CN100388950C - Application of human urokinase-type peptidase in preparing medicine for treating diabetes combined cerebral infraction - Google Patents
Application of human urokinase-type peptidase in preparing medicine for treating diabetes combined cerebral infraction Download PDFInfo
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Abstract
The present invention relates to new medicinal use of human urokininogenase. Human urokininogenase is used in preparing medicine for preventing and treating diabetes combined cerebral infraction. Clinically, the dosage of human urokininogenase in intravenous injection is 1-2 kilounit each time and once or twice a day. Human urokininogenase has obvious curative effect on diabetes combined cerebral infraction.
Description
Technical field
The present invention relates to the pharmaceutical chemistry field.Particularly, the present invention relates to Human Urinary Kallidinogenase's novel medical use, promptly the Human Urinary Kallidinogenase treats and/or prevents application in the diabetes combined cerebral infraction medicine in preparation.
Background technology
The Human Urinary Kallidinogenase extracts purified glycoprotein from the healthy male Urina Hominis, molecular weight is about 54000 dalton, have the blood vessel dilating blood flow increasing, improve sanguimotor effect, and increase the effect that erythrocytic morphotropism and anticoagulant, prolongation recalcification time improve hyperlipidemia in addition.
It is reported that incidence rate that the diabetes patient merges cerebral infarction is 2～4 times of non-diabetic people, its sickness rate obviously raises.The sickness rate of domestic statistics diabetes combined cerebral infraction accounts for 14% of Patients with Cerebral Infarction.
The clinical manifestation of diabetes combined cerebral infraction is various informative, and clinical symptoms can be arranged, and also can show as the silent cerebral infarction.The diabetes combined cerebral infraction patient is heavier than non-diabetic patients with cerebral infarction clinical symptoms, and neurologic impairment is more, and dysarthria sees that the disturbance of consciousness incidence rate is higher more, easily concurrent infection.Infarction patient the 36h state of an illness after the morbidity still the progress (advancing stroke) patient in, diabetic occupies the majority, and the acute myocardial infarction (AMI) that occurs together after acute apoplexy easily.It is also more common that diabetes merge the silent cerebral infarction, because of the general no clear and definite focal neurological signs of silent cerebral infarction, general symptom such as headache, giddy, hypophrenia is only arranged, only be expert at and confirm to have cerebral infarction when head CT or MRI check, or have location sign patient's head CT or MRI to find to have the infarction kitchen range that can't explain its symptom and sign, clinical easily out in the cold.Therefore, clinically, diabetes combined cerebral infraction is big than non-diabetic cerebral infarction treatment difficulty, and cure rate is low.
It is slower that diabetes combined cerebral infraction recovers, the relapse rate height, and prognosis is poorer, and sequela is many, and disability rate and mortality rate also obviously raise.
The inventor carries out the clinical research test and finds that the Human Urinary Kallidinogenase is remarkable especially to the therapeutic effect of diabetes combined cerebral infraction.
Summary of the invention
The purpose of this invention is to provide the Human Urinary Kallidinogenase and be used to prepare the purposes that treats and/or prevents the diabetes combined cerebral infraction medicine, promptly the Human Urinary Kallidinogenase is used to prepare the pharmaceutical composition that treats and/or prevents diabetes combined cerebral infraction.
The Human Urinary Kallidinogenase has the obvious treatment effect to diabetes combined cerebral infraction among the present invention, generally use with the form of pharmaceutical composition, this compositions contains the Human Urinary Kallidinogenase and the pharmaceutically acceptable auxiliaries as active component for the treatment of effective dose, active component and pharmaceutic adjuvant part by weight are 1: 1～1: 15000, and wherein preferred proportion is 1: 1～1: 2500.The main dosage form of this compositions comprises lyophilized injectable powder and injection liquor, usually with the intravenous injection administration.
Through Human Urinary Kallidinogenase's compositions of intravenous administration, generally be solid sterilization composition form, i.e. lyophilized injectable powder.These compositionss can also contain a kind of or its any mixture in pharmaceutic adjuvant, particularly mannitol, dextran, gelatin hydrolysate, sodium citrate, glycine or the Polyethylene Glycol etc.Be dissolved in use in sterilized water for injection or other injection sterile medium.
Human Urinary Kallidinogenase's compositions through intravenous administration also can be the aqueous solution form, promptly injects liquor.Compositions can also contain a kind of or its any mixture in pharmaceutic adjuvant, particularly mannitol, sodium chloride, glucose or the Polyethylene Glycol etc.
Use the dosage of Human Urinary Kallidinogenase's combination treatment diabetes cerebral infarction and decide according to the order of severity, the treatment time of the state of an illness, the general each 0.1-0.2 of intravenous administration ten thousand units, every day, administration was 1-2 time.
Specific embodiment
Embodiment 1 Human Urinary Kallidinogenase is to diabetes combined cerebral infraction patient's treatment
Experimental subject and grouping: clinical picked at random morbidity was divided into treatment group and matched group with interior Patients with Cerebral Infarction 646 examples in 48 hours.The treatment group selects for use the Human Urinary Kallidinogenase to treat, and matched group gives the troxerutin conventional therapy.Non-diabetic Patients with Cerebral Infarction 532 examples (matched group 149 examples, 383 examples are organized in treatment) wherein, diabetes combined cerebral infraction patient 114 examples (matched group 32 examples, 82 examples are organized in treatment)
Analysis project: before patient's medication and the function of nervous system after the medication change, adopt European apoplexy standards of grading (EuropeanStroke Scale (ESS)).Be 21 days the course of treatment.
Curative effect index: judge curative effect to increase the branch rate, computational methods are as follows:
Increase the branch rate be divided into level Four judge curative effect (be almost recovered and marked improvement as effective), classification is as follows:
A. be almost recovered: increase branch rate 86-100%
B. marked improvement: increase branch rate 46-85%
C. progressive: as to increase branch rate 16-45%
D. invalid: as to increase branch rate＜16%
Result: ESS increases branch rate ratio (%) and reaches and be almost recovered and significantly to improve (ESS increases the branch ratio) ratio be effective percentage, and two groups of ESS increase the branch rate and relatively see Table 1.
Table 1 ESS increases the branch rate relatively
Show with the analysis of Cochran-Mantel-Haenszel statistic: the diabetes combined cerebral infraction patient is to more remarkable (P＜0.0001 of non-diabetic Patients with Cerebral Infarction difference, table 1), show that the Human Urinary Kallidinogenase obviously is better than non-diabetic cerebral infarction group to the curative effect of diabetes combined cerebral infraction group.
Embodiment 2 Human Urinary Kallidinogenases are to the rheol influence of diabetes combined cerebral infraction blood samples of patients
Case is selected: diabetes combined cerebral infraction patient 95 examples (be divided into matched group 44 examples at random, 51 examples are organized in treatment), non-diabetic Patients with Cerebral Infarction 92 examples (be divided into matched group 42 examples at random, 50 examples are organized in treatment).Two groups of patient ages, sex, diseased region and neurological deficits score differences do not have significance (P＞0.05), have comparability.
Experimental technique: matched group gives the troxerutin conventional therapy, and the treatment group gives the urinary kallidinogenase treatment, and be 7 days the course of treatment.
Experimental index: each organize the patient before treatment and the course of treatment when finishing each blood drawing once, mensuration blood rheology parameter such as whole blood viscosity, blood plasma viscosity and fibrinogenic situation of change.
The result: the result of blood rheology parameter relatively sees Table 2 before and after each group treatment.
The comparison of hemorheology index before and after table 2 treatment
Annotate:
*Relatively preceding with treatment, P＜0.01; # and matched group compare, P＜0.01.
Analyze with the Cochran-Mantel-Haenszel statistic; the hemorheology of diabetes combined cerebral infraction group improves degree and obviously is better than non-diabetic cerebral infarction group (P＜0.0001; table 2; illustrate that the Human Urinary Kallidinogenase can significantly improve the hypercoagulability of diabetes combined cerebral infraction blood samples of patients rheology and blood, thereby play the effect that improves cerebral blood circulation and protection brain cell.
Claims (8)
1. the Human Urinary Kallidinogenase is used to prepare the purposes that treats and/or prevents the diabetes combined cerebral infraction medicine.
2. purposes according to claim 1, wherein said medicine contain as the Human Urinary Kallidinogenase of active component and pharmaceutically acceptable auxiliaries, and Human Urinary Kallidinogenase and pharmaceutic adjuvant part by weight are 1: 1～1: 15000.
3. purposes according to claim 2, wherein Human Urinary Kallidinogenase and pharmaceutic adjuvant part by weight are 1: 1～1: 2500.
4. purposes according to claim 3, wherein said medicine is a lyophilized injectable powder.
5. purposes according to claim 4, wherein said pharmaceutic adjuvant are selected from a kind of or its any mixture in mannitol, dextran, gelatin hydrolysate, sodium citrate, glycine or the Polyethylene Glycol.
6. purposes according to claim 3, wherein said medicine are the injection liquors.
7. purposes according to claim 6, wherein said pharmaceutic adjuvant are selected from a kind of or its any mixture in mannitol, sodium chloride, glucose or the Polyethylene Glycol.
8. according to claim 5 or 7 described purposes, the dosage of wherein said medicine is administration every day 1-2 time, each 0.1-0.2 ten thousand units.
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| CNB2006101279563A CN100388950C (en) | 2006-09-05 | 2006-09-05 | Application of human urokinase-type peptidase in preparing medicine for treating diabetes combined cerebral infraction |
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| CNB2006101279563A CN100388950C (en) | 2006-09-05 | 2006-09-05 | Application of human urokinase-type peptidase in preparing medicine for treating diabetes combined cerebral infraction |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101024073A (en) * | 2007-04-16 | 2007-08-29 | 广东天普生化医药股份有限公司 | Use of humanbody kinino genase in preparing medicine for treating and preventing hypertension and cerebral infraction |
| CN101134105B (en) * | 2007-07-02 | 2011-04-20 | 广东天普生化医药股份有限公司 | Pharmaceutical composition containing recombination human pancreatic kininogenase for treating and/or preventing cerebral infarction |
| CN107802827B (en) * | 2017-11-29 | 2019-01-22 | 广东天普生化医药股份有限公司 | A kind of recombination kallikrein freeze-dried powder preparation |
| CN108969758B (en) * | 2018-09-07 | 2020-03-24 | 广东天普生化医药股份有限公司 | Application of human urinary kallidinogenase in preparing medicine for treating thromboangiitis obliterans |
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| CN1403156A (en) * | 2002-05-13 | 2003-03-19 | 广东天普生化医药股份有限公司 | Application of human urokininogenase in preparing medicine for preventing and treating cerebral infraction |
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| CN1403156A (en) * | 2002-05-13 | 2003-03-19 | 广东天普生化医药股份有限公司 | Application of human urokininogenase in preparing medicine for preventing and treating cerebral infraction |
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