CN106038538A - Premixed preparation for dexmedetomidine - Google Patents
Premixed preparation for dexmedetomidine Download PDFInfo
- Publication number
- CN106038538A CN106038538A CN201610231269.XA CN201610231269A CN106038538A CN 106038538 A CN106038538 A CN 106038538A CN 201610231269 A CN201610231269 A CN 201610231269A CN 106038538 A CN106038538 A CN 106038538A
- Authority
- CN
- China
- Prior art keywords
- mixed formulation
- dexmedetomidine
- plastic
- mixed
- layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- 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
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D31/00—Bags or like containers made of paper and having structural provision for thickness of contents
- B65D31/02—Bags or like containers made of paper and having structural provision for thickness of contents with laminated walls
Abstract
The invention relates to a premixed preparation for dexmedetomidine. Specifically, the invention relates to a ready-to-use premixed preparation of dexmedetomidine packaged in a container containing plastic or a pharmaceutically acceptable salt thereof. The ready-to-use premixed preparation can be used for sedation of patients in an intensive care unit or procedural sedation.
Description
Technical field
Dexmedetomidine or the instant of its pharmaceutically acceptable salt that the present invention is packaged in the container containing plastics premix
Close (premixed, ready to use) preparation, town when its calmness that may be used for intensive care unit(ICU) (ICU) sufferer and operation
Quiet (Procedural Sedation).
Background technology
Right U.S. torr pyrimidine is α 2-adrenoceptor agonists, and its chemistry is entitled: (+)-4-(S)-[1-(2,3-3,5-dimethylphenyl)
Ethyl]-1H-imidazoles.Dexmedetomidine is used for the calmness when initially intubating of ICU patient with severe symptoms or injury or was treating
In journey, calmness during mechanical ventilation is it can also be used to non-intubated patient operation or short-term process are calm.
Originally, dexmedetomidine is the concentrated injection mode list marketing with 200mcg/2mL, need during use by
Patient can be used after being diluted by it.Comprise the pre-mixed formulation (Precedex of the instant of dexmedetomidineTM
(dexmedetomidine hydrochloride) in 0.9%Sodium Chloride Injection) in May, 2013 by
HOSPIRA company takes the lead in pushing American market to, has three specifications 80mcg/20mL (4mcg/mL), 200mcg/50mL
(4mcg/mL)、400mcg/100mL(4mcg/mL).Said preparation and the 200mcg/2mL (100 of listing in 1999
Mcg/mL) dexmedetomidine hydrochloride concentrated injection is compared, and decreases dilution step again, has saved time and cost, has had
Help pollution and the risk of excess avoiding human operational error to cause.And US8242158, US8338470,
US8455527, US8648106 point out the reduction using this product of some plastics package easily to cause content, and/or impurity
Raise.
Up to now, the instant pre-mixed formulation comprising dexmedetomidine is made into uses glass bottle packaging, and vial
There is a following inferior position: 1. infusion model: air must be introduced in bottle by the breather through communicating with the external world in infusion process
Produce pressure, and dust, the microorganism in air can be infected hence into causing transfusion in vial.2. vial material
Material: vial, in preparing sterilization packaging transportation, may occur in which flake phenomenon, causes solid particle and enters transfusion or occur
Slight crack is damaged and causes infection, and this breakage is subtle, often just finds after infusion reaction occurs in patient, and this gives defeated
Liquid causes safely the biggest hidden danger.3. glass bottle liquid is during transport and storing, taken up space big and be easily broken,
Production easily causes pollution because cleaning difficulty.
Summary of the invention
The invention provides one and pack pre-mixed formulation in a reservoir, its contain the dexmedetomidine as active component or
Its salt, wherein said container has and active ingredient contacts layer, and described contact layer is plastic components.Preferred in the present invention
Embodiment in, described container generally plastic containers.
In a preferred embodiment of the present invention, described pre-mixed formulation is instant preparation, and it need not the dilutest
Release and can directly use to patient.
In further preferred embodiment of the present invention, described plastic containers can be plastic soft bag, plastic bottle, mould
The one of material pre-encapsulated injector, plastics clamped bottle etc..
The packaging pre-mixed formulation in a reservoir that the present invention provides, the plastic components of contact layer is preferably non-PVC
(PVC).The material of described non-PVC can be polypropylene (pp), polyethylene (PE), ethene improved/propylene polymerization
Thing, ethylene-vinyl acetate copolymer (EVA), cyclic olefine copolymer (COC), cyclopolyolefin (Cyclic
Polyolefin, COP) one or more materials.
The packaging pre-mixed formulation in a reservoir that the present invention provides, can also increase by one wherein in the plastic components of contact layer
Kind or multiple safe material or additive, such as styrene-ethylene-butadiene (SEB polymer), antioxidant, stearic acid
Calcium etc..
The plastic containers of the stored instant premixing dexmedetomidine compositions that the present invention provides can be plastic soft bag,
Plastic soft bag can be single component single or multiple lift co-extrusion, it is also possible to be heterogeneity monolayer or heterogeneity multi-layer co-extruded.
Internal layer (with the medicament contact layer) optimization polypropylene (pp) of plastic soft bag, polyethylene (PE), ethene improved/propylene polymerization
Thing, ethylene-vinyl acetate copolymer (EVA), cyclic olefine copolymer (COC), the one of cyclopolyolefin (COP)
Plant or multiple material composition.
In a preferred embodiment of the present invention, the plastic containers provided are plastic soft bags, and plastic soft bag can be single
Single multi-component layer or single component are multi-layer co-extruded, it is also possible to be heterogeneity monolayer or heterogeneity is multi-layer co-extruded obtains.Mould
The internal layer (with medicament contact layer) of material soft bag preferably cyclic olefine copolymer (COC), cyclopolyolefin (COP).
The plastic containers of the stored instant premixing dexmedetomidine compositions that the present invention provides can be plastic bottles, mould
The one of material pre-encapsulated injector, plastics clamped bottle etc., the material optimization polypropylene (pp) that it contacts with medicinal liquid, poly-second
Alkene (PE), ethene improved/acrylic polymers, ethylene-vinyl acetate copolymer (EVA), cyclic olefine copolymer (COC),
One or more of cyclopolyolefin (COP), preferably cyclic olefine copolymer (COC) or cyclopolyolefin (COP).
In a particularly preferred embodiment of the invention, described plastic containers are purchased from river foreign firm of Japan, its trade name
ForEHC。
What the present invention provided is packaged in the container containing plastics pre-mixed formulation, and it is about 0.05 μ g/mL containing dexmedetomidine
Between 50 μ g/mL.
What the present invention provided is packaged in the container containing plastics pre-mixed formulation, and it is about containing dexmedetomidine concentration
4μg/mL。
What the present invention provided is packaged in the container containing plastics pre-mixed formulation, also can contain isotonic agent further, preferably
Concentration is about the sodium chloride of the percentage by weight of 0.9%.
The present invention provide be packaged in the container containing plastics pre-mixed formulation, its cumulative volume be about 20mL, 50mL or
100mL。
What the present invention provided is packaged in the container containing plastics pre-mixed formulation, can be used for ICU patient with severe symptoms or injury
Calmness when calmness when initially intubating or over the course for the treatment of mechanical ventilation is it can also be used to non-intubated patient operation or short
Phase process is calm.
What the present invention provided is packaged in the container containing plastics pre-mixed formulation, and its " dexmedetomidine compositions " refers to one
Plant drug solution, comprise dexmedetomidine or pharmaceutically acceptable salt form, sodium chloride and water for injection.Its Chinese materia medica
Upper acceptable salt form can include hydrochloric acid, sulphuric acid, phosphoric acid, acetic acid, maleic acid, oxalic acid, methanesulfonic acid.Preferably
For dexmedetomidine hydrochloride.Its structural formula is as follows:
The preferred Parenteral administration of said composition.
What the present invention provided is packaged in the container containing plastics pre-mixed formulation, can keep physics, change in a long time
The stable in properties such as, biology.Select plastic containers in outward appearance, content, have related substance, microbial limit, endogenous toxin
Elements etc. the most within the acceptable range, can be consistent with the product quality of glass bottle packaging.Particularly, through detection, this
The pre-mixed formulation that is packaged in the container containing plastics of bright offer is investigated three months under the conditions of (40 DEG C/75%RH), lives
Property component content does not reduces or impurity content does not increases.
The storage that the present invention provides instant premixing dexmedetomidine compositions in a reservoir, its " instant premixing "
Refer to that medical personnel can use said preparation directly to patient, require no extra preparation, such as dilution, contribute to keeping away
Exempt from pollution and the risk of excess that human operational error causes.
What the present invention provided is packaged in the container containing plastics pre-mixed formulation, and its " plastic containers " refer to can be used for medicine
The plastic containers stored, the plastics of the most non-pvc, can be plastic soft bag, plastic bottle, plastics prefilled syringe,
Plastics clamped bottle etc..Plastic soft bag can be single component single or multiple lift co-extrusion, it is also possible to be heterogeneity monolayer or many
Layer co-extrusion, all can carry out sterilization treatment, for Parenteral administration.
What the present invention provided is packaged in the container containing plastics pre-mixed formulation, its preferred Parenteral administration, preparation process
Including solution preparation, filtration, fill, sterilizing.
The instant premixing dexmedetomidine compositions being stored in provided container that the present invention provides, stability can
Matching in excellence or beauty with the product with glass bottle packaging, plastics package simultaneously can overcome the defect of prior art, such as plastic infusion bag to exist
Infusion process is not required to use air pipe line, it is to avoid liquid-to-air contacts, reduces transfusion and pollute, and plastics package is held
Body amasss little, lightweight, the most broken.
Detailed description of the invention
It is used for further describing the present invention below in conjunction with embodiment, but these embodiments unrestricted the scope of the present invention.
Embodiment 1: the selection of instant premixing dexmedetomidine compositions plastic package material
Respectively dexmedetomidine hydrochloride and sodium chloride are dissolved in water for injection, are configured to every milliliter containing 4 μ g dexmedetomidines
With the instant premixing medicinal liquid of 9mg sodium chloride, after the PVDF membrane filtration of 0.22 μ, subpackage 50mL at internal layer is
In the multi-layer co-extrusion infusion soft bag of unlike material, carry out 121 degree, the sterilizing of 15min.Sample after sterilizing is placed on and adds
Under the conditions of speed, (40 DEG C/75%RH) carry out study on the stability.Internal layer is the multi-layer co-extrusion infusion soft bag difference of unlike material
Sealed by the transfusion thin film of different manufacturers and prepare, including Germany Pohle western Buddhist nun APP114 (internal layer is polypropylene), Germany's Pohle
Western Buddhist nun APP114-LP (internal layer is polypropylene), the M312-C (ethene improved/acrylic polymers) of Cryovac, day
The AE1 (internal layer is polyethylene) of this Xi Chuan foreign firm, the EHC (internal layer is cyclopolyolefin) of Xi Chuan foreign firm of Japan, and with
Vial contrasts.
Table 1: instant premixing dexmedetomidine compositions stability data (40 DEG C of %/75%RH) in Different Package
Result shows, by right U.S. torr pyrimidine liquid medicine filling in different packaging material, has carried out trimestral acceleration for stabilization
Property investigate, detection level, have related substance and pH.Medicinal liquid is contained in the transfusion flexible bag that internal layer is cop material and is contained in vial
Middle result is close, content, has related substance and pH all not to occur substantially to change.And being contained in internal layer is PE and ethene improved/propylene
Medicinal liquid content in the transfusion bag of copolymer reduces more obvious after sterilization, but impurity does not increase, and right U.S. torr is described
Miaow surely adsorbs and causes content to reduce on the transfusion flexible bag of these two kinds of materials.And be contained in the transfusion flexible bag that internal layer is pp material
Medicinal liquid content and pH have no substantially change, but the most miscellaneous increased under acceleration conditions.
Claims (13)
1. a packaging pre-mixed formulation in a reservoir, its contain the dexmedetomidine as active component or its
Salt, wherein said container has and active ingredient contacts layer, and described contact layer is plastic components.
Pre-mixed formulation the most according to claim 1, the plastic components of wherein said contact layer is non-pvc
Plastics.
Pre-mixed formulation the most according to claim 1, the plastic components of wherein said contact layer is selected from poly-third
Alkene, polyethylene, ethene improved/acrylic polymers, ethylene-vinyl acetate copolymer (EVA), cycloolefin are common
One or more in polymers, cyclopolyolefin.
Pre-mixed formulation the most according to claim 1, wherein the concentration of dexmedetomidine is 0.05 μ g/mL
Between 50 μ g/mL.
Pre-mixed formulation the most according to claim 1, wherein the concentration of dexmedetomidine is about 4 μ g/mL.
Pre-mixed formulation the most according to claim 1, is wherein about the weight percent of 0.9% possibly together with concentration
The sodium chloride of ratio.
Pre-mixed formulation the most according to claim 1, its cumulative volume is about 20mL, 50mL or 100mL.
Pre-mixed formulation the most according to claim 1, wherein said container generally plastic containers.
Pre-mixed formulation the most according to claim 1, wherein said container selected from plastic soft bag, plastic bottle,
Plastics prefilled syringe or plastics clamped bottle.
Pre-mixed formulation the most according to claim 9, wherein said plastic soft bag is single component monolayer
Or single component is multi-layer co-extruded, or heterogeneity monolayer or heterogeneity is multi-layer co-extruded obtains.
11. pre-mixed formulations according to claim 1, wherein said container isEHC。
12. pre-mixed formulations according to claim 1, wherein the officinal salt of dexmedetomidine is hydrochloric acid
Salt.
Pre-mixed formulation described in 13. any one of claim 1 to 12 is used for the town of ICU patient with severe symptoms in preparation
Calm or non-intubated patient's hands when quiet, injury is when initially intubating calmness, over the course for the treatment of mechanical ventilation
Purposes in the medicine of art or the calmness of short-term process.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015101837516 | 2015-04-17 | ||
| CN201510183751 | 2015-04-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106038538A true CN106038538A (en) | 2016-10-26 |
Family
ID=57484306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610231269.XA Pending CN106038538A (en) | 2015-04-17 | 2016-04-14 | Premixed preparation for dexmedetomidine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106038538A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20190262314A1 (en) * | 2018-02-26 | 2019-08-29 | Slayback Pharma Llc | Ready-to-use dexmedetomidine compositions |
| CN113116815A (en) * | 2021-06-07 | 2021-07-16 | 辰欣药业股份有限公司 | Preparation method of dexmedetomidine hydrochloride injection |
| US11786508B2 (en) | 2016-12-31 | 2023-10-17 | Bioxcel Therapeutics, Inc. | Use of sublingual dexmedetomidine for the treatment of agitation |
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103281902A (en) * | 2012-01-04 | 2013-09-04 | 赫思公司 | Dexmedetomidine premix formulation |
| JP2013203675A (en) * | 2012-03-28 | 2013-10-07 | Terumo Corp | Diluted dexmedetomidine preparation |
-
2016
- 2016-04-14 CN CN201610231269.XA patent/CN106038538A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103281902A (en) * | 2012-01-04 | 2013-09-04 | 赫思公司 | Dexmedetomidine premix formulation |
| JP2013203675A (en) * | 2012-03-28 | 2013-10-07 | Terumo Corp | Diluted dexmedetomidine preparation |
Non-Patent Citations (2)
| Title |
|---|
| ANDERSON CR ET AL.: ""Stability of dexmedetomidine 4 μg/mL in polypropylene syringes"", 《AM J HEALTH SYST PHARM》 * |
| 周健丘等: ""药品包装材料对药品质量和安全性的影响"", 《药物不良反应杂志》 * |
Cited By (7)
| 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 |
| US20190262314A1 (en) * | 2018-02-26 | 2019-08-29 | Slayback Pharma Llc | Ready-to-use dexmedetomidine compositions |
| 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 |
| CN113116815A (en) * | 2021-06-07 | 2021-07-16 | 辰欣药业股份有限公司 | Preparation method of dexmedetomidine hydrochloride injection |
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| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161026 |
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| WD01 | Invention patent application deemed withdrawn after publication |