CN107693485A - A kind of nasal drops for being used to anaesthetize and preparation method thereof - Google Patents
A kind of nasal drops for being used to anaesthetize and preparation method thereof Download PDFInfo
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Abstract
A kind of nasal drops for being used to anaesthetize, it is characterized in that, it is using hydrochloric acid Dexmedetomidine and ketalar as raw material, adds a certain amount of osmotic pressure regulator, bacteriostatic agent, antioxidant, cosolvent, pH adjusting agent, by concentrated compounding, it is dilute match somebody with somebody, filling, sterilizing, outsourcing step is made.A kind of nasal drops for being used to anaesthetize of the present invention need not establish special administration channel, patient medication process no pain, compliance is good, and product storage process stability is good, will not crystallization go bad, pH value of solution is almost unchanged in the effect phase, and microbial limit is qualified, and keeping life is up to more than 24 months, preparation process impurity increment is smaller, whole preparation process impurity increment is only 0.01%, and preparation process is simple and easy, is worth marketing.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of nasal drops for being used to anaesthetize and preparation method thereof.
Background technology
It is calm before inspection, particularly children check before calmness be urgent clinical needs solution problem, effective medicine safe to use
Thing is to ensure that infant smoothly completes the key of various inspections.
Downern is chloraldurate oral medicine or midazolam oral medicine before inspection domestic conventional at present, Rumi sodium flesh
Meat injection.Problems be present in the drug effect of these downerns and use：(1) chloraldurate oral agents：Be current outpatient service most
Calm medicament before conventional children check, because its mouthfeel is very bitter, many children refuse to take or caused after taking
Vomiting, cause air draught by mistake nearly to increase, or even be in peril of one's life.In addition, chloraldurate metabolite is active, also draws sometimes
Play Delayed recovery；Meanwhile the medicament first pass effect is obvious, sedation effect is not known, and 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 are entitled：(+) -4- (S)-[1- (2,3- 3,5-dimethylphenyl) ethyl] -1H- imidazole hydrochlorides, is acted on
Alpha-2 receptor in brain stem nucleus ceruleus and produce good sedation, but be used alone 2ug/kg Dexmedetomidine calmness after, easily
Waken up with a start by environmental stimuli, turn awake rate up to 50% or so, cause calm failure；Larger dose hydrochloric acid Dexmedetomidine (>2ug/
Kg), bradycardia phenomenon can be produced.
Ketamine is nmda receptor antagonist, has antalgic and sedative and induced sympathetic activation, but general its uses the agent needed
Measure larger, easily cause elevation of the blood pressure and that waking is restless be present.
Nasal drops, which means to specialize in, instills the liquid preparation that uses in nasal cavity, the nasal drops developed in the past using local action as
It is main, it is widely used for treating various nasal cavities and disease of nasal sinus, also can closes on organ disease for relevant with rhinopathy as adjuvant drug
Suffer from.Recently as the further investigation of this method of administration, it is about 150cm to find mankind's nasal mucosal surface product2, respiratory region glues
Film surface epithelial cells have many fine hair, can increase the effective area of drug absorption, and there is abundant hair in nasal epithelial lower floor
Thin blood vessel, venous sinus, arterio-venous anastomosis and lobule intertexture net, make the medicine of absorption to quickly enter blood and follow
Ring, to improve the bioavilability of nasal cavity applied medicine.
In summary, research of the prior art to hydrochloric acid Dexmedetomidine and ketamine can not still meet the need of Clinical practice
Ask, it is a kind of for Clinical practice to be convenient, work rapid, safely and effectively compound anesthesia nasal drops to be badly in need of exploitation；At present, nasal drops
There are still storage process stability is poor, easy crystallization, pH value of solution is changed greatly, and microbial limit is difficult to control, shelf life is short,
Preparation process impurity increases the technical problem urgent need to resolve such as obvious.
The content of the invention
It is an object of the invention to provide a kind of stability is good, product will not layer crystallization be used for the nasal drops anaesthetized.
Another object of the present invention is to provide the preparation method of the above-mentioned nasal drops for being used to anaesthetize.
The purpose of the present invention is realized by following technical measures：
A kind of nasal drops for being used to anaesthetize, it is characterised in that it is using hydrochloric acid Dexmedetomidine and ketalar as original
Material, adds a certain amount of osmotic pressure regulator, bacteriostatic agent, antioxidant, cosolvent, pH adjusting agent, by concentrated compounding, dilute match somebody with somebody, fills
Dress, sterilizing, outsourcing step are made.
Further, a kind of nasal drops for being used to anaesthetize, it is characterised in that the osmotic pressure regulator is sodium chloride, chlorination
One or more in potassium, glucose, mannitol；The bacteriostatic agent is methyl hydroxybenzoate, ethyl hydroxy benzoate, butyl hydroxybenzoate, benzene bundle chlorine
One or more in ammonium, benzalkonium bromide, benzoic acid, sodium benzoate；The antioxidant is vitamin C, METHIONINE, thio
One or more in sodium sulphate, sodium sulfite, sodium pyrosulfite, cysteine；The cosolvent is glycerine, propane diols, second
One kind in alcohol, polyethylene glycol 200；The pH adjusting agent be hydrochloric acid, sulfuric acid, phosphoric acid, sodium acid carbonate, sodium carbonate, sodium hydroxide,
One kind in potassium hydroxide.
A kind of nasal drops for being used to anaesthetize, it is characterised in that it is the supplementary material for including following weight proportion：The right U.S. of hydrochloric acid
Hold in the palm 1 part of miaow pyridine, 500~1000 parts of ketalar, 1000~3000 parts of glucose, 20~80 parts of ethyl hydroxy benzoate, thiosulfuric acid
200~500 parts of sodium, 15~35 parts of glycerine, 20~60 parts of polyethylene glycol 200,1~80 part of sodium acid carbonate, purified water 5000~
15000 parts.
Inventor has found that specific supplementary material species and consumption proportion are specific during preparing in research process
PH, then coordinate specific supplementary material processing method, may be such that the above-mentioned nasal drops for being used to anaesthetize total impurities in preparation process
Increment is smaller, storage process stability well will not crystallization, it is above-mentioned be used for anaesthetize nasal drops, it is characterised in that it include it is following
The supplementary material of weight proportion：1 part of hydrochloric acid Dexmedetomidine, 600~800 parts of ketalar, 1800~2300 parts of glucose, hydroxyl
30~60 parts of phenethyl ester, 300~400 parts of sodium thiosulfate, 20~29 parts of glycerine, 30~50 parts of polyethylene glycol 200, bicarbonate
22~51 parts of sodium, 9000~12000 parts of purified water；The purified water of 1/5 recipe quantity is added into material-compound tank, adds the salt of recipe quantity
Sour Dexmedetomidine, ketalar, glucose, ethyl hydroxy benzoate, sodium thiosulfate, setting rotating speed are 60~80 turns/min, are stirred
Mix, make to dissolve to obtain solution 1, it is standby；A material-compound tank separately is taken, the purified water as wherein adding 2/5 recipe quantity, adds recipe quantity
Glycerine, polyethylene glycol 200, setting rotating speed are 60~80 turns/min, and temperature is 40~50 DEG C, stirs and evenly mixs to obtain solution 2, standby；
Obtained solution 1 and solution 2 are mixed, stir and evenly mix to obtain solution 3, it is standby；The sodium acid carbonate of recipe quantity is added into solution, is adjusted
It is 5.5~6.0 to save pH value of solution, then adds the activated carbon that mass fraction is 0.1%~0.3%, adsorption bleaching, with 0.45 μm
Filter membrane filtration, collect filtrate, add the remaining pure water of recipe quantity, stir and evenly mix, through middle product examine conjunction is tested after ultrasound degassing
Upper streamline is carried out filling after lattice, and the nitrogen that pouring process need to be filled with purity 99.99% causes oxygen content in tank in solution not
More than 0.01%, sealed after inflated with nitrogen.
A kind of preparation method for the nasal drops for being used to anaesthetize, it is characterised in that it is obtained as follows：
1. concentrated compounding：The purified water of 1/5 recipe quantity is added into material-compound tank, adds hydrochloric acid Dexmedetomidine, the salt of recipe quantity
Sour ketamine, glucose, ethyl hydroxy benzoate, sodium thiosulfate, setting rotating speed are 60~80 turns/min, stirring, make to dissolve to obtain solution
1, it is standby；A material-compound tank separately is taken, the purified water as wherein adding 2/5 recipe quantity, adds glycerine, the polyethylene glycol of recipe quantity
200, setting rotating speed is 60~80 turns/min, and temperature is 40~50 DEG C, stirs and evenly mixs to obtain solution 2, standby；
2. dilute match somebody with somebody：Obtained solution 1 and solution 2 in step 1 are mixed, stir and evenly mix to obtain solution 3, it is standby；Into solution
The sodium acid carbonate of recipe quantity is added, regulation pH value of solution is 5.5~6.0, and it is 0.1%~0.3% then to add mass fraction
Activated carbon, adsorption bleaching, filtered with 0.45 μm of filter membrane, collect filtrate, added the remaining pure water of recipe quantity, stir and evenly mix,
It is qualified to be tested after ultrasound degassing through middle product examine, you can；
3. embedding：Upper streamline progress is filling after the assay was approved for intermediate, and pouring process need to be filled with the nitrogen of purity 99.99%
Gas causes the oxygen content in tank in solution to be no more than 0.01%, is sealed after inflated with nitrogen；
4. sterilizing：Canned nasal drops semi-finished product are sent into steam sterilization pan sterilizing, 115 DEG C of sterilizing 32min, sterilized
Into being hunted leak by rated condition；
5. examine：Sample checks visible foreign matters after sterilizing, and qualified sample will be examined to be packed, full inspection, storage.
The present invention has following beneficial effect：
A kind of nasal drops for being used to anaesthetize of the present invention need not establish special administration channel, and patient medication process no pain is suitable
Answering property is good, product storage process stability it is good, will not crystallization go bad, pH value of solution is almost unchanged in the effect phase, microbial limit close
Lattice, keeping life are up to more than 24 months, and preparation process impurity increment is smaller, and whole preparation process impurity increment is only
0.01%, preparation process is simple and easy, is worth marketing.
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 limiting the scope of the invention is interpreted as, without departing substantially from spirit of the invention
In the case of essence, the modifications or substitutions made to the inventive method, step or condition belong to the scope of the present invention.
Embodiment 1
A kind of nasal drops for being used to anaesthetize, is made according to the following steps：
| Composition | Dosage (parts by weight) |
| Hydrochloric acid Dexmedetomidine | 1 part |
| Ketalar | 720 parts |
| Glucose | 2100 parts |
| Ethyl hydroxy benzoate | 50 parts |
| Sodium thiosulfate | 350 parts |
| Glycerine | 25 parts |
| Polyethylene glycol 200 | 40 parts |
| Sodium acid carbonate | 36 parts |
| Purified water | 11000 parts |
Preparation process：
1. concentrated compounding：The purified water of 1/5 recipe quantity is added into material-compound tank, adds hydrochloric acid Dexmedetomidine, the salt of recipe quantity
Sour ketamine, glucose, ethyl hydroxy benzoate, sodium thiosulfate, setting rotating speed are 60~80 turns/min, stirring, make to dissolve to obtain solution
1, it is standby；A material-compound tank separately is taken, the purified water as wherein adding 2/5 recipe quantity, adds glycerine, the polyethylene glycol of recipe quantity
200, setting rotating speed is 60~80 turns/min, and temperature is 40~50 DEG C, stirs and evenly mixs to obtain solution 2, standby；
2. dilute match somebody with somebody：Obtained solution 1 and solution 2 in step 1 are mixed, stir and evenly mix to obtain solution 3, it is standby；Into solution
The sodium acid carbonate of recipe quantity is added, regulation pH value of solution is 5.5~6.0, and it is 0.1%~0.3% then to add mass fraction
Activated carbon, adsorption bleaching, filtered with 0.45 μm of filter membrane, collect filtrate, added the remaining pure water of recipe quantity, stir and evenly mix,
It is qualified to be tested after ultrasound degassing through middle product examine, you can；
3. embedding：Upper streamline progress is filling after the assay was approved for intermediate, and pouring process need to be filled with the nitrogen of purity 99.99%
Gas causes the oxygen content in tank in solution to be no more than 0.01%, is sealed after inflated with nitrogen；
4. sterilizing：Canned nasal drops semi-finished product are sent into steam sterilization pan sterilizing, 115 DEG C of sterilizing 32min, sterilized
Into being hunted leak by rated condition；
5. examine：Sample checks visible foreign matters after sterilizing, and qualified sample will be examined to be packed, full inspection, storage.
In order to be better understood from the present invention, having for invention medicine is expanded on further below by way of stability test of the present invention
Beneficial effect, rather than limitation of the present invention.
Experiment one：A kind of nasal drops stability experiment for being used to anaesthetize of the present invention
Experiment material：
A kind of nasal drops sample for being used to anaesthetize：It is made for embodiment 1
Acceleration study method：Nasal drops made from embodiment 1 is packed by listing, put in Acceleration study case, certain time
Sampling, tests to investigation project.
Acceleration study temperature：40±2℃
Humidity：RH75% ± 5%
Investigate the time：0th, 1,2,3, June
Inspection target：Character, pH, content, relevant material, clarity, microbial limit
Accelerated test stability records：
Acceleration study result shows：Acceleration sample in June is suitable with 0 month sample items Testing index quality, shows that this product adds
Speed is tested June, and quality keeps stable, and this product stability is preferable.
Long-term experiment method：The obtained nasal drops for being used to anaesthetize of embodiment 1 is packed by listing, puts the long-term case that keeps sample
In, certain time sampling, investigation project is tested.
Acceleration study temperature：25±2℃
Humidity：RH60% ± 10%
Investigate the time：0th, 3,6,9,12,18,24 months
Inspection target：Character, pH, content, relevant material, clarity, microbial limit
Long term test stability records：
Long term test shows：24 months characters of this product long term test, pH, content, relevant material, clarity, microorganism limit
Degree checks that indices without significant changes, meet every relevant regulations of production quality standard draft.This product is tried for a long time
Test 24 months steady qualities, therefore minimum 24 months of this product term of validity, long term test is still during investigation is continued.
Experiment two：A kind of nasal drops supplementary product kind for being used to anaesthetize of the present invention and preparation process are on the increased influence of impurity
1. test method：
A kind of nasal drops sample for being used to anaesthetize：Prepared by embodiment 1.
A kind of nasal drops control sample 1 for being used to anaesthetize：To lack sample made from the prescription of sodium thiosulfate, it is prepared
Technique is the same as embodiment 1.
A kind of nasal drops control sample 2 for being used to anaesthetize：To lack sample made from the prescription of glycerine, its preparation technology is same
Embodiment 1.
A kind of nasal drops control sample 3 for being used to anaesthetize：To lack sample made from the prescription of polyethylene glycol 200, it is made
Standby technique is the same as embodiment 1.
A kind of nasal drops control sample 4 for being used to anaesthetize：Prescription is the prescription of embodiment 1, and the method for being prepared as follows is made：
1. concentrated compounding：The purified water of 3/5 recipe quantity is added into material-compound tank, add the hydrochloric acid Dexmedetomidine of recipe quantity, ketalar,
Glucose, ethyl hydroxy benzoate, sodium thiosulfate, glycerine, polyethylene glycol 200, setting rotating speed are 60~80 turns/min, stirring, are made molten
Solution is solved, it is standby；2. dilute match somebody with somebody：Into step 1, obtained solution adds the sodium acid carbonate of recipe quantity, and regulation pH value of solution is 5.5
~6.0, the activated carbon that mass fraction is 0.1%~0.3% is then added, adsorption bleaching, is filtered with 0.45 μm of filter membrane, is received
Collect filtrate, add the remaining pure water of recipe quantity, stir and evenly mix, it is qualified to be tested after ultrasound degassing through middle product examine, you can；3. fill
Envelope：Intermediate after the assay was approved upper streamline carry out it is filling, pouring process need to be filled with purity 99.99% nitrogen cause it is molten in tank
Oxygen content in liquid is no more than 0.01%, is sealed after inflated with nitrogen；4. sterilizing：Canned nasal drops semi-finished product are sent into steam
Autoclave is sterilized, and 115 DEG C of sterilizing 32min, sterilizing is completed, hunted leak by rated condition；5. examine：Sample checks visible after sterilizing
Foreign matter, qualified sample will be examined to be packed, full inspection, storage.
A kind of nasal drops raw material control sample for being used to anaesthetize：Take hydrochloric acid Dexmedetomidine, the ketalar of recipe quantity
Add purified water, direct injected, face with newly matching somebody with somebody, as impurity basic data.
2. result of the test see the table below：
3. experimental result and conclusion：The prescription of embodiment 1, coordinate specific preparation technology, relevant material increase is only
0.01%, hence it is evident that better than other control samples.
Embodiment 2
A kind of nasal drops for being used to anaesthetize, is made according to the following steps：
| Composition | Dosage (parts by weight) |
| Hydrochloric acid Dexmedetomidine | 1 part |
| Ketalar | 600 parts |
| Glucose | 1800 parts |
| Ethyl hydroxy benzoate | 30 parts |
| Sodium thiosulfate | 300 parts |
| Glycerine | 20 parts |
| Polyethylene glycol 200 | 30 parts |
| Sodium acid carbonate | 22 parts |
| Purified water | 9000 parts |
Preparation process：It is made according to the preparation technology of embodiment 1.
By the test method of embodiment 1, the sample stability result of the test of embodiment 2 shows to accelerate sample quality stabilization in June,
Long-term 24 months steady qualities, therefore minimum 24 months of this product term of validity；Supplementary product kind and preparation process are on the increased influence of impurity
Result of the test shows the prescription of embodiment 2, coordinates specific preparation technology, and relevant material increase is substantially better than its control sample.
Embodiment 3
A kind of nasal drops for being used to anaesthetize, is made according to the following steps：
| Composition | Dosage (parts by weight) |
| Hydrochloric acid Dexmedetomidine | 1 part |
| Ketalar | 800 parts |
| Glucose | 2300 parts |
| Ethyl hydroxy benzoate | 60 parts |
| Sodium thiosulfate | 400 parts |
| Glycerine | 29 parts |
| Polyethylene glycol 200 | 50 parts |
| Sodium acid carbonate | 51 parts |
| Purified water | 12000 parts |
Preparation process：It is made according to the preparation technology of embodiment 1.
By the test method of embodiment 1, the sample stability result of the test of embodiment 3 shows to accelerate sample quality stabilization in June,
Long-term 24 months steady qualities, therefore minimum 24 months of this product term of validity；Supplementary product kind and preparation process are on the increased influence of impurity
Result of the test shows the prescription of embodiment 3, coordinates specific preparation technology, and relevant material increase is substantially better than its control sample.
Embodiment 4-6：A kind of nasal drops for being used to anaesthetize, is prepared, preparation method is same by the supplementary material of following weight
Embodiment 1：
By the test method of embodiment 1, the sample stability result of the test of embodiment 4,5,6 shows to accelerate sample quality in June
It is stable, long-term 24 months steady qualities, therefore minimum 24 months of this product term of validity；Supplementary product kind and preparation process are increased to impurity
The prescription that result of the test shows embodiment 4,5,6 is influenceed, coordinates specific preparation technology, it is right that relevant material increase is substantially better than its
Product in the same old way.
Claims (5)
1. it is a kind of be used for anaesthetize nasal drops, it is characterised in that it be using hydrochloric acid Dexmedetomidine and ketalar as raw material,
Add a certain amount of osmotic pressure regulator, bacteriostatic agent, antioxidant, cosolvent, pH adjusting agent, by concentrated compounding, it is dilute match somebody with somebody, it is filling,
Sterilizing, outsourcing step are made.
2. the as claimed in claim 1 nasal drops for being used to anaesthetize, it is characterised in that the osmotic pressure regulator be sodium chloride,
One or more in potassium chloride, glucose, mannitol；The bacteriostatic agent is methyl hydroxybenzoate, ethyl hydroxy benzoate, butyl hydroxybenzoate, benzene
The one or more pricked in oronain, benzalkonium bromide, benzoic acid, sodium benzoate；The antioxidant be vitamin C, METHIONINE,
One or more in sodium thiosulfate, sodium sulfite, sodium pyrosulfite, cysteine；The cosolvent is glycerine, the third two
One kind in alcohol, ethanol, polyethylene glycol 200；The pH adjusting agent is hydrochloric acid, sulfuric acid, phosphoric acid, sodium acid carbonate, sodium carbonate, hydrogen-oxygen
Change one kind in sodium, potassium hydroxide.
3. the nasal drops as claimed in claim 1 or 2 for being used to anaesthetize, it is characterised in that it includes following weight proportion
Supplementary material：1 part of hydrochloric acid Dexmedetomidine, 500~1000 parts of ketalar, 1000~3000 parts of glucose, ethyl hydroxy benzoate 20
~80 parts, 200~500 parts of sodium thiosulfate, 15~35 parts of glycerine, 20~60 parts of polyethylene glycol 200, sodium acid carbonate 1~80
Part, 5000~15000 parts of purified water.
4. the nasal drops for being used to anaesthetize as described in claim 1,2 or 3, it is characterised in that it includes following weight proportion
Supplementary material：1 part of hydrochloric acid Dexmedetomidine, 600~800 parts of ketalar, 1800~2300 parts of glucose, ethyl hydroxy benzoate 30~
60 parts, 300~400 parts of sodium thiosulfate, 20~29 parts of glycerine, 30~50 parts of polyethylene glycol 200,22~51 parts of sodium acid carbonate,
9000~12000 parts of purified water；The purified water of 1/5 recipe quantity is added into material-compound tank, adds the right U.S. support miaow of hydrochloric acid of recipe quantity
Pyridine, ketalar, glucose, ethyl hydroxy benzoate, sodium thiosulfate, setting rotating speed are 60~80 turns/min, stirring, make to dissolve
Solution 1, it is standby；A material-compound tank separately is taken, the purified water as wherein adding 2/5 recipe quantity, adds glycerine, the poly- second two of recipe quantity
Alcohol 200, setting rotating speed are 60~80 turns/min, and temperature is 40~50 DEG C, stirs and evenly mixs to obtain solution 2, standby；By obtained solution
1 and solution 2 mix, stir and evenly mix to obtain solution 3, it is standby；The sodium acid carbonate of recipe quantity is added into solution, regulation pH value of solution is
5.5~6.0, the activated carbon that mass fraction is 0.1%~0.3% is then added, adsorption bleaching, is filtered with 0.45 μm of filter membrane
Cross, collect filtrate, add the remaining pure water of recipe quantity, stir and evenly mix, it is upper after the assay was approved through middle product after ultrasound degassing
Waterline progress is filling, and pouring process need to be filled with the nitrogen of purity 99.99% so that the oxygen content in tank in solution is no more than
0.01%, sealed after inflated with nitrogen.
5. a kind of preparation method for the nasal drops for being used to anaesthetize, it is characterised in that it is obtained as follows：
A. concentrated compounding：The purified water of 1/5 recipe quantity is added into material-compound tank, adds hydrochloric acid Dexmedetomidine, the hydrochloric acid chlorine of recipe quantity
Amine ketone, glucose, ethyl hydroxy benzoate, sodium thiosulfate, setting rotating speed are 60~80 turns/min, stirring, make to dissolve to obtain solution 1, standby
With；A material-compound tank separately is taken, the purified water as wherein adding 2/5 recipe quantity, adds glycerine, the polyethylene glycol 200 of recipe quantity, if
It is 60~80 turns/min to put rotating speed, and temperature is 40~50 DEG C, stirs and evenly mixs to obtain solution 2, standby；
B. it is dilute to match somebody with somebody：Obtained solution 1 and solution 2 in step 1 are mixed, stir and evenly mix to obtain solution 3, it is standby；Added into solution
The sodium acid carbonate of recipe quantity, regulation pH value of solution is 5.5~6.0, then adds the activity that mass fraction is 0.1%~0.3%
Charcoal, adsorption bleaching, filtered with 0.45 μm of filter membrane, collect filtrate, added the remaining pure water of recipe quantity, stir and evenly mix, ultrasound
It is qualified to be tested after degassing through middle product examine, you can；
C. embedding：Upper streamline progress is filling after the assay was approved for intermediate, and the nitrogen that pouring process need to be filled with purity 99.99% makes
Obtain the oxygen content in tank in solution and be no more than 0.01%, sealed after inflated with nitrogen；
D. sterilize：Canned nasal drops semi-finished product are sent into steam sterilization pan sterilizing, 115 DEG C of sterilizing 32min, sterilizing is completed,
Hunted leak by rated condition；
E. examine：Sample checks visible foreign matters after sterilizing, and qualified sample will be examined to be packed, full inspection, storage.
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| CN201710272858.7A CN107693485A (en) | 2017-04-24 | 2017-04-24 | A kind of nasal drops for being used to anaesthetize and preparation method thereof |
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| CN201710272858.7A CN107693485A (en) | 2017-04-24 | 2017-04-24 | A kind of nasal drops for being used to anaesthetize and preparation method thereof |
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| CN107693485A true CN107693485A (en) | 2018-02-16 |
Family
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20190262314A1 (en) * | 2018-02-26 | 2019-08-29 | Slayback Pharma Llc | Ready-to-use dexmedetomidine compositions |
| WO2021014108A1 (en) * | 2019-07-25 | 2021-01-28 | Laboratoires Grimberg | Nasal or oral spray composition containing sulfur |
| CN114306219A (en) * | 2020-09-30 | 2022-04-12 | 四川普锐特药业有限公司 | Stable R-ketamine pharmaceutical composition |
| 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 |
| US11478422B2 (en) | 2018-06-27 | 2022-10-25 | 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 |
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| RAVI BHAT等: "Comparison of intranasal dexmedetomidine and dexmedetomidineketamine for premedication in pediatrics patients: A randomized doubleblind study", 《ANESTH ESSAYS RES》 * |
| 方亮: "《药剂学》", 31 March 2016, 中国医药科技出版社 * |
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US11786508B2 (en) | 2016-12-31 | 2023-10-17 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| US20190262314A1 (en) * | 2018-02-26 | 2019-08-29 | Slayback Pharma Llc | Ready-to-use dexmedetomidine compositions |
| US11478422B2 (en) | 2018-06-27 | 2022-10-25 | 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 |
| 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 |
| US11806429B2 (en) | 2018-06-27 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US12109196B2 (en) | 2019-07-19 | 2024-10-08 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11998529B2 (en) | 2019-07-19 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11890272B2 (en) | 2019-07-19 | 2024-02-06 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| FR3099051A1 (en) * | 2019-07-25 | 2021-01-29 | Laboratoires Grimberg | Nasal or oral spray composition containing sulfur |
| WO2021014108A1 (en) * | 2019-07-25 | 2021-01-28 | Laboratoires Grimberg | Nasal or oral spray composition containing sulfur |
| CN114306219B (en) * | 2020-09-30 | 2023-09-26 | 四川普锐特药业有限公司 | Stable R-ketamine pharmaceutical composition |
| 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 |
| CN114306219A (en) * | 2020-09-30 | 2022-04-12 | 四川普锐特药业有限公司 | Stable R-ketamine pharmaceutical composition |
| 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 |
| 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 |
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