CN104784174A - New pharmaceutical use of dexmedetomidine - Google Patents
New pharmaceutical use of dexmedetomidine Download PDFInfo
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- CN104784174A CN104784174A CN201510100208.5A CN201510100208A CN104784174A CN 104784174 A CN104784174 A CN 104784174A CN 201510100208 A CN201510100208 A CN 201510100208A CN 104784174 A CN104784174 A CN 104784174A
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Abstract
The invention discloses a new use of dexmedetomidine. The new use of the dexmedetomidine or its pharmaceutically acceptable salt provided by the invention refers to application in preparation of: 1) products for prevention and/or treatment of postoperative sleep disorders; 2) products for prevention and/or reduction of postoperative complications; and 3) products for improvement of postoperative determination. Efficacy tests show that for the elderly non-cardiac surgery patients, small dose dexmedetomidine intravenous infusion can significantly improve the postoperative sleep structure and subjective sleep quality, and at the same time can improve patient prognosis, which includes lowering pain degree, reducing postoperative delirium and non-delirium complications and shortening ICU retention time.
Description
Technical field
The present invention relates to a kind of new medicine use of dexmedetomidine.
Background technology
Dexmedetomidine (dexmedetomidine) is a kind of high selectivity alpha 2-adrenoceptor agonist, its chemistry is by name: (S)-4-[1-(2,3-3,5-dimethylphenyl) ethyl]-1H-imidazoles, its molecular formula is: C
13h
16n
2.Dexmedetomidine mainly produces calmness, analgesia and anti-sympathesis clinically, this is the result of its exciting different parts alpha 2-adrenoceptor: exciting brain stem nucleus ceruleus receptor mainly produces sedation, exciting spinal receptors mainly produces analgesic activity, exciting oblongata receptor mainly produces anti-sympathesis [1,2].
The dexmedetomidine of current Clinical practice is the ejection preparation of its hydrochlorate, be mainly used in the calmness of ICU ventilated patients and the adjuvant drug of perianesthesia care patient, calm and calm etc. when having wound to check treatment operation when ancillary drug, regional block anestesia when the latter comprises general anesthesia.The indication that domestic dispensatory provides is for the calmness [3] when the patient with operation tracheal intubation of row general anesthesia and mechanical ventilation.
Sleep disorder comprises sleep deprivation, sleep disordered and Sleep architecture abnormal [4,5].Especially usually there is sleep disorder [6] after major operation accepting surgical operation in elderly patients, polysomnography figure shows as circadian rhythm disorder, Sleep latency prolongation, sleep fragmentation, Sleep efficiency reduction, 1 phase and 2 phase non rapid eye movement sleep, NREMSs extremely increase and S sleep and REM sleep minimizing [7,8].The generation of sleep disorder can bring many adverse effects to the postoperative rehabilitation of patient, comprises that cardiovascular event risk increases, mechanical ventilation event extends, bring out delirium, muscle power and the hypophrenia and immunologic function gets involved (may increase postoperative infection and acceleration Malignant tumor of bonal metastasis) [9-15].
Due to the importance of sleep to patient's postoperative rehabilitation, people have employed a lot of measure with improving water flood.Non-drug measure comprises the noise reducing night and loosens measure with light, the measure of integration night care, use earplug and eyeshield, employing and increase [16-20] such as white noises.But the effect of these measures is limited, patient still needs medicine sleeping [21] sometimes.The medicine in order to improving water flood that postoperative patient is commonly used comprises tranquilizer (propofol, Benzodiazepines) and analgesic (opiates), but these medicines can not improving water flood structure, even can increase the weight of sleep disordered and cause the generation [22,23] of the complication such as delirium.Different from traditional downern, dexmedetomidine is by acting on brain stem nucleus ceruleus, activating endogenous short sleep path and producing sedation [24].But can it improve the sleep of old postoperative patient, and pass through improving water flood and improve the prognosis of old postoperative patient and unclear.
List of references:
[1]Kamibayashi T,Maze M.Clinical uses of alpha2-adrenergic agonists.Anesthesiology 2000；93:1345-1349
[2]Chalikonda SA.Alpha2-adrenergic agonists and their role in the prevention of perioperativeadverse cardiac events.AANA J 2009；77:103-108
[3] Chinese Medical Association's anesthesiology branch.Dexmedetomidine clinical practice instruction (2013).Chinese Medical Journal 2013; 93:2775-2777.
[4]Friese RS:Sleep and recovery from critical illness and injury:a review of theory,currentpractice,and future directions.Crit Care Med 2008；36:697-705
[5]Elliott R,McKinley S,Cistulli P:The quality and duration of sleep in the intensive caresetting:an integrative review.Int J Nurs Stud 2011；48:384-400
[6]Bohrer T,Koller M,Neubert T,et al:How do general surgery patients experience theintensive care unit？Results of a prospective observational study.Chirurg 2002；73:443-450
[7]Aurell J,Elmqvist D:Sleep in the surgical intensive care unit:continuous polygraphicrecording of sleep in nine patients receiving postoperative care.Br Med J(Clin Res Ed)1985；290:1029-1032
[8]Friese RS,Diaz-Arrastia R,McBride D,et al:Quantity and quality of sleep in the surgicalintensive care unit:are our patients sleeping？J Trauma 2007；63:1210-1214
[9]Palmblad J,Petrini B,Wasserman J,et al:Lymphocyte and granulocyte reactions during sleepdeprivation.Psychosom Med 1979；41:273-278
[10]Kamdar BB,Needham DM,Collop NA:Sleep deprivation in critical illness:its role inphysical and psychological recovery.J Intensive Care Med 2012；27:97-111
[11]BaHammam A:Sleep in acute care units.Sleep Breath 2006；10:6-15
[12]Salas RE,Gamaldo CE:Adverse effects of sleep deprivation in the ICU.Crit Care Clin 2008；24:461-476,v-vi
[13]Weinhouse GL,Schwab RJ,Watson PL,et al:Bench-to-bedside review:delirium in ICUpatients-importance of sleep deprivation.Crit Care 2009；13:234
[14]Roche Campo F,Drouot X,Thille AW,et al:Poor sleep quality is associated with latenoninvasive ventilation failure in patients with acute hypercapnic respiratory failure.Crit CareMed 2010；38:477-485
[15]Ackermann K,Revell VL,Lao O,et al:Diurnal rhythms in blood cell populations and theeffect of acute sleep deprivation in healthy young men.Sleep 2012；35:933-940
[16]Xie H,Kang J,Mills GH:Clinical review:The impact of noise on patients’sleep and theeffectiveness of noise reduction strategies in intensive care units.Crit Care 2009；13:208
[17]Li SY,Wang TJ,Vivienne Wu SF,et al:Efficacy of controlling night-time noise andactivities to improve patients’sleep quality in a surgical intensive care unit.J Clin Nurs 2011；20:396-407
[18]Le Guen M,Nicolas-Robin A,Lebard C,et al:Earplugs and eye masks vs routine careprevent sleep impairment in post-anaesthesia care unit:a randomized study.Br J Anaesth2014；112:89-95
[19]Richards K,Nagel C,Markie M,et al:Use of complementary and alternative therapies topromote sleep in critically ill patients.Crit Care Nurs Clin North Am 2003；15:329-340
[20]Stanchina ML,Abu-Hijleh M,Chaudhry BK,et al:The influence of white noise on sleep insubjects exposed to ICU noise.Sleep Med 2005；6:423-428
[21]Ouslander JG,Connell BR,Bliwise DL,et al:A nonpharmacological intervention to improvesleep in nursing home patients:results of a controlled clinical trial.J Am Geriatr Soc 2006；54:38-47
[22]Pandharipande P,Ely EW:Sedative and analgesic medications:risk factors for delirium andsleep disturbances in the critically ill.Crit Care Clin 2006；22:313-327,vii
[23]Sanders RD,Maze M:Contribution of sedative-hypnotic agents to delirium via modulation ofthe sleep pathway.Can J Anaesth 2011；58:149-156
[24]Nelson LE,Lu J,Guo T,et al:The alpha2-adrenoceptor agonist dexmedetomidine convergeson an endogenous sleep-promoting pathway to exert its sedative effects.Anesthesiology 2003；98:428-436
Summary of the invention
The object of this invention is to provide the novelty teabag of a kind of dexmedetomidine or its pharmaceutically acceptable salt.
The novelty teabag of dexmedetomidine provided by the invention or its pharmaceutically acceptable salt is that it is preparing the application in following product: the product 1) preventing and/or treating postoperative sleep disorder; 2) product of prevention or reduction post-operative complication; 3) product of Postoperative determination is improved.
Wherein, described pharmaceutically acceptable salt is inorganic acid salt, specifically can be dexmedetomidine hydrochloride.
Described product specifically can be medicine or health product.
Described postoperative sleep disorder specifically refers to the postoperative sleep disorder of old age (being often referred to over-65s crowd) patients undergoing noncardiac surgery, comprises the sleep disorder under postoperative non-sedating state.
Described sleep disorder is embodied in Sleep architecture exception and subjective sleep quality reduces.
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 venoclysis dexmedetomidine can obviously extend total sleep time, reduces by 1 phase non rapid eye movement sleep, NREMS percentage ratio, improve Sleep efficiency and 2 phase non rapid eye movement sleep, NREMS percentage ratios.
Described low dose is 0.1 μ g/kg/h, Intravenous Infusion 15 hours.
Described post-operative complication specifically refers to the post-operative complication of old age (being often referred to over-65s crowd) patients undergoing noncardiac surgery.
Described post-operative complication comprises delirium, non-delirium complication and adverse events.
Described 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, at least one in gastrointestinal hemorrhage, wound infection, severe sepsis and urinary tract infection.
Described adverse events comprises at least one in bradycardia, hypotension, tachycardia, hypertension and hypoxemia.
The described Postoperative determination that improves comprises following at least one: reduce pain degree, reduce Postoperative Delirium and the generation of non-delirium complication, shorten the ICU time of staying, in ventilated patients, shorten Mechanical ventilation time.
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.
The test of pesticide effectiveness shows, for elder patients undergoing noncardiac surgery patient, low dose of dexmedetomidine venoclysis can obviously improve postoperative Sleep architecture and subjective sleep quality; And also can improve the prognosis of patient simultaneously, comprise and reduce pain degree, minimizing Postoperative Delirium and the generation of non-delirium complication and shorten the ICU time of staying.
figure of description
Fig. 1 is subjective sleep quality numeral grading scale.
Fig. 2 is pain degree numeral grading scale.
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.
Embodiment 1, low dose of dexmedetomidine are on the impact of the postoperative sleep of elderly patients
Our small-scale is random, double blinding, placebo-controlled study incorporate 76 example 65 years old or more, enter ICU after non-cardiac surgery and do not need the patient of mechanical ventilation.Dexmedetomidine group patient (n=38) lights to 8 Intravenous Infusion dexmedetomidine hydrochloride 0.1 μ g/kg/h in postoperative morning next day from operation that afternoon 5, and placebo patients (n=38) is at infusion normal saline at the same rate of same time.Record polysomnogram continuously during trial drug infusion, 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 (see Fig. 1).61 routine patients (dexmedetomidine group 31 example, placebo group 30 example) are finally had to obtain complete analyzable polysomnogram.
Acquired results is in table 1.
Table 1 liang group patient analysis of sleeping structure
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.
His-and-hers watches 1 interpretation of result is known, compared with placebo, dexmedetomidine infusion obviously extends total sleep time, reduce 1 phase non rapid eye movement sleep, NREMS percentage ratio, improve Sleep efficiency and 2 phases non rapid eye movement sleep, NREMS percentage ratio (table 1), and significantly improve whole selected patients (placebo group: 4.0 [2.0-8.0] are than dexmedetomidine group: 1.5 [0.8-4.3], and participate in analysis of sleeping structure patient (placebo group: 3.0 [2.0-7.3] are than dexmedetomidine group: 1.0 [0.0-3.0] p=0.004), p=0.005) subjective sleep quality.Illustrate that low dose of dexmedetomidine infusion improves the overall sleep quality of elderly patients.
The impact on the postoperative sleep of elderly patients of embodiment 2, low dose of dexmedetomidine and the impact of prognosis
Our one is extensive random, double blinding, placebo-controlled study incorporate 700 example 65 years old or more, enter patient's (wherein 383 routine patients receive mechanical ventilation, and 317 routine patients do not need mechanical ventilation) of ICU after non-cardiac surgery.Dexmedetomidine group patient (n=350) lights to 8 Intravenous Infusion dexmedetomidine hydrochloride 0.1 μ g/kg/h in postoperative morning next day from operation that afternoon 5, and placebo patients (n=350) is at infusion normal saline at the same rate of same time.Postoperative first 3 day every day, 8am adopted 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=completely not bitterly, the most severe pain of 10=) evaluate Principle of Pain degree (see Fig. 2); Postoperative first 7 day every day adopted ICU confusion of consciousness Evaluation Method (CAM-ICU) to assess delirium 2 times, and a situation arises.
Acquired results is in table 2 and table 3.
Table 2 liang group patient efficacy analysis
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.
bnon-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.
Table 3 liang group patient safety index analysis
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.
Result display is compared with placebo, dexmedetomidine infusion obviously alleviates the pain degree of postoperative first 24 hours, the subjective sleep quality improving postoperative front 3 evenings, the delirium incidence rate decreased in postoperative 7 days, non-delirium complication rate during considerably reducing postoperative hospital, shorten the ICU time of staying, in ventilated patients, also obviously shorten Mechanical ventilation time (see table 2); Dexmedetomidine infusion does not obviously increase the generation of adverse events, considerably reduces the generation (see table 3) of tachycardia, hypertension and hypoxemia on the contrary.Illustrate that low dose of dexmedetomidine infusion also improves analgesic effect and recent prognosis while improving the postoperative sleep quality of elderly patients, and be safe.
Claims (10)
1. dexmedetomidine or the application of its pharmaceutically acceptable salt in the following product of preparation: the product 1) preventing and/or treating postoperative sleep disorder; 2) product of prevention or reduction post-operative complication; 3) product of Postoperative determination is improved.
2. application according to claim 1, is characterized in that: described pharmaceutically acceptable salt is inorganic acid salt, is specially dexmedetomidine hydrochloride.
3. application according to claim 1, is characterized in that: described product is medicine or health product.
4. the application according to any one of claim 1-3, is characterized in that: described postoperative sleep disorder refers to the postoperative sleep disorder of elder patients undergoing noncardiac surgery patient, comprises the sleep disorder under postoperative non-sedating state.
5. application according to claim 4, is characterized in that: described sleep disorder comprises Sleep architecture exception and subjective sleep quality reduces.
6. application according to claim 5, is characterized in that: described Sleep architecture is abnormal comprises following at least one: 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.
7. the application according to any one of claim 1-3, is characterized in that: described post-operative complication refers to the post-operative complication of elder patients undergoing noncardiac surgery patient.
8. application according to claim 7, is characterized in that: described post-operative complication comprises delirium, non-delirium complication and adverse events; Described non-delirium complication comprises circulatory insufficiency, 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, at least one in gastrointestinal hemorrhage, wound infection, severe sepsis and urinary tract infection; Described adverse events comprises at least one in bradycardia, hypotension, tachycardia, hypertension and hypoxemia.
9. the application according to any one of claim 1-3, is characterized in that: the described Postoperative determination that improves comprises following at least one: reduce pain degree, reduce Postoperative Delirium and the generation of non-delirium complication, shorten the ICU time of staying, in ventilated patients, shorten Mechanical ventilation time.
10. the application according to any one of claim 1-9, is characterized in that: the using dosage of described dexmedetomidine or its pharmaceutically acceptable salt is 0.1 μ g/kg/h, Intravenous Infusion 15 hours.
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| CN201510100208.5A CN104784174A (en) | 2015-03-06 | 2015-03-06 | New pharmaceutical use of dexmedetomidine |
| CN201510783901.7A CN105287519A (en) | 2015-03-06 | 2015-11-16 | Pharmaceutical composition preventing postoperative delirium |
| CN201510783469.1A CN105287518A (en) | 2015-03-06 | 2015-11-16 | Pharmaceutical composition overcoming postoperative sleep disorder |
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| CN201510783901.7A Pending CN105287519A (en) | 2015-03-06 | 2015-11-16 | Pharmaceutical composition preventing postoperative delirium |
| CN201510783469.1A Pending CN105287518A (en) | 2015-03-06 | 2015-11-16 | Pharmaceutical composition overcoming postoperative sleep disorder |
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Cited By (6)
| 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 |
| 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 |
| 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 |
| US11998528B1 (en) | 2023-03-23 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130096170A1 (en) * | 2011-10-14 | 2013-04-18 | Hospira, Inc. | Methods of treating pediatric patients using dexmedetomidine |
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2015
- 2015-03-06 CN CN201510100208.5A patent/CN104784174A/en active Pending
- 2015-11-16 CN CN201510783901.7A patent/CN105287519A/en active Pending
- 2015-11-16 CN CN201510783469.1A patent/CN105287518A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11839604B2 (en) | 2016-12-31 | 2023-12-12 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| 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 |
| US11517524B2 (en) | 2018-06-27 | 2022-12-06 | 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 |
| US11497711B2 (en) | 2018-06-27 | 2022-11-15 | 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 |
| US11806429B2 (en) | 2018-06-27 | 2023-11-07 | 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 |
| 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 |
| US11806334B1 (en) | 2023-01-12 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11998528B1 (en) | 2023-03-23 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11998529B2 (en) | 2023-06-30 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105287518A (en) | 2016-02-03 |
| CN105287519A (en) | 2016-02-03 |
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Application publication date: 20150722 |