alcohol is eluted, and is collected eluent, is recycled to proportion 1.10, obtains flavones, polyphenol, glycoside extracts.
Merge motherwort total alkaloid, inclusion compound ultrafiltrate, extractive of volatile oil and flavones, polyphenol, glycoside extracts, use
Brown sugar powder 340g marumerizations are pelletized, and whole grain produces novel biochemical particles granulation.
Embodiment 4：Novel biochemical particles quality evaluation
Active ingredient in novel biochemical particles and conventional production process that embodiment 1-3 is prepared is analyzed, inspection
Survey method is：
Sample preparation：Precision weighs the sample 3g under content uniformity, in conical flask with cover, and precision adds methanol 20mL, claims
Determine weight, ultrasonically treated 1 hour, taking-up was let cool, and weight is supplied with methanol, is shaken up, filter, take subsequent filtrate, produce, golden liquid phase inspection
Survey.
Forulic acid testing conditions：：Zorbax SB-C18 chromatographic columns, with the phosphate aqueous solution of acetonitrile -0.1%（11:89）For stream
Dynamic phase, Detection wavelength：316nm, flow velocity：1mL/min;Stachydrine testing conditions：It is filler with propyl amides bonded silica gel；Second
The acetic acid aqueous solution of nitrile -0.2% (87：13) it is mobile phase；Evaporative light-scattering condition：78 DEG C of temperature, gas flow rate 2.0L/min;Wormwood artemisia
This lactone testing conditions：Zorbax SB-C18 chromatographic columns, with the acetic acid aqueous solution of methanol -1% (75：25) it is mobile phase, detects ripple
Long 280 nm, flow velocity：1mL/min;Sydroxy carthamin testing conditions：Zorbax SB-C18 chromatographic columns, with methanol -0.5%
Phosphate aqueous solution (40：60) it is mobile phase, the nm of Detection wavelength 400, flow velocity：0.8mL/min;Amarogentin testing conditions：
Zorbax SB-C18 chromatographic columns, with water-methanol-acetonitrile (75:20:5) mobile phase, the nm of Detection wavelength 210, flow velocity：0.8mL/
min;6-gingerol testing conditions：Zorbax SB-C18 chromatographic columns, with the acetic acid aqueous solution of methanol -1% (50:50) mobile phase, detection
The nm of wavelength 280, flow velocity：1mL/min;Liquiritin testing conditions：Kromasil-C18 chromatographic columns, the acetic acid aqueous solution of acetonitrile -0.5%
(20:80) it is mobile phase, Detection wavelength 276nm, flow velocity：1mL/min;Glycyrrhizic acid testing conditions：Mobile phase be methanol-
0.2mol·L-1Ammonium acetate solution-glacial acetic acid (67:32:1), Detection wavelength 252nm, flow velocity：1mL/min;It the results are shown in Table 1.
Novel biochemical particles quality versus prepared by the various processes of table 1
The present invention is by using the modern pharmaceutical technique such as resin purification, UF membrane, phenolic acid, Huang in the novel biochemical particles prepared
Ketone, alkaloid and volatile ingredient are obviously higher than conventional production process, while quality gets a promotion, and production control is more conventional
Technique is easier the foundation for realizing manufacturing parameter standardization control and quality tracing system.
Embodiment 5：Influence to rat Uterus in vivo smooth muscle
Experimental method：By SD rats according to female-male proportion 2：1 mates, the morning 8:00 checks the cloudy bolt of female mice or vaginal smear, to send out
The same day of existing the moon bolt or sperm is pregnant 1st day.Pregnant rat is divided into normal pregnancy group, mifepristone group, Xinshenghua at random
The basic, normal, high dosage group of particle, totally 5 groups, every group 10.In gestation the 7th day, during normal pregnancy group 8,18 when according to 2 mL/100g
1 physiological saline of body weight gavage, gavage mifepristone 8.3mg/kg during remaining each group rat 8, according to 100 μ g/kg gavages when 18
Modeling.Gestation begins on the 8th day, normal pregnancy group and the daily mL/100g of gavage physiological saline 2 of mifepristone group, novel biochemical particles
Basic, normal, high dosage group 39.3,59.0,78.8g/kg.Gestation the 14th day, in addition to normal pregnancy group, after remaining each group rat weight
With 25% urethane (12g/kg) intraperitoneal injection of anesthesia.It is fixed on platform, opens abdomen and find out side cornua uteri, gently peels off surrounding
Tissue.Be about 2 cm one section is chosen in the side cornua uteri, the oval foramen in plastic barrel bottom rubber membrane center is drawn it through, with even
The frog heart clip for having cotton thread is gently clamped；Muscle tone transducer is connected, Magnus' bath, and 36 ~ 37 DEG C of the injection in groove is fixed
Tyrode's solution 20mL, Water Tank with Temp.-controlled keeps operating temperature in (37 ± 0.5) DEG C, and constantly leads to oxygen (60 ~ 80 gas into nutrient solution
Bubble/min), after uterine contractile is steady (about 10 ~ 20m in), is recorded by physiograph before each group administration and gavage is to life
30,60,90 min uterine smooth muscle activity curve after reason salt solution, the basic, normal, high dosage group of novel biochemical particles.Observe uterus
Energy (frequency × amplitude).Specific experiment result is as shown in table 2.
Influence of the novel biochemical particles of table 2 to rat Uterus in vivo contraction movement power（）
Note:Contrasted with mifepristone group, *P<0.05, * *P<0.01；With being contrasted before administration, #P<0.05, ##P<0.01。
Novel biochemical particles middle dose group administration after 30,60min can dramatically increase uterine myometrium energy (P<
0.05,P<0.01).The middle and high dosage group of Xinshenghua can dramatically increase uterine smooth muscle in 30,60min relative to mifepristone and receive
Contracting energy (P<0.05,P<0.01)。
Embodiment 6：Influence to mouse bleeding and cotting time
By Kunming kind healthy mice 70, the basic, normal, high dosage group of blank control group, novel biochemical particles, every group are randomly divided into
14, male and female half and half.The daily gavage physiological saline 2mL/100g of blank control group, basic, normal, high dosage group gavage Xinshenghua successively
The g/kgd of particle 57.7,86.5,115.4.It is administered once daily, continuous 7d.In 60min after last dose, cut respectively with profit by
Mousetail starts to use manual time-keeping when blood voluntarily overflows, inhaled every 30s with filter paper from cross-section at tail point 0.5cm
Drop of blood is removed 1 time, until blood stops naturally（Without blood during filter paper suction）Untill, calculate the bleeding time.Blood is overflowed at mouse docking end
Liquid, drips in the two ends on cleaning slide, immediately begins to timing respectively, is hereafter chosen every 30s with syringe needle is dried from drop of blood edge
Dynamic 1 time, untill syringe needle can provoke fiber protein yarn, as clotting time.Another bleed supplies retrial.Specific experiment result such as table
Shown in 3.
Influence of the novel biochemical particles of table 3 to mouse bleeding and cotting time（）
Note:Contrasted with blank group group, *P<0.05, * *P<0.01。
The middle and high dosage group of novel biochemical particles can be obviously prolonged bleeding and the clotting time of elimination, be compared with blank control group
Have more significant sex differernce (P<0.05).Low dose group has the trend of extension mouse bleeding and cotting time.
Embodiment 7：Volatile ingredient study on the stability in novel biochemical particles
Using the novel biochemical particles preparation method in embodiment 1, the novel biochemical particles prepared, in selective volatilization composition
Ligustilide carries out study on the stability, the results are shown in Table 4.
The novel biochemical particles stability of table 4
Find that the volatile ingredient ligustilide content in novel biochemical particles is stablized relatively by study on the stability, pasted with β-ring
Essence-volatile oil association state form is in the presence of can effectively lift the stability of volatile oil in granule, so that quality assurance is homogeneous
Property and clinical drug effect.
Claims (7)
1. a kind of preparation method of novel biochemical particles, it is characterised in that comprise the steps of：
A. raw material is weighed by following weight：20-40 parts of motherwort, 20-30 parts of Radix Angelicae Sinensis, 8-10 parts of Ligusticum wallichii, peach kernel 2-5
Part, 1-5 parts of honey-fried licorice root, 1-5 parts of carbonized Rhizoma Zingiberis, 1-5 parts of safflower；
B. take motherwort to add water to cook 1-3 times, be every time 8-10 times of amount of water, extraction time is 1 hour, and extract solution is used
1000-5000 Da milipore filters remove big molecular impurity, and small molecular weight impurity is removed using molecular cut off 100-800 Da NF membranes
And dehydration is concentrated into proportion 1.10, obtains motherwort total alkaloid；
C. Radix Angelicae Sinensis, Ligusticum wallichii is taken to be ground into meal, supercritical extraction unit extracts volatile oil, and 50-90% ethanol is entrainer, extraction
Pressure is 30-45Mpa, and 35-55 DEG C of temperature prepares volatile oil, 400-800 parts of purifying dissolvings of beta-schardinger dextrin is weighed, to waving
Hair oil carries out scattered inclusion, and inclusion solution uses the Ultra filtration membrane of 10000-50000 Da molecular cut offs, collects inclusion compound
Ultrafiltrate；
D. peach kernel, honey-fried licorice root, carbonized Rhizoma Zingiberis, safflower is taken to merge with the Radix Angelicae Sinensis in step c, the Ligusticum wallichii dregs of a decoction, plus 8-12 times is measured water progress
Steam distillation collects distillate, and distillate is added 80-160 parts of stirrings of beta-schardinger dextrin, received using molecular cut off 100-500 Da
Filter membrane dehydration concentration, to proportion 1.10, obtains extractive of volatile oil；
E. the aqueous extract after step d distillations is released, and the dregs of a decoction add 8-10 times of water again, decoct 1-2 hours, merge extract solution, 10%
Aqueous hydrochloric acid solution adjusts pH value 2-3, is separated using macroporous resin adsorption, after 2-4 times of column volume of washing, using concentration 50-85% concentration
Ethanol elution, collects eluent, is recycled to proportion 1.10, obtains flavones, polyphenol, glycoside extracts；
F. by step b motherwort total alkaloids, step c inclusion compound ultrafiltrates, step d extractive of volatile oil is step e flavones, more
Phenol, glycoside extracts merge, and add brown sugar powder and are pelletized using marumerization, and whole grain produces novel biochemical particles granulation.
2. a kind of preparation method of novel biochemical particles according to claim 1, it is characterised in that：The parts by weight of raw materials is matched somebody with somebody
Than for：30 parts of motherwort, 24 parts of Radix Angelicae Sinensis, 9 parts of Ligusticum wallichii, 3 parts of peach kernel, 3 parts of honey-fried licorice root, 3 parts of carbonized Rhizoma Zingiberis, 3 parts of safflower.
3. a kind of preparation method of novel biochemical particles according to claim 1, it is characterised in that：Sun in the step b
Ion exchange resin type number is one kind in D-001, D-113,001 × 8.
4. a kind of preparation method of novel biochemical particles according to claim 1, it is characterised in that：In the step b and c
The material of milipore filter is one kind in polyether sulfone, Kynoar and cellulose.
5. a kind of preparation method of novel biochemical particles according to claim 1, it is characterised in that：In the step b and d
NF membrane is one kind in aromatic polyamides class composite membrane, polypiperazine-amide class composite membrane and sulfonated polyether sulfone class composite membrane.
6. a kind of preparation method of novel biochemical particles according to claim 1, it is characterised in that：Beating in the step e
Hole resin model is one kind in D-101, AB-8, HPD-800.
7. a kind of preparation method of novel biochemical particles according to claim 1, it is characterised in that：Brown sugar in the step f
Parts by weight be 180-340 parts.
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