CN106727524A - A kind of pharmaceutical composition and its application - Google Patents
A kind of pharmaceutical composition and its application Download PDFInfo
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- CN106727524A CN106727524A CN201610980450.0A CN201610980450A CN106727524A CN 106727524 A CN106727524 A CN 106727524A CN 201610980450 A CN201610980450 A CN 201610980450A CN 106727524 A CN106727524 A CN 106727524A
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- Prior art keywords
- pharmaceutical composition
- ketalar
- dexmedetomidine
- hydrochloric acid
- standby
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Otolaryngology (AREA)
- Emergency Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A kind of pharmaceutical composition, it is characterised in that：It includes the effective ingredient that hydrochloric acid Dexmedetomidine and ketalar are constituted.Pharmaceutical composition of the present invention has synergistic function, it is especially useful in calm, effect is especially prominent before children check, infant is safely and effectively completed various inspections；Its calm success rate is up to more than 96%, and drug effect is fast, revival controllability is strong；Meanwhile, Small side effects, without obvious adverse reaction, heart rate, blood pressure etc. are all very normal, the phenomenons such as waking is restless do not occur, safe.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition, more particularly to a kind of downern composition.
Background technology
Calmness is the problem that urgent clinical needs are solved before calmness, particularly children check before checking, uses safely and effectively medicine
Thing is to ensure that infant smoothly completes the key of various inspections.
Downern is chloraldurate oral medicine or midazolam oral medicine, Rumi sodium flesh before domestic conventional inspection at present
Meat injection.The drug effect of these downerns and using there is problems with：(1) chloraldurate oral agents：Be current outpatient service most
Conventional children calm medicament before checking, because its mouthfeel is very pained, many children refuse to take or cause after taking
Vomiting, causes air draught by mistake nearly to increase, or even be in peril of one's life.In addition, chloraldurate metabolite is active, also draw sometimes
Play Delayed recovery；Meanwhile, substantially, sedation effect does not know the medicament first pass effect, frequently results in calm failure, and many children are normal
Often need repeated multiple times medication.(2) midazolam oral agents：Sedation effect is bad, and success rate is only 60~75%.(3) Rumi
Sodium intramuscular dose：Calm success rate is 80% or so, but with pain stimulation, injury is produced to infant.
Hydrochloric acid Dexmedetomidine is the dextroisomer of Medetomidine, belongs to the derivative of imidazoles, is a kind of high selectivity α
2 receptor stimulating agents, chemistry is entitled：(+) -4- (S)-[1- (2,3- 3,5-dimethylphenyl) ethyl] -1H- imidazole hydrochlorides, acts on
Alpha-2 receptor in brain stem nucleus ceruleus and produce good sedation, intranasal instill hydrochloric acid Dexmedetomidine bioavilability be
81.8% (72.6-92.1%), therefore adult and children's intranasal can produce obvious sedation after instilling Dexmedetomidine, and to exhaling
The unrestraint of suction maincenter is acted on；But after the calmness of 2ug/kg Dexmedetomidines is used alone, easily waken up with a start by environmental stimuli, turning awake rate can
Up to 50% or so, cause calm failure；Larger dose hydrochloric acid Dexmedetomidine (＞ 2ug/kg) collunarium, can produce bradycardia to show
As.
Ketamine picks up anti-agent for nmda receptor, there is antalgic and sedative and induced sympathetic activation, but general its uses the agent for needing
Amount is larger, easily causes elevation of the blood pressure and exist the restless situation of waking.
The content of the invention
Present invention aim at providing, a kind of success rate is high, few side effects downern compositions.
The object of the invention is achieved through the following technical solutions：
A kind of pharmaceutical composition, it is characterised in that：It includes the medicine that hydrochloric acid Dexmedetomidine and ketalar are constituted
Active ingredient.Inventor has found that the pharmaceutical composition can produce obvious synergistic function in research process, the medicine group
Compound is used to various check that calm success rates are high, almost be occurred without during medication calmness and wake up with a start situation, nothing by environmental stimuli
Apparent side effect.
Preferably, in the pharmaceutical composition that the present invention is provided, the mass ratio of hydrochloric acid Dexmedetomidine and ketalar is
1-5∶500-3000。
It is furthermore preferred that the mass ratio of hydrochloric acid Dexmedetomidine and ketalar is 2 in pharmaceutical composition of the present invention:
1000。
Application of the aforementioned pharmaceutical compositions in downern is prepared.
The present invention also provides a kind of downern, and it includes the pharmaceutical composition of above-mentioned offer of the invention and can pharmaceutically connect
The auxiliary material received.
Downern of the present invention can be aerosol, nasal spray, powder spray, sublingual tablets, injection, oral administration solution, mouth
Take tablet, capsule etc..
Preferably, the downern that the present invention is provided is nasal spray.
A kind of nasal spray for calmness, it includes supplementary material of following weight proportion, it is characterised in that：The right U.S. of hydrochloric acid
0.002~0.01 part of support miaow pyridine, 1~5 part of ketalar, Macrogol 4000 .01~0.05 part, sodium chloride 0.1~1.5
Part, 0.03~0.16 part of natrium adetate, 0.3~0.9 part of phenmethylol, 0.02~0.18 part of glycerine, sodium acid carbonate 0.01~3.9
Part；
Preparation method of the present invention for calm nasal spray, it is characterised in that it is to carry out as follows：
1. take purified water 2L to be placed in Agitation Tank, setting mixes speed for 60~80 turns/min, be slowly added to the poly- of recipe quantity
Ethylene glycol 400, stirring while adding, PEG400 is added after finishing, and continues to stir, standby；
2. continue stir 20 minutes after, sequentially add dexmedetomidine hydrochloride, ketalar, glycerine, sodium chloride, according to
Ground acid disodium, phenmethylol, add purified water to liquor capacity to continue to be stirred to dissolve after 8L, standby；
3. manganese hydrogen sodium regulating solution pH to 5.0~7.0 under agitation, is added, solution body is made after adding purified water
Product is 10L, then with being transferred to after 0.22 micron of filtering with microporous membrane in the appropriate vessel with ultrasound functions, sets supersonic frequency
Rate is 50KHZ, ultrasound 10~20 minutes, is de-gassed treatment, standby；
4. filling to sterilized spray bottle after middle product passed examination, and add the bottle cap with spraying constant displacement pump, labeling,
Packaging is obtained final product.
More preferably say, the dosage of the downern that the present invention is provided is each 1.1mg/kg.
The present invention has following beneficial effect：
Pharmaceutical composition of the present invention has synergistic function, it is especially useful in calm, effect is especially prominent before children check,
Infant is set safely and effectively to complete various inspections；Its calm success rate is up to more than 96%, and drug effect is fast, revival controllability
By force；Meanwhile, Small side effects, without obvious adverse reaction, heart rate, blood pressure etc. are all very normal, the restless grade of waking do not occur and show
As safe.
Brief description of the drawings
Fig. 1：Murine brain HE dyes micrograph；1：Control group CA1；2：Control group CA3；3：Experimental group CA1；4：Experimental group
CA3。
Fig. 2：Murine brain Nissl's staining micrograph；1：Control group CA1；2：Control group CA3；3：Experimental group CA1；4：Experiment
Group CA3.
Specific embodiment
The present invention is specifically described below by embodiment, it is necessary to it is pointed out here that be that following examples are only used
It is further described in the present invention, it is impossible to be interpreted as limiting the scope of the invention, person skilled in art can
Some nonessential modifications and adaptations are made to the present invention with according to the invention described above content.
Embodiment 1
A kind of downern, hydrochloric Dexmedetomidine and ketalar and pharmaceutically acceptable auxiliary material, are made
For into nasal spray, it is obtained according to the following steps：
Prescription is constituted：
1. take purified water 2L to be placed in Agitation Tank, setting mixes speed for 60~80 turns/min, be slowly added to the poly- of recipe quantity
Ethylene glycol 400, stirring while adding, PEG400 is added after finishing, and continues to stir, standby；
2. continue stir 20 minutes after, sequentially add dexmedetomidine hydrochloride, ketalar, glycerine, sodium chloride, according to
Ground acid disodium, phenmethylol, add purified water to material liquid volume to continue to be stirred to dissolve after 8L, standby；
3. under agitation, add manganese hydrogen sodium regulating solution pH to 5.0~7.0, used after supplying remaining purified water
It is transferred to after 0.22 micron of filtering with microporous membrane in the appropriate vessel with ultrasound functions, setting supersonic frequency is 50KHZ, ultrasound
10~20 minutes, treatment is de-gassed, it is standby；
4. filling to sterilized spray bottle after middle product passed examination, and add the bottle cap with spraying constant displacement pump, labeling,
Packaging is obtained final product.
Embodiment 2
A kind of downern, hydrochloric Dexmedetomidine and ketalar and pharmaceutically acceptable auxiliary material, are made
Standby parenteral solution, is obtained according to the following steps：
| Composition | Consumption (weight portion) |
| Dexmedetomidine hydrochloride | 0.005 part |
| Ketalar | 0.5 part |
| Mannitol | 3.7 parts |
| Sodium chloride | 1.1 parts |
| Sterilized water for injection | Add to 2000ml |
Preparation process：
1. concentrated compounding：By in above-mentioned supplementary material addition material-compound tank, the sterilized water for injection of 1/3 recipe quantity is added immediately, stir,
Dissolving, obtains concentrated wiring liquid；
2. it is dilute to match somebody with somebody：Concentrated wiring liquid is taken, 0.1mol/L sodium bicarbonate solutions are added, PH to 6.5~7.0 is adjusted, stirring is mixed,
Filtered with 0.8 μm of filter membrane, add the activated carbon of the mass volume ratio of cumulative volume 0.1%~0.3%, adsorption bleaching, with 0.45 μm
Filter membrane filtration, collect filtrate, plus sterilized water for injection tests qualified to recipe quantity through middle product examine, you can；
3. embedding：Intermediate is filtered with 0.22 μm of filter after the assay was approved, checks visible foreign matters, and bacterial endotoxin is closed
After lattice, upper streamline is filling into 2ml/ branch, sealing；
4. sterilize：Canned peace is cutd open into 121 DEG C of semi-finished product feeding steam sterilization pan sterilizing to sterilize 15 minutes, by regulation bar
Part is hunted leak；
5. check：Sample checks visible foreign matters after sterilizing, and qualified sample will be checked to carry out outsourcing, full inspection, storage, i.e.,
.
Embodiment 3
A kind of downern, hydrochloric Dexmedetomidine and ketalar and pharmaceutically acceptable auxiliary material, are made
Standby tablet, is obtained according to the following steps：
Preparation process：
1. by dexmedetomidine hydrochloride, ketalar, magnesium stearate, Stepanol MG, sodium carboxymethyl starch and
Starch is crushed respectively, crosses 80 mesh sieves, standby；
2. dexmedetomidine hydrochloride, ketalar, Stepanol MG, sodium carboxymethyl starch and starch are mixed equal
It is even, add 20% ethanol solution to be made softwood；
3. above-mentioned gained softwood is taken, is pelletized with 18 mesh sieves, the particle that will be made is placed in hot-air oven, temperature 60 is set
DEG C, dry to pellet moisture≤3%, 18 mesh sieve whole grains；
4. above-mentioned particle is taken, lubricant is added, is well mixed；
5. compressing tablet：Tablet press machine is regulated, compressing tablet is 0.3g/ pieces in setting piece, notes controlling loading amount；
6. packaging is obtained final product.
The sedative experiment of embodiment 4
Experimental technique：Influence to mouse autonomic activities：Take mouse 30,22~25g of body weight, male and female half and half, random point
Into 3 groups, i.e., drug regimen parenteral solution (specification obtained in embodiment 2：Hydrochloric Dexmedetomidine 0.1mg/ml, ketalar
0.05g/ml, dosage by 0.1ml/10g be administered), dexmedetomidine hydrochloride parenteral solution (specification：2ml：0.2mg, to medicament
Amount by 0.1ml/10g be administered), Ketamine Hydrochloride Inj. (specification：2ml/0.1g, dosage is administered by 0.1ml/10g).Respectively
Experiment mice oral administration gavage gives corresponding medicine, and the mouse of each group is placed into transparent small chest respectively first before administration, first
Adapt to 2 minutes, then start to observe and record walking about and other active situation number of times for each group mouse respectively, record 10 minutes,
, after being then administered by relevant dose, be placed into mouse in transparent small chest again by the number of activities before being administered, same first
Adapt to 2 minutes, then start to observe and record walking about and other active situation number of times for each group mouse respectively, record 10 minutes,
Every spontaneous activity inhibiting rate of mouse is calculated, computing formula is as follows：
Spontaneous activity inhibiting rate=100% × (spontaneous activity in mice number after spontaneous activity in mice number-administration before administration)/give
Spontaneous activity in mice number before medicine
Efficient=100% × effectively suppress mouse quantity/total mice
Note：Inhibiting rate >=50% is considered as effectively suppression.
Meanwhile, monitor heart rate, blood pressure are needed in experimentation, while observing waking whether there is restless phenomenon.
Result of the test see the table below：
Test result indicate that, pharmaceutical composition inhibiting rate of the present invention is with effective percentage obviously higher than control group.Heart rate, blood pressure
And waking situation pharmaceutical composition of the present invention is superior to control group.
The neurotoxicity of embodiment 5 is tested
Experimental technique：
One, experimental animals and packet
Mouse 30 is taken, be divided into mouse 2 groups (n=10) at random by 22~25g of body weight, male and female half and half：Control (N) group and
Experiment (D) group.
Two, administering modes and dosage
Experiment (D) group is using instillation Dexmedetomidine (0.1ml/10g) in nasal cavity and ketamine (0.1ml/10g) mixing
Liquid.Control (N) group is using the physiological saline that same volume is instilled in nasal cavity.
The collection and treatment of three, samples
Give sacrificed by decapitation after the daily 4%PFA rows heart perfusion of administration time fixes newborn rat, be rapidly separated newborn rat brain
Tissue, takes out brain tissue 4%PFA and irrigates and fix, and through dehydration, after FFPE, paraffin section is made, for HE dyeing and Buddhist nun
Albert'stain Albert.
Four, histopathology morphological observations
1.HE is dyeed
Paraffin section routinely dewaxes through dimethylbenzene, gradient (100%, 95%, 80%, 70%) alcohol aquation, distilled water drift
Enter brazilwood extract dyeing 10min after washing, running water rinses 1min, and 1% ethanol solution hydrochloride color separation promotees blue liquid and returns indigo plant, and flowing water is rinsed,
Enter 0.5% Yihong alcohol dyeing 1min, ascending gradient alcohol (80%, 95%, 100%) dehydration, dimethylbenzene is transparent, neutral gum
Simultaneously take pictures in CA1 the and CA3 regions of mounting optical microphotograph Microscopic observation mouse cerebral hippocampal.
2. Nissl's staining
Paraffin section routinely dewaxes through dimethylbenzene, is put into preheating 57 degree of 1% toluidine blue 60min, ddH20 and washes 3 times, 95%
Ethanol breaks up, and decolourizes, and microscopy understands to background, absolute ethyl alcohol dehydration, dimethylbenzene are transparent, neutral gum mounting optical microphotograph
Simultaneously take pictures in CA1 the and CA3 regions of Microscopic observation mouse cerebral hippocampal.
Experimental result：HE dyeing is shown in that Fig. 1, Nissl's staining are shown in Fig. 2；
Conclusion：As can be seen from the results, experimental group impassivity toxic action.
Claims (8)
1. a kind of pharmaceutical composition, it is characterised in that：It includes that the medicine that hydrochloric acid Dexmedetomidine and ketalar are constituted has
Effect composition.
2. pharmaceutical composition as claimed in claim 1, it is characterised in that：The hydrochloric acid Dexmedetomidine and ketalar
Mass ratio is 1-5:500-3000.
3. pharmaceutical composition as claimed in claim 1, it is characterised in that：The hydrochloric acid Dexmedetomidine and ketalar
Mass ratio is 2:1000.
4. the pharmaceutical composition as described in claim 1,2 or 3, it is characterised in that：Described pharmaceutical composition is preparing sedative
Application in thing.
5. the pharmaceutical composition as described in claim 1,2 or 3, it is characterised in that：It includes described pharmaceutical composition and medicine
Acceptable auxiliary material on.
6. a kind of pharmaceutical composition as claimed in claim 5, it is characterised in that：Described pharmaceutical composition is aerosol, nose spray
Mist agent, powder spray, sublingual tablets, injection, oral administration solution, oral tablet or capsule.
7. a kind of pharmaceutical composition as claimed in claim 6, it is characterised in that：The nasal spray includes following weight proportion
Supplementary material：0.002 ~ 0.01 part of hydrochloric acid Dexmedetomidine, 1 ~ 5 part of ketalar, 0.01 ~ 0.05 part of PEG400,
0.1 ~ 1.5 part of sodium chloride, 0.03 ~ 0.16 part of natrium adetate, 0.3 ~ 0.9 part of phenmethylol, 0.02 ~ 0.18 part of glycerine, carbonic acid
0.01 ~ 3.9 part of hydrogen sodium.
8. a kind of preparation method of nasal spray, it is characterised in that it is to carry out as follows:
A. take purified water 2L to be placed in Agitation Tank, setting mixes speed for 60 ~ 80 turns/min, is slowly added to the polyethylene glycol of recipe quantity
400, stirring while adding, PEG400 is added after finishing, and continues to stir, standby；
B. after continuing to stir 20 minutes, dexmedetomidine hydrochloride, ketalar, glycerine, sodium chloride, edetic acid(EDTA) are sequentially added
Disodium, phenmethylol, add purified water to liquor capacity to continue to be stirred to dissolve after 8L, standby；
C. under agitation, manganese hydrogen sodium regulating solution pH to 5.0 ~ 7.0 is added, makes the liquor capacity be after adding purified water
10L, then with being transferred to after 0.22 micron of filtering with microporous membrane in the appropriate vessel with ultrasound functions, setting supersonic frequency is
50KHZ, ultrasound 10 ~ 20 minutes, is de-gassed treatment, standby；
D. filling to sterilized spray bottle after product passed examination in the middle of, and add the bottle cap with spraying constant displacement pump, labeling, packaging
Obtain final product.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610980450.0A CN106727524A (en) | 2016-11-08 | 2016-11-08 | A kind of pharmaceutical composition and its application |
| PCT/CN2017/109597 WO2018086498A1 (en) | 2016-11-08 | 2017-11-06 | Pharmaceutical composition and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610980450.0A CN106727524A (en) | 2016-11-08 | 2016-11-08 | A kind of pharmaceutical composition and its application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106727524A true CN106727524A (en) | 2017-05-31 |
Family
ID=58972661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610980450.0A Pending CN106727524A (en) | 2016-11-08 | 2016-11-08 | A kind of pharmaceutical composition and its application |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN106727524A (en) |
| WO (1) | WO2018086498A1 (en) |
Cited By (9)
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| WO2018086498A1 (en) * | 2016-11-08 | 2018-05-17 | 重庆羽贝海科技有限公司 | Pharmaceutical composition and application thereof |
| CN109620802A (en) * | 2018-12-05 | 2019-04-16 | 杜皓 | A kind of anesthesia nasal spray and preparation method thereof |
| US10792246B2 (en) | 2018-06-27 | 2020-10-06 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| WO2020259440A1 (en) * | 2019-06-28 | 2020-12-30 | 四川普锐特药业有限公司 | Nasal spray of dexmedetomidine, preparation method therefor and use thereof |
| CN114306218A (en) * | 2020-09-30 | 2022-04-12 | 四川普锐特药业有限公司 | R-ketamine pharmaceutical composition for transmucosal administration meeting pharmaceutical antibacterial requirements |
| 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 |
| US11998529B2 (en) | 2023-06-30 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
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|---|---|---|---|---|
| WO2018086498A1 (en) * | 2016-11-08 | 2018-05-17 | 重庆羽贝海科技有限公司 | Pharmaceutical composition and application thereof |
| US11931340B2 (en) | 2016-12-31 | 2024-03-19 | 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 |
| US11839604B2 (en) | 2016-12-31 | 2023-12-12 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| 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 |
| 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 |
| 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 |
| CN109620802A (en) * | 2018-12-05 | 2019-04-16 | 杜皓 | A kind of anesthesia nasal spray and preparation method thereof |
| WO2020259440A1 (en) * | 2019-06-28 | 2020-12-30 | 四川普锐特药业有限公司 | Nasal spray of dexmedetomidine, preparation method therefor and use thereof |
| US11890272B2 (en) | 2019-07-19 | 2024-02-06 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| CN114306218A (en) * | 2020-09-30 | 2022-04-12 | 四川普锐特药业有限公司 | R-ketamine pharmaceutical composition for transmucosal administration meeting pharmaceutical antibacterial requirements |
| CN114306218B (en) * | 2020-09-30 | 2023-11-10 | 四川普锐特药业有限公司 | Transmucosal administration R-ketamine pharmaceutical composition meeting pharmaceutical bacteriostasis requirements |
| 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 |
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| WO2018086498A1 (en) | 2018-05-17 |
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