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CN103830220A - Pharmaceutical composition, and applications thereof in preparation of medicines used for treating cardiovascular and cerebrovascular diseases - Google Patents

Pharmaceutical composition, and applications thereof in preparation of medicines used for treating cardiovascular and cerebrovascular diseases Download PDF

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Publication number
CN103830220A
CN103830220A CN201210474876.0A CN201210474876A CN103830220A CN 103830220 A CN103830220 A CN 103830220A CN 201210474876 A CN201210474876 A CN 201210474876A CN 103830220 A CN103830220 A CN 103830220A
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China
Prior art keywords
danshensu
carthamus yellow
yellow
pharmaceutical composition
carthamus
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CN201210474876.0A
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Chinese (zh)
Inventor
姜易恒
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Qingdao Baicaohui Institute of Chinese Herbal Medicine
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Qingdao Baicaohui Institute of Chinese Herbal Medicine
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Priority to CN201210474876.0A priority Critical patent/CN103830220A/en
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract

The invention provides a pharmaceutical composition composed of carthamin yellow and salvianic acid, wherein the carthamin yellow comprises 50% of 100% hydroxysafflor yellow A, and the content of 100% salvianic acid is 50%. The invention also provides applications of the pharmaceutical composition in preparation of medicines used for treating cardiovascular and cerebrovascular diseases.

Description

A kind of pharmaceutical composition and the application in the medicine of preparation treatment cardiovascular and cerebrovascular disease thereof
Summary
The invention provides the pharmaceutical composition being formed by Carthamus yellow and danshensu, the S-A Hydroxysafflor yellow A 350% that wherein Carthamus yellow contains 100%>, 100%> content of Danshensu 350%.The present invention also provides the application in the medicine of this pharmaceutical composition in preparation treatment cardiovascular and cerebrovascular disease.
Technical field
The present invention relates to a kind of pharmaceutical composition being formed by Carthamus yellow and danshensu, also relate to its application in the medicine of preparation treatment cardiovascular and cerebrovascular disease.
Background technology
Carthamus yellow is the effective ingredient extracting from Flos Carthami, there is multiple pharmacology's effects such as coronary artery dilator, blood pressure lowering, antithrombotic, anoxia enduring, immunosuppressant, see [the modern study general introduction of Carthamus yellow, Wang Huiling, China's Chinese medicine science and technology, the 5th the 5th phase of volume in 1998].
Danshensu, phenol aromatic acid compound, brown color powder or yellow powder.Be used for blood circulation promoting and blood stasis dispelling, regulating QI to relieve pain, feels oppressed for breast, angina pectoris.
The inventor, by a large amount of experimentatioies, provides a kind of pharmaceutical composition being made up of Carthamus yellow, danshensu and the application in the medicine of preparation treatment cardiovascular and cerebrovascular disease thereof.
Summary of the invention
The invention provides a kind of pharmaceutical composition being made up of Carthamus yellow, danshensu, wherein the weight ratio of Carthamus yellow and danshensu is 1:20~20:1; In Carthamus yellow, contain 100%> S-A Hydroxysafflor yellow A 350%, 100%> content of Danshensu 350%.
The invention provides the application of the pharmaceutical composition being formed by Carthamus yellow, danshensu in the medicine of preparation treatment cardiovascular and cerebrovascular disease.
The invention provides the application of this pharmaceutical composition in the medicine of preparation treatment brain injury.
The invention provides the application of this pharmaceutical composition in the medicine of preparation treatment myocardial ischemia.
Pharmaceutical composition provided by the invention can be according to preparation needs, add corresponding adjuvant, exist with tablet, pill, granule, capsule, suspension, solution, syrup, injection, cream, ointment, spray, chewing agent or patch form, be preferably freeze-dried powder.Various dosage form provided by the invention all can adopt pharmacy conventional method to be prepared from.
Pharmaceutical composition provided by the invention is when for cardiovascular and cerebrovascular disease, and its using dosage scope is 35mg-1000mg, is preferably 50mg-400mg.
Pharmaceutical composition provided by the invention, while existence with dosage form, the content of its effective ingredient is 35-400mg.
Carthamus yellow of the present invention is from Flos Carthami, to extract to separate to obtain, and preferably adopts water extracting method, with macroporous adsorbent resin column chromatography method and the combination of polycaprolactam method, obtains Carthamus yellow.Danshensu of the present invention is from Radix Salviae Miltiorrhizae, to extract to separate to obtain.
The inventor has carried out following test and has confirmed that the pharmaceutical composition being made up of Carthamus yellow and danshensu, in the effect of preparing in the medicine for the treatment of cardiovascular and cerebrovascular disease, has synergism.
The specific embodiment:
Preparation example 1: the preparation of Carthamus yellow, danshensu
Get flos carthami 5kg, 30 times of water gaging percolation, filter, with absorption with macroporous adsorbent resin (the volume ratio 3:1 of extracting solution and resin), with 2 column volumes of deionized water eluting, then continue with 5 column volumes of deionized water eluting, collect eluent, use again polycaprolactam, be first washed till colourlessly with deionized water, then use 95% ethanol elution of meta-alkalescence, collect eluent, in rotary evaporator, concentrate and remove ethanol, lyophilization obtains Carthamus yellow, wherein hydroxyl carthamin yellow A-containing 75.8%.
Danshensu press document [Deng Xiling, Chen Xuemin. the synthetic and pharmacological action of danshensu. land-reclaimable medical science .2002,24 (5): 362~364] described method preparation.
Preparation example 2: the freeze-dried powder that preparation is made up of Carthamus yellow and danshensu
Under cleaning condition, get Carthamus yellow 190g, danshensu 10g, be dissolved in 1000 ml waters for injection, add 100
G mannitol, stirring and dissolving, ultrafiltration, obtains apyrogenic clear liquor, by the lyophilizing of freeze-dried powder technique, makes the freeze-dried powder containing Carthamus yellow 190 mg, danshensu 10 mg.
Preparation example 4: the freeze-dried powder that preparation is made up of Carthamus yellow and danshensu
Under cleaning condition, get Carthamus yellow 10g, danshensu 190g, be dissolved in 1000 ml waters for injection, stirring and dissolving, ultrafiltration, obtains apyrogenic clear liquor, press the lyophilizing of freeze-dried powder technique, make the freeze-dried powder containing Carthamus yellow 10 mg, danshensu 190 mg.
Preparation example 5: the freeze-dried powder that preparation is made up of Carthamus yellow and danshensu
Under cleaning condition, get Carthamus yellow 20 g, danshensu 80 g, be dissolved in 1000 ml waters for injection, add 100 g low molecular dextrans, stirring and dissolving, ultrafiltration, obtains apyrogenic clear liquor, press the lyophilizing of freeze-dried powder technique, make the freeze-dried powder containing Carthamus yellow 20 mg, danshensu 80 mg.
Preparation example 6: the freeze-dried powder that preparation is made up of Carthamus yellow and danshensu
Under cleaning condition, get Carthamus yellow 80 g, danshensu 20 g, be dissolved in 1000 ml waters for injection, add 100 g low molecular dextrans, stirring and dissolving, ultrafiltration, obtains apyrogenic clear liquor, press the lyophilizing of freeze-dried powder technique, make the freeze-dried powder containing Carthamus yellow 80 mg, danshensu 20 mg.
Preparation example 7: the freeze-dried powder that preparation is made up of Carthamus yellow and danshensu
Under cleaning condition, get Carthamus yellow 25 g, danshensu 75 g, be dissolved in 1000 ml waters for injection, stirring and dissolving, ultrafiltration, obtains apyrogenic clear liquor, press the lyophilizing of freeze-dried powder technique, make the freeze-dried powder containing Carthamus yellow 25 mg, danshensu 75 mg.
Test example 1: various dose Carthamus yellow, danshensu, the impact of compositions on focal cerebral ischemia in rats damage
(1) material:
Carthamus yellow, danshensu, compositions: prepare by preparation example 1.
Red tetrazolium: Sigma company of U.S. product, is made into 4% solution with normal saline before use.
Laboratory animal: regular grade SD rat, male, body weight 280 g-350 g.
(2) method and result:
Animal is divided into sham operated rats (normal saline) at random, model control group (normal saline), nimodipine group (Nim, 1.0 mg/kg), Carthamus yellow small dose group (1.5 mg/kg), dosage group in Carthamus yellow (3.5 mg/kg), the heavy dose of group of Carthamus yellow (45 mg/kg), danshensu small dose group (2 mg/kg), dosage group in danshensu (3.5 mg/kg), the heavy dose of group of danshensu (60 mg/kg), compositions low dose [Carthamus yellow (1.5 mg/kg)+danshensu (2 mg/kg)], 10 every group of compositions heavy doses [Carthamus yellow (45 mg/kg)+danshensu (60 mg/kg)].After fasting 12 hours, chloral hydrate (350 mg/kg, i.p.) anesthesia, separates right carotid, and folder closes in neck, common carotid artery, external carotid artery proximal part and distal end ligation, and cut off centre.External carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24 mm nylon wire, length 5.0 cm) is inserted into intracranial by external carotid artery, while meeting slight resistance, stop, insertion depth is about 2 cm.Ligation external carotid artery opening, and open common carotid artery bulldog clamp, disinfection and stitching wound, causes right side middle cerebral artery ischemia model; Sham operated rats is only carried out the separation (above experiment is all carried out at 23 ℃~25 ℃) of right carotid, internal carotid artery, external carotid artery.Postoperative each treated animal intravenous injection relative medicine.After 24 hours, press document [Liu little Guang, Xu Lina, a kind of rat brain medium-sized artery model that can evaluate thrombolytic and anti-thrombolytic, Acta Pharmaceutica Sinica, 1995,30:662] described method and standard observe and record the behavior disorder of rat: (A) carry Mus tail and observe forelimb flexing situation, as two forelimb symmetries are stretched to ground, count 0 point, count 1 point as wrist flexing appears in operation offside forelimb, elbow flexing is counted 2 points, shoulder inward turning is counted 3 points, existing wrist flexing and/or elbow flexing, have again shoulder inward turning person, counts 4 points.(B) animal is placed on plane earth, pushes away respectively both shoulders to side shifting, check resistance.As bilateral resistance equity and strong, count 0 point, resistance descender as promoted to operation offside time, according to decline degree difference be divided into gently, in, weigh three degree, count respectively 1,2 and 3 point.(C) two animal forelimbs are put on a wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 point.Count 1,2 and 3 point according to operation offside muscular tension decline degree difference equally.(D) animal has ceaselessly to a side person of turn-taking, and counts 1 point.According to standard scoring, full marks are 11 points, and mark is higher, represent that animal behavior obstacle is more serious.
After behavior scoring, put to death rat, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, brain is red tetrazolium (TTC) dyeing for sheet, after normal structure is dyed, takes on a red color, and blocking tissue is white in color, after dyeing, take a picture, ask infarct size ratio with China Aviation space flight university pathological image analysis software.Data are used ± SD represents, between organizing fstatistical procedures is carried out in check.
Result is as shown in table 1, and ischemia is after 24 hours, and model group rat shows obvious behavior disorder, and obvious kitchen range shape ischemic region also appears in rat cerebral tissue, reaches 25% left and right of full brain.
1.5 mg/kg Carthamus yellows and 2 mg/kg danshensu groups are failed to improve rat behavior obstacle, are reduced ischemic areas; 3.5 mg/kg Carthamus yellows and 3.5 mg/kg danshensu groups have all been improved to a certain extent rat behavior obstacle, have been reduced ischemic areas.
Compositions small dose group [Carthamus yellow (1.5 mg/kg)+danshensu (2 mg/kg)] is improved very significantly rat behavior obstacle, is reduced ischemic areas, with relatively p < 0.01 of model group, and more also there is significant difference (P < 0.05) with 3.5 mg/kg Carthamus yellows, 3.5 mg/kg danshensus.In prompting combination thing, Carthamus yellow and danshensu have synergism.Compositions heavy dose [Carthamus yellow (45 mg/kg)+danshensu (60 mg/kg)] is improved extremely significantly rat behavior obstacle, is reduced ischemic areas, with relatively P < 0.001 of model group.
Table 1 Carthamus yellow, danshensu, the impact of compositions on focal cerebral ischemia in rats damage
Figure 262855DEST_PATH_IMAGE003
Test example 2: Carthamus yellow, danshensu, the impact of compositions on myocardial ischemia in rats damage
(1) material:
Carthamus yellow, danshensu, compositions: prepare by preparation example 1.
Painstaking effort pellet (compound Salviae Miltiorrhizae) injection: Guizhou Shenqi Pharmaceutical Co., Ltd.
NBT (N-BT), is provided by Military Medical Science Institute's medical supply station.
Laboratory animal: regular grade Wistar rat, male, body weight 280 g-350 g.
(2) method and result:
Animal is divided into sham operated rats (normal saline) at random, model control group (normal saline), FUFANG DANSHEN ZHUSHEYE group (DS, 10 mg/kg), Carthamus yellow small dose group (1.5 mg/kg), dosage group in Carthamus yellow (3.5 mg/kg), the heavy dose of group of Carthamus yellow (45 mg/kg), danshensu small dose group (2 mg/kg), dosage group in danshensu (3.5 mg/kg), the heavy dose of group of danshensu (60 mg/kg), compositions low dose [Carthamus yellow (1.5 mg/kg)+danshensu (2mg/kg)], 10 every group of compositions heavy doses [Carthamus yellow (45 mg/kg)+danshensu (60 mg/kg)].After fasting 12 hours, ip urethane (1.2 g/kg) anesthesia, surveys limbs II lead electrocardiogram.Cut off left front fur, iodine tincture and alcohol disinfecting, along left border of sternum 1cm place, cut off thoracic wall muscle and two ribs, open rapidly thoracic cavity, expose heart, between arterial cone and left auricle, ligation left coronary artery, puts back to heart immediately, squeezes thoracic cavity air, use mosquito forceps closed-chest, cause Model Rats with Acute Myocardial Ischemia.Postoperative each treated animal intravenous injection relative medicine.Record before administration and administration after 1.5h, 3h electrocardiogram, after 6h, take out heart, after cleaning with cold saline ,-20 ℃ of refrigerator freezings spend the night.Next day, freezing heart is cut into 5 by ligation place to apex uniform thickness, immerse in freshly prepared 0.5% NBT phosphate buffer (pH 7.4).37 ℃ of water-bath jolting 10~15 min.Blot the dyeing liquor of slice surface with filter paper, separate coloured portions and the part of being unstained, weigh, compute infarct size.Infarct size (%)=infarction part weight/(non-infarction part weight+infarction part weight) × 100%.
Result demonstration, myocardial ischemia is after 6 hours, and there is obvious kitchen range shape ischemic region in model group rat heart muscle, reaches 25% left and right.1.5 mg/kg Carthamus yellows and 2 mg/kg danshensu groups are failed to improve rat electrocardio, are reduced ischemic areas; 3.5 mg/kg Carthamus yellows and 3.5 mg/kg danshensu groups all reduce rising, the minimizing ischemic areas of the limb lead electrocardiogram J point being caused by myocardial ischemia to a certain extent; Compositions small dose group [Carthamus yellow (1.5 mg/kg)+danshensu (2 mg/kg)] reduces rising, the minimizing ischemic areas of limb lead electrocardiogram J point very significantly, with relatively P < 0.01 of model group, and more also there is significant difference (P < 0.05) with 3.5 mg/kg Carthamus yellows, 3.5 mg/kg danshensus; Compositions heavy dose [Carthamus yellow (45 mg/kg) danshensu (60 mg/kg)] reduces rising, the minimizing ischemic areas of limb lead electrocardiogram J point extremely significantly, with relatively P < 0.001 of model group.

Claims (6)

1. a pharmaceutical composition, is made up of Carthamus yellow and danshensu, and its weight ratio is 1:20~20:1; Wherein in Carthamus yellow, contain 100%> S-A Hydroxysafflor yellow A 350%, 100%> content of Danshensu 350%.
2. require the compositions described in 1 according to right profit, Carthamus yellow is from Flos Carthami, to extract to separate to obtain, and preferably adopts water extracting method, with macroporous adsorbent resin column chromatography method and the combination of polycaprolactam method, obtains Carthamus yellow.
3. compositions according to claim 1, danshensu is from Radix Salviae Miltiorrhizae, to extract to separate to obtain.
4. the application of the arbitrary described compositions of claim 1-3 in the medicine of preparation treatment cardiovascular and cerebrovascular disease.
5. the application of stating according to claim 4, the application of said composition in the medicine of preparation treatment brain injury.
6. the application of stating according to claim 4, the application of said composition in the medicine of preparation treatment myocardial ischemia.
CN201210474876.0A 2012-11-21 2012-11-21 Pharmaceutical composition, and applications thereof in preparation of medicines used for treating cardiovascular and cerebrovascular diseases Pending CN103830220A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113350357A (en) * 2020-03-05 2021-09-07 上海市普陀区中心医院 Application of composition of hydroxysafflor yellow A and polygala tenuifolia sapogenin in preparation of medicine for treating ischemic stroke

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113350357A (en) * 2020-03-05 2021-09-07 上海市普陀区中心医院 Application of composition of hydroxysafflor yellow A and polygala tenuifolia sapogenin in preparation of medicine for treating ischemic stroke
CN113350357B (en) * 2020-03-05 2022-11-01 上海市普陀区中心医院 Application of composition of hydroxysafflor yellow A and polygala tenuifolia sapogenin in preparation of medicine for treating ischemic stroke

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Application publication date: 20140604