CN108143780A - A kind of pharmaceutical composition for treating acute cerebral infarction - Google Patents
A kind of pharmaceutical composition for treating acute cerebral infarction Download PDFInfo
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Abstract
The present invention relates to a kind of pharmaceutical compositions for treating acute cerebral infarction, which is characterized in that is prepared by the raw material of following weight percent：Chinese medicinal compound extract 10~15%, bisulfate clopidogrel 12~15%, filler 10~55%, disintegrant 5~30%, adhesive 0.5~10%, lubricant 0.01~3%.Using Chinese and Western medicine compound preparation, active constituents of medicine is extracted using the preparation means of modernization, reaches preferable therapeutic effect.
Description
Technical field
The present invention relates to drug field, more particularly, to a kind of Chinese and Western medicine compound preparation for treating acute cerebral infarction.
Background technology
1st, the harm and prediction of transient ischemic attack (being abbreviated as TIA)
There is expert to think in recent years, TIA is the prime time of preventing brain stroke stage of attack.The incidence of TIA is annual
180/100000, and be the significant risk signal of cerebral infarction.Conventionally 1/3 TIA patient can develop into cerebral infarction；It is existing
The study found that about 50% Patients with Cerebral Infarction premorbid has TIA medical histories；Li Jianping et al. thinks, 7d after TIA morbidities,
In 90d, 180d, the incidence of cerebral infarction is respectively 12.64%, 13.22%, 14.37%；
TIA once develops into cerebral infarction, and hospital stays, medical expense, disability rate and the death rate will be caused significantly to increase.Cause
This, TIA was increasingly becoming the hot spot of Neurology field concern in recent years.
2nd, meaning of the d-dimer (being written as D-D) in ischemic cerebrovascular disease
Fibrinolytic system is the most important anticoagulation system of human body, is made of 4 kinds of major parts：Plasminogen, fibre
Dissolved preferment activator, fibrinolysin, plasmin inhibitor.When fibrin coagula is formed, in depositing for plasminogen activator
Under, Plasminogen activation is converted into fibrinolysin, and plasmin solution preocess starts, plasmin degradation fibrin coagula shape
Into various solvable segments, fibrin product (FDP) is formed, FDP is by following substance：X- oligomer (X-oligomer), D- bis-
Aggressiveness (D-Dimer), intermediate segment (Intermediate fragments), segment E (Fragment E) compositions.Wherein, X-
Oligomer and D- aggressiveness unit containing d-dimer.
Human body fibrinolytic system, it maintains the flow regime and tissue repair of blood to keeping the normal permeability of vascular wall
It plays an important role.D-dimer plasma levels increase explanation there are secondary fibrinolytic process, and first generate fibrin ferment, afterwards again
There is fibrinolytic system activation；And it is more than blood plasma 2 ‰-anti-fibrinolytic to also be reflected in the local plasmin activity of thrombosis or concentration
Enzymatic activity or concentration.In fibrinolytic protein catabolite, only d-dimer crosslinking fragment can reflect the thrombolysis activity after thrombosis.
Therefore, theoretically, the quantitative detection of d-dimer can quantitative response drug thrombolytic effect and available for diagnosing, screening new shape
Into thrombus.
Since it is closely related with coagulation function, prompt cerebrovascular disease especially cerebral infarction associated therewith.It is reported that find,
Increasing for D-D is closely related with artery sclerosis and cerebral arterial thrombosis.On this basis, medical investigator speculates D-D perhaps
There are great causality, existing research confirms for occurrence and development with TIA, and D-dimer level raising is the risk factor of TIA.
Some researches show that the D-D of patients with ischemic cerebral vascular disease is significantly height, and recognize compared with normal person and other Diseases
It is of great significance for D-D to the prognosis of ischemic cerebrovascular disease (cerebral thrombosis and TIA).
Also research confirms that the TIA duration is longer, and D-D values are higher, and is proportionate with cerebral infarction, therefore recognizes
It can be as it is currently understood that old age TIA severity and the important indicator of prognosis for D-D.
To improve therapeutic effect, clinically frequently with the mode of Chinese and western drugs administering drug combinations, document report also has very much, but
It is that there are certain drawbacks for administering drug combinations, the medication amount taken is more, and often, also there are patient's determining treatments against medical advice
Scheme often has the phenomenon that missing or take wrong dosage, causes curative effect bad.Therefore a kind of answering for Chinese and Western medicine administering drug combinations is needed
Square preparation fills up above-mentioned therapy field blank.
Invention content
The present invention is intended to provide a kind of traditional Chinese medical science medicine composite preparation for treating polarity cerebral infarction, by selecting suitable Chinese medicine
Medicinal material and bisulfate clopidogrel obtain a kind of good compound preparation of therapeutic effect using the preparation means of modernization.In order to reach
To above-mentioned purpose, the present invention uses following technical scheme：
A kind of pharmaceutical composition for treating acute cerebral infarction, which is characterized in that prepared by the raw material of following weight percent
It forms：Chinese medicinal compound extract 10~15%, bisulfate clopidogrel 12~15%, filler 10~55%, disintegrant 5~
30%th, adhesive 0.5~10%, lubricant 0.01~3%.
Preferably, it is prepared by the raw material of following weight proportion：Chinese medicinal compound extract 12~14%, hydrogen sulfate chlorine
Pyrrole Gray 13~14%, filler 25~50%, disintegrant 15~25%, adhesive 1.0~8%, lubricant 0.1~2%；
It is furthermore preferred that it is prepared by the raw material of following weight proportion：Chinese medicinal compound extract 13%, hydrogen sulfate chlorine pyrrole
Gray 14%, filler 42.5%, disintegrant 25%, adhesive 5.0%, lubricant 0.5%.
Further, the Chinese medicinal compound extract is prepared by the medicinal material of following weight proportion：Radix Astragali 5~10
Part, 5~10 parts of Radix Angelicae Sinensis, 3~8 parts of the radix paeoniae rubrathe, 2~4 parts of leech；Preferably, the Chinese medicinal compound extract is matched by following weight
The medicinal material of ratio is prepared：10 parts of Radix Astragali, 8 parts of Radix Angelicae Sinensis, 6 parts of the radix paeoniae rubrathe, 3 parts of leech.
A kind of preparation method for the treatment of acute cerebral infarction pharmaceutical composition as described above, which is characterized in that including as follows
Step：
1) it weighs：Chinese medicinal compound extract is weighed by weight percentage, bisulfate clopidogrel, filler, disintegrant, is glued
Then mixture, lubricant cross 60 mesh sieve respectively, spare；
2) mixing granulation：The Chinese medicinal compound extract of sieving, bisulfate clopidogrel and above-mentioned filler, disintegrant are mixed
It closes uniformly, then adds in adhesive wet granulation；
3) it is dry：Particle obtained above is placed in fluidized-bed coating machine, dry below 50 DEG C of inlet air temperature, drying is extremely
Moisture is sieved 1% hereinafter, crossing 15-20 mesh, carries out whole grain；
4) mixed pressuring plate：By the particle obtained after above-mentioned whole grain addition lubricant mix, then tabletting to get.
Further, the preparation method of the Chinese medicinal compound extract described in step 1) includes the following steps：
A. weighing is cleaned：It cleans and dries ingredients in prescription, remove impurity, then weigh by weight ratio spare；
B. sieving crushes：Radix Astragali, Radix Angelicae Sinensis, the radix paeoniae rubrathe are crushed respectively and cross 80 mesh sieve, leech is subjected to ultramicro grinding, mistake
200 mesh sieve；
C. refluxing extraction：Radix Astragali, Radix Angelicae Sinensis, the radix paeoniae rubrathe after above-mentioned pulverize and sieve is added in 40~70% 5~10 times of amounts
Ethanol water carries out refluxing extraction, and 50~65 DEG C of reflux temperature, return time 30~60 minutes filters while hot, then by filter residue
The above-mentioned reflux operation of repetition 1~2 time, filtering, merging filtrate is condensed into medicinal extract；
D. it mixes：Then the leech Ultramicro-powder obtained in step b is added in, is stirred and evenly mixed to get Chinese medicinal compound extract.
Further, the present invention also provides a kind of aforementioned pharmaceutical compositions to prepare the use in treating acute cerebral infarction drug
On the way.
Advantageous effect
1. the principles of formulating prescriptions：
Radix Astragali
【Source】For pulse family Astragalus astragalus mongolicus (Astragalus membranaceus (Fisch.)
) or the dry root of Astragalus membranacus (Astragalus membranaceus) Bge.var.mongholicus；
【Major function】Tonifying Qi and lifting yang, strengthening exterior and reducing sweat, inducing diuresis for removing edema, blood-nourishing of promoting the production of body fluid, the stagnant logical numbness of row, pus draining and toxin expelling, sore
The effect of myogenic.
Radix Angelicae Sinensis
【Source】The dry root of Umbelliferae section archangel Radix Angelicae Sinensis Radix Angelicae Sinensis (Angelica sinensis)；
【Major function】With blood-nourishing and blood, tonifying blood and regulating menstruation, promoting blood circulation and stopping pain, effect of relaxing bowel.
The radix paeoniae rubrathe
【Source】Ranunculaceae plant Chinese herbaceous peony Paeonia lactiflora Pall. or river Chinese herbaceous peony Paeonia veitchii
The dry root of Lynch；
【Major function】There is clearing heat and cooling blood, removing blood stasis and analgesics.
Leech
【Source】Hirudinidae animal whitmania Whitmania Pigra Whitman, leech Hirudo nipponica
Whitman's or willow leaf leech Whitmania acranutata Whitman is dry all；
【Major function】With blood-breaking promoting menstruation, the effect of Zhu Yu Xiao Disorder.For blood stasis, addiction lump in the abdomen lump in the abdomen, hemiplegia,
The effect of injury from falling down.
Bisulfate clopidogrel
The drug for white or off-white color crystalline powder, chemical name：2- (2- chlorphenyls) -2- (6,7- dihydro-thiophenes
And [3,2-c] pyridine -5- bases) acetate hydrogensulfate, it is platelet aggregation inhibitor, selectively inhibits ADP and blood small
The combination of plate receptor and the activation of II h/ of glycoprotein GP, III a compounds that ADP is inhibited to mediate, and inhibit platelet aggregation.Also may be used
Platelet aggregation caused by inhibiting non-ad P.Effect to platelet ADP receptor is irreversible.Oral absorption is rapid, blood plasma
Middle protein binding rate is 98%, and in liver metabolism, main metabolites are without antiplatelet aggregative activity.Clinically for prevent and
The treatment heart, brain and other arterial circulation disorder diseases caused by blood platelet height is assembled, the cerebral apoplexy such as to break out in the recent period, cardiac muscle stalk
Peripheral arterial disease that is dead and making a definite diagnosis.
The present invention selection preferable drug of Chinese traditional treatment acute cerebral infarction effect, Chinese medicine compound prescription is prepared into according to combination principle
Extract, Radix Astragali have the effect of benefiting qi and nourishing blood, row stagnant logical numbness for monarch drug in a prescription；When being classified as ministerial drug nourishing the blood and yin, promoting blood circulation and stopping pain；The radix paeoniae rubrathe
Clearing heat and cooling blood removing blood stasis and analgesics；Leech blood-breaking is by silt, and the two is combined into adjuvant object, and silt analgesic is broken in entire prescription nourshing blood and promoting blood circulation, to urgency
The therapeutic effect of property cerebral infarction is preferable.
2. synergistic effect
Clinical test shows after sharing Chinese medical extract and bisulfate clopidogrel of the present invention that therapeutic effect greatly improves,
It is substantially better than and Chinese prescription and chemicals is used alone, have good therapeutic effect for the acute attack stage of cerebral infarction,
The state of an illness can be significantly controlled, restores tool more afterwards for patient and has very great help.
The preparation of embodiment 1 --- Chinese medicinal compound extract 1
A. weighing is cleaned：It cleans and dries ingredients in prescription, remove impurity, then weigh Radix Astragali by weight ratio
10g, Radix Angelicae Sinensis 8g, radix paeoniae rubrathe 6g, leech 3g are spare；B. sieving crushes：Above-mentioned Radix Astragali, Radix Angelicae Sinensis, the radix paeoniae rubrathe are crushed respectively and cross 80 mesh
Leech is carried out ultramicro grinding by sieve, crosses 200 mesh sieve；C. refluxing extraction：Radix Astragali, Radix Angelicae Sinensis, the radix paeoniae rubrathe after above-mentioned pulverize and sieve is added
10 times of amount ethanol waters for entering 60% carry out refluxing extraction, 50 DEG C of reflux temperature, and return time 30 minutes filters while hot, then
Filter residue is repeated into above-mentioned reflux operation 2 times, filtering, merging filtrate is condensed into medicinal extract；D. it mixes：It is added in step b into medicinal extract
The leech Ultramicro-powder of acquisition, stirs and evenly mixs to get Chinese medicinal compound extract 1.
The preparation of embodiment 2 --- Chinese medicinal compound extract 2
A. weighing is cleaned：It cleans and dries ingredients in prescription, remove impurity, then weigh Radix Astragali by weight ratio
10g, Radix Angelicae Sinensis 9g, radix paeoniae rubrathe 8g, leech 2g are spare；B. sieving crushes：Above-mentioned Radix Astragali, Radix Angelicae Sinensis, the radix paeoniae rubrathe are crushed respectively and cross 80 mesh
Leech is carried out ultramicro grinding by sieve, crosses 200 mesh sieve；C. refluxing extraction：Radix Astragali, Radix Angelicae Sinensis, the radix paeoniae rubrathe after above-mentioned pulverize and sieve is added
8 times of amount ethanol waters for entering 50% carry out refluxing extraction, 55 DEG C of reflux temperature, and return time 60 minutes filters while hot, then will
The above-mentioned reflux operation of filter residue repetition 2 times, filtering, merging filtrate is condensed into medicinal extract；D. it mixes：It adds in step b and obtains into medicinal extract
The leech Ultramicro-powder obtained, stirs and evenly mixs to get Chinese medicinal compound extract 2.
The preparation 1 of embodiment 3 --- pharmaceutical composition
1) it weighs：Chinese medicinal compound extract 13%, bisulfate clopidogrel 13%, filler are proportionally weighed respectively
40%th, then disintegrant 25%, adhesive 7%, lubricant 2% cross 60 mesh sieve respectively, spare；2) mixing granulation：By sieving
Chinese medicinal compound extract, bisulfate clopidogrel are uniformly mixed with above-mentioned filler, disintegrant, then add in adhesive wet method system
Grain；3) it is dry：Particle obtained above is placed in fluidized-bed coating machine, it is dry below 50 DEG C of inlet air temperature, it is dry to moisture
1% hereinafter, crossing 20 mesh sieve, whole grain is carried out；4) mixed pressuring plate：The particle obtained after above-mentioned whole grain is added in lubricant to carry out
Mixing, then tabletting to get.
The preparation 2 of embodiment 4 --- pharmaceutical composition
1) it weighs：Chinese medicinal compound extract 13%, bisulfate clopidogrel 14%, filler are proportionally weighed respectively
42.5%th, then disintegrant 25%, adhesive 5.0%, lubricant 0.5% cross 60 mesh sieve respectively, spare；2) mixing granulation：It will
Chinese medicinal compound extract, the bisulfate clopidogrel of sieving are uniformly mixed with above-mentioned filler, disintegrant, then add in adhesive
Wet granulation；3) it is dry：Particle obtained above is placed in fluidized-bed coating machine, it is dry below 50 DEG C of inlet air temperature, it is dry
It is sieved to moisture 1% hereinafter, crossing 20 mesh, carries out whole grain；4) mixed pressuring plate：The particle obtained after above-mentioned whole grain is added in and is lubricated
Agent is mixed, then tabletting to get.
Experimental example
1. data and method
All cases of 1.1 general information are cured from the court (Nanjing Pukou Central Hospital) and Jiangsu Province's combination of Chinese tradiational and Western medicine
Institute's in January, 2015 in January, 2016, meet national Second cerebrovascular disease academic conference by diagnostic criteria and MRI or
CT confirmations, case 100, wherein man 67, female 33,45~80 years old age, average age disease time to 7-26h.It is divided into
Three groups, be group 1 respectively：Bisulfate clopidogrel group 25；Group 2：Embodiment 1 group 25；Group 3：3 composition group 25 of embodiment
Example；Group 4：4 composition group of embodiment 25；Control group：After our hospital checks physical examination UP hurtless measure, tumour, liver and kidney disease,
Angiocardiopathy, diabetes, pregnancy and the physical examination of healthy population without thrombotic disease.1~4 group of clinical manifestation is substantially similar,
Statistically indifference.Four groups of patients are averaged internal venous blood d-dimer content as 0.89 ± 0.12.
1.2 two groups of therapy patient's absolute bed rests, and keep ward peace and quiet and patients with respiratory tract unobstructed, it maintains to suffer from
Person's water/electrolyte balance controls the blood pressure of patient and blood glucose situation.Control group is oral using group 1, each 75mg, one time a day；
Group 2 gives the preparation of embodiment 1 drug after being admitted to hospital is taken orally；Group 3 be admitted to hospital after give embodiment 3 prepare drug into
Row is oral；Group 4 gives the preparation of embodiment 4 drug after being admitted to hospital is taken orally.
1.3 criterion of therapeutical effect references《Apoplexy diagnoses and efficacy assessment standard (tentative)》.It is almost recovered：Language and limbs fortune
Dynamic function returns to normal, and can take care of oneself.It is effective：Language competence is significantly restored, and basic self-care of living, muscular strength exist
III grade or more.Effectively：Language competence is centainly restored, and basic self-care of living, and muscular strength is at IV grade or more.In vain：Before treatment
Afterwards, the symptom of patient does not obtain any improvement.Efficient=(be almost recovered+effective+effectively)/total number of cases × 100.0%.
D-dimer content is managed with BD companies CTAD in 1.4 monitoring patients blood plasmas accurately takes subject's venous blood, with
109mmol/L sodium citrates 9:The abundant mixing of 1 anti-freezing, 2 000r/min centrifugations 15min.Divide using Nycocard Reader II
Analyzer, goldstandard quantify the detection of percolation matched reagent box, strictly illustrate that requirement uses before the deadline by reagent, by operation journey
Sequence is operated.And statistical procedures are carried out, it is examined using t.
2. treatment results
2.1 4 groups of pretherapy and post-treatment comparable situations are shown in Table 1.
1 curative effect comparison result of table
| Group | n | It is almost recovered | It is effective | Effectively | In vain | Total effective rate (%) |
| Group 1 | 25 | 2 (8%) | 8 (32%) | 5 (20%) | 40% | 60% |
| Group 2 | 25 | 1 (4%) | 4 (16%) | 6 (24%) | 56% | 44% |
| Group 3 | 25 | 3 (12%) | 13 (52%) | 6 (24%) | 12% | 88% |
| Group 4 | 25 | 3 (12%) | 14 (64%) | 7 (28%) | 6% | 94% |
As a result it shows：Individually had using clopidogrel bisulfate tablet, Chinese medicinal compound extract 1 to Cerebral Infarction Patients and controlled
Treatment acts on, but effect is not notable, and two compound preparations being prepared using the embodiment of the present invention 1,2 treat acute cerebral infarction
Extremely there is remarkable result.
2.2 organize 1-4 patient's body d-dimer testing results before and after treatment is shown in Table 2.
D-dimer testing result (x ± s mg/L) in 2 each group body of table
The experimental results showed that：The application of compound medicament composition of the present invention can significantly reduce acute cerebral infarction patients D- bis-
The content of aggressiveness.
Claims (5)
1. a kind of pharmaceutical composition for treating acute cerebral infarction, which is characterized in that by the raw material preparation of following weight percent
Into：Chinese medicinal compound extract 10~15%, bisulfate clopidogrel 12~15%, filler 10~55%, disintegrant 5~
30%th, adhesive 0.5~10%, lubricant 0.01~3%；Preferably, it is prepared by the raw material of following weight proportion：Chinese medicine
Compound extract 12~14%, bisulfate clopidogrel 13~14%, filler 25~50%, disintegrant 15~25%, bonding
Agent 1.0~8%, lubricant 0.1~2%；It is furthermore preferred that it is prepared by the raw material of following weight proportion：Chinese medicine compound prescription is extracted
Object 13%, bisulfate clopidogrel 14%, filler 42.5%, disintegrant 25%, adhesive 5.0%, lubricant 0.5%.
2. the pharmaceutical composition of acute cerebral infarction is treated according to claim 1, which is characterized in that the Chinese medicine compound prescription carries
Object is taken to be prepared by the medicinal material of following weight proportion：5~10 parts of Radix Astragali, 5~10 parts of Radix Angelicae Sinensis, 3~8 parts of the radix paeoniae rubrathe, leech 2~4
Part；Preferably, the Chinese medicinal compound extract is prepared by the medicinal material of following weight proportion：10 parts of Radix Astragali, 8 parts of Radix Angelicae Sinensis,
6 parts of the radix paeoniae rubrathe, 3 parts of leech.
3. the preparation method for the treatment of acute cerebral infarction pharmaceutical composition according to claim 1 or 2, which is characterized in that packet
Include following steps：
1) it weighs：Chinese medicinal compound extract, bisulfate clopidogrel, filler, disintegrant, bonding are weighed by weight percentage
Then agent, lubricant cross 60 mesh sieve respectively, spare；
2) mixing granulation：The Chinese medicinal compound extract of sieving, bisulfate clopidogrel are mixed with above-mentioned filler, disintegrant
It is even, then add in adhesive wet granulation；
3) it is dry：Particle obtained above is placed in fluidized-bed coating machine, it is dry below 50 DEG C of inlet air temperature, it is dry to moisture
1% hereinafter, crossing 15-20 mesh sieve, whole grain is carried out；
4) mixed pressuring plate：By the particle obtained after above-mentioned whole grain addition lubricant mix, then tabletting to get.
4. preparation method according to claim 3, which is characterized in that the preparation of the Chinese medicinal compound extract described in step 1)
Method includes the following steps：
A. weighing is cleaned：It cleans and dries ingredients in prescription, remove impurity, then weigh by weight ratio spare；
B. sieving crushes：Radix Astragali, Radix Angelicae Sinensis, the radix paeoniae rubrathe are crushed respectively and cross 80 mesh sieve, leech is subjected to ultramicro grinding, crosses 200 mesh
Sieve；
C. refluxing extraction：Radix Astragali, Radix Angelicae Sinensis, the radix paeoniae rubrathe after above-mentioned pulverize and sieve is added in the ethyl alcohol of 40~70% 5~10 times of amounts
Aqueous solution carries out refluxing extraction, 50~65 DEG C of reflux temperature, and return time 30~60 minutes filters, then filter residue is repeated while hot
Above-mentioned reflux operation 1~2 time, filtering, merging filtrate are condensed into medicinal extract；
D. it mixes：Then the leech Ultramicro-powder obtained in step b is added in, is stirred and evenly mixed to get Chinese medicinal compound extract.
5. a kind of claim 1-2 any one of them pharmaceutical composition is preparing the purposes in treating acute cerebral infarction drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711407749.8A CN108143780A (en) | 2017-12-22 | 2017-12-22 | A kind of pharmaceutical composition for treating acute cerebral infarction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711407749.8A CN108143780A (en) | 2017-12-22 | 2017-12-22 | A kind of pharmaceutical composition for treating acute cerebral infarction |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113073093A (en) * | 2021-04-25 | 2021-07-06 | 山东中医药大学 | Leech fibrinolytic active protein and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105687261A (en) * | 2014-11-26 | 2016-06-22 | 黑龙江省智诚医药科技有限公司 | Compound preparation for treating cerebral infarction and preparation method of compound preparation |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105687261A (en) * | 2014-11-26 | 2016-06-22 | 黑龙江省智诚医药科技有限公司 | Compound preparation for treating cerebral infarction and preparation method of compound preparation |
Non-Patent Citations (2)
| Title |
|---|
| 侯安会: "《脑梗死中西医结合治疗学》", 30 June 2008, 黑龙江人民出版社 * |
| 梁森森: "黄芪桂枝五物加水蛭汤联合西药治疗脑梗死随机平行对照研究", 《实用中医内科杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113073093A (en) * | 2021-04-25 | 2021-07-06 | 山东中医药大学 | Leech fibrinolytic active protein and preparation method thereof |
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