CN103990131B - A kind of freeze-drying composition for injection and preparation method - Google Patents
A kind of freeze-drying composition for injection and preparation method Download PDFInfo
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- CN103990131B CN103990131B CN201410263235.XA CN201410263235A CN103990131B CN 103990131 B CN103990131 B CN 103990131B CN 201410263235 A CN201410263235 A CN 201410263235A CN 103990131 B CN103990131 B CN 103990131B
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- 239000000203 mixture Substances 0.000 title claims abstract description 32
- 238000004108 freeze drying Methods 0.000 title claims abstract description 15
- 238000002347 injection Methods 0.000 title claims abstract description 11
- 239000007924 injection Substances 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims description 14
- MJIHNNLFOKEZEW-RUZDIDTESA-N dexlansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1C[S@@](=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-RUZDIDTESA-N 0.000 claims abstract description 46
- 229960003568 dexlansoprazole Drugs 0.000 claims abstract description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 102
- 239000000243 solution Substances 0.000 claims description 75
- 239000011734 sodium Substances 0.000 claims description 45
- 229910052708 sodium Inorganic materials 0.000 claims description 45
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 44
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 22
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 229960003174 lansoprazole Drugs 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000008215 water for injection Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 abstract description 11
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000000047 product Substances 0.000 description 12
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 10
- 229930195725 Mannitol Natural products 0.000 description 10
- 239000000594 mannitol Substances 0.000 description 10
- 235000010355 mannitol Nutrition 0.000 description 10
- 230000005496 eutectics Effects 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000003002 pH adjusting agent Substances 0.000 description 3
- 150000003851 azoles Chemical class 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010042220 Stress ulcer Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- -1 salt Compound Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of freeze-drying composition for injection and its production and use.Relate in particular to a kind of freeze-drying composition for injection containing Dexlansoprazole or its salt and its production and use.The Dexlansoprazole or the freeze-dried composition of its salt obtained by the present invention is compared with prior art, with product is attractive in appearance, redissolution clarity is good, save the remarkable result of energy.
Description
Technical field
The present invention relates to a kind of freeze-drying composition for injection and its production and use.One kind is related in particular to contain
Freeze-drying composition for injection of Dexlansoprazole or its salt and its production and use.
Background technology
Lansoprazole（Lansoprazole, Cas No.：103577-45-3）Developed by Japanese Takeda Pharmaceutical Company Limited
Benzimidazoles derivative with gastric acid secretion inhibitory action, was synthesized first in 1986 by Novara Akira etc., and
By clinical trial certificate, the compound has antiulcer activity, control gastric acid secretion, protection stomach lining, the low feature of toxicity,
In 1992 first in Japan's listing.The chemical entitled 2- [3- methyl -4- of Lansoprazole（2,2,2- trifluoroethyls）- 2- pyridines
Base]-methylsulfinyl -1H- benzimidazoles, with the chemical constitution shown in following formula.
Above formula（Ⅱ）The single optical isomer of Lansoprazole is represented, Dexlansoprazole, Barbaric et al. is reported
The drug effect of Dexlansoprazole apparently higher than racemization Lansoprazole, and toxic side effect but be less than racemization Lansoprazole.It is existing
Result of study show that the drug effect of Dexlansoprazole is better than the Lansoprazole of laevo-configuration, the drug effect of raceme essentially from
Dexlansoprazole.
Lansoprazole is equally unstable under acidic condition with other proton pump inhibitors, and technical staff is prepared into
Sodium salt is to improve its stability and dissolubility.It is demonstrated experimentally that the lyophilized formulations into the Dexlansoprazole sodium after salt are more blue than dextrorotation
The lyophilized formulations solubility that rope draws azoles and sodium hydroxide to be obtained during preparation of preparation into salt is more preferable, and excitant is smaller.
Our experiment finds that either Dexlansoprazole is freezed, or Dexlansoprazole salt is lyophilized, in production
In preparation process, there are following shortcoming or deficiency.
First, freeze finished product often occur redissolve in bad order, the underproof situation of clarity, especially with 0.9% chlorine
Change more obvious when sodium solution redissolves.
Because the pH value of the chloride injection liquid product of in the market existing 0.9% is wider, the sodium chloride solution of lower ph is answered
Occur solution muddy phenomenon during molten Dexlansoprazole lyophilized formulations to happen occasionally, though regulation water redissolves in specification, very
To being equipped with special solvent, but this brings obvious inconvenience to Clinical practice.
2nd, because lyophilized formulations need to consume substantial amounts of energy, the eutectic point of Dexlansoprazole in itself determines that it freezes
The production in enormous quantities power consumption of dry preparation is obvious.
Lyophilized formulations freeze-drying process includes pre-freeze process, lyophilization, parsing-desiccation, and wherein pre-freeze must be in lyophilization
Preceding that all products are frozen real, pre-freezing temperature should be less than 10 DEG C or so of eutectic temperature, and pre-freeze process is general between 2 ~ 4 hours.
Temperature have to be lower than its and be disintegrated temperature in lyophilization, and the disintegration temperature of Dexlansoprazole is close to eutectic temperature, because
This, eutectic temperature is lower, and the temperature of pre-freeze process and lyophilization control is lower, and the energy of consumption is bigger, and dextrorotation is blue
Rope draws the eutectic point of azoles at -15 DEG C or so.
The content of the invention
The present invention is based on above mentioned problem generation, and o-benzoic sulfimide sodium is unexpectedly used for dextrorotation by inventor
In the lyophilized formulations preparation process of Lansoprazole or its salt, pass through lyophilized group of the obtained Dexlansoprazole of the present invention or its salt
Compound is compared with prior art, with product is attractive in appearance, redissolution clarity is good, save the remarkable result of energy.
O-benzoic sulfimide sodium is commonly called as saccharin sodium, is widely used in food as sweetener and needs the oral drugs of flavoring
In preparation.Meanwhile, o-benzoic sulfimide sodium can be administered as a kind of diagnostic reagent intravenous administration, for diagnosing patient's blood
Circulation time, safe administration dosage is up to 1g.There is not open source literature to report that o-benzoic sulfimide sodium is lyophilized for injection
Auxiliary material.
The present invention has used adjacent benzene first in the lyophilized formulations preparation process of Dexlansoprazole and Dexlansoprazole sodium
Acyl sulfimide sodium, it is found that when both are applied in combination, it is possible to increase the eutectic point of Dexlansoprazole and Dexlansoprazole sodium；
And can accelerate the redissolution time of Dexlansoprazole and Dexlansoprazole sodium, it still is able to protect after the redissolution of low ph value solution
Hold clarification；Product after lyophilized is smooth solid.
Nitrogen is a kind of inert gas, has been widely used for preparing in lyophilized formulations, but prior art is not disclosed also
The control of the flow to being passed through nitrogen is crossed, the present invention is ensureing the protective effect of nitrogen, on the premise of reducing cost as far as possible again
Obtain preferably flow and be passed through limit handling.
Specifically, the present invention is a kind of freeze-drying composition for injection, it is characterised in that contain dextrorotation in the composition
Lansoprazole or its salt and o-benzoic sulfimide sodium；The Dexlansoprazole or its salt and o-benzoic sulfimide sodium
Part by weight be 1 ~ 10:1；Also contain pH adjusting agent in the composition, the pH adjusting agent includes sodium hydroxide and hydrochloric acid；
The salt of the Dexlansoprazole is selected from Dexlansoprazole sodium, Dexlansoprazole magnesium.
Freeze-dried composition as described above, it is characterised in that the Dexlansoprazole or its salt and o-benzoyl sulphonyl
The part by weight of imines sodium is 1 ~ 6:1.
Preferably, freeze-dried composition as described above, it is characterised in that the single dose of the composition, which is constituted, is：
10 ~ 30mg of Dexlansoprazole sodium（In terms of Lansoprazole）
5 ~ 10mg of o-benzoic sulfimide sodium
Sodium hydroxide and appropriate hydrochloric acid.
Single dose refers to minimum single lyophilized formulations form（Bottle）In each constituent consumption.
Present invention additionally comprises a kind of preparation method of freeze-dried composition as described above, it is characterised in that methods described bag
Include step：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 10 ~ 11 to make pH, then by o-benzoic sulfimide
Sodium dissolving is complete, obtains solution 1；
（2）Dexlansoprazole or its salt are added while inert gas is passed through into solution 1, fully obtains molten after dissolving
Liquid 2；
（3）PH adjusting agent and solution 2 are mixed, it is 10 ~ 11 to make pH, obtains solution 3；
（4）Solution 3 is subjected to the lyophilized freeze-dried composition obtained as described in any one of claim 1 ~ 6.
Preferably, preparation method as described above, it is characterised in that the inert gas is nitrogen, controls the stream being passed through
Measure as 0.1 ~ 0.3MPa.
It is highly preferred that preparation method as described above, it is characterised in that the flow that the control inert nitrogen gas is passed through
For 0.2 MPa.
Present invention additionally comprises a kind of purposes of the freeze-dried composition described in freeze-dried composition as described above, controlled for preparing
Treat gastric acid related disorder or prevent the medicine of stress ulcer.
Figure of description
Solution character of the sample of Fig. 1 embodiments 5~8 after the redissolution of 0.9% sodium chloride solution
Inventive embodiments
In order to further illustrate the effect of the present invention, the following example is enumerated, but the present invention is not limited to following embodiments.
Embodiment 1
Prescription（1000 bottles）：
Dexlansoprazole 30g
O-benzoic sulfimide sodium 10g
Sodium hydroxide 20g
Technique：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 10.5 to make pH, then by o-benzoic sulfimide
Sodium dissolving is complete, obtains solution 1；
（2）Dexlansoprazole is added while being passed through nitrogen into solution 1 with 0.25MPa speed, fully after dissolving
Obtain solution 2；
（3）Sodium hydroxide or hydrochloric acid and solution 2 are mixed, it is 10.5 to make pH, obtains solution 3；
（4）Solution 3 is subjected to lyophilized finished product.
Embodiment 2
Prescription（1000 bottles）：
Dexlansoprazole 30g
O-benzoic sulfimide sodium 30g
Sodium hydroxide 10g
Technique：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 10.0 to make pH, then by o-benzoic sulfimide
Sodium dissolving is complete, obtains solution 1；
（2）Dexlansoprazole is added while being passed through nitrogen into solution 1 with 0.30MPa speed, fully after dissolving
Obtain solution 2；
（3）Sodium hydroxide or hydrochloric acid and solution 2 are mixed, it is 10.0 to make pH, obtains solution 3；
（4）Solution 3 is subjected to lyophilized finished product.
Embodiment 3
Prescription（1000 bottles）：
Dexlansoprazole sodium 30g（In terms of Lansoprazole）
Mannitol 30g
O-benzoic sulfimide sodium 25g
Sodium hydroxide 20g
Technique：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 10.3 to make pH, then by mannitol and o-benzoyl
The dissolving of sulfimide sodium is complete, obtains solution 1；
（2）Dexlansoprazole sodium, fully dissolving are added while being passed through nitrogen into solution 1 with 0.15MPa speed
After obtain solution 2；
（3）Sodium hydroxide or hydrochloric acid and solution 2 are mixed, it is 10.3 to make pH, obtains solution 3；
（4）Solution 3 is subjected to lyophilized finished product.
Embodiment 4
Prescription（1000 bottles）：
Dexlansoprazole magnesium 30g（In terms of Lansoprazole）
Mannitol 30g
O-benzoic sulfimide sodium 3g
Sodium hydroxide 20g
Technique：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 11.0 to make pH, then by mannitol and o-benzoyl
The dissolving of sulfimide sodium is complete, obtains solution 1；
（2）Dexlansoprazole magnesium, fully dissolving are added while being passed through nitrogen into solution 1 with 0.10MPa speed
After obtain solution 2；
（3）Sodium hydroxide or hydrochloric acid and solution 2 are mixed, it is 11.0 to make pH, obtains solution 3；
（4）Solution 3 is subjected to lyophilized finished product.
Embodiment 5
Prescription（1000 bottles）：
Dexlansoprazole 30g
Mannitol 40g
O-benzoic sulfimide sodium 5g
Sodium hydroxide 10g
Technique：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 10.8 to make pH, then mannitol and by o-benzoyl
The dissolving of sulfimide sodium is complete, obtains solution 1；
（2）Dexlansoprazole is added while being passed through nitrogen into solution 1 with 0.20MPa speed, fully after dissolving
Obtain solution 2；
（3）Sodium hydroxide or hydrochloric acid and solution 2 are mixed, it is 10.8 to make pH, obtains solution 3；
（4）Solution 3 is subjected to lyophilized finished product.
Embodiment 6
Prescription（1000 bottles）：
Dexlansoprazole sodium 30g（In terms of Lansoprazole）
O-benzoic sulfimide sodium 15g
Sodium hydroxide 10g
Technique：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 10.6 to make pH, then by o-benzoic sulfimide
Sodium dissolving is complete, obtains solution 1；
（2）Dexlansoprazole sodium, fully dissolving are added while being passed through nitrogen into solution 1 with 0.20MPa speed
After obtain solution 2；
（3）Sodium hydroxide or hydrochloric acid and solution 2 are mixed, it is 10.6 to make pH, obtains solution 3；
（4）Solution 3 is subjected to lyophilized finished product.
Embodiment 7（Comparative example）
Prescription（1000 bottles）：
Dexlansoprazole 30g
Mannitol 40g
Sodium hydroxide 10g
Technique：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 10.5 to make pH, then mannitol is dissolved into complete, is obtained
To solution 1；
（2）Dexlansoprazole is added into solution 1, fully solution 2 is obtained after dissolving；
（3）Sodium hydroxide or hydrochloric acid and solution 2 are mixed, it is 10.5 to make pH, obtains solution 3；
（4）Solution 3 is subjected to lyophilized finished product.
Embodiment 8（Comparative example）
Prescription（1000 bottles）：
Dexlansoprazole sodium 30g（In terms of Lansoprazole）
Mannitol 40g
O-benzoic sulfimide sodium 5g
Sodium hydroxide 10g
Technique：
（1）By water for injection and sodium hydroxide in 10 ~ 20 DEG C of mixing, it is 10.5 to make pH, then by mannitol and o-benzoyl
The dissolving of sulfimide sodium is complete, obtains solution 1；
（2）Dexlansoprazole sodium is added into solution 1, fully solution 2 is obtained after dissolving；
（3）Sodium hydroxide or hydrochloric acid and solution 2 are mixed, it is 10.5 to make pH, obtains solution 3；
（4）Solution 3 is subjected to lyophilized finished product.
Embodiment 9
By embodiment 5,6 and embodiment 7,8（Comparative example）Eutectic temperature be measured
Dong Fulong freeze dryers lyo-o.5 is taken to carry platinum electrode measurement, it is as a result as follows.
The eutectic temperature of embodiment 5,6 increases 5 DEG C or so than the eutectic temperature of embodiment 7,8, and this was being freezed
Both the time of lyophilization had been saved in journey, the power consumption of freeze dryer is saved again, the reduction of water power consumption brings economic benefit.
Embodiment 10
By embodiment 5,6 and embodiment 7,8（Comparative example）Finished appearance, redissolution, relevant material test experience press
Method according to States Pharmacopoeia specifications is compared, and its result is as follows（Solution character of the sample after the redissolution of 0.9% sodium chloride injection
See Figure of description 1.
The above results can significantly find out that preferably, relevant material is low, redissolves solution for embodiments of the invention 5,6 outward appearances
Clear, and the embodiment 7 without o-benzoic sulfimide sodium（Comparative example）After being redissolved with sodium chloride injection
It is substantially muddy；The embodiment 8 of obstructed nitrogen in technique（Comparative example）Relevant material about material than the embodiment of the present invention
It is higher by several times.
Claims (2)
1. a kind of freeze-drying composition for injection, it is characterised in that the freeze-dried composition is according to 1000 bottles of prescription inventory, respectively
The weight of component is as follows：
Dexlansoprazole sodium calculates 30g with Lansoprazole
O-benzoic sulfimide sodium 15g
Sodium hydroxide 10g；
Also, above-mentioned freeze-dried composition is according to obtained by the preparation of following technique：
(1) by water for injection and sodium hydroxide in 10-20 DEG C of mixing, it is 10.6 to make pH, then o-benzoic sulfimide sodium is molten
Solution is complete, obtains solution 1；
(2) Dexlansoprazole sodium is added while being passed through nitrogen into solution 1 with 0.20MPa speed, fully after dissolving
To solution 2；
(3) sodium hydroxide or hydrochloric acid are mixed with solution 2, it is 10.6 to make pH, obtains solution 3；
(4) solution 3 is subjected to lyophilized finished product.
2. a kind of method for preparing freeze-drying composition for injection as claimed in claim 1, it is characterised in that this method prepares institute
Freeze-dried composition according to 1000 bottles of prescription inventory, the weight of each component is as follows：
Dexlansoprazole sodium calculates 30g with Lansoprazole
O-benzoic sulfimide sodium 15g
Sodium hydroxide 10g；
Also, the preparation method of above-mentioned freeze-dried composition is as follows：
(1) by water for injection and sodium hydroxide in 10-20 DEG C of mixing, it is 10.6 to make pH, then o-benzoic sulfimide sodium is molten
Solution is complete, obtains solution 1；
(2) Dexlansoprazole sodium is added while being passed through nitrogen into solution 1 with 0.20MPa speed, fully after dissolving
To solution 2；
(3) sodium hydroxide or hydrochloric acid are mixed with solution 2, it is 10.6 to make pH, obtains solution 3；
(4) solution 3 is subjected to lyophilized finished product.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101129368A (en) * | 2007-08-23 | 2008-02-27 | 姚俊华 | Freeze-dried powder needle containing lansoprazole |
| CN101874789A (en) * | 2007-08-23 | 2010-11-03 | 姚俊华 | Lansoprazole-contained freeze-dried powder injection |
| CN102552181A (en) * | 2012-01-20 | 2012-07-11 | 江苏吴中医药集团有限公司 | Lansoprazole lyophilized powder injection preparation and its preparing method |
-
2014
- 2014-06-14 CN CN201410263235.XA patent/CN103990131B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101129368A (en) * | 2007-08-23 | 2008-02-27 | 姚俊华 | Freeze-dried powder needle containing lansoprazole |
| CN101874789A (en) * | 2007-08-23 | 2010-11-03 | 姚俊华 | Lansoprazole-contained freeze-dried powder injection |
| CN102552181A (en) * | 2012-01-20 | 2012-07-11 | 江苏吴中医药集团有限公司 | Lansoprazole lyophilized powder injection preparation and its preparing method |
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| CN103990131A (en) | 2014-08-20 |
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