Application of terazosin and dextroborneol in preparation of medicine for treating cerebral apoplexy

Abstract

The invention belongs to the technical field of biological medicines, and relates to application of terazosin and dextroborneol in preparation of a medicine for treating cerebral apoplexy. Researches show that the combined use of terazosin and dextrocamphol has a synergistic effect of improving the effect of treating the cerebral apoplexy, so that the neurological defect symptom can be remarkably improved, the brain deficiency rate can be remarkably reduced, and a good cerebral apoplexy treatment effect is reflected, so that the terazosin and dextrocamphol can be used as a medicine for treating the cerebral apoplexy.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine and relates to the application of terazosin and dextroborneol in preparing a medicine for treating cerebral stroke. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Stroke is an acute cerebrovascular disease characterized by high morbidity, high disability and high mortality. The main type of stroke is ischemic stroke, which accounts for about 80% of the total number of strokes. The treatment goals of stroke are to restore cerebral blood flow, protect neurons, reduce brain damage, and improve neurological deficits. At present, the treatment drugs for stroke mainly include thrombolytic drugs, neuroprotectants, antiplatelet drugs, anticoagulants, etc. Although the research on the treatment of stroke has made certain progress, it still faces many challenges. Therefore, there is still a need to provide new drugs for the treatment of stroke. Summary of the invention

[0004] In order to overcome the deficiencies of the prior art, the object of the present invention is to provide an application of terazosin and dextroborneol in the preparation of a drug for treating stroke. The combined use of terazosin and dextroborneol has a synergistic effect in improving the effect of treating stroke, thereby being able to be used as a drug for treating stroke.

[0005] In order to achieve the above object, the technical solution of the present invention is: First, the application of terazosin and dextroborneol in the preparation of drugs for treating stroke.

[0006] The drug described in the present invention can be a drug product, for example, terazosin and dextroborneol are made into a drug product, and when the drug is administered to a subject or a patient, only the drug product containing both terazosin and dextroborneol is administered; it can also be two drug products used in combination, for example, terazosin and dextroborneol are made into two drug products respectively, and when the drug is administered to a subject or a patient, the two drug products containing terazosin and dextroborneol respectively are administered in combination or after mixing, so as to achieve the purpose of administering terazosin and dextroborneol in combination.

[0007] The present invention experiments found that the combined use of terazosin and dextroborneol has a synergistic effect of improving the effect of treating stroke. The combined use of terazosin and dextroborneol in the present invention can ensure that blood pressure is maintained at a relatively normal level, thereby alleviating the problem of blood pressure drop caused by the use of terazosin in stroke.

[0008] When the present invention adopts terazosin and dextroborneol to prepare a drug for treating stroke, terazosin and dextroborneol are both in the dosage of conventional clinical medication, for example, the dosage of terazosin can be 0.01-10 mg / day, and the dosage of dextroborneol can be 1-40 mg / day. In some embodiments, the mass ratio of terazosin to dextroborneol is 1:1-1:9. Studies have shown that the effect under this ratio is more obvious.

[0009] The mass ratio of terazosin to borax can be 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, etc. or the range between any two ratios thereof. In some embodiments, the mass ratio of terazosin to borax is 1:2~1:7.

[0010] In some embodiments, the mass ratio of terazosin to borax is 1:2.5 to 1:6.5.

[0011] In some embodiments, the mass ratio of terazosin to borax is 1:5.5 to 1:6.5.

[0012] In some embodiments, the mass ratio of terazosin to borneol is 1:6.

[0013] In some embodiments, the dosage of the drug is: calculated as terazosin, 0.5-10 mg / day, preferably 0.5-5 mg / day, and more preferably 0.5-2 mg / day.

[0014] In some embodiments, the dosage of the drug is: 2-10 mg / day, calculated as dextroborneol.

[0015] In some embodiments, the terazosin used in the medicament is terazosin or a pharmaceutically acceptable salt thereof.

[0016] In a second aspect, a pharmaceutical composition comprises terazosin or a pharmaceutically acceptable salt thereof and borneol; wherein the mass ratio of terazosin or a pharmaceutically acceptable salt thereof to borneol is 1:1 to 1:9 based on terazosin.

[0017] The mass ratio of terazosin to borax can be 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, etc. or the range between any two ratios thereof. In some embodiments, the mass ratio of terazosin to borax is 1:2~1:7.

[0018] In some embodiments, the mass ratio of terazosin to borax is 1:2.5 to 1:6.5.

[0019] In some embodiments, the mass ratio of terazosin to borax is 1:5.5 to 1:6.5.

[0020] In some embodiments, the mass ratio of terazosin to borneol is 1:6.

[0021] In some embodiments, the dosage of the pharmaceutical composition is: 0.5-10 mg / day, preferably 0.5-5 mg / day, and more preferably 0.5-2 mg / day, calculated as terazosin.

[0022] In some embodiments, the dosage of the pharmaceutical composition is: 2-10 mg / day, calculated as dextroborneol.

[0023] In some embodiments, pharmaceutical excipients are also included. Specifically, the pharmaceutical excipients can be pharmaceutical carriers and / or excipients. The pharmaceutical carrier can be glycerol, ion exchangers, polyacrylates, beeswax, sorbitol, potassium sorbate, sodium carboxymethyl cellulose, aluminum stearate, aluminum oxide, serum protein, polyvinyl pyrrolidone, polyethylene glycol, lecithin, physiological saline, buffer solution, etc. The excipient can be a binder, a filler, a disintegrant, a pH regulator, an antioxidant, a preservative, etc.

[0024] In some embodiments, the dosage form can be tablets, capsules, powders, solutions, suspensions, emulsions, granules, dripping pills, pills, etc. The tablets of the present invention can be oral tablets according to the route of administration or function, such as ordinary tablets, coated tablets, effervescent tablets, dispersible tablets, sustained-release tablets, controlled-release tablets, etc.

[0025] The pharmaceutically acceptable salts described in the present invention may be inorganic salts, such as hydrochlorides, sulfates, nitrates, phosphates, etc.; or may be organic salts, such as acetates, propionates, lactates, maleates, fumarates, etc.

[0026] A third aspect provides a use of the above-mentioned pharmaceutical composition in the preparation of a drug for treating cerebral stroke.

[0027] The drugs or medicines described in the present invention are used to treat stroke and its complications, and the complications of stroke include nervous system complications (such as cerebral edema, epilepsy, impaired consciousness), respiratory system complications (such as respiratory failure, etc.), cardiovascular system complications (such as arrhythmia, myocardial infarction, etc.), digestive system complications (such as stress ulcers, etc.), urinary system complications (such as urinary tract infection, urinary incontinence, etc.), musculoskeletal system complications (such as joint contracture, deep vein thrombosis, etc.), psychological and psychiatric complications (such as depression and anxiety, cognitive dysfunction, etc.), etc.

[0028] The beneficial effects of the present invention are: The present invention uses the middle cerebral artery occlusion cerebral ischemia-reperfusion model as an animal experimental model for studying cerebral stroke. Experiments show that the combined administration of terazosin and dextroborneol can not only significantly improve the symptoms of neurological deficits, but also significantly reduce the brain loss rate, reflecting a good therapeutic effect of cerebral stroke; therefore, terazosin combined with dextroborneol can be used as a drug for treating cerebral stroke. The combined administration of terazosin and dextroborneol can alleviate the problem of blood pressure drop when terazosin is used in stroke. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0030] Figure 1 The Bederson score diagram in Example 1 of the present invention, the data are expressed as mean ± standard deviation (Mean ± SD); Figure 2 This is a graph showing the NSS score results of animals one day after drug intervention in Example 1 of the present invention. The data are expressed as Mean±SD, ** indicates P<0.01 compared with the animals in the model control group, *** indicates P<0.001 compared with the animals in the model control group, and **** indicates P<0.0001 compared with the animals in the model control group; Figure 3 This is a graph showing the NSS score results of animals 7 days after drug intervention in Example 1 of the present invention. The data are expressed as Mean±SD, * indicates P<0.05 compared with the animals in the model control group, ** indicates P<0.01 compared with the animals in the model control group, and **** indicates P<0.0001 compared with the animals in the model control group; Figure 4 This is a graph showing the NSS score results of animals 14 days after drug intervention in Example 1 of the present invention. The data are expressed as Mean±SD, and ** indicates P<0.01 compared with the animals in the model control group; Figure 5 This is a graph showing the NSS score results of animals 21 days after drug intervention in Example 1 of the present invention. The data are expressed as Mean±SD, and * indicates P<0.05 compared with the animals in the model control group; Figure 6 This is a graph showing the NSS score results of animals 28 days after drug intervention in Example 1 of the present invention. The data are expressed as Mean±SD, and * indicates P<0.05 compared with the animals in the model control group; Figure 7 This is a trend chart of animal NSS changes after drug intervention in Example 1 of the present invention; Figure 8This is a graph showing the results of the fatigue rotarod test of rats in Example 1 of the present invention 7 days after drug intervention, and the data are expressed as Mean±SD, * indicates P<0.05 compared with the animals in the model control group, and ** indicates P<0.01 compared with the animals in the model control group; Fig. 9 This is a graph showing the results of the fatigue rotarod test of rats in Example 1 of the present invention 14 days after drug intervention. The data are expressed as Mean±SD, and * indicates P<0.05 compared with the model control group animals; Fig.10 This is a graph showing the results of the fatigue rotarod test of rats in Example 1 of the present invention 28 days after drug intervention. The data are expressed as Mean±SD, and * indicates P<0.05 compared with the model control group animals; Fig.11 This is a trend diagram of the fatigue rotarod of rats after drug intervention in Example 1 of the present invention, and the data are expressed as Mean±SD; Fig.12 This is a graph showing the loss rate of rats in Example 1 of the present invention 29 days after drug intervention, brain loss rate; * indicates P<0.05 compared with the model control group animals; Fig.13 The graph of the arterial systolic blood pressure (SBP) of the rats in Example 1 of the present invention, data Mean±SD, where * indicates P<0.05 compared with the model group; Fig.14 The diastolic blood pressure (DBP) curve of the rats in Example 1 of the present invention is shown in Mean±SD, where * indicates P<0.05 compared with the model group; Fig.15 This is a graph of mean arterial pressure (MAP) of rats in Example 1 of the present invention. The data are expressed as Mean±SD, where * indicates P<0.05 compared with the model group, and ** indicates P<0.01 compared with the model group. DETAILED DESCRIPTION

[0031] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0032] Example 1 Animals: SPF-grade SD rats, male, 263.0 ~235.4 g, purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd. Housing environment: temperature: 20.0~26.0 ℃; humidity: 40.0~70.0%; light: ≥200 Lux (12h / 12h light and dark alternation); ventilation: >8~10 times / h, fresh air.

[0033] 1. Experimental methods: The contents and procedures related to animal experiments involved in this example are in compliance with the relevant laws and regulations on the use and management of experimental animals and the relevant regulations of the Institutional Animal Care and Use Committee (IACUC) of this institution. The number of animals, experimental design and animal handling have been approved by IACUC and are strictly implemented in accordance with the contents reported to IACUC.

[0034] 1. Construct a cerebral ischemia-reperfusion model of middle cerebral artery occlusion (MCAO). The modeling process is as follows: (1) Anesthesia: Preparation of anesthetic stock solution: Take 1 box of Shutai 50 (250 mg lyophilized powder; 5 mL solvent), transfer all 5 mL solvent into the lyophilized powder, and shake gently until completely dissolved.

[0035] Mix the dissolved Shutai 50 and Suminxin II injection in a ratio of 10:1 and store at 2-8°C away from light.

[0036] (2) Anesthetic dose and method for rats: The prepared anesthetic stock solution was diluted 10 times with normal saline and injected intraperitoneally at 3.75 mL / kg for anesthesia. Erythromycin ointment was applied to the eyes to protect the cornea. (100,000 units of penicillin were injected intraperitoneally half an hour before the operation).

[0037] (3) Fixation: After anesthesia induction, the animals were transferred to the operating table and the eyelid reflex and pain response of the rats were observed. The surgery could be started only after the eyelid reflex and the pain response of the limbs and tail disappeared.

[0038] (4) Cerebral ischemia-reperfusion surgery: A. Separation and exposure of blood vessels: After the surgical area is prepared, the rat skin is cut with ophthalmic scissors along the midline, with a length of about 2 cm. Through the right paracervical approach, the micro forceps are used to bluntly separate and retract the muscle tissue on the right side of the neck to expose the right common carotid artery (CCA), and then the common carotid artery is separated upward to continue to expose the external carotid artery (ECA) and internal carotid artery (ICA); B. Ligate the ECA and temporarily clamp the ICA; thread the proximal and distal ends of the CCA, tie the proximal end tightly, tie a loose knot at the distal end for later use, and cut a small opening between the two threads; C. Pushing the suture plug: insert the suture plug through the incision of CCA, and then slowly and gently push it into the internal carotid artery, pause at the artery clamp of ICA, further tighten the pre-ligated wire (to avoid excessive bleeding when pushing the suture plug), then remove the artery clamp that blocks the blood flow of ICA, and immediately push the suture plug into ICA until it enters the skull; D. Fix the suture and suture the incision: When the suture is inserted to a depth of about 18 mm from the bifurcation of the common carotid artery, if there is a slight resistance, it means that the head of the suture has entered the anterior cerebral artery (ACA) and the side wall of the suture has blocked the opening of the middle cerebral artery. At this time, stop inserting and record the time. Close the incision after observing no active bleeding. E. Cerebral reperfusion: The ischemic rats were placed in an incubator after surgery to maintain body temperature at 37 ± 0.5°C. After 90 minutes of ischemia, the suture was gently pulled back into the common carotid artery under anesthesia to achieve middle cerebral artery reperfusion. F. Disinfect the incision with iodine.

[0039] After modeling, the rats were randomly divided into groups. The treatment regimens of each group are shown in Table 1.

[0040] Table 1 Treatment options for each group

[0041] Note: Terazosin analog (CO.1) has similar chemical structure and activity to terazosin, and its structural formula is as follows:

[0042] 2. Behavioral Evaluation of Rats (1) Bederson score: 1-2 h after reperfusion (when the animals are awake, used to evaluate whether the ischemia of rats is successful); Bederson scoring criteria are shown in Table 2.

[0043] Table 2 Bederson scoring standard table

[0044] (2) NSS score of rats: The first NSS score was scored 24 hours after surgery and once a week after modeling, for a total of 5 scores. The animals were tested for motor function, sensory testing, balance testing, and reflex and abnormal movement testing. For details, please refer to the rat neurological function score table 3 (NSS).

[0045] Table 3 Neurological Score (NSS) of rats

[0046] (3) Fatigue Rotating Rod: The rat fatigue rotarod instrument was used for testing at 1, 2, and 4 weeks after surgery. The rats were placed on the rotating rod and the uniform acceleration test mode was used. The speed was uniformly accelerated from 5 r / min to 30 r / min within 200 seconds. Four rats were tested at the same time each time, with one in each compartment. The time from the start of the rotarod to the fall of the rotarod was recorded. The rest period between each test was not less than 1 hour, and the test was repeated 3 times in a row.

[0047] 3. Determination of brain loss rate: After the animals were anesthetized, the brain was removed, the cerebellum and olfactory bulbs were removed, and the brain was cut into two halves along the midbrain suture with a blade. The liquid on the brain surface and the infarct area was absorbed with absorbent paper, and the weight of the two halves of the brain was weighed.

[0048] The brain loss rate of each dose group was counted to calculate the efficacy of each drug treatment group. The brain loss rate calculation formula is as follows: .

[0049] 4. Blood pressure measurement: The non-invasive rat tail artery blood pressure measurement and analysis system was used to monitor the arterial pressure of rats at 6 time points: 1 day before surgery, 30 min after immediate administration, 1 day, 7 days, 14 days, and 28 days after surgery. The blood pressure was measured twice and the average value was taken.

[0050] 5. Statistical analysis: The measurement indicators are expressed as mean ± standard deviation (X ± SD). When the sample size is less than 3, the data of this group will not be included in the statistical comparison.

[0051] The data were entered and statistically analyzed using Excel and GraphPad Prism 8.0 software. The measurement indicators were first tested for homogeneity of variance using the LEVENE test. When the variances were homogeneous (P>0.05), the results of the variance analysis could be directly cited to determine whether the overall differences were statistically significant. When the overall differences were statistically significant (P<0.05), the Dunnett-t test was used to compare the differences between the groups. When the overall differences were not statistically significant (P≥0.05), the statistical analysis ended. When the LEVENE test for homogeneity of variance showed that the variances were not homogeneous (P≤0.05), a nonparametric test (Kruskal-Wallis H test) was used. When the Kruskal-Wallis H test showed that the overall differences were statistically significant (P<0.05), the Mann-Whitney U test was used to compare the differences between the groups. When the Kruskal-Wallis H test showed that the overall differences were statistically significant (P≥0.05), the statistical analysis ended.

[0052] 3. Test results 1. Behavioral evaluation of rats: (1) Bederson score: The rats were scored with Bederson scores 1-2 hours after reperfusion to determine the ischemic condition of the animals. Rats with scores below 2 were excluded. The Bederson scores of the sham-operated group were 0, and the Bederson scores of the model control group and the drug-treated groups were 2-3 points, indicating that the rats that underwent surgical modeling had successful ischemia. The Bederson score results of the experimental rats are shown in Figure 1 .

[0053] (2) NSS score: The neurological function damage of all rats was evaluated by NSS score at 24h, 7 days, 14 days, 21 days and 28 days after modeling. The NSS score of rats is shown in Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 The NSS score of the animals in the sham operation group was 0 throughout the entire experimental period.

[0054] Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 The results showed that the NSS scores of the model control group and the animals in each drug group were the highest on the first day after surgery. As the drug intervention time prolonged, the NSS scores gradually decreased, indicating that the neurological function gradually recovered with the drug intervention. The MCAO model of rats has a certain degree of self-healing. As the treatment time prolonged, the NSS scores of each dosage group gradually decreased, and the gap gradually narrowed.

[0055] After 1 day of drug intervention, each drug group had an improvement effect on the neurobehavioral damage of postoperative rats, which were all statistically significant. Among them, the positive control group, dextroborneol, terazosin group and terazosin analogs + dextroborneol p < 0.01, terazosin + dextroborneol (1:3) group and terazosin + dextroborneol (1:6) group p < 0.001, terazosin + dextroborneol (1:9) group p < 0.0001; after 7 days of drug intervention, the neurobehavioral damage of rats was further improved, among which the terazosin group p was less than 0.05, the terazosin + dextroborneol (1:3) group and terazosin + dextroborneol (1:6) group p < 0.0001, especially The p of terazosin + dextroborneol (1:9) group was <0.01; after 14 days of drug intervention, the p of terazosin + dextroborneol (1:3) group, terazosin + dextroborneol (1:6) group and terazosin + dextroborneol (1:9) group were <0.01; after 21 days of drug intervention, the p of positive drug group, terazosin + dextroborneol (1:6) group and terazosin + dextroborneol (1:9) group were <0.05; after 28 days of drug intervention, the p of terazosin + dextroborneol (1:6) group and terazosin + dextroborneol (1:9) group were <0.05; with the drug intervention, the improvement effect of terazosin + dextroborneol in each treatment group on neurological function was better than that of positive drug.

[0056] Judging from the NSS score results during the entire drug intervention period, as the observation time prolonged, the neurological functions of the animals in the model control group and each drug-treated group were effectively restored. However, after the combined intervention of terazosin and dextroborneol, the neurological functions of the animals were effectively restored in a shorter time, that is, the combination of terazosin and dextroborneol could accelerate the recovery of the neurological functions of the animals and had a synergistic effect.

[0057] (3) Assessment of functional motor ability: The functional motor ability of experimental rats was evaluated by the fatigue rotarod test (Rotarod test). The test results of the fatigue rotarod test are shown in Figure 8 , Fig. 9 , Fig.10 , Fig.11 .

[0058] Fatigue rotarod test was performed on the 7th, 14th and 28th day after surgery. The results showed that there was a significant difference in the latent fall time between the model group and the sham operation group, indicating that the model was successfully established. Compared with the model control group, the latent fall time of other drug groups was prolonged on the 7th, 14th and 28th days after surgery. On the 7th day, the latent fall time of the positive drug control group, terazosin group, terazosin + dextroborneol (1:3) group, terazosin + dextroborneol (1:6) group and terazosin + dextroborneol (1:9) group was significantly different from that of the model group; on the 14th day, the latent fall time of the positive drug control group, terazosin + dextroborneol (1:3) group, terazosin + dextroborneol (1:6) group and terazosin + dextroborneol (1:9) group was significantly different from that of the model group; on the 28th day, the latent fall time of the terazosin + dextroborneol (1:3) group, terazosin + dextroborneol (1:6) group and terazosin + dextroborneol (1:9) group was significantly different from that of the model group.

[0059] Judging from the results of the fatigue rotarod test, the combined administration of terazosin and dextroborneol improved the state of motor nerve dysfunction in the model and improved the functional movement parameters of the model animals.

[0060] 2. Brain loss rate detection On the 29th day after surgery, the brains were taken out and weighed to calculate the brain loss rate of each dose group. The brain loss rate of animals is shown in Fig.12 .

[0061] Fig.12 The brain loss rates in the sham operation group and the model control group were -0.39%±1.28% and 24.49%±6.27%, respectively. The brain loss rate in the model control group was significantly increased compared with that in the sham operation group (P<0.0001).

[0062] The brain loss rate of each drug-treated group showed a significant downward trend compared with the model control group. Compared with the animals in the model control group, the brain loss rates of the positive drug control group, terazosin and terazosin combined with dextroborneol were significantly reduced (P<0.05). The brain loss rate of each dose group of terazosin hydrochloride combined with dextroborneol was more significantly reduced than that of the positive drug group, terazosin hydrochloride group and dextroborneol group, and had the same synergistic effect.

[0063] 3. Systolic blood pressure test results Blood pressure was tested on rats in each group at 30 min after immediate administration, 1 day, 7 days, 14 days and 28 days after surgery. Fig.13 shown.

[0064] Fig.13In the study, the arterial systolic blood pressure of the model control group decreased significantly after surgery, but recovered to the same level as the sham operation group 1 day after surgery. The arterial systolic blood pressure of the terazosin group was lower from 1 day to 28 days after surgery, and there were significant differences compared with the model control group 1 day, 7 days and 14 days after surgery. This shows that the use of terazosin alone has the side effect of lowering systolic blood pressure. The arterial systolic blood pressure of each dose group of terazosin combined with dextroborneol was not much different from that of the model control group and the sham operation group, indicating that the combined use of terazosin and dextroborneol can alleviate the side effect of hypotension caused by the use of terazosin alone.

[0065] 3. Diastolic blood pressure test results Blood pressure was tested on rats in each group at 30 min after immediate administration, 1 day, 7 days, 14 days and 28 days after surgery. Fig.14 shown.

[0066] Fig.14 In the model control group, the arterial diastolic pressure decreased significantly after surgery, but recovered to the same level as the sham operation group 1 day after surgery. The average diastolic pressure of the terazosin group was lower from 1 day to 28 days after surgery, and there were significant differences between the 7th, 14th and 28th days after surgery and the model control group, indicating that the use of terazosin alone has the side effect of lowering diastolic pressure. The arterial diastolic pressure of each dose group of terazosin + dextroborneol was not much different from that of the model control group and the sham operation group, indicating that the combination of terazosin and dextroborneol can alleviate the hypotensive effect caused by the use of terazosin alone.

[0067] 3. Mean arterial pressure (MAP=DBP+1 / 3(SBP-DBP)) test results The test time was 30 minutes after immediate administration, 1 day, 7 days, 14 days and 28 days after surgery. The test results were as follows: Fig.15 shown.

[0068] Fig.15 In the model control group, the mean arterial pressure decreased significantly after surgery, but recovered to the same level as the sham operation group 1 day after surgery. The mean arterial pressure of the terazosin group was lower from 1 day to 28 days after surgery, and there were significant differences between the 7th, 14th and 28th days after surgery and the model control group, indicating that terazosin alone has the side effect of lowering blood pressure; the mean arterial pressure of each dose group of terazosin + dextroborneol was not much different from that of the model control group and the sham operation group, indicating that the combination of terazosin and dextroborneol can alleviate the side effect of hypotension caused by the use of terazosin alone.

[0069] Example 2 A tablet preparation of terazosin combined with dextroborneol, the mass ratio of terazosin hydrochloride (calculated as terazosin): dextroborneol is 1:3. The prescription is shown in Table 4.

[0070] Table 4 Prescription 1

[0071] The preparation method is as follows: the raw materials and auxiliary materials are respectively passed through a 60-mesh sieve, and then the prescribed amount of microcrystalline cellulose, mannitol, silicon dioxide and magnesium stearate are added into a mixing barrel, and finally terazosin hydrochloride and dextroborneol are added. The mixer speed is set to 15 rpm and mixed for 40 minutes. The tableting mold is 7 mm shallow arc punch, the tablet thickness is controlled to be about 2.7 mm, and the hardness is greater than ≥3.0 kg tableting.

[0072] Example 3 A tablet preparation of terazosin combined with dextroborneol, the mass ratio of terazosin hydrochloride (calculated as terazosin): dextroborneol is 1:6. The prescription is shown in Table 5.

[0073] Table 5 Prescription 2

[0074] Note: The preparation method is the same as Example 2.

[0075] Example 4 A tablet preparation of terazosin combined with dextroborneol, the mass ratio of terazosin hydrochloride (calculated as terazosin): dextroborneol is 1:9. The prescription is shown in Table 6.

[0076] Table 6 Prescription 3

[0077] Note: The preparation method is the same as Example 2.

[0078] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. Application of terazosin and dextroborneol in the preparation of drugs for treating stroke.

2. The use according to claim 1, characterized in that: The mass ratio of terazosin to dextroborneol is 1:1 to 1:9; Or, the mass ratio of terazosin to dextroborneol is 1:2-1:7; Or, the mass ratio of terazosin to dextroborneol is 1:2.5-1:6.5; Or, the mass ratio of terazosin to dextroborneol is 1:5.5-1:6.5; Or, the mass ratio of terazosin to borneol is 1:

6.

3. The use according to claim 1, characterized in that: The dosage of the drug is: 0.5-5 mg / day based on terazosin; Alternatively, the dosage of the drug is: 2-10 mg / day, calculated as dextroborneol.

4. The use according to claim 1, characterized in that: The terazosin used in the medicine is terazosin or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition, characterized in that: It comprises terazosin or a pharmaceutically acceptable salt thereof and borneol; wherein, the mass ratio of terazosin or a pharmaceutically acceptable salt thereof to borneol is 1:1 to 1:9 based on terazosin.

6. The pharmaceutical composition according to claim 5, characterized in that: The mass ratio of terazosin to dextroborneol is 1:2~1:7; Or, the mass ratio of terazosin to dextroborneol is 1:2.5-1:6.5; Or, the mass ratio of terazosin to dextroborneol is 1:5.5-1:6.5; Or, the mass ratio of terazosin to borneol is 1:

6.

7. The pharmaceutical composition according to claim 5, characterized in that: The dosage of the pharmaceutical composition is: 0.5-5 mg / day in terms of terazosin; Alternatively, the dosage of the pharmaceutical composition is: 2-10 mg / day, calculated as dextroborneol.

8. The pharmaceutical composition according to claim 5, characterized in that: Also includes pharmaceutical excipients.

9. The pharmaceutical composition according to claim 5, characterized in that: The dosage form is tablet, capsule, powder, solution, suspension, emulsion, granule, pellet or pill.

10. Use of the pharmaceutical composition according to any one of claims 5 to 9 in the preparation of a drug for treating cerebral stroke.

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