CN101496801A - Dexmedetomidine and use of pharmaceutical salt thereof - Google Patents
Dexmedetomidine and use of pharmaceutical salt thereof Download PDFInfo
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- CN101496801A CN101496801A CNA2008100453491A CN200810045349A CN101496801A CN 101496801 A CN101496801 A CN 101496801A CN A2008100453491 A CNA2008100453491 A CN A2008100453491A CN 200810045349 A CN200810045349 A CN 200810045349A CN 101496801 A CN101496801 A CN 101496801A
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Abstract
The invention discloses application of dexmedetomidine and medicinal salts of the same. The dexmedetomidine or the medicinal salts of the same are used for preparing a medicine used for sedateness by preoperative patients, intraoperative patients, postoperative patients and patients requiring trachea cannulas and endoscope cannulas. The medicine contains clinically effective quantity of the dexmedetomidine or the medicinal salts of the same, and the dexmedetomidine or the medicinal salts of the same is an only active agent and made into the medicine for intravenous administration; and the medicine is fed under the condition of administration until the blood plasma concentration is between 0.1 and 2 ng/ml. The invention increases a method for using the dexmedetomidine or the medicinal salts of the same, and not only widens the medicine application of the dexmedetomidine but also can make more non-ICU patients acquire good mitigative and analgesic effects and reduce the dosage of other similar medicines and the incidence rate of untoward reactions.
Description
Technical field
The invention belongs to the pharmaceutical preparations technology field, particularly MPV-1440 and pharmaceutical salts thereof are used for, operation, operation back patient preceding to performing the operation and need tracheal intubation or endoscope's intubated patient is implemented purposes aspect calmness and the analgesic medicine in preparation.
Background technology
In clinical, before various operations, patients after surgery can feel anxiety, fear and uneasy usually, need use analgesics to ease the pain at patients after surgery.And normally used medicine has Benzodiazepines (anxiety reduction), propofol (anxiety reduction), opiates (easing the pain) etc.
Benzodiazepine has Midazolam (midazolam), tavor (lorazepam) and stable (diazepam) etc., too fast or the dosage of Midazolam injection can cause respiration inhibition, blood pressure drops when excessive, the Hypovolemia patient is outstanding especially, continues slow venoclysis and can effectively reduce its side effect; Also have the prolongation of accumulating with sedation effect after the long-time medication of Midazolam, patient is particularly evident in renal failure; Part patient also can produce the tolerance phenomenon.The advantage of tavor is that blood pressure, heart rate and Peripheral resistance are not had obvious influence, to breathing the unrestraint effect; Shortcoming is to be easy to accumulate in vivo, and it is slow to revive; The long-term heavy dose of infusion of its solvent propylene glycol may cause acute tubular necrosis, metabolic acidosis and hyperosmosis state.Stable heavy dose can cause certain respiration inhibition and blood pressure drops; Intravenous injection can cause injection site pain; Its metabolite demethyldiazepam and oxazepam all have similar stabile pharmacologically active, and long half time; Medication can cause and accumulate and sedation is prolonged repeatedly.
Temporary respiration inhibition and blood pressure drops, bradycardia can appear during the propofol single injection, and relevant to the influence of blood pressure with dosage, see especially that the heart reservation function is poor, the patient of Hypovolemia.The peripheral intravenous injection pain also can appear in propofol when using, in addition, inducible resistance may occur behind part patient's life-time service.The solvent of propofol is a chyle fat, provides calorie 1.1 card/milliliters, and long-term or extensive application also may cause hypertriglyceridemia.
Opioid analgesic is that representative also has analgesia and abirritative dual function with the morphine, but common clinical use is based on analgesic activity, and that the therapeutic dose morphine can cause sometimes is dizzy, nauseating, vomiting, constipation, dysuria, biliary colic, respiration inhibition, side effect such as drowsiness.The most important thing is that continuously repeated multiple times is used morphine and easily produced toleration and addiction, in case withdrawal symptom promptly appears in drug withdrawal, show as excitement, have a sleepless night, shed tears, watery nasal discharge, perspire, tremble, vomit, suffer from diarrhoea, even collapse, loss of consciousness etc.
In recent years, a kind of new α-2 receptor stimulating agents-MPV-1440 is applied to clinical gradually, is mainly used in to strengthen the calm processing of the monitoring patient of unit (ICU).
MPV-1440, chemistry is by name: (+)-(S)-4-[1-(2, the 3-3,5-dimethylphenyl) ethyl]-the 1H-imidazoles, have following general formula:
MPV-1440 is strong to the selectivity of maincenter α-2 adrenoceptor excitement, and the half-life is short, and consumption is very little.Very strong calmness, angst resistance effect are arranged simultaneously, and have analgesic activity, can reduce the consumption of opioid drug, and do not have obvious cardiovascular to suppress, bounce after respiration inhibition and the drug withdrawal.
MPV-1440 is used for the treatment of/prevents the nervus retrogression damage that alcoholism causes in European patent EP 0719141.US patent US7008444 has discussed the purposes of the regulate body temperature therapy that MPV-1440 shivers as reduction.US patent US723243 has disclosed MPV-1440 as a kind of medicine in the anti-heart failure combination treatment.European patent EP 437030 is used for glaucoma, reduces intraocular pressure.
Existing before discovery MPV-1440 and pharmaceutical salts thereof are that IUC patient's administration is made its comfortable ideal tranquilizer, therefore are usually used in IUC patient sedation treatment.
Summary of the invention
The inventor finds: be not only in the ICU patient care, before MPV-1440 and the medicinal multiple art that also can be used for non-ICU thereof, in the art, postoperative patient and in the patient who needs tracheal intubation and endoscope's intubate, before can significantly alleviating operation, in the operation and operation back patient's nervous anxiety symptom, and, thereby also can alleviate in the art and postoperative patient pain minimizing anaesthetic consumption, in the patient who needs tracheal intubation and endoscope's intubate, MPV-1440 also can alleviate patient's nervous anxiety symptom and can reduce in the intubate and intubate after patient's pain, the resistance that runs into when conveniently alleviating intubate.
Therefore, purpose of the present invention just provide a kind of MPV-1440 and pharmaceutical salts thereof before the preparation art, in the art, postoperative patient and needing tracheal intubation and the medicine of the calm usefulness of the patient of endoscope's intubate in purposes.
The technical solution adopted for the present invention to solve the technical problems is:
The purposes of MPV-1440 and pharmaceutical salts thereof, before MPV-1440 or its pharmaceutical salts be used for preparing art, art, postoperative patient and at the medicine of the calm usefulness of the patient who needs tracheal intubation and endoscope's intubate, this medicine contains MPV-1440 or its pharmaceutical salts of clinical effective, and MPV-1440 or its pharmaceutical salts are wherein unique activating agents, make the medicine of intravenous administration; Be that the amount of 0.1-2ng/ml gives to reach plasma concentration during administration, can give MPV-1440 or its pharmaceutical salts of loading and maintenance dose, also can not give loading, directly with infusion MPV-1440s such as Syrinjector infusion pumps, speed input with 6ml/hr continues infusion 20 hours.
The dosage range of MPV-1440 is to describe with the final concentration of blood plasma.Give to need the patient group of operation to provide calm and ease pain desirable plasma concentration scope between 0.1-2ng/ml, and depend on needed calmness and analgesia degree and patient's general situation etc. and change.By making medication group's dosage (loading) administration and can reaching these plasma concentration by the stable maintenance transfusion.For example, the medicine group dosage range that makes the people reach aforementioned plasma concentration scope is about 0.4-0.8ug/kg, administration in 5-10 minute, and then maintenance dose is at 0.4ug/kg/h.
The chemical species of MPV-1440 is free alkali or acid-addition salts.This acid-addition salts can with for example mineral acid example hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, phosphoric acid etc., and formation such as organic acid such as acetic acid, propanoic acid, hydroxyacetic acid, acetone acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, Fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethyl sulfonic acid, p-methyl benzenesulfonic acid, salicylic acid.
Compared with prior art, the invention has the beneficial effects as follows:
The present invention by before giving MPV-1440 or its pharmaceutical salts and making operation, the postoperative patient of operation neutralization and need tracheal intubation and the calmness of endoscope's intubated patient and analgesic are used, increased the using method of at least a MPV-1440 or its pharmaceutical salts, both enlarged the medical usage of MPV-1440, also can make more non-ICU patient obtain good sedative and analgesic effect, and reduce the use amount of other similar medicine, reduce incidence rate of adverse reaction.
The specific embodiment
The present invention is described in further detail below in conjunction with the specific embodiment.
But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.
Embodiment 1
Calming effects in the art before the art of present embodiment research dexmedetomidine.
Select 50 routine young patients (ASA I～II) be divided into two groups at random, the calm group of Dex (D group) and matched group (C group), every group of 25 examples respectively, all patients are without premedicant.
Open median cubital vein after going into operating room.After epidural puncture was put Guan Qianping bed rest 10min, the D group was used Graseby 3500 pump venoclysis hydrochloric acid MPV-1440 loading doses 0.4 μ g/kg (the 5min infusion is intact), keeps vein infusion 30min with 0.4 μ g/ (kgh) then; The C group is with the same manner infusion normal saline.
Monitor all patients brain electricity bispectrum index (BIS), Auditory Evoked Potential Index (A-line ARXIndex, AAI), MAP (mean arterial pressure), HR (heart rate), SpO
2(detecting sphygmus and blood oxygen saturation), PETCO
2The calm scoring of (partial pressure of carbon dioxide in endexpiratory gas), OAA/S and Ramsay (its standards of grading are stated table one and table two respectively as follows), and adopt AU4 type color Doppler instrument to measure common carotid artery, internal carotid artery internal diameter, rate of blood flow, blood flow.Continuous record basic value (T
0), (T at once behind the loading dose
1) and lasting infusion hydrochloric acid MPV-1440 after 5min, 10min, 15min, 20min, 25min, 30min (T
2～7) above-mentioned every index.
Table one OAA/S standards of grading
| Reactive | Voice | Facial expression | Eyes | Scoring |
| Exhale the name reaction fast to normal intonation | Normally | Normally | Limpid, no blepharoptosis | 5 is clear-headed |
| A lukewarm response exhaled in normal intonation | Slow down slightly or ambiguous | Semi-coast | Stare or eyelid slightly sagging | 4 |
| Only to exhaling name to respond loudly and/or repeatedly | Unclear or obviously slow down | Obviously loosen | Stare or eyelid obviously sagging | 3 shallow sleeping |
| Only to touching moving responding | Pronounce indistinctly | 2 | ||
| Reactionless to promoting | 1 sound sleep |
Table two Ramsey standard
| Clinical scores | The sedation degree that reaches |
| 1 2 3 4 5 6 | The patient anxiety, excitement maybe can't the rest patient be cooperated, and can adapt to order to be responded drowsiness with quiet patient, has fast reaction drowsiness but the illumination of glabella or loud audition stimulated, illumination or loud audition irritant reaction to glabella are slow drowsiness, reactionless |
Experimental result is estimated, and to the influence of sedation degree, two groups of bases BIS and AAI values are respectively 94 ± 3 and 83 ± 8; OAA/S and Ramsay grading are respectively 5 grades and 2 minutes.The loading dose infused and keep during BIS and AAI reduce by 17.0%～30.9% (P＜0.05) and 30.1%～43.4% (P＜0.05) respectively than basic value; Correspondingly the calm scoring of OAA/S and Ramsay also obviously reduces (P＜0.05～0.01).
To the influence of circulatory and respiratory, Dex loading dose infused and keep during, patient HR except that T4, T6 than basic slight reduction (P＜0.05), all the other time point HR reduce not obvious; MAP is than the obvious reduction of basic value (P＜0.05).All patient SpO2 and PETCO2 are stable, obvious respiration inhibition do not occur.
This embodiment illustrates that Dex loading dose 0.4 μ g/kg continues and keeps infusion with 0.4 μ g/ (kgh) patient in the operation is produced obvious calmness that BIS, AAI value reduce respectively and reach 57 and 43, reduce the ICAF amount simultaneously, do not have obvious respiration inhibition.
Embodiment 2
Before present embodiment research dexmedetomidine (Dex) art and the calming effects in the art and to the influence of general anesthesia patient depth of anesthesia.
Patient's 60 examples of choosing date for operation (ASA I～II level).Be divided into calm group and anesthesia group, every group 40 example according to different medication situation in period.
Calm group 40 examples are divided into Dex group (D again
1Organize) and matched group (C
1Group), every group 20 example.All patients are all without premedicant.D
1The preceding vein of group art adds uses Dex; C
1The group art is preceding without Dex.Enter the room behind the flat 10min of crouching D
1Group is used Graseby 3500 pump vein infusion Dex, and loading dose 0.4ug/kg (the 5min infusion is intact) is then with 0.4ugkg-1h
-1Keep vein infusion 30min; C
1Group is with the same manner infusion normal saline.(T before the record administration
0), (T at once behind the infusion loading dose
1), continue 5min (T behind the infusion
2), 10min (T
3), 15min (T
4), 20min (T
5), 25min (T
6), 30min (T
7) brain electricity bispectral index (BIS), MAP, HR, SpO
2, and the patient carried out the calm scoring of OAA/S and Ramesay.
Anesthesia is organized 40 routine general anesthesia patients and also is divided into D at random
2And C
2Group, every group 20 example.Observe in the art with the influence of Dex general anesthesia patient calming effects.D
2Art medium-sized vein Dex0.4ug/kg behind the group general anesthesia induction is diluted to 5ml vein infusion 5min with normal saline; C
2Group normal saline 5ml, the same D of method
2Group.Employing is built-in with the ALARIS pump of Diprifusor, propofol PFS is that target carries out target controlled infusion (TCI) with the plasma drug level, target control concentration (Ct) is 4ug/kg, continue infusion remifentaniliva 1ug/kg with Graseby 3500 pumps simultaneously, treat that the patient realizes the quiet notes Rocuronium Bromide 0.6mg/kg in back that disappears, endotracheal intubation behind the 1min.In the art with remifentaniliva 0.2ugkg
-1Min
-1Keep anesthesia, regularly append muscle relaxant, the Ct value (propofol target plasma concentration) of regulating the propofol target controlled infusion makes BIS maintain 50 ± 3 (T
8); Append adjuvant drug behind the 5min, BIS variation (T occurs behind the ancillary drug 20min if give
9), the Ct value of adjustment propofol makes BIS return to 50 ± 3 (T behind the lasting 5min
10), write down BIS, Ct, HR, MAP, and stopped propofol and remifentaniliva during the seam skin, record propofol and remifentaniliva consumption in per 2 minutes.
Dex is to the influence of conscious patient sedation degree.D
1Group basic value BIS is 94 ± 3, OAA/S scoring is 5 minutes, and Ramesay is calm, and scoring is 2 minutes, the loading dose infused and keep during BIS reduce (P＜0.05) than basic value, correspondingly the calm scoring of OAA/S and Ramesay also obviously reduces (P＜0.05, P＜0.01); C
1Group does not then have significant change.
Dex is to the influence of general anesthesia patient sedation depth and propofol TCI (TCI pump) consumption.D
2Further descending (17.0～30.9%) appearred in BIS after the group patient gave Dex, reduced the Ct value of propofol, and BIS is recovered; C
2Group remains unchanged; D
2The amount ratio C of group patient propofol
2Group reduces by 8%～14% (P＜0.05), and the consumption of two groups of remifentanilivas then is respectively (1378 ± 623) ug and (1338 scholar 525) ug (P〉0.05).
This embodiment proves that Dex produces obvious calming effects to conscious patient, and can deepen general anesthesia patient's depth of anesthesia, in propofol-remifentaniliva-Rocuronium Bromide vein general anesthesia, can reduce the consumption of target controlled infusion propofol, suit before operation and in the operation, to use.
Embodiment 3
The influence of inducing effect and blood circulation in present embodiment research MPV-1440, propofol, three kinds of medicine arts of etomidate.
The patient that chooses date for operation of 45 routine I～II levels is divided into three groups at random, i.e. MPV-1440 (D group), different pool phenol (P) group, etomidate (E) group.Every group of each 15 example are mainly observed the influence of inducing effect and blood circulation of three kinds of medicines.
Sex, age, body weight and height there are no significant difference between above-mentioned each group (P〉0.05).The operation kind comprises pulmonary lobectomy, craniocerebral operations, radical operation of mastocarcinoma, radical operation for carcinoma of stomach, cholecystectomy etc.Anesthesia: sodium phenobarbital 0.1mg, atropine 0.5mg, art intramuscular injection in preceding 1 hour.Elder generation's mask oxygen-inspiration after 5 minutes when inducing, quiet notes MPV-1440 0.8ug/kg respectively, injection finishes in the 5min, and injection finishes in propofol 2.5mg/kg or the etomidate 0.4gmg/kg, 1min.After falling asleep, quiet notes succinylcholine 1.5～2.0mg/kg treats flesh pine back endotracheal intubation control breathing fully, closes circulation or suction isoflurane or enflurane and keeps anesthesia, and vein is aided with fentanyl 2ug/kg as required, pancuronium bromide 0.03mg/kg.Measure systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP), heart rate (HR), pulse oxygen saturation (SpO with the multi-functional monitor of noinvasive
2) value, and the tidal volume (VT) on the record anesthetic machine, respiratory frequency (RR), minute ventilation (MV).Assay method: patient is flat to crouch 15 minutes, treat patient's emotion and breathing, stable circulation after, measure parameters as inducing preceding value (control value).Record is 1 minute and 3 minutes after the induction of anesthesia, during tracheal intubation, and the change of 5 minutes and 10 minutes parameters after the intubate.
The variation of blood pressure and heart rate before and after three groups of patient's intubate: propofol administration bleeding from anus is pressed with one and crosses property decline, but the level to the art of ging up during intubate, blood pressure does not have significant change during the MPV-1440 intubate, and blood pressure is before operation during etomidate group intubate.Propofol group, MPV-1440 heart rate when administration front and back and intubate is steady substantially, and the etomidate group significantly increases before HR, SBP, DBP and the injection (P＜0.01) when intubate.
The inhibition degree of side reaction during tracheal intubation is to estimate commonly used clinical the accusing of of intravenous anesthesia revulsive.Propofol group and MPV-1440 group, every index of cardiovascular system changes and the preceding no significant difference of art after the intubate.Illustrate that propofol and MPV-1440 do not have obvious inhibitory action to cardiovascular system.HR, SBP, DBP do not have obvious change (P〉0.05) before and after the injection of etomidate group, and in the tracheal intubation, significantly increase before SBP, DBP, HR and the injection in 5 minutes after the intubate (P＜0.01), owing to this medicine is that hypnotic does not have analgesic activity, spy on the cardiovascular response that causes with intubate so can not suppress laryngoscope effectively.Originally studies show that stress when MPV-1440 and propofol can suppress tracheal intubation is effectively compared safer, quick, effective with etomidate.Be suitable for the general anesthesia induction medication.
Embodiment 4
Present embodiment is the clinical efficacy research that MPV-1440 is used for the respiratory tract endoscopy.
Current domestic respiratory tract endoscopy generally adopts under local anaesthesia and carries out, but the postoperative patient majority is thought the operation process misery, patient who has even because the frightened and splanchnoscopy refusal respiratory tract.For alleviate bear in patient's art do not accommodate misery, guarantee to carry out endoscopy smoothly, for inspection provides optimum condition, require general anesthesia lower respiratory tract splanchnoscopy person 33 examples, patient age 20 years old～74 years old, body weight 45～80kg, conventional fasting is 8 hours before the ASA I level～II level, art.Preceding 5 minutes intravenous injection atropine 10mg/kg of art.The intravenously administrable MPV-1440, with 0.8 μ g/kg (10min infusion intact), Ramsay is calm, and scoring all reaches 2 fens, the row endoscopy, finish opening eyes of waiting after the inspection to exhale and can movable limbs and vital signs steady.
The result proves that MPV-1440 can effectively be used for the general anesthesia before endoscope's intubate, alleviates patient's misery, makes patient finish splanchnoscopy smoothly.
Embodiment 5
Present embodiment is the clinical research that MPV-1440 is used for abdominal operation patient postoperative sedation effect.
A kind of medication of novelty can alleviate patient's misery, reduces the anaesthetic consumption.
The patient of the abdominal operation of 40 I～II levels is divided into 2 groups at random: placebo group and MPV-1440 group, induction of anesthesia and keep administration with propofol and fentanyl, the consumption of meter record propofol and fentanyl.In whole anesthesia process, propofol is instiled keeps BIS about about 50, and fentanyl is kept blood pressure and heart rate in about 20% of basic value by instiling.When operation finished, the fentanyl infusion reached the effective site concentration of a hypothesis at 1.5-2ng/ml.In case patient's tube drawing, will begin in a minute with Syrinjector infusion pump venoclysis MPV-1440, before need not any loading with the input of the speed of 6ml/hr, placebo group is then used the normal saline of total amount 120ml, and the MPV-1440 group is used the normal saline of the total amount 120ml that contains the 120ug MPV-1440.Patient continues infusion 20 hours.Write down the VRS (PASCAL evaluation PASCAL scale) of pain in per 30 minutes and be used for abirritative Ramsay mark behind tube drawing, continue to write down 2 hours in PACU (care unit that the anesthesia back is strengthened), patient changes public ward over to subsequently.The MPV-1440 plasma concentration infusion begin back 2 hours determined, according to the medicine codes or data of MPV-1440,2 hours plasma concentration reach the peak behind infusion.
The result: average Ramsay mark significantly increases (2.9vs2.1) in the MPV-1440 group, the pentazocine that on average is used for pain significantly reduces (1.5vs2.8) in the MPV-1440 group, and the Ramsay mark is 3 in the report in the past.The plasma concentration of MPV-1440 is 0.5 ± 0.24ng/ml beginning to instil back 2 hours the time.
MPV-1440 is the effective and safe preceding pain medication of art, does not need to instil other at the abdominal post-operation public ward again.Enough calmness and analgesia use the Syrinjector infusion pump to be easy to obtain after 20 hours at surgery.Therefore, instil the after surgery method of MPV-1440 is economical and safe.
Prove by above each embodiment, MPV-1440 of the present invention has following advantage when being used for performing the operation calmness preceding, that the back patient that performs the operation, performs the operation needs tracheal intubation and endoscope's intubated patient etc. and analgesia processing: calmness and analgesic effect are obvious, compared with prior art have no obvious respiration inhibition, cardiovascular system is not had obvious inhibitory action; Can reduce other tranquilizer medicine such as propofol, the consumption of analgesic such as morphine; When being used to need the calmness of tracheal intubation and endoscope's intubated patient and easing pain, cardiovascular system there is not obvious inhibitory action, there is not obvious respiration inhibition effect simultaneously yet.
Claims (5)
1. the purposes of MPV-1440 and pharmaceutical salts thereof, before MPV-1440 or its pharmaceutical salts be used for preparing art, art, postoperative patient and at the medicine of the calm usefulness of the patient who needs tracheal intubation and endoscope's intubate, this medicine contains MPV-1440 or its pharmaceutical salts of clinical effective, and MPV-1440 or its pharmaceutical salts are wherein unique activating agents, make the medicine of intravenous administration; Be that the amount of 0.1-2ng/ml gives to reach plasma concentration during administration.
2. the purposes of MPV-1440 according to claim 1 and pharmaceutical salts thereof is characterized in that: described administration is to give the MPV-1440 of loading and maintenance dose or its pharmaceutical salts.
3. the purposes of MPV-1440 according to claim 2 and pharmaceutical salts thereof is characterized in that: described loading is 0.4-0.8ug/kg, gives in 5-10 minute.
4. the purposes of MPV-1440 according to claim 2 and pharmaceutical salts thereof is characterized in that: described maintenance dose is 0.4ug/kg.
5. the purposes of MPV-1440 according to claim 1 and pharmaceutical salts thereof is characterized in that:
Described administration is not give loading, and directly the infusion MPV-1440 is imported with the speed of 6ml/hr, continues infusion 20 hours.
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|---|---|---|---|
| CNA2008100453491A CN101496801A (en) | 2008-02-02 | 2008-02-02 | Dexmedetomidine and use of pharmaceutical salt thereof |
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| CNA2008100453491A CN101496801A (en) | 2008-02-02 | 2008-02-02 | Dexmedetomidine and use of pharmaceutical salt thereof |
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| US10792246B2 (en) | 2018-06-27 | 2020-10-06 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| CN112386703A (en) * | 2020-01-15 | 2021-02-23 | 李启芳 | Combined medicine for treating ALS and application thereof |
| 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 |
-
2008
- 2008-02-02 CN CNA2008100453491A patent/CN101496801A/en active Pending
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|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| CN112386703A (en) * | 2020-01-15 | 2021-02-23 | 李启芳 | Combined medicine for treating ALS and application thereof |
| 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 |
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