CN106361811B - One kind is promoted blood circulation pharmaceutical composition and preparation method thereof - Google Patents
One kind is promoted blood circulation pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN106361811B CN106361811B CN201610836289.XA CN201610836289A CN106361811B CN 106361811 B CN106361811 B CN 106361811B CN 201610836289 A CN201610836289 A CN 201610836289A CN 106361811 B CN106361811 B CN 106361811B
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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
- A61K36/537—Salvia (sage)
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- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/488—Pueraria (kudzu)
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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
- 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 or 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
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A61K2236/30—Extraction of the material
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Abstract
Ischemic angiocardiopathy and cerebrovascular disease is treated the present invention relates to a kind of, artery sclerosis, cerebral thrombosis, cerebral ischemia, coronary heart disease, anginal pharmaceutical composition and preparation method thereof, the composition is prepared by 100 parts of Radix Salviae Miltiorrhizaes, 100 parts of Rhizoma Chuanxiongs, 100 parts of pueraria lobatas for primary raw material, preparation method is: after Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, pueraria lobata extract respectively, crossing macroporous resin column purifying respectively, remixes uniformly.The present composition has better curative effect compared with using the composition of homogeneous raw material other methods preparation.
Description
Technical field
Ischemic angiocardiopathy and cerebrovascular disease, artery sclerosis, cerebral thrombosis, cerebral ischemia, coronary heart disease, the heart are treated the present invention relates to a kind of
Composition of colic pain and preparation method thereof belongs to pharmaceutical technology field.
Background technique
The side of promoting blood circulation is the Chinese medicine compound prescription of Chinese tradition, is made of Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, 3 taste medicine of pueraria lobata, the function with blood circulation and channel invigorating
Effect.For ischemic angiocardiopathy and cerebrovascular disease, artery sclerosis, cerebral thrombosis, cerebral ischemia, coronary heart diseases and angina pectoris etc..Present market circulation
The side of promoting blood circulation mainly have the different dosage forms such as oral pulse-invigorating liquid, blood circulation promoting injecta, TONGMAI CHONGJI, freeing granules and pulse invigorating capsule,
It is process by pueraria lobata, Radix Salviae Miltiorrhizae, 3 taste Chinese medicine of Rhizoma Chuanxiong through Modern preparations technique.Wherein TONGMAI CHONGJI, freeing granules and mouth of promoting blood circulation
Taking liquid is the Sanitation Ministry medicine standard Traditional Chinese medicine historical preparation.
The freeing granules now listed are according to drug standards WS3- B-0824-91-2015 preparation.Its specific preparation method
Be: Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, pueraria lobata are according to 500g: 500g: 500g compatibility.Above three taste adds water to cook secondary, 1.5 hours first times,
Second 1 hour, collecting decoction filtered, and filtrate is concentrated into relative density 1.08 (80 DEG C), filters while hot, filtrate is concentrated into suitable
Amount, addition cane sugar powder is appropriate, particle is made, 1000g is made in low temperature drying；Or spray drying, addition cane sugar powder is appropriate, it mixes,
Be made particle 1000g to get.This method is simple, easy to operate, but stability of drug products is poor, and quality is not easy to control, not due to extract
By refining so drug dose is larger (daily 20~30g), especially clinical efficacy needs to be further increased.
Document 1 (preparation process that promotes blood circulation revalue and corresponding granule molding research, Yang Fengmei, Chengdu University of Traditional Chinese Medicine,
Master's thesis in 2014) use 55% ethanol solution to carry out refluxing extraction, the method purpose to Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, three taste Chinese medicine of pueraria lobata
It is the water soluble ingredient and liposoluble constituent retained in prescription simultaneously, the extracting solution of method preparation is shown than applying in the market
Oral pulse-invigorating liquid have more superior therapeutic effect.But the method is because directlying adopt after extracting solution is concentrated and dried without purification
The mode being directly used as medicine still remains the larger problem of drug taking dose.(the preparation process and quality of pulse invigorating pill of document 2
Research on standard, Zheng Yanan, University Of Tianjin, Master's thesis in 2011) disclose it is a kind of by Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, three taste Chinese medicine of pueraria lobata into
Row extracts the method refined after macroporous resin purification, can reduce drug taking dose by the purification to extracting solution, still
The method extracts Radix Salviae Miltiorrhizae, pueraria lobata simultaneously, and extracting solution crosses large pore resin absorption column simultaneously, does not consider effective component in red sage group
And absorption and the desorption performance difference of kudzu vine root group, and the molecular structure of two effective component groups differs greatly,
The property of absorption and elution is different, therefore is carried out simultaneously to Radix Salviae Miltiorrhizae and pueraria lobata concentration mixed liquor using same large pore resin absorption column
It can attend to one thing and lose sight of another when purifying, be difficult to make two kinds of effective component groups while be able to maximum enrichment；Similarly, work is extracted using same
Skill is also related to similar problems.Document 3 (study of pharmacy for sustained release tablets of promoting blood circulation, Liu Yang, Chengdu University of Traditional Chinese Medicine, master's opinion in 2007
Text) provide the process for refining of a kind of Radix Salviae Miltiorrhizae, pueraria lobata, Rhizoma Chuanxiong, the method consider three kinds of Radix Salviae Miltiorrhizae, pueraria lobata, Rhizoma Chuanxiong medicinal materials effectively at
The difference divided is respectively adopted different extraction processes to Radix Salviae Miltiorrhizae, pueraria lobata, Rhizoma Chuanxiong and extracted, then refined using different macroreticular resins
Technique is refined；Document 3 chooses one or two specific ingredient (tanshin polyphenolic acid B, tanshinone IIA, ligustilide, ferulic acid respectively
Deng) it is that index respectively optimizes three taste traditional Chinese medicine extractions and purifying process.But the ingredient of Chinese medicine, especially herbal mixture is non-
It is often complicated, it means that the only raising of three or five active constituent contents may not be able to improve drug effect, and each effective component
(including micro constitutent) reasonable compatibility gives full play to the key that synergistic effect is only drug effect raising, and document 3 does not provide the method
Data in terms of the drug effect of the product of preparation, therefore whether the product of method preparation there is clinical use meaning to need further to be examined
Card.Therefore it still remains in the market and preparation of promoting blood circulation is furtherd investigate, and further enhance drug effect, reduce dosage, protect
Hinder the demand of drug safety.
Summary of the invention
The applicant advanced optimizes the preparation process for prescription of promoting blood circulation, tanshin polyphenolic acid B, former youngster in making extract
Tea aldehyde, ligustrazine, ferulic acid, Puerarin and isoflavones yield and the rate of transform properly increase under conditions of, further mention
The high drug effect of three taste Traditional Chinese medicine compound compositions.
The primary purpose of the present invention is that providing a kind of new pharmaceutical composition of promoting blood circulation.
To achieve the goals above, the invention adopts the following technical scheme: it is a kind of to treat ischemic angiocardiopathy and cerebrovascular disease,
Artery sclerosis, cerebral thrombosis, cerebral ischemia, coronary heart disease, anginal pharmaceutical composition, the pharmaceutical composition are by following weight parts
Made of bulk pharmaceutical chemicals: 100 parts of Radix Salviae Miltiorrhizae, 100 parts of Rhizoma Chuanxiong, 100 parts of pueraria lobata；Preparation method includes the preparation of Salvia root P.E, river
The preparation of rhizome of chuanxiong extract and the preparation of kudzu root extract.Wherein, the preparation method of Salvia root P.E comprises the following steps: taking Radix Salviae Miltiorrhizae
Medicinal material, the water that 8 times of parts by weight of red rooted salvia are added are decocted 1 time, are decocted 1 hour, then are decocted with the water of 5 times of parts by weight of red rooted salvia
2 times, every time 0.5 hour；Collecting decoction, filtration, ethyl alcohol, which is added, makes alcohol content up to 80%, refrigerates, filtering, filtrate is concentrated into 60 DEG C
At a temperature of relative density be 1.10~1.15, obtained concentrate is injected into HPD600 type large pore resin absorption column, wherein described
The diameter height of large pore resin absorption column is than controlling the elution requirement between 1:6~1:8 are as follows: the weight ratio of Radix Salviae Miltiorrhizae and dried resin is 4:
1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；The purifying water elution of 8 times of amount column volumes is first used when elution, then is measured with 8 times
20% ethanol elution of column volume, discards eluent, then with 6 times of amount 75% ethanol elutions of column volume, collects 75% ethanol eluate；
Obtained eluent is concentrated to dryness to obtain Salvia root P.E.The preparation method of Rhizoma Chuanxiong extract comprises the following steps: taking Rhizoma Chuanxiong medicine
Material, 70% alcohol reflux that 8 times of parts by weight of Rhizoma Chuanxiong are added are extracted 1 time, are extracted 2 hours, then with 70% second of 6 times of parts by weight of Rhizoma Chuanxiong
Alcohol reflux extracts 2 times, extracts 1 hour every time；Combined extract, filtration, at a temperature of being concentrated into 60 DEG C relative density be 1.10~
1.15；Obtained concentrate is injected into NKA type large pore resin absorption column, wherein the diameter height of the large pore resin absorption column is than control
Between 1:6~1:8, elution requirement are as follows: the weight ratio of Rhizoma Chuanxiong and dried resin is 5:1, adsorption flow rate 3ml/min, elution flow rate
4ml/min；When elution, the purifying water elution of column volume is first measured with 5 times, then with 5 times of amount 30% ethanol elutions of column volume, is discarded and washed
De- liquid, then measures 60% ethanol elution of column volume with 4 times, collects 60% ethanol eluate；Obtained eluent is concentrated into
Do to obtain Rhizoma Chuanxiong extract；The preparation method of kudzu root extract comprises the following steps: taking pueraria lobata medicinal material, 10 times of parts by weight of pueraria lobata are added
30% alcohol reflux extract 1 time, extract 2 hours, then with 30% alcohol reflux of 8 times of parts by weight of pueraria lobata extraction 2 times, mention every time
It takes 1 hour；Combined extract, filtration, ethyl alcohol, which is added, makes alcohol content up to 80%, refrigerates, filtering, filtrate is concentrated at a temperature of 60 DEG C
Relative density is 1.10~1.15；Obtained concentrate is injected into D101 type large pore resin absorption column, wherein the macroporous absorption
The diameter height of resin column is than controlling the elution requirement between 1:6~1:8 are as follows: the weight ratio of pueraria lobata and dried resin is 6:1, absorption stream
Fast 3ml/min, elution flow rate 4ml/min；When elution, the purifying water elution of column volume is first measured with 8 times, then with 6 times of amount column volumes
10% ethanol elution discards eluent, and 30% ethanol elution of column volume is then measured with 4 times, collects 30% ethanol eluate；It will
Obtained eluent is concentrated to dryness to obtain kudzu root extract.
Scheme as a further preference: it is used in the preparation method of Salvia root P.E described in the present composition
The diameter height of HPD600 type large pore resin absorption column compares for 1:7.
Scheme as a further preference: the NKA used in the preparation method of Rhizoma Chuanxiong extract described in the present composition
The diameter height of type large pore resin absorption column compares for 1:7.
Scheme as a further preference: the D101 used in the preparation method of kudzu root extract described in the present composition
The diameter height of type large pore resin absorption column compares for 1:7.
Second object of the present invention is to provide a kind of preparation method of new pharmaceutical composition of promoting blood circulation.
To achieve the goals above, the invention adopts the following technical scheme: a kind of preparation method of the present composition,
The preparation of preparation, Rhizoma Chuanxiong extract including Salvia root P.E and the preparation of kudzu root extract.Wherein, the preparation of Salvia root P.E
Method comprises the following steps: taking red rooted salvia, the water that 8 times of parts by weight of red rooted salvia are added decocts 1 time, decocts 1 hour, then with red
The water for joining 5 times of parts by weight of medicinal material decocts 2 times, every time 0.5 hour；Collecting decoction, filtration, ethyl alcohol, which is added, makes alcohol content up to 80%,
Refrigeration, filtering, relative density is 1.10~1.15 at a temperature of filtrate is concentrated into 60 DEG C, and obtained concentrate is injected HPD600 type
Large pore resin absorption column, wherein the diameter height of the large pore resin absorption column is than controlling the elution requirement between 1:6~1:8 are as follows: red
The weight ratio for participating in dried resin is 4:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；8 times of amount column volumes are first used when elution
Purifying water elution, then with 8 times of amount 20% ethanol elutions of column volume, discard eluent, then washed with 6 times of amount 75% ethyl alcohol of column volume
It is de-, collect 75% ethanol eluate；Obtained eluent is concentrated to dryness to obtain Salvia root P.E.The preparation method of Rhizoma Chuanxiong extract
It comprises the following steps: taking Ligusticum chuanxiong Hort, 70% alcohol reflux that 8 times of parts by weight of Rhizoma Chuanxiong are added extracts 1 time, extracts 2 hours, then use
70% alcohol reflux of 6 times of parts by weight of Rhizoma Chuanxiong extracts 2 times, extracts 1 hour every time；Combined extract, filtration, is concentrated into 60 DEG C of temperature
Spending lower relative density is 1.10~1.15；Obtained concentrate is injected into NKA type large pore resin absorption column, wherein the macropore is inhaled
The diameter height of attached resin column is than controlling the elution requirement between 1:6~1:8 are as follows: the weight ratio of Rhizoma Chuanxiong and dried resin is 5:1, absorption
Flow velocity 3ml/min, elution flow rate 4ml/min；When elution, the purifying water elution of column volume is first measured with 5 times, then with 5 times of amount cylinders
30% ethanol elution of product, discards eluent, and 60% ethanol elution of column volume is then measured with 4 times, collects 60% ethanol eluate；
Obtained eluent is concentrated to dryness to obtain Rhizoma Chuanxiong extract.The preparation method of kudzu root extract comprises the following steps: taking pueraria lobata medicine
Material, 30% alcohol reflux that 10 times of parts by weight of pueraria lobata are added are extracted 1 time, are extracted 2 hours, then with the 30% of 8 times of parts by weight of pueraria lobata
Alcohol reflux extracts 2 times, extracts 1 hour every time；Combined extract, filtration, ethyl alcohol, which is added, makes alcohol content up to 80%, refrigerates, mistake
Filter, relative density is 1.10~1.15 at a temperature of filtrate is concentrated into 60 DEG C；Obtained concentrate is injected into D101 type macroporous absorption
Resin column, wherein the diameter height of the large pore resin absorption column is than controlling the elution requirement are as follows: pueraria lobata and Gan Shu between 1:6~1:8
The weight ratio of rouge is 6:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；When elution, the purifying of column volume is first measured with 8 times
Water elution, then with 6 times of amount 10% ethanol elutions of column volume, eluent is discarded, 30% ethyl alcohol for then measuring column volumes with 4 times is washed
It is de-, collect 30% ethanol eluate；Obtained eluent is concentrated to dryness to obtain kudzu root extract.
Scheme as a further preference: in the preparation method of Salvia root P.E described in present composition preparation method
The diameter height of the HPD600 type large pore resin absorption column used compares for 1:7.
Scheme as a further preference: in the preparation method of Rhizoma Chuanxiong extract described in present composition preparation method
The diameter height of the NKA type large pore resin absorption column used compares for 1:7.
Scheme as a further preference: in the preparation method of kudzu root extract described in present composition preparation method
The diameter height of the D101 type large pore resin absorption column used compares for 1:7.
Third object of the present invention is to provide a kind of new treatment ischemic angiocardiopathy and cerebrovascular disease, artery sclerosis, brain
Thrombus, cerebral ischemia, coronary heart disease, anginal preparation.The technical solution adopted is that the preparation be above-mentioned composition of the present invention and
Pharmaceutic adjuvant is mixed together, and is prepared according to a conventional method, the preparation preferred tablet, capsule, pill, granule, injection
Agent.The pharmaceutic adjuvant can be selected from adhesive, diluent, disintegrating agent, sweetener, antioxidant etc..
Fourth object of the present invention be to provide it is a kind of treat ischemic angiocardiopathy and cerebrovascular disease, artery sclerosis, cerebral thrombosis,
Cerebral ischemia, coronary heart disease, anginal granule.It is the injection using technical solution is above-mentioned composition of the present invention and medicinal
Auxiliary material is mixed together, and granule, pharmaceutic adjuvant preferably sucrose are prepared according to a conventional method.
The present invention the 5th, which is designed to provide, a kind of treats ischemic angiocardiopathy and cerebrovascular disease, artery sclerosis, cerebral thrombosis, brain
Ischemic, coronary heart disease, the preparation method of anginal granule.The technical solution of use are as follows: the process for producing granula includes
Following steps: it is appropriate that cane sugar powder is added in the present composition, then particle is made.
Compared with prior art, the present invention has the advantage that
1, animal experiment shows that the present composition has better drug effect.This may be main with the present composition
Effective ingredient content is higher related, while being more likely to also promote blood circulation and other non-principal effective components are retained, and respectively at
It is related that distribution ratio can preferably play synergistic effect.
2, the prior art does not study the critical technical parameter of its composition, it is possible to cause to combine between batch
Object is main or proportion difference between non-principal effective component yield and each ingredient is huge, the pharmaceutical composition prepared by the method
Drug effect is unstable, is not able to satisfy drug safety and validity requirement.The present invention is to preparation method of composition key technology of promoting blood circulation
Parameter is controlled, to ensure that the requirement of drug quality, drug efficacy stability.
Specific embodiment
Following is that in conjunction with specific embodiments and experimental example, the present invention is further explained.But these embodiments and experimental example are only
It is limited to illustrate rather than for limiting the scope of the invention.
First part: process study
1, Radix Salviae Miltiorrhizae extraction process
Medicinal Radix Salviae Miltiorrhizae has various pharmacological actions: can increase coronary flow to cardiovascular system, reduce myocardium excitation
Property and conductibility, improve microcirculation, antiplatelet aggregation and thrombosis decline blood viscosity, anti-oxidant, enhance oxytolerant
Ability, antibacterial anti-inflammatory improve renal function, the effects of to the protection of brain tissue ischemia and reperfusion injury.The effective component of Radix Salviae Miltiorrhizae
It can be divided into fat-soluble and water-soluble, wherein water soluble ingredient mainly has Sodium Danshensu, former youngster based on salvianolic acid
Boheic acid, protocatechualdehyde, salviandic acid A, tanshin polyphenolic acid B, salvianolic acid C etc..Therefore, active component-Radix Salviae Miltiorrhizae in order to obtain in Radix Salviae Miltiorrhizae is total
Phenolic acid, applicant are investigated and have been optimized to its extraction process, propose total phenolics as far as possible, and utilize macroporous absorbent resin
Purification technique makes total phenolics reach maximum enrichment, to reach the technical requirements to feed intake with active component.
Specific test method are as follows: take salvia piece 100g, using extracting under water counterflow condition, combined extract is placed to room
Wen Hou, filtering, filtrate decompression are concentrated and are evaporated, dissolved and be transferred in 50ml measuring bottle with water, be diluted with water to scale, shake up.
Precision measures solution 5ml, is extracted with ethyl acetate 4 times, and dosage is respectively 20ml, 10ml, 10ml, 10ml, merges acetic acid second
Ester extracts part, and evaporated under reduced pressure is dissolved with methanol and is transferred in 25ml measuring bottle, adds methanol dilution to scale, shakes up, measurement is former
The content of catechu aldehyde.Table 1 lists the result of representative part test.
1 salvianolic acid extraction process of table investigates test result
Applicant in experiments it is found that, with extraction time increase and the extension of extraction time, the dissolution of protocatechualdehyde
The reason of trend being improved, but consider the time and at the applicant finally it is confirmed that first using 8 times of parts by weight of red rooted salvia
Water decoct 1 time, decoct 1 hour, then with the water of 5 times of parts by weight of red rooted salvia decoction 2 times, every time 0.5 hour.
2, Radix Salviae Miltiorrhizae purifying process
After Radix Salviae Miltiorrhizae is extracted, it is contemplated that liposoluble ingredient can be wrapped up and be lost wherein by alcohol precipitation process, while consider water
It is higher to mention part containing sugar in concentrate, it is sticky larger, it is unfavorable for macroreticular resin elution, therefore consider only with an alcohol precipitation process, then
Carry out macroreticular resin elution.It is cleaned using macroporous adsorbent resin column chromatography method, the water-solubility impurities such as carbohydrate, amino acid, polypeptide are all
Removing can be washed with water to go, then eluted total phenolics with certain density ethyl alcohol.Therefore red sage root extract depressurizes in the present invention
Ethyl alcohol is recycled to certain relative density, large pore resin absorption column is directly injected into, carries out gradient elution with different concentration ethanol, so that it may
To play the role of impurity removal and purification salvianolic acid.Applicant passes through a large amount of experiment sieving, finds HPD600 type macroporous absorption
Resin is best to the adsorption capacity of salvianolic acid and the resultant effect of desorption, therefore the present invention is inhaled using HPD600 type macropore
Attached resin purifies Salvia root P.E.
Test method: the resin column (Φ=3cm, 4cm, 5cm) of different-diameter is taken, Salvia root P.E concentrate is used respectively
Processed HPD600 type purification with macroreticular resin according to diameter height than different weight is added, first measures column volume with 8 times
Water elution is purified, then with 8 times of amount 20% ethanol elutions of column volume, discards eluent, then washed with 6 times of amount 75% ethyl alcohol of column volume
It is de-, 75% ethanol eluate is collected, ethyl alcohol is recovered under reduced pressure to doing, is dissolved and is transferred in 25ml measuring bottle with 60% ethyl alcohol, is used in combination
60% ethyl alcohol is diluted to scale, shakes up.Measure the content of protocatechualdehyde and tanshin polyphenolic acid B.Table 2 lists representative part
The result of test.
2 salvianolic acid purifying process of table investigates test result
Test result show the diameter height of the large pore resin absorption column in Salvia root P.E purification process than control 1:6~
Between 1:8, elution requirement are as follows: the weight ratio of Radix Salviae Miltiorrhizae and dried resin is 4:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min
When, rate of transform of the paste-forming rate and protocatechualdehyde of resin and tanshin polyphenolic acid B etc. is more satisfactory.
3, Rhizoma Chuanxiong extraction process
Medicinal Rhizoma Chuanxiong is the dry rhizome of umbelliferae Rhizoma Chuanxiong, and effective component has: the ligustrazine of alkaloids, organic
The ferulic acid etc. of acids.Ligustrazine on cardiovascular system system has powerful activity, has spasmolysis to vascular smooth muscle, to by adrenal gland
The contraction of aorta caused by element or potassium chloride has obvious antagonism；CAMP content in blood platelet can be improved, to thromboxane A2
(TXA2) activity and biosynthesis have inhibiting effect；There is smooth muscle spasmolysis effect.Ferulic acid also plays the role of similar.Therefore I
Extraction process is investigated and has been optimized, dissolve out ligustrazine, organic acid ingredient as far as possible, and other impurities are less molten
Out, and purification with macroreticular resin technology is utilized, has reached effective component and be utmostly enriched with, satisfaction is fed intake with active component
Technical requirements.
Test method are as follows: using in Rhizoma Chuanxiong total extract ligustrazine and ferulic acid as index, investigate extraction time, extract time
The influences of the factors to Rhizoma Chuanxiong active constituent extract yield such as several and solvent dosage.Ligusticum chuanxiong Hort 100g is specially taken, using difference
It is extracted under concentration ethanol solution counterflow condition, combined extract is placed to room temperature, and filtering, filtrate decompression is concentrated and is evaporated, and is surveyed
Determine the relative amount of ferulic acid and ligustrazine (in terms of peak area).Table 3 lists the result of representative part test.
3 Rhizoma Chuanxiong extraction process of table investigates test result
Test result shows to comprehensively consider two kinds of effective component extraction rates of ferulic acid and ligustrazine, 70% concentration ethanol
Extraction effect is preferable.With extraction time increase and the extension of extraction time, what the dissolution of ferulic acid and ligustrazine was improved
The reason of trend, but consider the time and finally determine that 70% alcohol reflux of 8 times of parts by weight of Rhizoma Chuanxiong extracts 1 time at the applicant,
It extracts 2 hours, then is extracted 2 times with 70% alcohol reflux of 6 times of parts by weight of Rhizoma Chuanxiong, extracted 1 hour every time.
4, Rhizoma Chuanxiong purifying process
The Extraction solvent of Rhizoma Chuanxiong use 70% ethyl alcohol, the polysaccharide amount of dissolution is not many, by extracting solution be placed directly in 5 DEG C it is cold
A night is stood in library, only a small amount of glycocalix precipitates, and concentration of alcohol is adjusted once to have par-tial polysaccharide precipitating again to 85% alcohol precipitation
Get off, is lost wherein due to consideration that alcohol precipitation can wrap up the effective components such as ferulic acid, and technique is relatively complicated, cost
Also high, it is not best purification process.In addition, have in extracting solution after extracted a small amount of carbohydrate, amino acid and polypeptide etc. at
Point, these impurity are removed in purification process as far as possible, to improve the content of Rhizoma Chuanxiong effective component extracting.According to these changes
The property of object is closed, applicant has selected macroreticular resin absorbing method to isolate and purify Rhizoma Chuanxiong effective active composition.Using macropore
Adsorption resin method removal of impurities, the impurity such as carbohydrate, amino acid can be washed with water removing and go, then be eluted total phenolics with certain density ethyl alcohol
Getting off, therefore ethyl alcohol is recovered under reduced pressure to certain relative density in extracting solution, it is not necessary to alcohol precipitation is directly injected into large pore resin absorption column processing,
It can play the role of impurity removal and purification Rhizoma Chuanxiong extract.
Applicant passes through a large amount of experiment sieving, adsorption capacity of the discovery NKA type macroporous absorbent resin to Rhizoma Chuanxiong extract
It is best with the resultant effect of desorption, therefore the present invention purifies Rhizoma Chuanxiong extract using NKA type macroporous absorbent resin.
Test method: the resin column (Φ=3cm, 4cm, 5cm) of different-diameter is taken, Rhizoma Chuanxiong extract concentrate is used respectively
Processed NKA type purification with macroreticular resin according to diameter height than different weight is added, is first eluted with water to sugar-free and reacts,
Again with 30% ethanol elution, 5 times of bed volumes, then with 60% ethanol elution, 4 times of bed volumes.60% ethanol eluate is collected, is returned
It receives ethyl alcohol and is concentrated to dryness, then dissolved and be transferred in 25ml measuring bottle with dehydrated alcohol, be diluted to scale with dehydrated alcohol, shake
It is even, measure the amount of wheat ferulic acid and ligustrazine.Table 4 lists the result of representative part test.
4 Rhizoma Chuanxiong extract purifying process of table investigates test result
Test result show the diameter height of the large pore resin absorption column in Rhizoma Chuanxiong extract purification process than control 1:6~
Between 1:8, elution requirement are as follows: the weight ratio of Rhizoma Chuanxiong and dried resin is 5:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min
When, rate of transform of the paste-forming rate and ferulic acid of resin and ligustrazine etc. is more satisfactory.
5, Extracting Technology for Pueraria lobata
Pueraria lobata mainly contains Flavonoid substances, such as Puerarin, isoflavones, daidzin and isoflavone aglycone and a large amount of shallow lakes
Powder substance.In recent years, by pueraria lobata chemical component, clinical pharmacology research shows that: the principle active component of pueraria lobata be it is different
Flavone compound, and the wherein content highest of Puerarin, are most important active constituents, therefore measure osajin in pueraria lobata
The content of ingredient (mainly Puerarin) becomes the important indicator of evaluation pueraria lobata medicinal material and its quality of the pharmaceutical preparations.Research shows that pueraria lobata
It is known as nitric oxide in significantly raised blood, reduces the effect of blood medium vessels contracting agent Endothelin, expansion of coronary artery improves
Brain blood circulation increases tissue blood fluid, fights cardiac-cerebral ischemia.Additionally there is blood pressure lowering, anti-arrhythmia reduces cardiac muscle consumption
The effect of oxygen amount protection ischemic myocardium and slight hypoglycemic effect.In addition, many internal and external test discoveries, kudzu root extract
Middle effective component isoflavones can reduce LDL, TC and cholesterol, antiatherosclerosis and antioxidation, to angiocarpy
System has protective effect.Therefore we are investigated and have been optimized to extraction process, make Puerarin and isoflavones as far as possible
Dissolution, and the less dissolution of other impurities, and purification with macroreticular resin technology is utilized, so that effective component has been reached utmostly rich
Collection meets the technical requirements to feed intake with active component.
Test method are as follows: using in pueraria lobata total extract Puerarin and isoflavones as index, investigate extraction time, mention
Take influence of the factors such as number and solvent dosage to pueraria lobata active constituent extract yield.Pueraria lobata medicinal material 100g is specially taken, is used
It is extracted under different concentration ethanol solution counterflow condition, combined extract is placed to room temperature, and filtering, filtrate decompression is concentrated and steams
It is dry, measure the relative amount of Puerarin (in terms of peak area).Table 5 lists the result of representative part test.
5 Extracting Technology for Pueraria lobata of table investigates test result
Test result shows to comprehensively consider two kinds of effective component extraction rates of Puerarin and isoflavones, 30% concentration second
The extraction effect of alcohol is preferable.With extraction time increase and the extension of extraction time, the dissolution of Puerarin and isoflavones
The trend being improved, but consider the time and finally determine that 30% alcohol reflux of 10 times of parts by weight of pueraria lobata extracts 1 at the applicant
It is secondary, it extracts 2 hours, then extracted 2 times with 30% alcohol reflux of 8 times of parts by weight of pueraria lobata, extracts 1 hour every time.
6, pueraria lobata purifying process
Except flavonoid beyond the region of objective existence is contained in root of kudzu vine extract, also containing some protein, alkaloid, tannin and a large amount of
Impurity, these impurity such as cellulose, starch, pectin can more or less reduce the drug effect of kudzu root flavone, need to be further purified.
Pueraria lobata of the present invention is extracted through 30% ethyl alcohol, and since concentration of alcohol is lower, starch contained by extract and carbohydrate impurity are more, is glued
Property it is larger, be unfavorable for macroreticular resin elution, influence purification effect, it is also contemplated that alcohol precipitation process can by effective component wrap up wherein
And lose, therefore consider only with an alcohol precipitation process, then carry out macroreticular resin elution.It is removed using macroporous adsorbent resin column chromatography method
Miscellaneous, the water-solubility impurities such as carbohydrate, amino acid, polypeptide can be washed with water removing and go, then with certain density ethyl alcohol that pueraria lobata is total
Flavones elutes.Therefore the present invention by root of kudzu vine extract through alcohol precipitation, filtering, decompression filtrate recycling ethanol to certain relative density
Afterwards, large pore resin absorption column is reinjected, is first eluted with water, then carries out gradient elution with different concentration ethanol, so that it may play and remove
The effect of miscellaneous purification Pueraria Flavonid.
Applicant passes through a large amount of experiment sieving, adsorption capacity of the discovery D101 type macroporous absorbent resin to Pueraria Flavonid
It is best with the resultant effect of desorption, therefore the present invention purifies kudzu root extract using D101 type macroporous absorbent resin.
Test method: the resin column (Φ=3cm, 4cm, 5cm) of different-diameter is taken, kudzu root extract concentrate is used respectively
Processed D101 type purification with macroreticular resin according to diameter height than different weight is added, first measures the pure of column volume with 8 times
Change water elution, then use 6 times of amount 10% ethanol elutions of column volume, discard eluent, then with 4 times amount column volumes 30% ethyl alcohol wash
It is de-, 30% ethanol eluate is collected, ethyl alcohol is recycled and is concentrated to dryness, then dissolved and be transferred in 25ml measuring bottle with dehydrated alcohol,
It is diluted to scale with dehydrated alcohol, is shaken up, the content of Puerarin and isoflavones is measured.Table 6 lists representative
The result of part test.
6 kudzu root extract purifying process of table investigates test result
Test result show the diameter height of the large pore resin absorption column in kudzu root extract purification process than control 1:6~
Between 1:8, elution requirement are as follows: the weight ratio of pueraria lobata and dried resin is 6:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min
When, rate of transform of the paste-forming rate and Puerarin of resin and isoflavones etc. is more satisfactory.
Two, the preparation of composition and preparation
Embodiment 1
Prescription:
Radix Salviae Miltiorrhizae 100g Rhizoma Chuanxiong 100g pueraria lobata 100g
Preparation method:
Red rooted salvia is weighed, is decocted 1 time, is decocted 1 hour with the water of 800g, then is decocted 2 times with the water of 500g, every time partly
Hour；Collecting decoction is down to room temperature, filtering, and ethyl alcohol, which is added, makes alcohol content up to 80%, refrigerates, filtering, filtrate is concentrated into 60 DEG C of temperature
Spending lower relative density is 1.10~1.15, and obtained concentrate is injected HPD600 type large pore resin absorption column, wherein described big
The diameter height of macroporous adsorbent resin column compares for 1:6, elution requirement are as follows: the weight ratio of Radix Salviae Miltiorrhizae and dried resin is 4:1, adsorption flow rate 3ml/
Min, elution flow rate 4ml/min；The purifying water elutions of 8 times of amount column volumes are first used when elution, then with 8 times of amount 20% ethyl alcohol of column volume
Elution, discards eluent, then uses 6 times of amount 75% ethanol elutions of column volume, 75% ethanol eluate of collection；The eluent that will be obtained
It is concentrated to dryness to obtain Salvia root P.E, wherein the sum of tanshin polyphenolic acid B and protocatechualdehyde content are 18.35%, tanshin polyphenolic acid B and protocatechualdehyde
The rate of transform of content is 88.28%, salvianolic acid content 41.35%.
Ligusticum chuanxiong Hort is taken, 70% alcohol reflux that 800g is added extracts 1 time, extracts 2 hours, then with 70% ethyl alcohol of 600g
It refluxing extraction 2 times, extracts 1 hour；Combined extract, refrigerate, filtering, at a temperature of being concentrated into 60 DEG C relative density be 1.10~
1.15；Obtained concentrate is injected into NKA type large pore resin absorption column, wherein it is 1 that the diameter height of the large pore resin absorption column, which compares:
6, elution requirement are as follows: the weight ratio of Rhizoma Chuanxiong and dried resin is 5:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；Elution
When, the purifying water elution of column volume is first measured with 5 times, then with 5 times of amount 30% ethanol elutions of column volume, eluent is discarded, then with 4
60% ethanol elution for measuring column volume again, collects 60% ethanol eluate；Obtained eluent is concentrated to dryness to obtain Rhizoma Chuanxiong extraction
Object, wherein the sum of ligustrazine and ferulaic acid content are 7.76%, ligustrazine and asafoetide acid transfer rate 84.27%.
Pueraria lobata medicinal material is weighed, is extracted 1 time, is extracted 2 hours with 30% alcohol reflux of 1000g, then with the 30% of 800g
Alcohol reflux extracts 2 times, every time 1 hour；Combined extract is down to room temperature, filtering, and ethyl alcohol, which is added, makes alcohol content up to 80%, cold
Hiding, filtering, relative density is 1.10~1.15 at a temperature of filtrate is concentrated into 60 DEG C, and obtained concentrate is injected D101 type macropore
Adsorption resin column, wherein the diameter height of the large pore resin absorption column compares for 1:6, elution requirement are as follows: the weight of Radix Salviae Miltiorrhizae and dried resin
Than for 6:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；The purifying water elution of 8 times of amount column volumes is first used when elution, then
With 6 times of amount 20% ethanol elutions of column volume, eluent is discarded, then with 4 times of amount 30% ethanol elutions of column volume, collect 30% ethyl alcohol
Eluent；Obtained eluent is concentrated to dryness to obtain kudzu root extract, wherein the sum of Puerarin and isoflavone content are
43.71%, the rate of transform of Puerarin and isoflavones is 90.73%, Pueraria Flavonid content 71.64%.
Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract are uniformly mixed up to the present composition.
Embodiment 2
Prescription:
Radix Salviae Miltiorrhizae 100g Rhizoma Chuanxiong 100g pueraria lobata 100g
Preparation method:
Red rooted salvia is weighed, is decocted 1 time, is decocted 1 hour with the water of 800g, then is decocted 2 times with the water of 500g, every time partly
Hour；Collecting decoction is down to room temperature, filtering, and ethyl alcohol, which is added, makes alcohol content up to 80%, refrigerates, filtering, filtrate is concentrated into 60 DEG C of temperature
Spending lower relative density is 1.10~1.15, and obtained concentrate is injected HPD600 type large pore resin absorption column, wherein described big
The diameter height of macroporous adsorbent resin column compares for 1:7, elution requirement are as follows: the weight ratio of Radix Salviae Miltiorrhizae and dried resin is 4:1, adsorption flow rate 3ml/
Min, elution flow rate 4ml/min；The purifying water elutions of 8 times of amount column volumes are first used when elution, then with 8 times of amount 20% ethyl alcohol of column volume
Elution, discards eluent, then uses 6 times of amount 75% ethanol elutions of column volume, 75% ethanol eluate of collection；The eluent that will be obtained
It is concentrated to dryness to obtain Salvia root P.E, wherein the sum of tanshin polyphenolic acid B and protocatechualdehyde content are 22.34%, tanshin polyphenolic acid B and protocatechualdehyde
The rate of transform of content is 90.32%, salvianolic acid content 40.67%.
Ligusticum chuanxiong Hort is taken, 70% alcohol reflux that 800g is added extracts 1 time, extracts 2 hours, then with 70% ethyl alcohol of 600g
It refluxing extraction 2 times, extracts 1 hour；Combined extract, refrigerate, filtering, at a temperature of being concentrated into 60 DEG C relative density be 1.10~
1.15；Obtained concentrate is injected into NKA type large pore resin absorption column, wherein it is 1 that the diameter height of the large pore resin absorption column, which compares:
7, elution requirement are as follows: the weight ratio of Rhizoma Chuanxiong and dried resin is 5:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；Elution
When, the purifying water elution of column volume is first measured with 5 times, then with 5 times of amount 30% ethanol elutions of column volume, eluent is discarded, then with 4
60% ethanol elution for measuring column volume again, collects 60% ethanol eluate；Obtained eluent is concentrated to dryness to obtain Rhizoma Chuanxiong extraction
Object, wherein the sum of ligustrazine and ferulaic acid content are 7.52%, ligustrazine and asafoetide acid transfer rate 85.64%.
Pueraria lobata medicinal material is weighed, is extracted 1 time, is extracted 2 hours with 30% alcohol reflux of 1000g, then with the 30% of 800g
Alcohol reflux extracts 2 times, every time 1 hour；Combined extract is down to room temperature, filtering, and ethyl alcohol, which is added, makes alcohol content up to 80%, cold
Hiding, filtering, relative density is 1.10~1.15 at a temperature of filtrate is concentrated into 60 DEG C, and obtained concentrate is injected D101 type macropore
Adsorption resin column, wherein the diameter height of the large pore resin absorption column compares for 1:7, elution requirement are as follows: the weight of Radix Salviae Miltiorrhizae and dried resin
Than for 6:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；The purifying water elution of 8 times of amount column volumes is first used when elution, then
With 6 times of amount 20% ethanol elutions of column volume, eluent is discarded, then with 4 times of amount 30% ethanol elutions of column volume, collect 30% ethyl alcohol
Eluent；Obtained eluent is concentrated to dryness to obtain kudzu root extract, wherein the sum of Puerarin and isoflavone content are
44.41%, the rate of transform of Puerarin and isoflavones is 93.64%, Pueraria Flavonid content 73.57%.
Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract are uniformly mixed up to the present composition.
Embodiment 3
Prescription:
Radix Salviae Miltiorrhizae 100g Rhizoma Chuanxiong 100g pueraria lobata 100g
Preparation method:
Red rooted salvia is weighed, is decocted 1 time, is decocted 1 hour with the water of 800g, then is decocted 2 times with the water of 500g, every time partly
Hour；Collecting decoction is down to room temperature, filtering, and ethyl alcohol, which is added, makes alcohol content up to 80%, refrigerates, filtering, filtrate is concentrated into 60 DEG C of temperature
Spending lower relative density is 1.10~1.15, and obtained concentrate is injected HPD600 type large pore resin absorption column, wherein described big
The diameter height of macroporous adsorbent resin column compares for 1:8, elution requirement are as follows: the weight ratio of Radix Salviae Miltiorrhizae and dried resin is 4:1, adsorption flow rate 3ml/
Min, elution flow rate 4ml/min；The purifying water elutions of 8 times of amount column volumes are first used when elution, then with 8 times of amount 20% ethyl alcohol of column volume
Elution, discards eluent, then uses 6 times of amount 75% ethanol elutions of column volume, 75% ethanol eluate of collection；The eluent that will be obtained
It is concentrated to dryness to obtain Salvia root P.E, wherein the sum of tanshin polyphenolic acid B and protocatechualdehyde content are 19.34%, tanshin polyphenolic acid B and protocatechualdehyde
The rate of transform of content is 87.54%, salvianolic acid content 41.72%.
Ligusticum chuanxiong Hort is taken, 70% alcohol reflux that 800g is added extracts 1 time, extracts 2 hours, then with 70% ethyl alcohol of 600g
It refluxing extraction 2 times, extracts 1 hour；Combined extract, refrigerate, filtering, at a temperature of being concentrated into 60 DEG C relative density be 1.10~
1.15；Obtained concentrate is injected into NKA type large pore resin absorption column, wherein it is 1 that the diameter height of the large pore resin absorption column, which compares:
8, elution requirement are as follows: the weight ratio of Rhizoma Chuanxiong and dried resin is 5:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；Elution
When, the purifying water elution of column volume is first measured with 5 times, then with 5 times of amount 30% ethanol elutions of column volume, eluent is discarded, then with 4
60% ethanol elution for measuring column volume again, collects 60% ethanol eluate；Obtained eluent is concentrated to dryness to obtain Rhizoma Chuanxiong extraction
Object, wherein the sum of ligustrazine and ferulaic acid content are 8.71%, ligustrazine and asafoetide acid transfer rate 88.51%.
Pueraria lobata medicinal material is weighed, is extracted 1 time, is extracted 2 hours with 30% alcohol reflux of 1000g, then with the 30% of 800g
Alcohol reflux extracts 2 times, every time 1 hour；Combined extract is down to room temperature, filtering, and ethyl alcohol, which is added, makes alcohol content up to 80%, cold
Hiding, filtering, relative density is 1.10~1.15 at a temperature of filtrate is concentrated into 60 DEG C, and obtained concentrate is injected D101 type macropore
Adsorption resin column, wherein the diameter height of the large pore resin absorption column compares for 1:8, elution requirement are as follows: the weight of Radix Salviae Miltiorrhizae and dried resin
Than for 6:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；The purifying water elution of 8 times of amount column volumes is first used when elution, then
With 6 times of amount 20% ethanol elutions of column volume, eluent is discarded, then with 4 times of amount 30% ethanol elutions of column volume, collect 30% ethyl alcohol
Eluent；Obtained eluent is concentrated to dryness to obtain kudzu root extract, wherein the sum of Puerarin and isoflavone content are
39.26%, the rate of transform of Puerarin and isoflavones is 87.63%, Pueraria Flavonid content 70.82%.
Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract are uniformly mixed up to the present composition.
Embodiment 4
Example 1 group is closed into object, 50g sucrose is added, is uniformly mixed, ethyl alcohol is sprayed into and softwood is made, pelletize in granulator,
60 DEG C of dryings, obtain granule.
Embodiment 5
By 2 composition of embodiment, 50g sucrose is added, is uniformly mixed, sprays into ethyl alcohol and softwood is made, pelletize in granulator,
60 DEG C of dryings, obtain granule.
Embodiment 6
By 3 composition of embodiment, 50g sucrose is added, is uniformly mixed, sprays into ethyl alcohol and softwood is made, pelletize in granulator,
60 DEG C of dryings, obtain granule.
Comparative example 1
Prescription:
Radix Salviae Miltiorrhizae 100g Rhizoma Chuanxiong 100g pueraria lobata 100g
Preparation method:
The preparation method of Salvia root P.E compares in addition to resin path height for 1:5, and the weight ratio of Radix Salviae Miltiorrhizae and dried resin is outside 5:1,
It is identical that other conditions with 1 Salvia root P.E of embodiment obtain preparation method；Tanshin polyphenolic acid B and protocatechualdehyde in Salvia root P.E obtained
The sum of content is 19.63%, and the rate of transform of tanshin polyphenolic acid B and protocatechualdehyde content is 80.82%, salvianolic acid content
35.13%.
The preparation method of Rhizoma Chuanxiong extract compares in addition to resin path height for 1:5, and the weight ratio of Rhizoma Chuanxiong and dried resin is outside 6:1,
It is identical that other conditions with 1 Rhizoma Chuanxiong extract of embodiment obtain preparation method；Ligustrazine and ferulic acid contain in Rhizoma Chuanxiong extract obtained
The sum of amount is 6.87%, ligustrazine and asafoetide acid transfer rate 70.31%.
The preparation method of kudzu root extract compares in addition to resin path height for 1:5, and the weight ratio of pueraria lobata and dried resin is outside 7:1,
It is identical that other conditions with 1 kudzu root extract of embodiment obtain preparation method；Puerarin and the different Huang of soybean in kudzu root extract obtained
The sum of ketone content is 38.65%, and the rate of transform of Puerarin and isoflavones is 74.43%, Pueraria Flavonid content
61.62%.
Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract are uniformly mixed up to 1 composition of comparative example.
Comparative example 2
Prescription:
Radix Salviae Miltiorrhizae 100g Rhizoma Chuanxiong 100g pueraria lobata 100g
Preparation method:
The preparation method of Salvia root P.E compares in addition to resin path height for 1:5, and the weight ratio of Radix Salviae Miltiorrhizae and dried resin is outside 3:1,
It is identical that other conditions with 1 Salvia root P.E of embodiment obtain preparation method；Tanshin polyphenolic acid B and protocatechualdehyde in Salvia root P.E obtained
The sum of content is 21.49%, and the rate of transform of tanshin polyphenolic acid B and protocatechualdehyde content is 77.72%, salvianolic acid content
36.57%.
The preparation method of Rhizoma Chuanxiong extract compares in addition to resin path height for 1:5, and the weight ratio of Rhizoma Chuanxiong and dried resin is outside 4:1,
It is identical that other conditions with 1 Rhizoma Chuanxiong extract of embodiment obtain preparation method；Ligustrazine and ferulic acid contain in Rhizoma Chuanxiong extract obtained
The sum of amount is 6.76%, ligustrazine and asafoetide acid transfer rate 73.61%.
The preparation method of kudzu root extract compares in addition to resin path height for 1:5, and the weight ratio of pueraria lobata and dried resin is outside 5:1,
It is identical that other conditions with 1 kudzu root extract of embodiment obtain preparation method；Puerarin and the different Huang of soybean in kudzu root extract obtained
The sum of ketone content is 36.18%, and the rate of transform of Puerarin and isoflavones is 73.52%, Pueraria Flavonid content
63.64%.
Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract are uniformly mixed up to 2 composition of comparative example.
Comparative example 3
Prescription:
Radix Salviae Miltiorrhizae 100g Rhizoma Chuanxiong 100g pueraria lobata 100g
Preparation method:
The preparation method of Salvia root P.E compares in addition to resin path height for 1:9, and the weight ratio of Radix Salviae Miltiorrhizae and dried resin is outside 5:1,
It is identical that other conditions with 1 Salvia root P.E of embodiment obtain preparation method；Tanshin polyphenolic acid B and protocatechualdehyde in Salvia root P.E obtained
The sum of content is 17.26%, and the rate of transform of tanshin polyphenolic acid B and protocatechualdehyde content is 76.08%, salvianolic acid content
35.76%.
The preparation method of Rhizoma Chuanxiong extract compares in addition to resin path height for 1:9, and the weight ratio of Rhizoma Chuanxiong and dried resin is outside 6:1,
It is identical that other conditions with 1 Rhizoma Chuanxiong extract of embodiment obtain preparation method；Ligustrazine and ferulic acid contain in Rhizoma Chuanxiong extract obtained
The sum of amount is 5.65%, ligustrazine and asafoetide acid transfer rate 72.43%.
The preparation method of kudzu root extract compares in addition to resin path height for 1:9, and the weight ratio of pueraria lobata and dried resin is outside 7:1,
It is identical that other conditions with 1 kudzu root extract of embodiment obtain preparation method；Puerarin and the different Huang of soybean in kudzu root extract obtained
The sum of ketone content is 33.29%, and the rate of transform of Puerarin and isoflavones is 64.82%, Pueraria Flavonid content
61.37%.
Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract are uniformly mixed up to 3 composition of comparative example.
Comparative example 4
Prescription:
Radix Salviae Miltiorrhizae 100g Rhizoma Chuanxiong 100g
The preparation method of Salvia root P.E compares in addition to resin path height for 1:9, and the weight ratio of Radix Salviae Miltiorrhizae and dried resin is outside 3:1,
It is identical that other conditions with 1 Salvia root P.E of embodiment obtain preparation method；Tanshin polyphenolic acid B and protocatechualdehyde in Salvia root P.E obtained
The sum of content is 16.45%, and the rate of transform of tanshin polyphenolic acid B and protocatechualdehyde content is 70.58%, salvianolic acid content
34.85%.
The preparation method of Rhizoma Chuanxiong extract compares in addition to resin path height for 1:9, and the weight ratio of Rhizoma Chuanxiong and dried resin is outside 4:1,
It is identical that other conditions with 1 Rhizoma Chuanxiong extract of embodiment obtain preparation method；Ligustrazine and ferulic acid contain in Rhizoma Chuanxiong extract obtained
The sum of amount is 6.34%, ligustrazine and asafoetide acid transfer rate 70.93%.
The preparation method of kudzu root extract compares in addition to resin path height for 1:9, and the weight ratio of pueraria lobata and dried resin is outside 5:1,
It is identical that other conditions with 1 kudzu root extract of embodiment obtain preparation method；Puerarin and the different Huang of soybean in kudzu root extract obtained
The sum of ketone content is 36.78%, and the rate of transform of Puerarin and isoflavones is 60.72%, Pueraria Flavonid content
66.48%.
Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract are uniformly mixed up to 3 composition of comparative example.
Comparative example 5
Prescription:
Radix Salviae Miltiorrhizae 100g Rhizoma Chuanxiong 100g
Preparation method:
By WS3The method that-B-0824-91-2015 standard provides prepares the extraction mixture of above-mentioned three Chinese medicine to get right
5 composition of ratio.
Comparative example 6
By document 2 (preparation process and quality standard research of pulse invigorating pill, Zheng Yanan, University Of Tianjin, master's opinion in 2011
Text) method disclosed in page 60 prepares Radix Salviae Miltiorrhizae, pueraria lobata dried cream powder and Rhizoma Chuanxiong dried cream powder, and it is uniformly mixed, obtains 6 composition of comparative example.
Comparative example 7
By document 3 (study of pharmacy for sustained release tablets of promoting blood circulation, Liu Yang, Chengdu University of Traditional Chinese Medicine, Master's thesis in 2007) the 36th
Method disclosed in page~37 prepares Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract, is uniformly mixed, and obtains the combination of comparative example 7
Object；Wherein Salvia root P.E purifying HPD600 type large pore resin absorption column, diameter height ratio 1:7, the weight ratio of Radix Salviae Miltiorrhizae and dried resin
For 4:1；Rhizoma Chuanxiong；The purifying of kudzu root extract D101 type large pore resin absorption column, diameter height ratio 1:7, the weight of pueraria lobata and dried resin
Amount is than being 6:1.
Part III: pharmacodynamic test
The influence of test example 1, the present composition to ischemic cerebral disease rat model
SD rat, male, weight 180-220g, experimental animal are randomly divided into 12 groups, and Normal group (waits capacity physiology salt
Water), model group (waiting capacity physiological saline), example 1 group (10mg/kg), 2 groups of embodiment (10mg/kg), 3 groups of embodiment
1 group of (10mg/kg), comparative example (10mg/kg), 2 groups of comparative example (10mg/kg), 3 groups of comparative example (10mg/kg), 4 groups of comparative example
5 groups of (10mg/kg), comparative example (10mg/kg), 6 groups of comparative example 7 groups of (10mg/kg) comparative examples (10mg/kg), 10/group.Often
Group rat daily gastric infusion 1 time, continuous 7 days.
Test 1h after being administered the 7th day, each experimental group rats by intraperitoneal injection 10% is hydrated chlorine ferment (0.35g/kg) anesthesia, separation
Right carotid, in addition to blank group, remaining each group rat injects arachidonic acid to cephalad direction inserting needle with No. 5 syringe needles
0.5mg/kg, blank group inject Isodose physiological saline.After crossing 15min, blood sampling 3mL is intubated by right common carotid artery, dress is added
There is the plastic test tube of 2% heparin of 0.3rn, mix at once, is saved in 4 DEG C.Then break end rapidly, take brain spare.Detection mind
Through mediator index: blood sampling 4000r/min centrifugation 15min, collection supernatant, Elisa method measurement blood plasma Glutamic Acid (Glu),
Aspartic acid (Asp), γ-aminobutyric acid (GABA) content.
It is for statistical analysis with 17.0 software of SPSS.Data are indicated with mean ± standard deviationDan Yin is used between group
Plain variance analysis, LSD inspection is carried out between the neat person's group of variance, and heterogeneity of variance person carries out Tamhane ' s T2 and examines.Testing result is shown in
Table 7.
7 present composition of table to ischemia/reperfusion in rats brain tissue neurotransmitter content influence (N=10)
Note: P < 0.05 * compared with model group；**P<0.01；Δ P < 0.05 compared with blank control group；ΔΔP<0.01
This experiment injects arachidonic acid by arteria carotis communis and causes rat cerebral ischemia model to the present composition and comparison
The pharmacological action of example composition is verified, the results showed that, the present composition has more superior therapeutic effect.
The influence of test example 2, the present composition to impatient ischemia model rat
SD rat, male, weight 180-220g, ad lib, after normal raising 7 days, experimental animal is randomly divided into 12 groups,
Normal group (waiting capacity physiological saline), model group (waiting capacity physiological saline), example 1 group (10mg/kg), embodiment 2
Group (10mg/kg), 3 groups of embodiment (10mg/kg), 1 group of comparative example (10mg/kg), 2 groups of comparative example (10mg/kg), comparative example 3
Group (10mg/kg), 4 groups of comparative example (10mg/kg), 5 groups of comparative example (10mg/kg), 6 groups of comparative example 7 groups of (10mg/kg) comparative examples
(10mg/kg), 10/group, medicine group drug is dissolved with distilled water, 1 time a day gastric infusion, and medication volume is based on 1mL/100g
It calculates, is administered 35 days.Except for the normal group, high lipid food is given once daily in other each groups.
Modeling: the 72h intraperitoneal injection pituitrin for the first time before last gastric infusion, after each gastric infusion 30min,
30 μ L/kg of pituitrin is injected intraperitoneally, continuous 3 times, every minor tick for 24 hours, forms coronary heart disease and myocardial ischemia model.Normal control
Group gives the physiological saline of the capacity such as corresponding injection.
Testing index and method:
(1) before modeling and after third time intraperitoneal injection pituitrin 24 hours, with 22% abdominal cavity urethane 4mL/kg
Injection links biological function pilot system after Animal Anesthesia, and needle electrode is inserted into rat left fore and double hind leg skins respectively
Under, the amplitude (mv) of record lead electrocardiogram ST section 15min variation.
(2) TC, TG content in measurement experiment animal blood serum.
It is for statistical analysis with 17.0 software of SPSS.Data are indicated with mean ± standard deviationDan Yin is used between group
Plain variance analysis, LSD inspection is carried out between the neat person's group of variance, and heterogeneity of variance person carries out Tamhane ' s T2 and examines.Testing result is shown in
Table 8.
8 present composition of table to myocardial infarction and ischemia model rat influence (N=10)
Note: P < 0.05 * compared with model group；**P<0.01；Δ P < 0.05 compared with blank control group；ΔΔP<0.01
Table 8 the result shows that, the present composition better therapeutic effect compared with comparative example composition.
It should be understood that after reading the above teachings of the present invention, those skilled in the art can make the present invention
Various changes or modification, these equivalent forms also fall within the scope of the appended claims of the present application.
Claims (7)
1. a kind of treat ischemic angiocardiopathy and cerebrovascular disease, artery sclerosis, cerebral thrombosis, cerebral ischemia, coronary heart disease, anginal medicine group
The preparation method of object is closed, wherein described pharmaceutical composition is made of the bulk pharmaceutical chemicals of following weight parts:
100 parts of Radix Salviae Miltiorrhizae
100 parts of Rhizoma Chuanxiong
100 parts of pueraria lobata
The preparation method includes the preparation of the preparation of Salvia root P.E, the preparation of Rhizoma Chuanxiong extract and kudzu root extract；
Wherein, the preparation method of the Salvia root P.E comprises the following steps: taking red rooted salvia, 8 times of weight of red rooted salvia are added
The water of part decocts 1 time, decocts 1 hour, then is decocted 2 times, every time 0.5 hour with the water of 5 times of parts by weight of red rooted salvia；Merge and decocts
Liquid, filtration, ethyl alcohol, which is added, makes alcohol content up to 80%, refrigerates, filtering, at a temperature of filtrate is concentrated into 60 DEG C relative density be 1.10~
1.15, obtained concentrate is injected into HPD600 type large pore resin absorption column, wherein the high ratio of the diameter of the large pore resin absorption column
Control is between 1:6~1:8, elution requirement are as follows: the weight ratio of Radix Salviae Miltiorrhizae and dried resin is 4:1, adsorption flow rate 3ml/min, elution
Flow velocity 4ml/min；The purifying water elutions of 8 times of amount column volumes are first used when elution, then with 8 times of amount 20% ethanol elutions of column volume, are discarded
Eluent, then with 6 times of amount 75% ethanol elutions of column volume, collect 75% ethanol eluate；Obtained eluent is concentrated to dryness
Salvia root P.E；
Wherein, the preparation method of the Rhizoma Chuanxiong extract comprises the following steps: taking Ligusticum chuanxiong Hort, 8 times of parts by weight of Rhizoma Chuanxiong are added
70% alcohol reflux extracts 1 time, extracts 2 hours, then is extracted 2 times with 70% alcohol reflux of 6 times of parts by weight of Rhizoma Chuanxiong, extracts 1 every time
Hour；Combined extract, filtration, relative density is 1.10~1.15 at a temperature of being concentrated into 60 DEG C；Obtained concentrate is injected
NKA type large pore resin absorption column, wherein the diameter height of the large pore resin absorption column is than controlling the elution requirement between 1:6~1:8
Are as follows: the weight ratio of Rhizoma Chuanxiong and dried resin is 5:1, adsorption flow rate 3ml/min, elution flow rate 4ml/min；When elution, first measured with 5 times
The purifying water elution of column volume, then with 5 times of amount 30% ethanol elutions of column volume, eluent is discarded, then column volume is measured with 4 times
60% ethanol elution collects 60% ethanol eluate；Obtained eluent is concentrated to dryness to obtain Rhizoma Chuanxiong extract；
Wherein, the preparation method of the kudzu root extract comprises the following steps: taking pueraria lobata medicinal material, 10 times of parts by weight of pueraria lobata are added
30% alcohol reflux extracts 1 time, extracts 2 hours, then is extracted 2 times with 30% alcohol reflux of 8 times of parts by weight of pueraria lobata, extracts 1 every time
Hour；Combined extract, filtration, ethyl alcohol, which is added, makes alcohol content up to 80%, refrigerates, filtering, and filtrate is opposite at a temperature of being concentrated into 60 DEG C
Density is 1.10~1.15；Obtained concentrate is injected into D101 type large pore resin absorption column, wherein the macroporous absorbent resin
The diameter height of column is than controlling the elution requirement between 1:6~1:8 are as follows: the weight ratio of pueraria lobata and dried resin is 6:1, adsorption flow rate
3ml/min, elution flow rate 4ml/min；When elution, the purifying water elution of column volume is first measured with 8 times, then with 6 times of amount column volumes 10%
Ethanol elution discards eluent, and 30% ethanol elution of column volume is then measured with 4 times, collects 30% ethanol eluate；By what is obtained
Eluent is concentrated to dryness to obtain kudzu root extract；
Salvia root P.E, Rhizoma Chuanxiong extract, kudzu root extract are uniformly mixed up to the composition.
2. preparation method as described in claim 1, which is characterized in that the high ratio of the diameter of the HPD600 type large pore resin absorption column
For 1:7.
3. preparation method as described in claim 1, which is characterized in that the diameter height of the NKA type large pore resin absorption column, which compares, is
1:7。
4. preparation method as described in claim 1, which is characterized in that the diameter height of the D101 type large pore resin absorption column, which compares, is
1:7。
5. ischemic angiocardiopathy and cerebrovascular disease is treated a kind of, artery sclerosis, cerebral thrombosis, cerebral ischemia, coronary heart disease, anginal preparation,
It is characterized in that the preparation is that composition described in claim 1,2,3 or 4 and pharmaceutic adjuvant are mixed together, routinely
Method is prepared.
6. preparation as claimed in claim 5, it is characterised in that the preparation is tablet, capsule, pill, granule or injection
Agent.
7. a kind of treat ischemic angiocardiopathy and cerebrovascular disease, artery sclerosis, cerebral thrombosis, cerebral ischemia, coronary heart disease, anginal particle
Agent, it is characterised in that the granule is that composition described in claim 1,2,3 or 4 and pharmaceutic adjuvant are mixed together, and is pressed
Conventional method is prepared, and the pharmaceutic adjuvant is sucrose.
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