CN101756967A - Application of methazolamide to preparation of medicaments for preventing and treating acute altitude diseases - Google Patents
Application of methazolamide to preparation of medicaments for preventing and treating acute altitude diseases Download PDFInfo
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- CN101756967A CN101756967A CN201010104645A CN201010104645A CN101756967A CN 101756967 A CN101756967 A CN 101756967A CN 201010104645 A CN201010104645 A CN 201010104645A CN 201010104645 A CN201010104645 A CN 201010104645A CN 101756967 A CN101756967 A CN 101756967A
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- methazolamide
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Abstract
The invention relates to novel use of methazolamide, namely the application of the methazolamide to the preparation of medicaments for preventing and treating acute altitude diseases. The methazolamide can effectively reduce the symptoms of altitude stress, reduce the HR of crowds quickly entering plateau, improve SatO2 of the crowds, and decrease the occurrence of the acute altitude diseases, and the methazolamide has wide application prospect in the preparation of the medicines for preventing and treating the acute altitude diseases.
Description
Technical field
The present invention relates to the new purposes of existing medicine, be specifically related to the application of methazolamide in preparation control acute high altitude sickness medicine.
Background technology
The China plateau is vast in territory, and only the highlands more than 3000 meters accounts for 1/4th of territory total area, mainly is distributed in Tibet, Xinjiang and Qinghai, annual from interiorly to the number on plateau surpass 1,000 ten thousand people/time.Yet the plateau is natural environment badly, has a strong impact on the health that enters the plateau crowd, according to statistics people from Plain enter fast height above sea level more than 3000 meters the area, acute high altitude sickness takes place in 60%-90%, has restricted the highlands development and national economy.Acute high altitude sickness, be that body is entered into highlands (plateau medically refers in the area of height above sea level more than 3000 meters) or occupied the plateau for a long time by the Plain and enters into more high altitude localities, in a few hours, fall ill, headache appears, dizzy, cardiopalmus, uncomfortable in chest, tachypnea, weak, sleep disorder, feeling sick appears in weight person, vomiting, cyanosis, symptom such as oliguria or hematuria, general no special vital sign, common have a hyperpnea, heart rate is accelerated, pale complexion, acra is sent out cold, small number of patients blood pressure mile abnormality, face is or/and edema of the limbs, through at plateau short-term regulation or symptomatic treatment, symptom and sign significantly alleviate or disappear, body can recover normally [Gao Yuqi chief editor, plateau military medicine, Chongqing publishing house (2005): 250-276] rapidly.
Take acetazolamide is the effective ways of a kind of prevention and treatment acute high altitude sickness always, and this medicine is by suppressing the active performance effect of carbonic anhydrase [Gao Yuqi chief editor, plateau military medicine, Chongqing publishing house (2005): 258].The effect of carbonic anhydrase is to promote carbon dioxide and water to be combined into carbonic acid, and the generation of cerebral blood flow increasing amount and minimizing cerebrospinal fluid makes the organism metabolism meta-acid simultaneously, with the alkalemia of antagonism because of the hyperpnea generation.Acetazolamide Ceng Zuowei diuretic and be used for clinical, but when using this medicine, should note following untoward reaction: sleepy, face and numb limbs and tense tendons, for a long time with causing metabolic acidosis and hypokalemia, more serious adverse effects is anaphylaxis and renal calculuss such as agranulocytosis, thereby it is extremely urgent to seek the medicine of the novel light-duty altitude sickness of prophylaxis of acute.
Summary of the invention
The new purposes that the purpose of this invention is to provide a kind of methazolamide, i.e. the application of methazolamide in preparation control acute high altitude sickness medicine, for the clinical prevention acute high altitude sickness increases a kind of new drug, being the clinical use of methazolamide increases a new indication.
The methazolamide chemical name is 5-acetamido-4-methyl isophthalic acid-sulfur-3,4-two pyrolle sulfonamide, and English name: Methazolamide Tablets, molecular formula is C5H8N4O3S2, molecular weight 236.26, structural formula is:
In view of the similar acetazolamide of chemical constitution of methazolamide, many methyl on nitrogen-atoms, therefore, the pharmacological action and the mechanism of action are identical with acetazolamide.But it is stronger by 60% than acetazolamide to suppress the carbonic anhydrase effect, the side effect incidence rate is obviously than little [the Foster TS.Maintenace of previouslycontrolled intraocular pressure patients with glaucoma or ocularhypertension:comparision of four regimens of methazolamide.Glaucoma of acetazolamide, 1989,11:6727].The dosage form of existing methazolamide is a tablet, comprises every 25mg, two kinds of specifications of every 50mg.Be used for primary open angle glaucoma, angle closure glaucoma and some secondary glaucoma, local control undesirable patient's auxiliary treatment, use 25mg, 2 times on the one during the initial medication of one-tenth human oral with the Betimol intraocular pressure.At present, also not this medicine at the application report of preventing and treating the acute mild altitude sickness.
Zoopery shows that methazolamide can effectively prolong the time-to-live under the mice airtight anoxia state, the duration of dehiscing after the sacrificed by decapitation, mouse cardiac muscle anoxia standard tolerance time; Human experimentation shows that this medicine can reduce the incidence rate of acute high altitude sickness symptom effectively, reduces and advances plateau crowd's heart rate fast, improves their blood oxygen saturation, reduces the sickness rate of acute high altitude sickness.
For better explanation the present invention, with zoopery and clinical experiment the effect of methazolamide in control acute high altitude sickness medicine is described below.
Buy Hangzhou Australia and cure the methazolamide sheet that precious miraculous cure industry company limited is produced, every contains methazolamide 25mg.The independent sample T of The data SPSS13.0 carries out statistical analysis and statistical analysis is carried out in X 2 test.
One. zoopery
With reference to the resisting oxygen lack of Research on experimental methods methazolamides such as Hui Jin [Hui Jin etc., octacosanol to the experimentation of mice resisting oxygen lack, southwestern national defence medicine, 2007,17 (2): 143-145].
1. airtight anoxia experiment
Get 20 male mices, be divided into 2 groups at random: 10 of experimental grouies are the liquid of concentration 20mg/mL with normal saline with the methazolamide dilution, and every mice is pressed the dosage lumbar injection of every 10g body weight administration 0.1mL, i.e. mice per kilogram of body weight administration 200mg; 10 of matched groups, every gives placebo-normal saline, and every mice is pressed the dosage lumbar injection of every 10g body weight administration 0.1mL.
After the administration 2 hours, each group mice is put into the wide mouthed bottle (the correction capacity all is filled with water before the wide mouthed bottle use) that fills the 5g sodica calx respectively, 1 every bottle, seal bottleneck with vaseline.According to last breathing is index, the record death time.According to death time basis of calculation tolerance time: T-T1/ (V-BW/0.94) x100.T is standard tolerance time (min/100ml) in the formula, T1 is death time (min), V is port grinding bottle volume (ml), and BW is mice body weight (g), and the result shows that the time-to-live highly significant that gives under the methazolamide processed group mice airtight anoxia state is higher than matched group (p＜0.01) (table 1).
Table 1 methazolamide is to the influence of mice airtight anoxia standard tolerance time
1.P＜0.01 VS. matched group
2. cerebrum ischemia anoxia experiment
Get 18 male mices, be divided into 2 groups at random, 9 every group: experimental group is the liquid of concentration 20mg/mL with normal saline with the methazolamide dilution, and every mice is pressed the dosage lumbar injection of every 10g body weight administration 0.1mL, i.e. mice per kilogram of body weight administration 200mg; Matched group gives placebo-normal saline, and every mice is pressed the dosage lumbar injection of every 10g body weight administration 0.1mL.
After the administration 2 hours, break end fast at mice ears line place with shears, the duration of dehiscing behind the record mice broken end, the result shows that giving methazolamide handles the duration elongated (p＜0.01) (table 2) of dehiscing after the mice sacrificed by decapitation.
Table 2 methazolamide is to the dehisce influence of duration of sacrificed by decapitation mice
1.P＜0.01 VS. matched group
3. myocardial ischemia experiment
Get 20 mices and be divided into administration group and matched group at random, 10 every group.Experimental group is the liquid of concentration 20mg/mL with normal saline with the methazolamide dilution, and every mice is pressed the dosage lumbar injection of every 10g body weight administration 0.1mL, i.e. mice per kilogram of body weight administration 200mg; Matched group gives placebo-normal saline, and every mice is pressed the dosage lumbar injection of every 10g body weight administration 0.1mL.
2h after the last administration, lumbar injection isoprenaline (15mg/kg) is put into the wide mouthed bottle that fills the 5g sodica calx respectively behind the 15min, observe mice asthmoid respiration time started for the first time, and is index with last breathing, the record death time.According to asthmoid respiration time of occurrence and death time calculating myocardium anoxia standard tolerance time, the result shows that giving the methazolamide processing mice time highly significant that asthmoid respiration occurs is later than matched group, and prompting administration group mouse cardiac muscle anoxia standard tolerance time prolongs (p＜0.01) (table 3).
Table 3 methazolamide is to the influence of mouse cardiac muscle anoxia standard tolerance time
①p＜0.01
Two. human experimentation
Enter height above sea level 4200m young male (first day lodging 3960m in the way fast from height above sea level 1400m by bus, second day lodging 4220m place, the 3rd day lodging 4460m place, the 4th day 4200m place that reaches the destination), setting out, it is oral a few days ago to begin to give methazolamide, each 1 (25mg), every day 2 times, successive administration 7 days; Matched group is taken placebo-sheet of batter, and every contains flour 25mg, each 1 (25mg), every day 2 times, successive administration 7 days.9 of every nights carry out heart rate (HR), blood oxygen saturation (SatO
2) and acute high altitude reaction symptom marking, add up the sickness rate of each acute high altitude sickness symptom incidence rate and acute high altitude sickness.Found that: significantly be lower than matched group (P＜0.05) at the 2nd day the HR that enters the plateau to the 5th day experimental group; Entering the 1st day the SatO on plateau to the 5th day experimental group
2Be significantly higher than matched group (P＜0.05); Entering the plateau the 3rd day, the acute high altitude sickness sickness rate of experimental group significantly is lower than matched group, the results are shown in Table 4 to table 10.
A situation arises at 3960m place acute high altitude sickness for table 4 the 1st day
| Number | Age (year) | ??SatO 2(％) | HR (inferior/minute) | Headache | Dizzy | Cyanosis | Brothers are numb | The acute high altitude sickness sickness rate | |
| Experimental group | ??29 | ??20.07±1.92 | ??89.76±1.94?? ① | ??80.55±11.06 | ??20.7??％ | ??6.9??％ | ??6.9??％ | ??6.9％ | ??3.45％ |
| Matched group | ??68 | ??19.5±1.29 | ??87.62±2.68 | ??84.35±10.27 | ??5.9％ | ??1.5??％ | ??1.5??％ | ??0％ | ??1.47％ |
1.P＜0.05 VS placebo group;
A situation arises at 4220m place acute high altitude sickness for table 5 the 2nd day
| Number | Age | ??SatO 2(％) | HR (inferior/minute) | Headache | Vomiting | Dizzy | Feel sick | Drowsiness | The acute high altitude sickness sickness rate | |
| Experimental group | ??29 | ??20.07±1.92 | ??87.69±2.21?? ① | ??83.34±9.82?? ① | ??10.3??％ | ??0％ | ??3.45??％ | ??0％ | ??0％ | ??3.45％ |
| Matched group | ??68 | ??19.5±1.29 | ??85.09±3.17 | ??90.44±11.45 | ??26.5??％ | ??1.5??％ | ??5.9??％ | ??1.5??％ | ??1.5??％ | ??10.3％ |
1.P＜0.05 VS placebo group;
A situation arises at 4460m place acute high altitude sickness for table 6 the 3rd day
| Number | Age (year) | ??SatO 2(％) | HR (inferior/minute) | Headache | Dizzy | Vomiting | Breathe hard | Cyanosis | The acute high altitude sickness sickness rate | |
| Experimental group | ??29 | ??20.07±1.92 | ??87.48±2.13?? ① | ??90.14±14.47?? ① | ??27.5??％ | ??6.9??％ | ??3.45??％ | ??0％ | ??0％ | ??3.45％ ① |
| Matched group | ??68 | ??19.5±1.29 | ??84.64±3.62 | ??98.24±13.83 | ??36.7??％ | ??8.8??％ | ??4.4％ | ??8.8％ | ??7.4％ | ??19.12％ |
1.P＜0.05 VS placebo group;
A situation arises at 4200m place acute high altitude sickness for table 7 the 4th day
| Number | Age (year) | ??SatO 2(％) | HR (inferior/minute) | Headache | Dizzy | Breathe hard | Cyanosis | Dizzy | Abdominal distention | The acute high altitude sickness sickness rate | |
| Experimental group | ??29 | ??20.07±1.92 | ??88.62±1.52?? ① | ??91.07±13.31?? ① | ??20.7％ | ??3.45％ | ??3.45％ | ??0％ | ??0％ | ??3.45％ | ??0％ |
| Matched group | ??68 | ??19.5±1.29 | ??86.41±3.10 | ??102.52±13.69 | ??10.3％ | ??1.5％ | ??7.4％ | ??1.5??％ | ??1.5??％ | ??0％ | ??0％ |
1.P＜0.05 VS placebo group;
A situation arises at 4200m place acute high altitude sickness for table 8 the 5th day
| Number | Age (year) | ??SatO 2(％) | HR (inferior/minute) | Brothers are numb | Dizzy | Feel sick | Breathe hard | Cyanosis | Abdominal distention | Nervous | Loss of appetite | The acute high altitude sickness sickness rate | |
| Experimental group | ??2??9 | ??20.07±1.??92 | ??89.14±1.??92 ① | ??90.14±14.??47 ① | ??3.45??％ | ??0％ | ??3.45??％ | ??6.9??％ | ??3.45??％ | ??3.45??％ | ??0％ | ??0％ | ??3.4??5％ |
| Matched group | ??6??8 | ??19.5±1.2??9 | ??87.72±2.??82 | ??85.93±10.??02 | ??0％ | ??2.9??％ | ??0％ | ??7.4??％ | ??0％ | ??2.9％ | ??1.??5??％ | ??5.9??％ | ??4.4??0％ |
1.P＜0.05 VS placebo group;
A situation arises at 4200m place acute high altitude sickness for table 9 the 6th day
| Number | Age (year) | ??SatO 2(％) | HR (inferior/minute) | Insomnia | Dizzy | Breathe hard | Nervous | Loss of appetite | The acute high altitude sickness sickness rate | |
| Experimental group | ??29 | ??20.07±1.92 | ??89.45±1.53 | ??88.86±13.20 | ??0％ | ??3.45％ | ??0％ | ??3.45％ | ??3.45％ | ??3.45％ |
| Matched group | ??68 | ??19.5±1.29 | ??87.97±2.31 | ??90.92±12.07 | ??1.5??％ | ??5.9％ | ??8.9％ | ??1.5％ | ??0％ | ??4.40％ |
A situation arises at 4200m place acute high altitude sickness for table 10 the 7th day
| Number | Age (year) | ??SatO 2(％) | HR (inferior/minute) | Drowsiness | Dizzy | Breathe hard | Nervous | The acute high altitude sickness sickness rate | |
| Experimental group | ??29 | ??20.07±1.92 | ??88.45±1.99 | ??88.86±13.20 | ??0％ | ??0％ | ??0％ | ??0％ | ??0％ |
| Matched group | ??68 | ??19.5±1.29 | ??88.12±2.49 | ??95.33±12.77 | ??1.5??％ | ??3.0％ | ??4.5％ | ??1.5??％ | ??0％ |
Conclusion: zoopery shows that methazolamide can effectively prolong the time-to-live under the mice airtight anoxia state, the duration of dehiscing after the sacrificed by decapitation, and mouse cardiac muscle anoxia standard tolerance time shows that methazolamide has tangible anti-hypoxia effect.Human experimentation shows that methazolamide can effectively reduce the altitude sickness symptom, reduces radical plateau crowd's HR, improves their SatO
2, reduce the generation of acute high altitude sickness.Thereby the interpretation of result of zoopery and clinical experiment shows that methazolamide has wide practical use in preparation acute high altitude sickness control medicine.
Claims (1)
1. the application of methazolamide in preparation control acute high altitude sickness medicine.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101921245A (en) * | 2010-08-30 | 2010-12-22 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Sulfonamides compound for inhibiting carbonic anhydrase II and synthesis method and application thereof |
| CN101972249A (en) * | 2010-09-26 | 2011-02-16 | 中国人民解放军第三军医大学 | Application of methazolamide to preparation of medicament for treating plateau fatigue |
| CN104013622A (en) * | 2014-06-09 | 2014-09-03 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Novel use of methazolamide |
| CN110870866A (en) * | 2018-09-03 | 2020-03-10 | 浙江医药股份有限公司新昌制药厂 | Application of pyrroloquinoline quinone in preparation of medicine for preventing and treating acute altitude reaction and acute altitude hypoxia injury |
| CN111961043A (en) * | 2020-10-21 | 2020-11-20 | 东南大学 | Acetazolamide derivative, preparation method thereof and application thereof in preparation of drugs for treating coronary heart disease |
| CN115887396A (en) * | 2023-01-06 | 2023-04-04 | 北京中科利华医药研究院有限公司 | Methazolamide orally disintegrating tablet and preparation method and application thereof |
-
2010
- 2010-02-02 CN CN201010104645A patent/CN101756967A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101921245A (en) * | 2010-08-30 | 2010-12-22 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Sulfonamides compound for inhibiting carbonic anhydrase II and synthesis method and application thereof |
| CN101921245B (en) * | 2010-08-30 | 2012-04-18 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Sulfonamides compound for inhibiting carbonic anhydrase II and synthesis method and application thereof |
| CN101972249A (en) * | 2010-09-26 | 2011-02-16 | 中国人民解放军第三军医大学 | Application of methazolamide to preparation of medicament for treating plateau fatigue |
| CN104013622A (en) * | 2014-06-09 | 2014-09-03 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Novel use of methazolamide |
| CN110870866A (en) * | 2018-09-03 | 2020-03-10 | 浙江医药股份有限公司新昌制药厂 | Application of pyrroloquinoline quinone in preparation of medicine for preventing and treating acute altitude reaction and acute altitude hypoxia injury |
| CN111961043A (en) * | 2020-10-21 | 2020-11-20 | 东南大学 | Acetazolamide derivative, preparation method thereof and application thereof in preparation of drugs for treating coronary heart disease |
| CN111961043B (en) * | 2020-10-21 | 2021-01-15 | 东南大学 | Acetazolamide derivative, preparation method thereof and application thereof in preparation of drugs for treating coronary heart disease |
| WO2022083617A1 (en) * | 2020-10-21 | 2022-04-28 | 东南大学 | Acetazolamide derivative, and preparation method therefor and use thereof in preparation of drug for treating coronary heart disease |
| CN115887396A (en) * | 2023-01-06 | 2023-04-04 | 北京中科利华医药研究院有限公司 | Methazolamide orally disintegrating tablet and preparation method and application thereof |
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