CN107412204A - A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize and preparation method thereof - Google Patents
A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize and preparation method thereof Download PDFInfo
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- CN107412204A CN107412204A CN201710272857.2A CN201710272857A CN107412204A CN 107412204 A CN107412204 A CN 107412204A CN 201710272857 A CN201710272857 A CN 201710272857A CN 107412204 A CN107412204 A CN 107412204A
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- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
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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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
Abstract
A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize, it is using hydrochloric acid Dexmedetomidine and ketalar as raw material, adds a certain amount of carrier, activity protecting agent, lubricant, pH adjusting agent, is made by the step such as pre-treatment, mixing, drying, always mixed, filling.A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize of the present invention need not establish special administration channel, patient medication process no pain, and compliance is good, product storage process stability is good, storage process pH changes are small, impurity increment is small, and impurity increment is only 0.06% in the effect phase, and keeping life is up to more than 36 months, powder flowbility is good, not sub- angle is less than 42 °, and content uniformity is good, and the content RSD of multiple points is less than 1%, 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 Foradil Aerolizer formoterol fumarate for being used to anaesthetize and its preparation side
Method.
Background technology
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.
In summary, research of the prior art to hydrochloric acid Dexmedetomidine and ketamine can not still meet the need of Clinical practice
Ask, be badly in need of that exploitation is a kind of to be used for that Clinical practice to be convenient, it is rapid to work, safely and effectively dry powder inhaler formulations；At present, dry powder sucks
Agent still have storage process stability it is poor, pH is changed greatly, and impurity is difficult to control, and shelf life is short, and powder flowbility difference is led
Cause to cause drug risk to increase the problems such as finished product content uniformity is larger, and preparation process content uniformity is poor.
The content of the invention
It is an object of the invention to provide the Foradil Aerolizer formoterol fumarate for being used to anaesthetize that a kind of stability is good, content uniformity is good.
Another object of the present invention is to provide the preparation method of the above-mentioned Foradil Aerolizer formoterol fumarate for being used to anaesthetize.
The purpose of the present invention is realized by following technical measures：
A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize, it is characterised in that it is with hydrochloric acid Dexmedetomidine and ketalar
For raw material, add a certain amount of carrier, activity protecting agent, lubricant, pH adjusting agent, by pre-treatment, mixing, drying, it is total mixed,
Filling step is made.
Further, a kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize, it is characterised in that the carrier is sodium chloride, lactose, chlorination
One or more in potassium, glucose, mannitol, calcium chloride；The activity protecting agent is albumin, lysine, alanine, bright
One or more in propylhomoserin, tyrosine, beta-schardinger dextrin, soybean lecithin；The lubricant is in magnesium stearate, talcum powder
It is a kind of；The pH adjusting agent is citric acid, tartaric acid, fumaric acid, adipic acid, malic acid, sodium acid carbonate, sodium carbonate, hydroxide
One kind in sodium, potassium hydroxide.
Inventor has found that specific supplementary material species coordinates specific supplementary material consumption proportion relation, can make in research process
Above-mentioned anesthesia Foradil Aerolizer formoterol fumarate storage process pH change it is smaller, impurity increment is smaller, and product stability is good, above-mentioned to be used for
The Foradil Aerolizer formoterol fumarate of anesthesia, it is characterised in that it includes the supplementary material of following weight proportion：1 part of hydrochloric acid Dexmedetomidine, hydrochloric acid
It is 500~1000 parts of ketamine, 2000~2500 parts of lactose, 1000~2000 parts of mannitol, 2000~3000 parts of beta-schardinger dextrin, hard
1500~3000 parts of fatty acid magnesium, 80~130 parts of sodium carbonate.
Further, larger in order to solve finished product content uniformity, the problem of preparation process content lack of homogeneity, above-mentioned anesthesia is used
Foradil Aerolizer formoterol fumarate, it is characterised in that it is the supplementary material for including following weight proportion：1 part of hydrochloric acid Dexmedetomidine, hydrochloric acid chlorine
700~900 parts of amine ketone, 2200~2300 parts of lactose, 1300~1500 parts of mannitol, 2200~2500 parts of beta-schardinger dextrin, tristearin
Sour 1800~2000 parts of magnesium, 100~120 parts of sodium carbonate；By hydrochloric acid Dexmedetomidine, the hydrochloric acid of the recipe quantity Jing Guo sterilization treatment
It is placed in after ketamine, beta-schardinger dextrin mixing in air-stream type ultrafine pulverizer, crushes and be less than 5 μm of powder for particle diameter, obtain powder
1, it is standby；Lactose, mannitol, the sodium carbonate of the recipe quantity of another sterilization treatment of learning from else's experience are placed in air-stream type ultrafine pulverizer after mixing
In, crush as the powder that particle diameter is 10~30 μm, obtain powder 2, it is standby；Powder 1 and powder 2 obtained above is taken to be placed in three-dimensional
In movement mixer, mix 20~30 minutes, take out, it is standby.
A kind of preparation method for the Foradil Aerolizer formoterol fumarate for being used to anaesthetize, it is characterised in that it is obtained as follows：
1. supplementary material pre-treatment：By the hydrochloric acid Dexmedetomidine, ketalar, β of the recipe quantity after sterilization treatment-ring paste
It is placed in after essence mixing in air-stream type ultrafine pulverizer, crushes and be less than 5 μm of powder for particle diameter, obtain powder 1, it is standby；Separately learn from else's experience
Lactose, mannitol, the sodium carbonate of recipe quantity after sterilization treatment are placed in air-stream type ultrafine pulverizer after mixing, and are crushed as particle diameter
For 10~30 μm of powder, powder 2 is obtained, it is standby；Separately take the magnesium stearate of recipe quantity to be placed in Universalpulverizer, crushed
200 mesh sieves, powder 3 is obtained, it is standby；
2. mixing：Take obtained powder 1 and powder 2 in step 1 to be placed in three-dimensional motion mixer, mix 20~30 points
Clock, take out, it is standby；
3. dry：Obtained mixed-powder in step 2 is placed in fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, opens
Beginning drying；Powder boiling situation, air blast situation are observed at any time, are prevented powder from clinging the bottom of a pan, are caused powder coking or gelatinization, dry
Time is 50~55 minutes, ensures aqueous powder≤3%；
It is 4. total mixed：Take in step 1 that dried mixed-powder is placed in trough type mixing machine in obtained powder 3, step 3,
Mixing 10~20 minutes, intermediate inspection is carried out, after qualified, carried out filling；
5. embedding：Upper streamline progress is filling after the assay was approved for intermediate；
6. examine, outsourcing：Qualified sample will be examined to be packed, full inspection, storage.
The present invention has following beneficial effect：
A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize of the present invention need not establish special administration channel, and patient medication process is painless
Hardship, compliance is good, and product storage process stability is good, and storage process pH change is small, impurity increment is small, and impurity increment is only in the effect phase
For 0.06%, keeping life is up to more than 36 months, and powder flowbility is good, and not sub- angle is less than 42 °, and content uniformity is good, more
The content RSD of individual point is less than 1%, and 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 Foradil Aerolizer formoterol fumarate 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 |
| Lactose | 2250 parts |
| Mannitol | 1450 parts |
| Beta-schardinger dextrin | 2350 parts |
| Magnesium stearate | 1900 parts |
| Sodium carbonate | 110 parts |
Preparation process：
1. supplementary material pre-treatment：By the hydrochloric acid Dexmedetomidine, ketalar, β of the recipe quantity after sterilization treatment-ring paste
It is placed in after essence mixing in air-stream type ultrafine pulverizer, crushes and be less than 5 μm of powder for particle diameter, obtain powder 1, it is standby；Separately learn from else's experience
Lactose, mannitol, the sodium carbonate of recipe quantity after sterilization treatment are placed in air-stream type ultrafine pulverizer after mixing, and are crushed as particle diameter
For 10~30 μm of powder, powder 2 is obtained, it is standby；Separately take the magnesium stearate of recipe quantity to be placed in Universalpulverizer, crushed
200 mesh sieves, powder 3 is obtained, it is standby；
2. mixing：Take obtained powder 1 and powder 2 in step 1 to be placed in three-dimensional motion mixer, mix 20~30 points
Clock, take out, it is standby；
3. dry：Obtained mixed-powder in step 2 is placed in fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, opens
Beginning drying；Powder boiling situation, air blast situation are observed at any time, are prevented powder from clinging the bottom of a pan, are caused powder coking or gelatinization, dry
Time is 50~55 minutes, ensures aqueous powder≤3%；
It is 4. total mixed：Take in step 1 that dried mixed-powder is placed in trough type mixing machine in obtained powder 3, step 3,
Mixing 10~20 minutes, intermediate inspection is carried out, after qualified, carried out filling；
5. embedding：Upper streamline progress is filling after the assay was approved for intermediate；
6. examine, outsourcing：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 Foradil Aerolizer formoterol fumarate stability experiment for being used to anaesthetize of the present invention
Experiment material：
A kind of Foradil Aerolizer formoterol fumarate sample for being used to anaesthetize：It is made for embodiment 1
Acceleration study method：Foradil Aerolizer formoterol fumarate made from embodiment 1 is packed by listing, put in Acceleration study case, necessarily
Time sampling, investigation project is tested.
Acceleration study temperature：40±2℃
Humidity：RH75% ± 5%
Investigate the time：0th, 1,2,3, June
Inspection target：Character, pH, content, relevant material, dosage delivered homogeneity, minuteness particle dosage, 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 Foradil Aerolizer formoterol fumarate for being used to anaesthetize of embodiment 1 is packed by listing, puts and keeps sample for a long time
In case, certain time sampling, investigation project is tested.
Acceleration study temperature：25±2℃
Humidity：RH60% ± 10%
Investigate the time：0th, 3,6,9,12,18,24,36 months
Inspection target：Character, pH, content, relevant material, dosage delivered homogeneity, minuteness particle dosage, microbial limit
Long term test stability records：
Long term test shows：36 months characters of this product long term test, pH, content, relevant material, dosage delivered homogeneity,
Minuteness particle dosage, limit test of microbe indices change smaller, impurity increment only 0.06% without significant changes, pH,
Meet every relevant regulations of production quality standard draft.36 months steady qualities of this product long term test, therefore this product is effective
Minimum 36 months of phase, long term test is still during investigation is continued.
Experiment two：Powder stops sub- angle measure
1. test material：Sample after the completion of always being mixed in the preparation process of embodiment 1
2. test method：After the completion of embodiment 1 is always mixed, distinguish respectively in the upper, middle and lower of trough type mixing machine, left and right each point
Angle of repose is measured by sampling, judges its mobility；
3. result of the test：
4. conclusion (of pressure testing)：It can be seen that by upper table result of the test, five times measurement angle of repose is respectively less than 42 °, shows flow of powder
Property is good.
Experiment three：Content uniformity
1. test material：Sample after the completion of being mixed in the preparation process of embodiment 1
2. test method：After the completion of embodiment 1 mixes, respectively in the upper, middle and lower of three-dimensional motion mixer, left and right each point
Separately sampled 5g, content detection is carried out according to content assaying method, the content RSD of each sample point is calculated, evaluates whether to be well mixed；
3. result of the test：
4. conclusion (of pressure testing)：It can be seen that by upper table result of the test, this product content uniformity is good, and RSD is less than 1%
Embodiment 2
A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize, is made according to the following steps：
| Composition | Dosage (parts by weight) |
| Hydrochloric acid Dexmedetomidine | 1 part |
| Ketalar | 700 parts |
| Lactose | 2200 parts |
| Mannitol | 1300 parts |
| Beta-schardinger dextrin | 2200 parts |
| Magnesium stearate | 1800 parts |
| Sodium carbonate | 100 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 36 months steady qualities, therefore minimum 36 months of this product term of validity；Powder is stopped sub- angle determination test result and is less than for not sub- angle
39 °, show that the powder flowbility of embodiment 2 is good；Content uniformity result of the test shows that this product RSD is less than 1%, shows this
Product content uniformity is good.
Embodiment 3
A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize, is made according to the following steps：
| Composition | Dosage (parts by weight) |
| Hydrochloric acid Dexmedetomidine | 1 part |
| Ketalar | 900 parts |
| Lactose | 2300 parts |
| Mannitol | 1500 parts |
| Beta-schardinger dextrin | 2500 parts |
| Magnesium stearate | 2000 parts |
| Sodium carbonate | 120 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 36 months steady qualities, therefore minimum 36 months of this product term of validity；Powder is stopped sub- angle determination test result and is less than for not sub- angle
39 °, show that the powder flowbility of embodiment 3 is good；Content uniformity result of the test shows that this product RSD is less than 1%, shows this
Product content uniformity is good.
Embodiment 4-6：A kind of Foradil Aerolizer formoterol fumarate for being used to anaesthetize, is prepared, preparation side by the supplementary material of following weight
Method is the same as 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 36 months steady qualities, therefore minimum 36 months of this product term of validity；The sample powder of embodiment 4,5,6 stops sub- angle measure
Result of the test is respectively smaller than 38 °, 41 °, 39 °, shows that the powder flowbility of embodiment 4,5,6 is good；Content uniformity is tested
As a result show that the sample RSD of embodiment 4,5,6 is respectively less than 1%, show that this product content uniformity is good.
Claims (5)
- A kind of 1. Foradil Aerolizer formoterol fumarate for being used to anaesthetize, it is characterised in that it be using hydrochloric acid Dexmedetomidine and ketalar as Raw material, a certain amount of carrier, activity protecting agent, lubricant, pH adjusting agent are added, by pre-treatment, mixing, drying, total mixed, filling The steps such as dress are made.
- A kind of 2. Foradil Aerolizer formoterol fumarate for being used to anaesthetize as claimed in claim 1, it is characterised in that the carrier be sodium chloride, One or more in lactose, potassium chloride, glucose, mannitol, calcium chloride；The activity protecting agent be albumin, lysine, One or more in alanine, leucine, tyrosine, beta-schardinger dextrin, soybean lecithin；The lubricant be magnesium stearate, One kind in talcum powder；The pH adjusting agent is citric acid, tartaric acid, fumaric acid, adipic acid, malic acid, sodium acid carbonate, carbonic acid One kind in sodium, sodium hydroxide, potassium hydroxide.
- 3. the Foradil Aerolizer formoterol fumarate 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, 2000~2500 parts of lactose, mannitol 1000 ~2000 parts, 2000~3000 parts of beta-schardinger dextrin, 1500~3000 parts of magnesium stearate, 80~130 parts of sodium carbonate.
- 4. the Foradil Aerolizer formoterol fumarate of anesthesia as claimed in claim 3, it is characterised in that it is the original for including following weight proportion Auxiliary material：1 part of hydrochloric acid Dexmedetomidine, 700~900 parts of ketalar, 2200~2300 parts of lactose, mannitol 1300~1500 Part, 2200~2500 parts of beta-schardinger dextrin, 1800~2000 parts of magnesium stearate, 100~120 parts of sodium carbonate；Sterilization treatment will be passed through The hydrochloric acid Dexmedetomidine of recipe quantity, ketalar, be placed in air-stream type ultrafine pulverizer after beta-schardinger dextrin mixing, crush It is less than 5 μm of powder for particle diameter, obtains powder 1, it is standby；Lactose, mannitol, the sodium carbonate of the recipe quantity of another sterilization treatment of learning from else's experience It is placed in after mixing in air-stream type ultrafine pulverizer, crushes as the powder that particle diameter is 10~30 μm, obtain powder 2, it is standby；Take above-mentioned Obtained powder 1 and powder 2 are placed in three-dimensional motion mixer, are mixed 20~30 minutes, are taken out, standby.
- 5. a kind of preparation method of Foradil Aerolizer formoterol fumarate for being used to anaesthetize as described in any one of Claims 1 to 4, its feature exist In it is obtained as follows：A. supplementary material pre-treatment：Hydrochloric acid Dexmedetomidine, ketalar, the beta-schardinger dextrin of recipe quantity after sterilization treatment are mixed It is placed in after conjunction in air-stream type ultrafine pulverizer, crushes and be less than 5 μm of powder for particle diameter, obtain powder 1, it is standby；Another sterilizing of learning from else's experience Lactose, mannitol, the sodium carbonate of recipe quantity after processing are placed in air-stream type ultrafine pulverizer after mixing, and it is 10 to crush as particle diameter ~30 μm of powder, powder 2 is obtained, it is standby；Separately take the magnesium stearate of recipe quantity to be placed in Universalpulverizer, crushed 200 mesh Sieve, obtains powder 3, standby；B. mix：Take obtained powder 1 and powder 2 in step A to be placed in three-dimensional motion mixer, mix 20~30 minutes, take Go out, it is standby；C. dry：Obtained mixed-powder in step B is placed in fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, hops to it It is dry；Powder boiling situation, air blast situation are observed at any time, are prevented powder from clinging the bottom of a pan, are caused powder coking or gelatinization, drying time For 50~55 minutes, ensure aqueous powder≤3%；D. it is total mixed：Take in step A that dried mixed-powder is placed in trough type mixing machine in obtained powder 3, step C, mixing 10~20 minutes, intermediate inspection is carried out, after qualified, is carried out filling；E. embedding：Upper streamline progress is filling after the assay was approved for intermediate；F. examine, outsourcing：Qualified sample will be examined to be packed, full inspection, storage.
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| 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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2017
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11786508B2 (en) | 2016-12-31 | 2023-10-17 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| US11839604B2 (en) | 2016-12-31 | 2023-12-12 | 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 |
| 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 |
| US11890272B2 (en) | 2019-07-19 | 2024-02-06 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| CN113331294A (en) * | 2021-06-03 | 2021-09-03 | 唐传生物科技（厦门）有限公司 | Preparation method of healthy sugar with low glycemic index |
| CN113331294B (en) * | 2021-06-03 | 2024-02-09 | 谷创芯生物科技(厦门)有限公司 | Preparation method of low glycemic index healthy sugar |
| US11806334B1 (en) | 2023-01-12 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
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