CN109568259A - A kind of liquid drugs injection and preparation method thereof containing s-ropivacaine mesylate - Google Patents
A kind of liquid drugs injection and preparation method thereof containing s-ropivacaine mesylate Download PDFInfo
- Publication number
- CN109568259A CN109568259A CN201811650296.6A CN201811650296A CN109568259A CN 109568259 A CN109568259 A CN 109568259A CN 201811650296 A CN201811650296 A CN 201811650296A CN 109568259 A CN109568259 A CN 109568259A
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- CN
- China
- Prior art keywords
- preparation
- injection
- ropivacaine
- liquid drugs
- added
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Classifications
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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
- A61K9/08—Solutions
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K47/02—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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
Abstract
The invention belongs to field of medicine preparing technology, are related to a kind of liquid drugs injection and preparation method thereof containing s-ropivacaine mesylate.The preparation method specific steps are as follows: the 1) water for injection of theoretical amount of preparation 80% is added in dispensing canister, the sodium chloride and s-ropivacaine mesylate of recipe quantity is added, the needle-use activated carbon soaked, stirring and adsorbing is added in stirring to Quan Rong；2) pH value is adjusted to 4.5~5.5 with pH adjusting agent, benefit adds to the full amount of water for injection, and draws circulation 10~20 minutes；3) with three-in-one device bottle, fill N2It is filling, it seals, sterilizes, packaging.Compared with prior art, the ropivacaine mesylate injection that the method for the invention is prepared is safe and reliable, stability is good, and isomers is few.In addition, the polypropylene ampoule of " blow-fill-seal " three-in-one sterile system is packed, compared with glass ampule packaging, it is not likely to produce fragment and particle fine powder in opening process, convenient transportation, securely and reliably.
Description
Technical field
The invention belongs to field of medicine preparing technology, it particularly relates to arrive a kind of water needle containing s-ropivacaine mesylate
Agent and preparation method thereof.
Background technique
Ropivacaine is local anesthetics of amide derivatives, is mainly used for surgical operation and anaesthetizes: caudal anaesthesia (including cesarean section is hard
It is anaesthetized outside film)；Local infiltration anesthesia.Acute Pain control: being used for postoperative or inhibiting pain in parturition, and Continual epidural infusion can be used,
It can also intermittent medication；Local infiltration anesthesia.It can delay the expansion cloth of nerve impulse by the threshold value of raising nerve action potential,
The raised speed of action potential is reduced, the generation of block nerves impulsion and the effect of conduction are played.
The pKa of Ropivacaine is 8.1, and distributive law is 141 (25 DEG C of n- octanol/phosphate buffer PH7.4).Ropivacaine
Plasma concentration depends on the vascular distribution of dosage, route of administration and injection site.Ropivacaine meets linear Dai Xue, maximum blood plasma
Concentration and dose proportional.Ropivacaine is complete and two-phase from peridural absorption, and half-life period sequence is respectively 14
Minute and 4 hours.The total plasma clearance 440ml/min of Ropivacaine, plasma clearance of dissociating are 8L/min, and kidney clearance rate is
1ml/min, the distribution volume 47L of stable state, non-half-life period is 1.8hr eventually.Ropivacaine is through liver intermediate supersession rate
0.4.Ropivacaine main and α 1- acid Glycoprotein binding in blood plasma, non-protein Percentage bound are 6%.
Ropivacaine is mainly acted on by aromatic hydroxy group and being sufficiently metabolized, and the 86% of accumulated dose passes through after intravenous injection
Urine excretes, wherein only 1% related with the drug not being metabolized.Major metabolite is 3- hydroxyl Ropivacaine, wherein about
37% is excreted from urine in the form of conjugate, and the 4- hydroxyl Ropivacaine excreted in urine, N- removes alkyl metabolin
Removing alkyl metabolin with 4- hydroxyl is about 1-3%.In conjunction with and uncombined 3- hydroxyl Ropivacaine only display can in blood plasma
The concentration predicted.
The preparation of medicinal Ropivacaine mainly uses left-handed Ropivacaine, but during production and storage, is easy to happen
Variation generates dextroisomer and other related impurities, and current preparation process is complex, higher cost.
Summary of the invention
In order to solve the above technical problems, the present invention provides a kind of simple processes, at low cost, safe and reliable, stability
Good, isomers is few, convenient for the liquid drugs injection and preparation method thereof containing s-ropivacaine mesylate of clinical use.
A kind of preparation method of liquid drugs injection containing s-ropivacaine mesylate of the present invention, the preparation method specifically walk
Suddenly are as follows: 1) water for injection of theoretical amount of preparation 80% is added in dispensing canister, the sodium chloride and methanesulfonic acid sieve piperazine of recipe quantity is added
The needle-use activated carbon soaked, stirring and adsorbing is added in cacaine, stirring to Quan Rong；2) with pH adjusting agent adjust pH value to 4.5~
5.5, benefit adds to the full amount of water for injection, and draws circulation 10~20 minutes；3) with three-in-one device bottle, fill N2Filling, sealing is gone out
Bacterium, packaging.
A kind of preparation method of liquid drugs injection containing s-ropivacaine mesylate of the present invention, the temperature of the water for injection
It is 30~40 DEG C.
A kind of preparation method of liquid drugs injection containing s-ropivacaine mesylate of the present invention, the needle-use activated carbon dosage
Account for 0.01%~0.03% (w/v) of full dose.
A kind of preparation method of liquid drugs injection containing s-ropivacaine mesylate of the present invention, the pH adjusting agent are selected from
0.01mol/L hydrochloric acid solution, 0.01mol/L sodium hydroxide solution.
A kind of preparation method of liquid drugs injection containing s-ropivacaine mesylate of the present invention, the s-ropivacaine mesylate
It is saved at -40 DEG C before being configured to liquid drugs injection with after 5 DEG C of -10 DEG C of recrystallizations of methanol.
Ropivacaine mesylate injection that compared with prior art, the method for the invention is prepared is safe and reliable,
Stability is good, and isomers is few.In addition, on simple and reliable Process ba- sis, we using it is international it is advanced " blow bottle-it is filling-
The polypropylene ampoule packaging of the three-in-one sterile system of sealing " is not likely to produce broken compared with glass ampule packaging in opening process
Piece and particle fine powder, convenient transportation, securely and reliably.
Specific embodiment
Liquid drugs injection and preparation method thereof to of the present invention containing s-ropivacaine mesylate combined with specific embodiments below
It is described further, but the scope of protection of the present invention is not limited thereto.
Embodiment 1
Prescription:
Preparation method:
(1) water for injection of 80L is added in dispensing canister, is cooled to 40 DEG C, the sodium chloride and 0.894kg of 0.75kg is added
S-ropivacaine mesylate, stir 30 minutes；The s-ropivacaine mesylate is before being configured to liquid drugs injection with 5 DEG C of methanol recrystallizations
It is saved at 0 DEG C afterwards.All after dissolution, the needle-use activated carbon of 0.03kg soaked, stirring and adsorbing is added in visual raw material
20 minutes.(2) pH value is adjusted to 5.5 with 0.01mol/L sodium hydroxide solution, benefit adds to the full amount of water for injection, and draws 20 points of circulation
Clock.(3) sample detection semi-finished product pH value, content, endotoxin.(4) it after semi-finished product detection is qualified, with three-in-one device bottle, fills
N2It is filling, sealing.(5) 121 DEG C sterilize 15 minutes, are cooled to 45 DEG C or less and offer for sale.(6) it is packed after lamp inspection is qualified, full inspection enters
Library.
Embodiment 2
Prescription:
Preparation method:
(1) water for injection of 80L is added in dispensing canister, is cooled to 40 DEG C, the sodium chloride and 0.894kg of 0.75kg is added
S-ropivacaine mesylate, stir 30 minutes；The s-ropivacaine mesylate is before being configured to liquid drugs injection with 5 DEG C of methanol recrystallizations
It is saved at -40 DEG C afterwards.All after dissolution, the needle-use activated carbon of 0.03kg soaked is added in visual raw material, and stirring is inhaled
Attached 20 minutes.(2) pH value is adjusted to 5.5 with 0.01mol/L sodium hydroxide solution, benefit adds to the full amount of water for injection, and draws circulation 20
Minute.(3) sample detection semi-finished product pH value, content, endotoxin.(4) after semi-finished product detection is qualified, with three-in-one device bottle,
Fill N2It is filling, sealing.(5) 121 DEG C sterilize 15 minutes, are cooled to 45 DEG C or less and offer for sale.(6) it is packed after lamp inspection is qualified, full inspection enters
Library.
Embodiment 3
Prescription:
Preparation method:
(1) water for injection of 80L is added in dispensing canister, is cooled to 40 DEG C, the sodium chloride and 0.894kg of 0.75kg is added
S-ropivacaine mesylate, stir 30 minutes；The s-ropivacaine mesylate is before being configured to liquid drugs injection with 5 DEG C of methanol recrystallizations
It is saved at -80 DEG C afterwards.All after dissolution, the needle-use activated carbon of 0.03kg soaked is added in visual raw material, and stirring is inhaled
Attached 20 minutes.(2) pH value is adjusted to 5.5 with 0.01mol/L sodium hydroxide solution, benefit adds to the full amount of water for injection, and draws circulation 20
Minute.(3) sample detection semi-finished product pH value, content, endotoxin.(4) after semi-finished product detection is qualified, with three-in-one device bottle,
Fill N2It is filling, sealing.(5) 121 DEG C sterilize 15 minutes, are cooled to 45 DEG C or less and offer for sale.(6) it is packed after lamp inspection is qualified, full inspection enters
Library.
Embodiment 4
Prescription:
Preparation method:
(1) water for injection of 80L is added in dispensing canister, is cooled to 40 DEG C, the sodium chloride and 0.894kg of 0.75kg is added
S-ropivacaine mesylate, stir 30 minutes；The s-ropivacaine mesylate is before being configured to liquid drugs injection with 5 DEG C of methanol recrystallizations
It is saved at -20 DEG C afterwards.All after dissolution, the needle-use activated carbon of 0.03kg soaked is added in visual raw material, and stirring is inhaled
Attached 20 minutes.(2) pH value is adjusted to 5.5 with 0.01mol/L sodium hydroxide solution, benefit adds to the full amount of water for injection, and draws circulation 20
Minute.(3) sample detection semi-finished product pH value, content, endotoxin.(4) after semi-finished product detection is qualified, with three-in-one device bottle,
Fill N2It is filling, sealing.(5) 121 DEG C sterilize 15 minutes, are cooled to 45 DEG C or less and offer for sale.(6) it is packed after lamp inspection is qualified, full inspection enters
Library.
In order to illustrate the stability of preparation prepared by the present invention, to preparation prepared by the present invention in 40 DEG C ± 2 DEG C of temperature,
Acceleration investigation is carried out under the conditions of relative humidity 75% ± 5%, as a result see the table below.
Accelerate to investigate result:
The result shows that: it according to finished product made from embodiment, is investigated by acceleration in 6 months, the ph value of preparation, related substance
With it is almost the same with batch formulation samples analysis result before the measurement result of content and experiment, product indices without significant change,
Stable product quality illustrates having good stability for invention formulation.
Claims (6)
1. a kind of preparation method of the liquid drugs injection containing s-ropivacaine mesylate, which is characterized in that the preparation method specific steps
Are as follows: 1) water for injection of theoretical amount of preparation 80% is added in dispensing canister, the sodium chloride and methanesulfonic acid sieve piperazine card of recipe quantity is added
The needle-use activated carbon soaked, stirring and adsorbing is added in cause, stirring to Quan Rong；2) with pH adjusting agent adjust pH value to 4.5~
5.5, benefit adds to the full amount of water for injection, and draws circulation 10~20 minutes；3) with three-in-one device bottle, fill N2Filling, sealing is gone out
Bacterium, packaging.
2. the preparation method of the liquid drugs injection according to claim 1 containing s-ropivacaine mesylate, which is characterized in that the note
Penetrating with the temperature of water is 30~40 DEG C.
3. the preparation method of the liquid drugs injection according to claim 1 containing s-ropivacaine mesylate, which is characterized in that the needle
The 0.01%~0.03% of full dose is accounted for activated carbon dosage.
4. the preparation method of the liquid drugs injection according to claim 1 containing s-ropivacaine mesylate, which is characterized in that the pH
It is worth regulator and is selected from 0.01mol/L hydrochloric acid solution, 0.01mol/L sodium hydroxide solution.
5. the preparation method of the liquid drugs injection according to claim 1 containing s-ropivacaine mesylate, which is characterized in that the first
Sulfonic acid Ropivacaine is saved at -40 DEG C before being configured to liquid drugs injection with after 5 DEG C of -10 DEG C of recrystallizations of methanol.
6. the liquid drugs injection containing s-ropivacaine mesylate made from -5 any preparation methods according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811650296.6A CN109568259A (en) | 2018-12-31 | 2018-12-31 | A kind of liquid drugs injection and preparation method thereof containing s-ropivacaine mesylate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811650296.6A CN109568259A (en) | 2018-12-31 | 2018-12-31 | A kind of liquid drugs injection and preparation method thereof containing s-ropivacaine mesylate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109568259A true CN109568259A (en) | 2019-04-05 |
Family
ID=65915595
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811650296.6A Pending CN109568259A (en) | 2018-12-31 | 2018-12-31 | A kind of liquid drugs injection and preparation method thereof containing s-ropivacaine mesylate |
Country Status (1)
| Country | Link |
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| CN (1) | CN109568259A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113116815A (en) * | 2021-06-07 | 2021-07-16 | 辰欣药业股份有限公司 | Preparation method of dexmedetomidine hydrochloride injection |
| CN113679667A (en) * | 2021-08-19 | 2021-11-23 | 石家庄四药有限公司 | Ropivacaine hydrochloride injection and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552126A (en) * | 2012-01-20 | 2012-07-11 | 清远嘉博制药有限公司 | High-safety ropivacaine hydrochloride injection and preparation method thereof |
| CN105125486A (en) * | 2015-10-15 | 2015-12-09 | 扬子江药业集团南京海陵药业有限公司 | Preparation method for ropivacaine mesylate injection solution |
| EP3285781A1 (en) * | 2015-04-23 | 2018-02-28 | BIOXIS Pharmaceuticals | Homogeneous aqueous solution of injectable chitosan having a ph close to physiological ph |
-
2018
- 2018-12-31 CN CN201811650296.6A patent/CN109568259A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552126A (en) * | 2012-01-20 | 2012-07-11 | 清远嘉博制药有限公司 | High-safety ropivacaine hydrochloride injection and preparation method thereof |
| EP3285781A1 (en) * | 2015-04-23 | 2018-02-28 | BIOXIS Pharmaceuticals | Homogeneous aqueous solution of injectable chitosan having a ph close to physiological ph |
| CN105125486A (en) * | 2015-10-15 | 2015-12-09 | 扬子江药业集团南京海陵药业有限公司 | Preparation method for ropivacaine mesylate injection solution |
Non-Patent Citations (1)
| Title |
|---|
| 国家食品药品监督管理局药品认证管理中心编写: "《药物GMP指南 无菌药物》", 31 August 2011, 中国医药科技出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113116815A (en) * | 2021-06-07 | 2021-07-16 | 辰欣药业股份有限公司 | Preparation method of dexmedetomidine hydrochloride injection |
| CN113679667A (en) * | 2021-08-19 | 2021-11-23 | 石家庄四药有限公司 | Ropivacaine hydrochloride injection and preparation method thereof |
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| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190405 |
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