CN105287519A - Pharmaceutical composition preventing postoperative delirium - Google Patents
Pharmaceutical composition preventing postoperative delirium Download PDFInfo
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- CN105287519A CN105287519A CN201510783901.7A CN201510783901A CN105287519A CN 105287519 A CN105287519 A CN 105287519A CN 201510783901 A CN201510783901 A CN 201510783901A CN 105287519 A CN105287519 A CN 105287519A
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Abstract
The invention relates to the field of pharmaceutical compositions, and especially relates to a pharmaceutical composition preventing postoperative delirium. The provided pharmaceutical composition contains a pharmaceutical solvent carrier and dexmedetomidine or pharmaceutically-acceptable salts dissolving in the solvent carrier. The pharmaceutical composition is applicable to improve postoperative patient sleep structure, thereby improving patient sleep quality. The pharmaceutical composition is capable of preventing postoperative patient delirium, also is capable of mitigating patient pain, is safe to use and low in cost, and is usable by being matched with one or more of other sedatives, narcotics, hypnotics and opioids.
Description
Technical field
The present invention relates to field of medicinal compositions, particularly relate to a kind of pharmaceutical composition of prevention of postoperative delirium.
Background technology
Delirium is a kind of old people's acute confusional state, with the transience organic brain syndrome of attention, impression, thinking, memory, psychomotor and sleep cycle obstacle, be the comparatively common and important post-operative complication of old people, constant error is examined as alzheimer disease clinically.
The generation of Postoperative Delirium is subject to the impact of many factors, serious postoperative pain is one of risk factor of Postoperative Delirium, pain is that body is to the reaction with noxious stimulation, pain lasts constantly can cause the emotional responses such as anxiety, anxiety, fear, cause physiological dysfunction, obviously affect the length of one's sleep and quality, and the incidence rate of Postoperative Delirium is disorderly relevant to sleep function.
Operation makes body be in stress state, stress time sympathetic activation, in blood plasma, catecholamine, epinephrine, norepinephrine and dopamine concentration raise, stimulate stronger, increase level higher, old people's physical stress ability reduces, regulating system reliability reduces, increase stressor sensitivity, stress is strong, and exaltation causes Elder Patients After easily delirium to occur.
Treatment at present for delirium uses Benzodiazepines mostly, such as stable 10mg vein is slowly injected, efficient Benzodiazepines is as alprazolam 0.8-1.6mg, roller 2-4mg or clonazepam 2-4mg etc., but there is the patient of physical disease to use said medicine can be more responsive, easily cause blood pressure drops or cause acute the extrapyramidal symptoms.Because delirium patient conscious obstacle, correctly can not judge surrounding, and may hurt sb.'s feelings by hallucination or halo effect, to ruin thing or self inflicted injury etc. unexpected, best mode to put prevention first, but should also not have effective preventive measure at present.
Summary of the invention
In order to solve the generation of Postoperative Delirium, the invention provides a kind of pharmaceutical composition of prevention of postoperative delirium, the pharmaceutical composition that its injection mainly through low dose contains dexmedetomidine realizes object of the present invention, can the generation of prevention of postoperative delirium significantly by intravenous injection pharmaceutical composition provided by the invention, and can also significantly improve postoperative patient Sleep architecture and sleep quality.
In order to realize object of the present invention, a kind of pharmaceutical composition preventing delirium provided by the invention, it comprises pharmaceutically useful solvent carrier and is dissolved in the salt of the dexmedetomidine in described solvent carrier.
Wherein, the described acceptable salt of dexmedetomidine pharmacy refers to dexmedetomidine hydrochloride.
Wherein, in described pharmaceutical composition, the concentration of dexmedetomidine or dexmedetomidine hydrochloride is 2-6 μ g/ml.
Preferably, in described pharmaceutical composition, the concentration of dexmedetomidine or dexmedetomidine hydrochloride is 3-5 μ g/ml.
Further preferably, in described pharmaceutical composition, the concentration of dexmedetomidine or dexmedetomidine hydrochloride is 4 μ g/ml.
Wherein, described pharmaceutically useful solvent carrier is the sodium-chloride water solution of 0.9% or the D/W of 5%.
Preferably, described pharmaceutically useful solvent carrier is the sodium-chloride water solution of 0.9%.
Wherein, described pharmaceutical composition is inject the injection in body.
Particularly, when injecting described pharmaceutical composition, adopt dose injection, injected dose is 0.08-0.12 μ g/kg/h.
Preferably, the injected dose of described pharmaceutical composition is 0.1 μ g/kg/h.
Particularly, the using method of described pharmaceutical composition is Intravenous Infusion 13-17h.
Particularly, described pharmaceutical composition can use with one or more in anaesthetic, calm medicine, sleeping medicine, opioid drug simultaneously.
Particularly, described anaesthetic, calm medicine, sleeping medicine, opioid drug are conventional anaesthetic, calm medicine, sleeping medicine, opioid drug.
Wherein, described sleep disorder is embodied in Sleep architecture exception and subjective sleep quality reduction.
Wherein, described Sleep architecture can comprise following at least one extremely: total sleep time reduces, Sleep efficiency reduces, 1 phase non rapid eye movement sleep, NREMS percentage ratio increases and reduces with 2 phase non rapid eye movement sleep, NREMS percentage ratios.
To elder patients undergoing noncardiac surgery patient, low dose of infusion dexmedetomidine vein obviously alleviate postoperative first 24 hours pain degree, improve postoperative front 3 evenings subjective sleep quality, decrease postoperative first 7 days delirium incidence rate, decrease postoperative hospital during non-delirium complication rate, and do not increase the incidence rate of (decreasing on the contrary) adverse events.
The said goods (especially medicine) being active fraction preparation with dexmedetomidine and pharmaceutically acceptable salt thereof also belongs to protection scope of the present invention.
Described medicine imports body as muscle, Intradermal, subcutaneous, vein, mucosal tissue by the method that injection, injection, collunarium, eye drip, infiltration, absorption, physics or chemistry mediate; Or to be mixed by other materials or to import body after wrapping up.
When needing, one or more pharmaceutically acceptable carriers can also be added in said medicine.Described carrier comprises the diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant etc. of pharmaceutical field routine.
The various ways such as injection, tablet, powder, granule, capsule, oral liquid can be made with the medicine that dexmedetomidine and pharmaceutically acceptable salt thereof are active fraction preparation.The medicine of above-mentioned various dosage form all can be prepared according to the conventional method of pharmaceutical field.
For realizing object of the present invention, the present invention provides a kind of preparation method of prevention of postoperative deliriant compositions on the other hand, comprising:
Prepare pharmaceutically useful solvent carrier; With
Dexmedetomidine or the acceptable salt of its pharmacy are dissolved in described pharmaceutically useful solvent carrier.
Wherein, described dexmedetomidine or the acceptable salt of its pharmacy and described pharmaceutically useful solvent carrier prepare the concentration of the pharmaceutical composition obtained is 0.08-0.12 μ g/kg.
Preferably, the concentration of described pharmaceutical composition is 0.1 μ g/kg.
Advantage of the present invention:
1, pharmaceutical composition provided by the invention is utilized, total sleep time extends 0.63 times compared with placebo, Sleep efficiency improves that about 50%, 1 phase non rapid eye movement sleep, NREMS reduces 33%, 2 phase non rapid eye movement sleep, NREMS time lengthening 7.26 times, sleep percentage adds 1.75 times, visible, the pharmaceutical composition of the application obviously extends total sleep time, improves the subjective sleep quality of postoperative patient.
2, pharmaceutical composition dose injection provided by the invention just can realize the object overcoming sleep disorder, and cost is low.
3, pharmaceutical composition provided by the invention can be used in conjunction with each other with other tranquillizer, anesthetis etc., is free from side effects, effective.
4, simple, the raw material of the preparation method of pharmaceutical composition provided by the invention is easy to get, and the suitability is wide, can realize suitability for industrialized production.
figure of description
Fig. 1 is the subjective sleep quality numeral grading scale of the embodiment of the present invention 4;
Fig. 2 is the pain degree numeral grading scale of the embodiment of the present invention 5;
Fig. 3 is the ill number of cases of postoperative delirium every day of the embodiment of the present invention 6.
Detailed description of the invention
Below by specific embodiment, the present invention will be described, but the present invention is not limited thereto.
Experimental technique described in following embodiment, if no special instructions, is conventional method; Described reagent and biomaterial, if no special instructions, all can obtain from commercial channels.
The preparation of embodiment 1 pharmaceutical composition
1, the preparation of pharmaceutical composition
The sodium chloride solution of 0.9% dilution dexmedetomidine is used to make its concentration for 4ug/ml.Concrete, can be that commercially available dexmedetomidine solution is joined in the sodium chloride injection of 48ml0.9%, forming cumulative volume is the solution of 50ml, shakes the sodium chloride injection adding dexmedetomidine solution gently and makes Homogeneous phase mixing, obtain the dexmedetomidine solution that concentration is 4ug/ml.It should be noted that, in operating process, strict aseptic technique must be maintained all the time.
2, patient medication
Enter ICU after selecting 76 example 65 years old or more, non-cardiac surgery and do not need the elderly patients of mechanical ventilation, elderly patients are carried out that small-scale is random, random, double blinding, placebo-controlled trial research.
The dexmedetomidine solution of 4ug/ml step 1 obtained is injected in patient body, as processed group with the dosage of 0.1 μ g/kg; Simultaneously by the placebo injection of same dosage 0.1 μ g/kg in patient body, as a control group.Wherein, described patient is each 38 examples of processed group and matched group.Described placebo is the normal saline of 0.9% concentration.
Concrete processing method is: to light that afternoon 5 to morning 8 postoperative next day to the routine processed group patient Intravenous Infusion dexmedetomidine hydrochloride 0.1 μ g/kg/h of 38 wherein, to remaining 38 examples according to the normal saline placebo of group patients in the time identical with processed group with identical rate infusion 0.9% concentration from operation.
The preparation of embodiment 2 pharmaceutical composition
1, the preparation of pharmaceutical composition
The sodium chloride solution of 0.9% dilution dexmedetomidine is used to make its concentration for 2ug/ml.Concrete, can be that commercially available dexmedetomidine solution is joined in the sodium chloride injection of 48ml0.9%, forming cumulative volume is the solution of 50ml, shakes the sodium chloride injection adding dexmedetomidine solution gently and makes Homogeneous phase mixing, obtain the dexmedetomidine solution that concentration is 2ug/ml.It should be noted that, in operating process, strict aseptic technique must be maintained all the time.
2, patient medication
Enter ICU after selecting 76 example 65 years old or more, non-cardiac surgery and do not need the elderly patients of mechanical ventilation, elderly patients are carried out that small-scale is random, random, double blinding, placebo-controlled trial research.
The dexmedetomidine solution of 4ug/ml step 1 obtained is injected in patient body, as processed group with the dosage of 0.08 μ g/kg; Simultaneously by the placebo injection of same dosage 0.12 μ g/kg in patient body, as a control group.Wherein, described patient is each 38 examples of processed group and matched group.Described placebo is the normal saline of 0.9% concentration.
Concrete processing method is: to light that afternoon 5 to morning 8 postoperative next day to the routine processed group patient Intravenous Infusion dexmedetomidine hydrochloride 0.12 μ g/kg/h of 38 wherein, to remaining 38 examples according to the normal saline placebo of group patients in the time identical with processed group with identical rate infusion 0.9% concentration from operation.
The preparation of embodiment 3 pharmaceutical composition
1, the preparation of pharmaceutical composition
The sodium chloride solution of 0.9% dilution dexmedetomidine is used to make its concentration for 6ug/ml.Concrete, can be that commercially available dexmedetomidine solution is joined in the sodium chloride injection of 48ml0.9%, forming cumulative volume is the solution of 50ml, shakes the sodium chloride injection adding dexmedetomidine solution gently and makes Homogeneous phase mixing, obtain the dexmedetomidine solution that concentration is 6ug/ml.It should be noted that, in operating process, strict aseptic technique must be maintained all the time.
2, therapeutic regimen
Enter ICU after selecting 76 example 65 years old or more, non-cardiac surgery and do not need the elderly patients of mechanical ventilation, elderly patients are carried out that small-scale is random, random, double blinding, placebo-controlled trial research.
The dexmedetomidine solution of 4ug/ml step 1 obtained is injected in patient body, as processed group with the dosage of 0.08 μ g/kg; Simultaneously by the placebo injection of same dosage 0.08 μ g/kg in patient body, as a control group.Wherein, described patient is each 38 examples of processed group and matched group.Described placebo is the normal saline of 0.9% concentration.
Concrete processing method is: to light that afternoon 5 to morning 8 postoperative next day to the routine processed group patient Intravenous Infusion dexmedetomidine hydrochloride 0.08 μ g/kg/h of 38 wherein, to remaining 38 examples according to the normal saline placebo of group patients in the time identical with processed group with identical rate infusion 0.9% concentration from operation.
Below be all make based on the medication patient of most preferred embodiment 1.
The analysis of embodiment 4 Sleep architecture
Conventional method is adopted to lead hypnotic instrument more and be arranged on the region of interest (operational approach with reference to WeinhouseGL.Sleepinthecriticallyill:Anepochadventure) of patient during infusion of drug, continuous record polysomnogram, obtain data result, according to the relevant criterion in " U.S.'s sleep medicine can be slept and dependent event scoring handbook in 2007 ", the data result obtained is determined that each phase sleeps, the rapid eye movement phase sleep is divided into sleep and the sleep of nonrapid eye movements (NREM) phase, the sleep of nonrapid eye movements (NREM) phase is divided into again the sleep of 1 nonrapid eye movements (NREM) phase phase and the sleep of 2 nonrapid eye movements (NREM) phases phase and 3 nonrapid eye movements (NREM) phases phase to sleep, then Profusion sleep analysis system is adopted to carry out tentatively by stages to sleep monitor result, determine a sleep event, analyze Sleep architecture, finally there is 61 routine patients (dexmedetomidine group 31 example, placebo group 30 example) obtain complete analyzable polysomnogram, analysis result is as shown in table 1.
8 digital grading scales of employing in postoperative morning next day (sleep of NRS, 0=the best, the poorest sleep of 10=) evaluates patient's subjective sleep quality, and record result as shown in Figure 1.
Table 1 liang group patient analysis of sleeping structure
Wherein: IQR, interquartile-range IQR; Min, minute; H, hour;
abetween postoperative monitoring period, (from art day 5pm to 8am postoperative next day) is in the temporal summation of any Sleep stages;
btotal sleep time accounts for the percentage ratio of summary journal time;
cthe average time of awakening between sleep period per hour or waking up;
Data results is as shown in Table 1 known, the total sleep time significant prolongation that the processed group of injecting dexmedetomidine records, P value reaches 0.028, and the median of processed group total sleep time is 1.6 times of matched group, data comparatively concentrate IQR to be 826.7-905.1), the median of Sleep efficiency comparatively matched group improves 1.49 times, visible, uses the pharmaceutical composition of the application obviously can improve the length of one's sleep and the Sleep efficiency of patient.
Sleep be have two different time phase cycle alternately, be divided into REM sleep state and non rapid eye movement sleep, NREMS state, data results is as shown in Table 1 known, the median of processed group 1 phase non rapid eye movement sleep, NREMS time is compared with the time lengthening 15min of matched group, 1 phase non rapid eye movement sleep, NREMS percentage ratio comparatively matched group reduces 27.8%, 2 phase non rapid eye movement sleep, NREMS time lengthening 71.7min, comparatively matched group extends 7.27 times, 2 phase non rapid eye movement sleep, NREMS percentage ratios add 27.7%, comparatively matched group adds 1.75 times, the S sleep time, S sleep percentage ratio, there is the number of cases of S sleep comparatively to many 3 examples of illumination, the pharmaceutical composition dexmedetomidine of visible use the application makes patient improve in the sleep in non-snap-action eye stage, and the REM sleep time, have REM sleep to be all 0, in sum, use the pharmaceutical composition of the dexmedetomidine of the application to make whole selected patients between sleep period, cerebral activity declines, releiving to a certain extent, subjective sleep quality is improved.Infusion obviously extends total sleep time, reduces 1 phase non rapid eye movement sleep, NREMS percentage ratio, improves Sleep efficiency and 2 phases non rapid eye movement sleep, NREMS percentage ratio (table 1), in whole selected patients, the subjective sleep quality evaluation result (4.0 [2.0-8.0]) of placebo infusion group is obviously high than infusion dexmedetomidine group (1.5 [0.8-4.3]), and to participate in analysis of sleeping structure patient placebo infusion group subjective sleep quality evaluation result for (3.0 [2.0-7.3]) higher than dexmedetomidine group (1.0 [0.0-3.0]), evaluate score higher, its sleep quality is poorer, otherwise, it is lower that it evaluates score, its sleep quality is better, according to the experimental result of the application, the pharmaceutical composition of infusion the application significantly improves the subjective sleep quality of whole selected patients, advantageously in the overall sleep quality improving patient.
The analysis of embodiment 5, sleep curative effect
After operation in patients, morning 8 first 3 day every day adopts digital grading scale (NRS, the sleep of 0=the best, the poorest sleep of 10=) evaluate patient's subjective sleep quality, the digital grading scale of same employing (NRS, 0=is not completely bitterly, the most severe pain of 10=) evaluate Principle of Pain degree, as shown in Figure 2, evaluating data result is as shown in table 2 for evaluation result.
Table 2 liang group patient efficacy analysis
Note: CI, credibility interval; H, hour; NRS, digital grading scale; IQR, interquartile-range IQR; Am, the morning; D, sky; ICU, intensive care unit.
awherein dexmedetomidine group 192 example, placebo group 191 example.
According to the data results shown in table 2, the extubation time of the patient of infusion dexmedetomidine shortens compared with the patient of placebo infusion, and ventilated patients extubation time shorten, reach significant level, and dispersion between subjects is low.
In postoperative 24 hours, the dispersion of patient's pain data between rest and active stage of infusion dexmedetomidine is lower, illustrates that the pain of patient is eased to a certain extent.
In postoperative 3 days, the sleep quality of infusion dexmedetomidine patient all reaches better level, reaches pole significant level (median=2).Illustrate that dexmedetomidine reaches the effect improving sleep quality.
In sum, the pharmaceutical composition to postoperative patient infusion dexmedetomidine of the present invention also improves analgesic effect while improving the postoperative sleep quality of elderly patients.
Embodiment 6 delirium is evaluated
Adopt the Clinical symptoms of the delirium assessment method evaluation delirium of CAM-CR (Chinese revised edition), comprise that polarity onset, attention deficit disorder, thinking are in disorder, level of consciousness changes, time disturbance of orientation to place, hypomnesis, perceptual disturbance, psychomotor are excited, psychomotor is slow, the change of undulatory property, sleep-wake cycle.Evaluation result is as shown in table 3.
Table 3 delirium evaluation result
Note: CI, credibility interval; H, hour; NRS, digital grading scale; IQR, interquartile-range IQR; Am, the morning; D, sky; ICU, intensive care unit.
A is dexmedetomidine group 192 example wherein, placebo group 191 example.
B non-delirium complication comprises circulatory insufficiency (positive inotropic medicament or vasoactive agent continuous infusion were more than 24 hours), acute myocardial infarction, newly sends out that arrhythmia, pulmonary infection, apoplexy, acute renal failure, wound dehiscence, fistula of operative incision, intestinal obstruction, surgery are hemorrhage, gastrointestinal hemorrhage, wound infection, severe sepsis, urinary tract infection etc.
Infusion as can be seen from Table 3, in postoperative 7 days, the delirium incidence rate of infusion dexmedetomidine processed group is only 9.1%, far below 22.3% of placebo infusion group matched group, and along with the prolongation of Post surgery duration, the delirium incidence rate of infusion dexmedetomidine processed group is reduced to 0.3% by 4.6%; The ill number of cases of postoperative delirium every day as shown in Figure 3, processed group ill number of cases every day of infusion dexmedetomidine significantly lower than placebo infusion matched group, and reduce amplitude comparatively matched group stablize; The processed group Postoperative Delirium onset time of infusion dexmedetomidine is later than matched group, and reaches pole significant level; The postoperative non-delirium complication rate number of cases always of processed group of infusion dexmedetomidine is only 52 examples, accounts for 14.9%, far below 73 examples of matched group, reaches significant level; Postoperative non-delirium complication onset time of the processed group of infusion dexmedetomidine comparatively matched group postpone to some extent, be up to 4 days.Visible, the dexmedetomidine pharmaceutical composition that infusion the application provides can effectively postpone delirium time of origin, reduces the incidence rate of delirium, the generation of effective prevention of postoperative elderly patients delirium.
Embodiment 7 patient safety index analysis
The safety indexs of 8 employings in morning first 3 day every day digital grading scale evaluation patient after operation in patients, whether the front patient of essential record drug withdrawal there is the phenomenons such as bradycardia, hypotension, tachycardia, hypertension, hypoxemia, and evaluating data result is as shown in table 4.
Table 4 liang group patient safety index analysis
Note: the restless sedation score of RASS, Richmond;
aheart rate <55 beat/min or comparatively basic value (before medication) reduce by more than 20%.
bsystolic pressure <95mmHg or comparatively basic value decrease beyond 20%, or diastolic pressure <50mmHg.
cheart rate >100 beat/min or comparatively basic value increase to over 20%.
dsystolic pressure >160mmHg or comparatively basic value increase to over 20%, or diastolic pressure >100mmHg.
epulse oxygen saturation <90% or comparatively basic value decrease beyond 5%.
ftest medication stops infusion because of adverse events.
According to the data results shown in table 3, dexmedetomidine infusion does not obviously increase the generation of adverse events, considerably reduce the generation of tachycardia, hypertension and hypoxemia on the contrary, illustrate and carry out the improvement of postoperative sleep to postoperative patient infusion dexmedetomidine provided by the invention pharmaceutical composition and prevention of postoperative delirium is safe.
Embodiment 8 and other medicines infusion efficacy analysis simultaneously
Certain 73 years old women, height 158cm, body weight 45kg, previously have hypertension, history of coronary heart disease.Open abdomen Dixon because of " rectal cancer " row to perform the operation.Postoperative band tracheal intubation enters SICU (SICU).Give propofol 40mg/h sedation treatment at ICU, morphine 0.5mg/h analgesia therapy, gives dexmedetomidine 4.5ug/h simultaneously.
Employing conventional method is arranged on the region of interest of patient more by leading hypnotic instrument, continuous record polysomnogram, and data result is analyzed, learn that patient sleeps reaches 240h the time, Sleep efficiency reaches 26.4, and 1 non rapid eye movement sleep, NREMS time phase reached 103h, 2 non rapid eye movement sleep, NREMS times phase reached 96h, occurred without delirium.
After operation in patients, morning 8 first 3 day every day adopts digital grading scale (NRS, the sleep of 0=the best, the poorest sleep of 10=) evaluate patient's subjective sleep quality, the digital grading scale of same employing (NRS, 0=is not completely bitterly, the most severe pain of 10=) evaluate Principle of Pain degree, known sleep degree reaches 1.0, is better sleep; Pain degree is 2.0, and pain degree is lighter.
During infusion, there is not the symptoms such as bradycardia, hypotension, tachycardia, hypertension, hypoxemia in patient.Visible, the bad time is not appearred in infusion while of the pharmaceutical composition-dexmedetomidine of the application and other anaesthetic, calm medicine, sleeping medicine, opioid drug, but also enhances its therapeutic effect, sleep quality improves, pain reduces, and occurs without delirium.
Claims (10)
1. a pharmaceutical composition for prevention of postoperative delirium, is characterized in that, it comprises pharmaceutically useful solvent carrier and the dexmedetomidine be dissolved in described solvent carrier or the acceptable salt of its pharmacy.
2. pharmaceutical composition as claimed in claim 1, it is characterized in that, the described acceptable salt of dexmedetomidine pharmacy refers to dexmedetomidine hydrochloride.
3. pharmaceutical composition as claimed in claim 2, it is characterized in that, the concentration of dexmedetomidine or dexmedetomidine hydrochloride is 2-6 μ g/ml.
4. pharmaceutical composition as claimed in claim 1, it is characterized in that, described pharmaceutically useful solvent carrier is the sodium-chloride water solution of 0.9% or the D/W of 5%.
5. pharmaceutical composition as claimed in claim 5, it is characterized in that, described pharmaceutically useful solvent carrier is the sodium-chloride water solution of 0.9%.
6. pharmaceutical composition as claimed in claim 2, is characterized in that, described pharmaceutical composition is inject the injection in body, and during its injection, injected dose is 0.08-0.12 μ g/kg/h.
7. pharmaceutical composition as claimed in claim 2, is characterized in that, described pharmaceutical composition is inject the injection in body, and during its injection, injected dose is 0.1 μ g/kg/h.
8. pharmaceutical composition as claimed in claim 7, it is characterized in that, its injecting method is Intravenous Infusion 13-17h.
9. pharmaceutical composition as claimed in claim 1, is characterized in that, described pharmaceutical composition can use with one or more in other anaesthetic, calm medicine, sleeping medicine, opioid drug simultaneously.
10. a preparation method for prevention of postoperative deliriant compositions, is characterized in that, comprising:
Prepare pharmaceutically useful solvent carrier; With
Dexmedetomidine or the acceptable salt of its pharmacy are dissolved in described pharmaceutically useful solvent carrier.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10792246B2 (en) | 2018-06-27 | 2020-10-06 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US11786508B2 (en) | 2016-12-31 | 2023-10-17 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| US11806334B1 (en) | 2023-01-12 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11890272B2 (en) | 2019-07-19 | 2024-02-06 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113827590A (en) * | 2020-06-08 | 2021-12-24 | 四川普锐特药业有限公司 | Application of dexmedetomidine in preparation of sleep-aiding medicine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103957906A (en) * | 2011-10-14 | 2014-07-30 | 赫思公司 | Methods of treating pediatric patients using dexmedetomidine |
-
2015
- 2015-03-06 CN CN201510100208.5A patent/CN104784174A/en active Pending
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- 2015-11-16 CN CN201510783469.1A patent/CN105287518A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103957906A (en) * | 2011-10-14 | 2014-07-30 | 赫思公司 | Methods of treating pediatric patients using dexmedetomidine |
Non-Patent Citations (4)
| Title |
|---|
| 邓辉铃等: ""亚麻醉剂量氯胺酮与右美托咪啶对老年骨科全麻患者术后谵妄发生率的影响"", 《右江医学》 * |
| 陈宁等: "《镇静药物使用手册》", 30 September 2013 * |
| 陈金篆等: ""右美托咪定对老年前列腺电切术后谵妄的影响"", 《中国老年学杂志》 * |
| 静脉用药物调配技术: "《静脉用药物调配技术》", 31 January 2015, 安徽科学技术出版社 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11786508B2 (en) | 2016-12-31 | 2023-10-17 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| US11931340B2 (en) | 2016-12-31 | 2024-03-19 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| US11839604B2 (en) | 2016-12-31 | 2023-12-12 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| US11806429B2 (en) | 2018-06-27 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US11559484B2 (en) | 2018-06-27 | 2023-01-24 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US11517524B2 (en) | 2018-06-27 | 2022-12-06 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US10792246B2 (en) | 2018-06-27 | 2020-10-06 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US11497711B2 (en) | 2018-06-27 | 2022-11-15 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US11478422B2 (en) | 2018-06-27 | 2022-10-25 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US11890272B2 (en) | 2019-07-19 | 2024-02-06 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11998529B2 (en) | 2019-07-19 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US12109196B2 (en) | 2019-07-19 | 2024-10-08 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11806334B1 (en) | 2023-01-12 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11998528B1 (en) | 2023-01-12 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US12090140B2 (en) | 2023-01-12 | 2024-09-17 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104784174A (en) | 2015-07-22 |
| CN105287518A (en) | 2016-02-03 |
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