CN106266343A - A kind of preparation method of dispersing brain blood - Google Patents
A kind of preparation method of dispersing brain blood Download PDFInfo
- Publication number
- CN106266343A CN106266343A CN201610783713.9A CN201610783713A CN106266343A CN 106266343 A CN106266343 A CN 106266343A CN 201610783713 A CN201610783713 A CN 201610783713A CN 106266343 A CN106266343 A CN 106266343A
- Authority
- CN
- China
- Prior art keywords
- water
- filtrate
- gained
- standby
- dispersing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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)
- A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
-
- 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)
- A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
-
- 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)
-
- 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
- A61K36/481—Astragalus (milkvetch)
-
- 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)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/708—Rheum (rhubarb)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses the preparation method of a kind of dispersing brain blood, comprise the following steps: (1) takes Rhizoma Acori Graminei and Cortex Moutan, extract volatile oil;(2,3,4) take the Radix Astragali, Radix Achyranthis Bidentatae, Rhizoma Chuanxiong and Radix Et Rhizoma Rhei, pulverize, merge with medicinal residues, and being sequentially added into pH value is 1.5~2.5,6.5~7.0, the water of 7.8~8.5, heating extraction;(5) water intaking trematodiasis, adds normal saline and soaks;(6,7,8) filtering residue is sequentially added into pH value 1.5~2.5,6.5~7.0, the water of 7.8~8.5, heating extraction;(9) gained filtrate in combining step (5,6,7,8), concentrate drying obtains hirudin;(10) gained filtrate in combining step (2,3,4), is concentrated into clear paste, adds volatile oil and hirudin, mixing, adds acceptable carrier or adjuvant on pharmaceutics, be prepared as pharmaceutical preparation.The naoxueshu preparations prepared by the method for the present invention, is had active constituent content height, bioavailability height, is more suitable for the advantages such as absorption of human body.
Description
Technical field
The present invention relates to the preparation method of a kind of Chinese medicine naoxueshu preparations treating apoplexy, belong to technical field of traditional Chinese medicine preparation.
Background technology
Cerebrovascular is one of three big diseases of world today's harm human health, is the frequently-occurring disease of middle-aged and elderly people, dead
Rate is the highest, accounts for the second of the cause of the death at China's cerebrovascular.Domestic report death from cerebral hemorrhage rate is 38%~43%, and survivor is about
Having 50%~70% patient to leave serious sequela, can't take care of oneself, not only patient suffers considerable distress, also give family and
Society causes burden.
Treatment by Chinese herbs cerebrovascular has the advantage of its uniqueness, such as the Chinese medicine dispersing brain blood oral liquid listed, its formula and
Technique is described in Chinese patent 200810100200.9 (Authorization Notice No. CN 101279018 B), " a kind of Chinese medicine dispersing brain blood system
Agent " in, that patent describes one and made Chinese medicine by Chinese medicine astragalus, Hirudo, Rhizoma Acori Graminei, Radix Achyranthis Bidentatae, Cortex Moutan, Radix Et Rhizoma Rhei, Rhizoma Chuanxiong etc.
Preparation, finds through experiment, said preparation have QI invigorating, invigorate blood circulation, blood stasis dispelling effect, cure mainly suffering from acute stroke and recover in early days, to belong to gas
Empty syndrome of blood stasis.Patent 201310002166.2 (Authorization Notice No. CN 102988643 B) then describes a kind of stable, safety, nothing
Zest, can meet the injection for dispersing brain blood of clinical demand.
Owing to the preparation technology of naoxueshu preparations of the prior art is part medicinal material extract volatile oil, part medical material is carried out
Water carries, the semifinished product of precipitate with ethanol, there are the deficiencies such as effective component content is low, dose big, absorb not exclusively, bioavailability is low
Place.Along with the development of science and technology and improving constantly of new drug development level, new theory, new technique, new technology, new equipment
Continuous application, its conventional preparation techniques is not in full conformity with the requirement of the modernization of Chinese medicine.
Summary of the invention
For above-mentioned prior art, the present invention has carried out multiple improvement on the basis of existing technology, is particularly extracting
Substantial amounts of screening has been carried out, it is provided that the preparation method of a kind of dispersing brain blood, the dispersing brain blood prepared by the method in technique
Preparation, has active constituent content height, bioavailability height, is more suitable for the advantages such as absorption of human body.
The present invention is achieved by the following technical solutions:
The preparation method of a kind of dispersing brain blood, described dispersing brain blood is made up of the crude drug of following weight portion: Radix Astragali 233g
~932g, Hirudo 150g~600g, Rhizoma Acori Graminei 84g~334g, Radix Achyranthis Bidentatae 84g~334g, Cortex Moutan 84g~334g, Radix Et Rhizoma Rhei 33g~
132g, Rhizoma Chuanxiong 84g~334g.
Preparation method comprises the following steps:
(1) take Rhizoma Acori Graminei and Cortex Moutan, pulverize, add medical material weight 2~the water of 8 times, be heated to reflux 1~3h distillation, collect
Just after distillate, redistillation 0.5~1.5h;Extract volatile oil;Distillate filters, and medicinal residues are standby;
(2) take the Radix Astragali, Radix Achyranthis Bidentatae, Rhizoma Chuanxiong and Radix Et Rhizoma Rhei, pulverize, merges with the medicinal residues in step (1), addition pH value be 1.5~
The water (add hydrochloric acid in water or phosphoric acid regulation is 1.5~2.5 to pH value) of 2.5, heating extraction 1~3 hours, filter, filtrate,
Filtering residue is standby;
Preferably, the amount of described addition water is that medical material weight (refers to the total of step (1) Chinese medicine slag and 4 kinds of crude drug such as the Radix Astragali
Weight) 2~4 times;
(3) step (2) gained medicinal residues add the water that pH value is 6.5~7.0, heating extraction 1~3 hours, filter, filtrate, filter
Slag is standby;
Preferably, described amount of water is 1~3 times of medical material weight (referring to the weight of step (2) Chinese medicine slag);
(4) step (3) gained medicinal residues add the water that pH value is 7.8~8.5, heating extraction 1~3 hours, filter, and filtrate is standby
With;
Preferably, described amount of water is 1~3 times of medical material weight (referring to the weight of step (3) Chinese medicine slag);
(5) water intaking trematodiasis, adds the normal saline of 0.5~1.5 times amount (weight multiple) after pulverizing, mistake after soaking 12~36h
Filter, filtering residue, filtrate are standby;
(6) water of step (5) gained filtering residue addition pH value 1.5~2.5 (adds hydrochloric acid in water or phosphoric acid regulates to pH value
It is 1.5~2.5), it is heated to 40~60 DEG C and extracts 0.5~1.5 hour, filter, filtrate, filtering residue are standby;
Preferably, described amount of water is 1~3 times of medical material weight (referring to the weight of filtering residue in step (5));
(7) step (6) gained filtering residue adds the water that pH value is 6.5~7.0, is heated to 40~60 DEG C of extractions 0.5~1.5 little
Time, filtering, filtrate, filtering residue are standby;
Preferably, described amount of water is 1~3 times of medical material weight (referring to the weight of filtering residue in step (6));
(8) step (7) gained medicinal residues add the water that pH value is 7.8~8.5, are heated to 40~60 DEG C of extractions 0.5~1.5 little
Time, filtering, filtrate is standby;
Preferably, described amount of water is 1~3 times of medical material weight (referring to the weight of filtering residue in step (7));
Described pH value is the water of 6.5~7.0, for the water of nature naturally occurring, it is not necessary to carrying out special handling can routine
Approach obtains;Described pH value is the water of 7.8~8.5, and the NaOH solution regulation of 0.1mol/L can be used to obtain;
(9) gained filtrate in combining step (5) (6) (7) (8), cryoconcentration to relative density be 1.05~1.10 clear
Cream, adds 95% (percentage by volume) above ethanol solution or dehydrated alcohol to alcohol content is 85% (percentage by volume) ,-30 DEG C
Lower standing 12~36 hours, centrifugal, take supernatant, low temperature (25~35 DEG C) is dried, and obtains hirudin;
(10) gained filtrate in combining step (2) (3) (4), is concentrated into the clear paste that relative density is 1.20~1.25, adds
Gained volatile oil and step (9) gained hirudin in step (1), mixing, add acceptable carrier or adjuvant on pharmaceutics, system
The pharmaceutical preparation of standby one-tenth.
Preferably, described dispersing brain blood is made up of the crude drug of following weight portion: Radix Astragali 466g, Hirudo 300g, stone Chang
Pu 167g, Radix Achyranthis Bidentatae 167g, Cortex Moutan 167g, Radix Et Rhizoma Rhei 66g, Rhizoma Chuanxiong 167g.
The dosage form of described pharmaceutical preparation can be the dosage forms such as oral liquid, tablet, capsule, drop pill, granule.
Preferably, described step of preparation process is as follows:
(1) take Rhizoma Acori Graminei and Cortex Moutan, pulverize, add the water of medical material weight 5 times, be heated to reflux 2h distillation, collect just distillation
After liquid, redistillation 1h;Extract volatile oil;Distillate filters, and medicinal residues are standby;
(2) taking the Radix Astragali, Radix Achyranthis Bidentatae, Rhizoma Chuanxiong and Radix Et Rhizoma Rhei, pulverize, merge with the medicinal residues in step (1), adding pH value is 2.0
Water, heating extraction 2 hours, filter, filtrate, filtering residue are standby;
Preferably, amount is medical material weight 3 times of described addition water;
(3) step (2) gained medicinal residues add the water that pH value is 6.8, heating extraction 2 hours, filter, and filtrate, filtering residue are standby;
Preferably, described amount of water is 2 times of medical material weight;
(4) step (3) gained medicinal residues add the water that pH value is 8.2, heating extraction 2 hours, filter, and filtrate is standby;
Preferably, described amount of water is 2 times of medical material weight;
(5) water intaking trematodiasis, filters after after pulverizing, the normal saline of the quality such as addition soaks 24h, and filtering residue, filtrate are standby;
(6) step (5) gained filtering residue adds the water of pH value 2.0, is heated to 50 DEG C and extracts 1 hour, filters, filtrate, filtering residue
Standby;
Preferably, described amount of water is 2 times of medical material weight;
(7) step (6) gained filtering residue adds pH value is the water of 6.8, is heated to 50 DEG C and extracts 1 hour, filters, filtrate, filter
Slag is standby;
Preferably, described amount of water is 2 times of medical material weight;
(8) step (7) gained medicinal residues add the water that pH value is 8.2, are heated to 50 DEG C and extract 1 hour, filter, and filtrate is standby;
Preferably, described amount of water is 2 times of medical material weight;
(9) gained filtrate in combining step (5) (6) (7) (8), cryoconcentration to relative density be 1.05~1.10 clear
Cream, adding more than 95% ethanol to alcohol content is 85%, and-30 DEG C stand 24 hours, centrifugal, take supernatant cold drying and obtain Hirudo
Element;
(10) gained filtrate in combining step (2) (3) (4), is concentrated into the clear paste that relative density is 1.20~1.25, adds
Gained volatile oil and step (9) gained hirudin in step (1), mixing, add acceptable carrier or adjuvant on pharmaceutics, system
The pharmaceutical preparation of standby one-tenth.
Half bionics method for preparation of the naoxueshu preparations of the present invention, in line with make preparation reach " three little (dosage is little, toxicity is little,
Side effect is little), triple effect (efficient, quick-acting, long-acting), five convenience (produce, transport, take, carry, preserve) " purpose, at prescription
On the basis of determining, carry out completely newly groping to the extraction and purification process of medical material, considered medical material physical property, effectively become
Factors such as intrinsic and production cost, and combine the new technique of modern biotechnology pharmaceutics, use semi-bionic extraction, creative
It is carried out extraction purification, effectively remains active component.Semi-biomimetic method is to imitate oral drugs to transport at gastrointestinal
Process and a kind of Chinese medicine extraction new technique of proposing, its acid water using selected pH value and alkaline water extract the most continuously, its
Purpose is to extract high " active mixture " Han index components.This method adhere in the design of extraction process " have composition opinion, not only
Composition opinion, focus on body pharmacodynamics reaction " viewpoint, with one or more effective ingredient, total extractives and opposed polarity part
Or main pharmacological does index, Comprehensive Evaluation, the theoretical principle of Optimized extraction techniques, mixture so can be given full play to
The comprehensive function feature divided, is conducive to again controlling the quality of the pharmaceutical preparations with monomer component, and the drug effect finally giving applicable absorption of human body becomes
Point.In the present invention, applicant has been obtained technical scheme by substantial amounts of experimentation, screening, has been eliminated medical material
Impurity that middle major part is not absorbed by the body also retains the effective ingredient of each flavour of a drug to greatest extent so that gained of the present invention refines brain
Blood is dredged the product drug loading of the more former technique of oral liquid and is improve close to 100% (with crude drug gauge), active constituent content phase simultaneously
To raising, make the dosage forms such as oral liquid, tablet, capsule, drop pill, granule with this effective ingredient, it is possible to preferably meet heart and brain blood
The medication demand of pipe Disease.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further illustrated.
Instrument involved in following embodiment, reagent, material etc., unless otherwise noted, be in prior art existing
Conventional instrument, reagent, material etc., can be either commercially available by regular.Experimental technique involved in following embodiment, inspection
Survey methods etc., unless otherwise noted, are existing normal experiment method in prior art, detection method etc..
Embodiment 1 prepares dispersing brain blood oral liquid
Formula is: Radix Astragali 466g, Hirudo 300g, Rhizoma Acori Graminei 167g, Radix Achyranthis Bidentatae 167g, Cortex Moutan 167g Radix Et Rhizoma Rhei 66g, Rhizoma Chuanxiong
167g。
Preparation method is as follows:
(1) take Rhizoma Acori Graminei and Cortex Moutan, pulverize, add the water of medical material weight 5 times, be heated to reflux 2h distillation, collect just distillation
After liquid, redistillation 1h;Extract volatile oil;Distillate filters, and medicinal residues are standby;
(2) taking the Radix Astragali, Radix Achyranthis Bidentatae, Rhizoma Chuanxiong and Radix Et Rhizoma Rhei, pulverize, merge with the medicinal residues in step (1), adding pH value is 2.0
Water (adding hydrochloric acid regulation in water is 2.0 to pH value), adds amount is medical material weight 3 times of water, heating extraction 2 hours, filter
Crossing, filtrate, filtering residue are standby;
(3) step (2) gained medicinal residues add the water that pH value is 6.8, and amount of water is 2 times of medical material weight, and heating extraction 2 is little
Time, filtering, filtrate, filtering residue are standby;
(4) step (3) gained medicinal residues add the water that pH value is 8.2, and amount of water is 2 times of medical material weight, and heating extraction 2 is little
Time, filtering, filtrate is standby;
(5) filtering after after Hirudo is pulverized, the normal saline of the quality such as addition soaks 24h, filtering residue, filtrate are standby;
(6) step (5) gained filtering residue adds the water (adding hydrochloric acid regulation in water is 2.0 to pH value) of pH value 2.0, adds water
Amount is 2 times of medical material weight, is heated to 50 DEG C and extracts 1 hour, filters, and filtrate, filtering residue are standby;
(7) step (6) gained filtering residue adds pH value is the water of 6.8, and amount of water is 2 times of medical material weight, is heated to 50 DEG C
Extracting 1 hour, filter, filtrate, filtering residue are standby;
(8) step (7) gained medicinal residues add the water that pH value is 8.2, and amount of water is 2 times of medical material weight, are heated to 50 DEG C and carry
Taking 1 hour, filter, filtrate is standby;
Described pH value is the water of 6.8, for the water of nature naturally occurring, it is not necessary to carrying out special handling can conventional route obtain
Arrive;Described pH value is the water of 8.2, uses the NaOH solution regulation of 0.1mol/L to obtain;
(9) gained filtrate in combining step (5) (6) (7) (8), cryoconcentration to relative density be 1.05~1.10 clear
Cream, adding 95% ethanol solution to alcohol content is 85%, and-30 DEG C stand 24 hours, centrifugal, take supernatant cold drying and obtain Hirudo
Element;
(10) gained filtrate in combining step (2) (3) (4), is concentrated into the clear paste that relative density is 1.20~1.25, adds
Gained volatile oil and step (9) gained hirudin in step (1), mixing, the adjustment total amount that adds water, to 1000ml, stirs evenly, embedding, goes out
Bacterium, to obtain final product.
Test the detection of 1 content of drug effect components and compare
The refined dispersing brain blood oral liquid that Example 1 prepares, dispersing brain blood oral liquid (the fertile China in Shandong produced with existing technique
Medical sci-tech limited company produces, and lot number 150210, in the patent specification according to Patent No. 200810100200.9
The method of embodiment 1 prepares;Lower with), dispersing brain blood injection (Shandong China Wo Medicine Co produces, batch
Numbers 150451, prepare according to the method for embodiment 1 in the patent specification of Patent No. 201310002166.2) compare,
Using high performance liquid chromatography and titration measuring main pharmacodynamics component content, (in table 1, each percent refers to result as shown in table 1
Mass percent).
Table 1
By the comparison in table 1 it can be seen that utilize refined dispersing brain blood oral liquid prepared by the method for the present invention, at each medicine
On the content of effect composition, hence it is evident that the content being better than dispersing brain blood oral liquid of the prior art and injection, especially hirudin has
Bigger lifting, difference is the most notable.
Test the detection of 2 bioavailability and compare
Measure refined dispersing brain blood oral liquid by human trial and dispersing brain blood oral liquid Radix Codonopsis in blood plasma the most in the same time is total
The concentration of alkali, draws blood concentration-time curve, calculates refined dispersing brain blood oral liquid and dispersing brain blood oral liquid main pharmacokinetic ginseng
Number and relative bioavailability.
(1) materials and methods
(1) instrument and medicine
Shimadzu high performance liquid chromatograph (SPD detector), HC2518 high speed centrifuge (Keda Innovation Co., Ltd),
XW-80A type blender;Refined dispersing brain blood oral liquid (preparing according to this patent embodiment 1), dispersing brain blood oral liquid (lot number
150731), deionized water be our company self-control, oxolane and acetonitrile are chromatographically pure, and other chemical reagent are analytical pure.
(2) experimenter
Healthy male volunteers 12,21.4 ± 1.9 years old mean age (20-24 year), 64.9 ± 11.3kg, average height
171.8 ± 10.5cm, carries out a medical examination before test, and the heart, hepatic and renal function are normally.Other is not taken in test the last fortnight
What medicine, forbids during test taking other medicines and cigarette, wine etc..
(2) testing program
(1) EXPERIMENTAL DESIGN
Using single dose own control cross matching method, each experimenter refined dispersing brain blood of all random successively acceptance is administered orally
Liquid or 2 tests of dispersing brain blood oral liquid.Intertrial interval is 7d every time.Tested front fasting 12h, gives unified mark after drug administration 4h
Quasi-meal.
(2) it is administered and takes a blood sample
12 volunteers are randomly divided into two groups, often organize 6 people, and after 12h fasting, one group the most oral refined early morning on the same day
Dispersing brain blood oral liquid 10ml, two groups are administered orally dispersing brain blood oral liquid 10ml, and after medication 4h, standard meal is entered in unification.Before taking medicine and after taking medicine
0h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 16h, 20h, 24h, 30h, 36h, 48h venous blood sampling.
(3) result and discussion
(1) determination of plasma concentration result
18 health volunteers are dense at the blood medicine of different time after refined dispersing brain blood oral liquid or dispersing brain blood oral liquid are administered orally
Degrees of data, respectively through mathematic(al) mean, draws blood concentration-time curve.
(2) main pharmacokinetic parameters
Utilize software to seek calculation pharmacokinetic parameters, calculate area under the drug-time curve AUC by trapezoidal method with measured concentration, the most raw
Thing availability F=AUCRefined dispersing brain blood/AUCDispersing brain blood。
Result of calculation shows: refined dispersing brain blood oral liquid and dispersing brain blood oral liquid, dispersing brain blood injection peak time tmaxPoint
Not Wei (2.11 ± 0.28) h, (2.87 ± 0.35) h, P < 0.05, have significant difference.Peak blood drug level cmaxIt is respectively
(248.35±43.61)ng·L-1And (189.45 ± 35.27) ng L-1, P < 0.05, there is significant difference.Main pharmacokinetic
Parametric results is shown in Table 2.
Table 2
(3) relative bioavailability
Refined dispersing brain blood oral liquid and the AUC of dispersing brain blood oral liquid0h~48hIt is respectively (2974.53 ± 118.44) ng h
L-1With (2158 ± 108.52) ng h L-1, check through t, P < 0.05, have marked difference.Refined dispersing brain blood oral liquid is to brain blood
The relative bioavailability dredging oral liquid is 137.82%.
(4) discuss
Under the refined dispersing brain blood oral liquid blood drug level of this result of the test display and drug-time curve, area is significantly greater than dispersing brain blood
Oral liquid, and draw through computed in software, the relative bioavailability of dispersing brain blood oral liquid is by refined dispersing brain blood oral liquid
137.82%, refined dispersing brain blood oral liquid bioavailability is significantly greater than dispersing brain blood oral liquid.Show refined dispersing brain blood oral liquid
It is more conducive to body absorb.
Claims (10)
1. the preparation method of a dispersing brain blood, it is characterised in that: described dispersing brain blood is made up of the crude drug of following weight portion:
The Radix Astragali 233g~932g, Hirudo 150g~600g, Rhizoma Acori Graminei 84g~334g, Radix Achyranthis Bidentatae 84g~334g, Cortex Moutan 84g~334g,
Radix Et Rhizoma Rhei 33g~132g, Rhizoma Chuanxiong 84g~334g.
Preparation method comprises the following steps:
(1) take Rhizoma Acori Graminei and Cortex Moutan, pulverize, add medical material weight 2~the water of 8 times, be heated to reflux 1~3h distillation, collect and just steam
After distillate, redistillation 0.5~1.5h;Extract volatile oil;Distillate filters, and medicinal residues are standby;
(2) taking the Radix Astragali, Radix Achyranthis Bidentatae, Rhizoma Chuanxiong and Radix Et Rhizoma Rhei, pulverize, merge with the medicinal residues in step (1), adding pH value is 1.5~2.5
Water, heating extraction 1~3 hours, filter, filtrate, filtering residue are standby;
(3) step (2) gained medicinal residues add the water that pH value is 6.5~7.0, heating extraction 1~3 hours, filter, and filtrate, filtering residue are standby
With;
(4) step (3) gained medicinal residues add the water that pH value is 7.8~8.5, heating extraction 1~3 hours, filter, and filtrate is standby;
(5) water intaking trematodiasis, adds the normal saline of 0.5~1.5 times amount after pulverizing, soak and filter after 12~36h, and filtering residue, filtrate are standby
With;
(6) step (5) gained filtering residue adds the water of pH value 1.5~2.5, is heated to 40~60 DEG C and extracts 0.5~1.5 hour, filter
Crossing, filtrate, filtering residue are standby;
(7) step (6) gained filtering residue adds the water that pH value is 6.5~7.0, is heated to 40~60 DEG C and extracts 0.5~1.5 hour,
Filtering, filtrate, filtering residue are standby;
(8) step (7) gained medicinal residues add the water that pH value is 7.8~8.5, are heated to 40~60 DEG C and extract 0.5~1.5 hour, filter
Crossing, filtrate is standby;
(9) gained filtrate in combining step (5) (6) (7) (8), cryoconcentration to relative density is the clear paste of 1.05~1.10, adds
Entering more than 95% ethanol solution or dehydrated alcohol to alcohol content is 85%, stands 12~36 hours at-30 DEG C, centrifugal, takes supernatant
Liquid, cold drying, obtain hirudin;
(10) gained filtrate in combining step (2) (3) (4), is concentrated into the clear paste that relative density is 1.20~1.25, adds step
(1) gained volatile oil and step (9) gained hirudin in, mixing, add acceptable carrier or adjuvant on pharmaceutics, be prepared as
Pharmaceutical preparation.
The preparation method of dispersing brain blood the most according to claim 1, it is characterised in that: in described step (2), described pH value is
The water of 1.5~2.5 is that addition hydrochloric acid or phosphoric acid regulation are 1.5~2.5 to pH value in water.
The preparation method of dispersing brain blood the most according to claim 1, it is characterised in that: in described step (2), add the amount of water
For medical material weight 2~4 times.
The preparation method of dispersing brain blood the most according to claim 1, it is characterised in that: in described step (3) (4), amount of water
For medical material weight 1~3 times.
The preparation method of dispersing brain blood the most according to claim 1, it is characterised in that: in described step (6) (7) (8), add water
Amount is 1~3 times of medical material weight.
The preparation method of dispersing brain blood the most according to claim 1, it is characterised in that: described pH value is the water of 7.8~8.5,
The NaOH solution regulation using 0.1mol/L obtains.
The preparation method of dispersing brain blood the most according to claim 1, it is characterised in that: described dispersing brain blood is by following weight portion
Crude drug make: Radix Astragali 466g, Hirudo 300g, Rhizoma Acori Graminei 167g, Radix Achyranthis Bidentatae 167g, Cortex Moutan 167g, Radix Et Rhizoma Rhei 66g, Rhizoma Chuanxiong
167g。
The preparation method of dispersing brain blood the most according to claim 1, it is characterised in that: the dosage form of described pharmaceutical preparation is oral
Liquid, tablet, capsule, drop pill, granule.
9. according to the preparation method of the dispersing brain blood according to any one of claim 1~8, it is characterised in that: described preparation technology
Step is as follows:
(1) take Rhizoma Acori Graminei and Cortex Moutan, pulverize, add the water of medical material weight 5 times, be heated to reflux 2h distillation, after collecting first distillate,
Redistillation 1h;Extract volatile oil;Distillate filters, and medicinal residues are standby;
(2) taking the Radix Astragali, Radix Achyranthis Bidentatae, Rhizoma Chuanxiong and Radix Et Rhizoma Rhei, pulverize, merge with the medicinal residues in step (1), adding pH value is the water of 2.0, adds
Enter amount is medical material weight 3 times of water, heating extraction 2 hours, filter, filtrate, filtering residue are standby;
(3) step (2) gained medicinal residues add the water that pH value is 6.8, and amount of water is 2 times of medical material weight, heating extraction 2 hours, filter
Crossing, filtrate, filtering residue are standby;
(4) step (3) gained medicinal residues add the water that pH value is 8.2, and amount of water is 2 times of medical material weight, heating extraction 2 hours, filter
Crossing, filtrate is standby;
(5) water intaking trematodiasis, filters after after pulverizing, the normal saline of the quality such as addition soaks 24h, and filtering residue, filtrate are standby;
(6) step (5) gained filtering residue adds the water of pH value 2.0, and amount of water is 2 times of medical material weight, is heated to 50 DEG C of extractions 1 little
Time, filtering, filtrate, filtering residue are standby;
(7) step (6) gained filtering residue adds pH value is the water of 6.8, and amount of water is 2 times of medical material weight, is heated to 50 DEG C and extracts 1
Hour, filtering, filtrate, filtering residue are standby;
(8) step (7) gained medicinal residues add the water that pH value is 8.2, and amount of water is 2 times of medical material weight, are heated to 50 DEG C of extractions 1 little
Time, filtering, filtrate is standby;
(9) gained filtrate in combining step (5) (6) (7) (8), cryoconcentration to relative density is the clear paste of 1.05~1.10, adds
Entering more than 95% ethanol to alcohol content is 85%, and-30 DEG C stand 24 hours, centrifugal, take supernatant cold drying and obtain hirudin;
(10) gained filtrate in combining step (2) (3) (4), is concentrated into the clear paste that relative density is 1.20~1.25, adds step
(1) gained volatile oil and step (9) gained hirudin in, mixing, add acceptable carrier or adjuvant on pharmaceutics, be prepared as
Pharmaceutical preparation.
10. utilize the naoxueshu preparations that the preparation method of the dispersing brain blood according to any one of claim 1~9 prepares.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610783713.9A CN106266343A (en) | 2016-08-31 | 2016-08-31 | A kind of preparation method of dispersing brain blood |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610783713.9A CN106266343A (en) | 2016-08-31 | 2016-08-31 | A kind of preparation method of dispersing brain blood |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106266343A true CN106266343A (en) | 2017-01-04 |
Family
ID=57672826
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610783713.9A Pending CN106266343A (en) | 2016-08-31 | 2016-08-31 | A kind of preparation method of dispersing brain blood |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106266343A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107748219A (en) * | 2017-11-23 | 2018-03-02 | 山东沃华医药科技股份有限公司 | A kind of assay method of naoxueshu preparations finger-print |
CN109620847A (en) * | 2018-12-11 | 2019-04-16 | 山东沃华医药科技股份有限公司 | A kind of preparation method of the anticoagulant ingredient of leech in dispersing brain blood oral solution |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101279018A (en) * | 2008-05-28 | 2008-10-08 | 山东沃华医药科技股份有限公司 | Chinese medicine naoxueshu preparations |
CN102286098A (en) * | 2011-08-18 | 2011-12-21 | 周维官 | Production method of natural hirudin |
CN102988643A (en) * | 2013-01-05 | 2013-03-27 | 山东沃华医药科技股份有限公司 | Traditional Chinese medicine injection for dispersing brain blood |
CN103705623A (en) * | 2013-12-18 | 2014-04-09 | 广州市中医医院 | Application of semi-bionic extraction method in eliminating precipitate in liquid traditional Chinese medicinal preparation |
CN104784248A (en) * | 2015-04-21 | 2015-07-22 | 四川国康药业有限公司 | Astragalus membranaceus extract, astragalus membranaceus tablet and preparation method thereof |
CN105434583A (en) * | 2015-12-29 | 2016-03-30 | 山东沃华医药科技股份有限公司 | Semi-bionic preparation method for Xinkeshu preparations |
-
2016
- 2016-08-31 CN CN201610783713.9A patent/CN106266343A/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101279018A (en) * | 2008-05-28 | 2008-10-08 | 山东沃华医药科技股份有限公司 | Chinese medicine naoxueshu preparations |
CN102286098A (en) * | 2011-08-18 | 2011-12-21 | 周维官 | Production method of natural hirudin |
CN102988643A (en) * | 2013-01-05 | 2013-03-27 | 山东沃华医药科技股份有限公司 | Traditional Chinese medicine injection for dispersing brain blood |
CN103705623A (en) * | 2013-12-18 | 2014-04-09 | 广州市中医医院 | Application of semi-bionic extraction method in eliminating precipitate in liquid traditional Chinese medicinal preparation |
CN104784248A (en) * | 2015-04-21 | 2015-07-22 | 四川国康药业有限公司 | Astragalus membranaceus extract, astragalus membranaceus tablet and preparation method thereof |
CN105434583A (en) * | 2015-12-29 | 2016-03-30 | 山东沃华医药科技股份有限公司 | Semi-bionic preparation method for Xinkeshu preparations |
Non-Patent Citations (2)
Title |
---|
杨茉 等: "半仿生技术在复方中药提取中的应用进展", 《时珍国医国药》 * |
赵余庆: "《中药及天然产物提取制备关键技术》", 31 January 2012, 中国医药科技出版社 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107748219A (en) * | 2017-11-23 | 2018-03-02 | 山东沃华医药科技股份有限公司 | A kind of assay method of naoxueshu preparations finger-print |
CN109620847A (en) * | 2018-12-11 | 2019-04-16 | 山东沃华医药科技股份有限公司 | A kind of preparation method of the anticoagulant ingredient of leech in dispersing brain blood oral solution |
CN109620847B (en) * | 2018-12-11 | 2022-07-26 | 山东沃华医药科技股份有限公司 | Preparation method of leech anticoagulant component in cerebroxemia dispelling oral liquid |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101837065B (en) | Medicine with anti-hepatitis, anti-tumour and organism immunity improving functions and preparation method thereof | |
CN106248842A (en) | A kind of content assaying method of four seasons SANHUANG PIAN | |
CN1923241B (en) | Medicine composition containing epimedium extract, uncaria extract, and gastrodine, and its preparation and use | |
CN100544758C (en) | A kind of compound Taizi ginsen preparation and production method thereof | |
CN105434583A (en) | Semi-bionic preparation method for Xinkeshu preparations | |
CN106266343A (en) | A kind of preparation method of dispersing brain blood | |
CN102920964B (en) | Traditional Chinese medicine preparation for curing cough | |
CN103432420B (en) | A kind of Chinese medicine composition for the treatment of diabetes and preparation method thereof and detection method | |
CN105999195A (en) | Preparation method of radix codonopsis, ramulus cinnamomi and poria cocos preparation | |
CN100500183C (en) | Preparation of Chinese medicinal mixture for treating gynecologic menstrual disease | |
CN1931233B (en) | Medicine composition of red sage and epimedium for treating cardiac and cerebral vascular diseases | |
CN108553506A (en) | Gelan Xinning soft capsule drug made from the preparation method and use this method of Pueraria Flavonid | |
CN100563682C (en) | A kind of pharmaceutical composition of making by Folium Crataegi and Radix Rhodiolae and preparation method thereof | |
CN101049355B (en) | Composition of medication prepared from safflower and leaves of hawthorn | |
CN103239618A (en) | Traditional Chinese medicine composition for treating chronic hepatitis and cirrhosis and preparation method thereof | |
CN103908571A (en) | Compound traditional Chinese medicine preparation for treating heart disease | |
CN106853021A (en) | Prevent and treat Chinese medicine composition of CKD and its preparation method and application | |
CN102813907A (en) | Medicine composition for treating cerebrovascular accident sequela and preparation method and application thereof | |
CN102100833A (en) | Drug composition for treating heart cerebrovascular diseases as well as preparation method and application thereof | |
CN100493522C (en) | Medicinal composition of oxymatrine and polysaccharide | |
CN106466396B (en) | Gynaecologic menstruation regulating sustained-release dropping pill and preparation method thereof | |
CN104873909B (en) | The herbal composite for treating asymptomatic non-metastatic castration-resistant prostate cancer | |
CN104069175A (en) | Extract used for preparing ligusticum wallichii tea modulator | |
CN100502912C (en) | Medicine for treating deficiency syndrome, its preparing process and usage | |
CN1931214B (en) | Medicine composition of rhodiola root and puerarin |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170104 |
|
RJ01 | Rejection of invention patent application after publication |